Most-cited articles · 2023

The 100 most-cited articles in Journal of Clinical Medicine, 2023

Ranked by OpenAlex citation count on 29 October 2026, out of 7,524 eligible articles Journal of Clinical Medicine published in 2023. Ranks are frozen; this page will not change. Number one, with 520 citations: Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics.

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7,524 articles
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Top 100 (1.3%)
Open access
100 of 100
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2026-10-29

The most-cited articles from the Journal of Clinical Medicine in 2023 are led by reviews and cohort studies, with several themes recurring near the top of the ranking. Endocrine and metabolic disorders feature prominently, including the top paper, "Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics" by Singh, Pal, Shubham and colleagues, with 520 citations. Inflammation and cardiovascular risk also appear early, exemplified by a 20-year cohort study of the Systemic Immune Inflammation Index and mortality, and by an update on sepsis and septic shock management in emergency departments.

For readers, the list offers a citation-based view of the work that attracted the most attention in this journal during 2023, drawn from 7,524 eligible articles. It spans clinical reviews, epidemiological analyses, and management updates across many specialties, and can serve as a starting point for exploring topics of broad interest. Citation counts reflect accumulated scholarly attention rather than a judgment of quality, and they continue to change over time.

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    Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics

    Samradhi Singh, Namrata Pal, Swasti Shubham, Devojit Kumar Sarma, Vinod Verma and 2 more

    520 citationsOpen access (CC-BY)doi:10.3390/jcm12041454OpenAlex

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    Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.

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    Systemic Immune Inflammation Index (SII), System Inflammation Response Index (SIRI) and Risk of All-Cause Mortality and Cardiovascular Mortality: A 20-Year Follow-Up Cohort Study of 42,875 US Adults

    Yiyuan Xia, Chunlei Xia, Li‐Da Wu, Zheng Li, Hui Li and 1 more

    502 citationsOpen access (CC-BY)doi:10.3390/jcm12031128OpenAlex

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    BACKGROUND AND AIM: Chronic low-grade inflammation is associated with various health outcomes, including cardiovascular diseases (CVDs) and cancers. Systemic immune inflammation index (SII) and system inflammation response index (SIRI) have lately been explored as novel prognostic markers for all-cause mortality and cardiovascular mortality. However, studies on prediction value in nationwide representative population are scarce, which limit their generalization. To bridge the knowledge gap, this study aims to prospectively assess the association of SII, SIRI with all-cause mortality and cardiovascular mortality in the National Health and Nutrition Examination Survey (NHANES). METHODS: From 1999 to 2018, 42,875 adults who were free of pregnancy, CVDs (stroke, acute coronary syndrome), cancers, and had follow-up records and participated in the NHANES were included in this study. SII and SIRI were quantified by calculating the composite inflammation indicators from the blood routine. To explore the characteristics of the population in different SII or SIRI levels, we divided them…

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    2023 Update on Sepsis and Septic Shock in Adult Patients: Management in the Emergency Department

    Matteo Guarino, Benedetta Perna, Alice Eleonora Cesaro, Martina Maritati, Michele Domenico Spampinato and 2 more

    297 citationsOpen access (CC-BY)doi:10.3390/jcm12093188OpenAlex

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    BACKGROUND: Sepsis/septic shock is a life-threatening and time-dependent condition that requires timely management to reduce mortality. This review aims to update physicians with regard to the main pillars of treatment for this insidious condition. METHODS: PubMed, Scopus, and EMBASE were searched from inception with special attention paid to November 2021-January 2023. RESULTS: The management of sepsis/septic shock is challenging and involves different pathophysiological aspects, encompassing empirical antimicrobial treatment (which is promptly administered after microbial tests), fluid (crystalloids) replacement (to be established according to fluid tolerance and fluid responsiveness), and vasoactive agents (e.g., norepinephrine (NE)), which are employed to maintain mean arterial pressure above 65 mmHg and reduce the risk of fluid overload. In cases of refractory shock, vasopressin (rather than epinephrine) should be combined with NE to reach an acceptable level of pressure control. If mechanical ventilation is indicated, the tidal volume should be reduced from 10 to 6 mL/kg.…

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    Understanding and Fostering Mental Health and Well-Being among University Faculty: A Narrative Review

    Dalal Hammoudi Halat, Abderrezzaq Soltani, Roua Dalli, Lama Alsarraj, Ahmed M Malki

    296 citationsOpen access (CC-BY)doi:10.3390/jcm12134425OpenAlex

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    In recent years, there has been increasing recognition of mental health concerns in academia, with stress, burnout, anxiety, and depression being reported among faculty members. The demanding work environment, the need to balance personal and professional duties, and the constant pressure of productivity while navigating multiple tasks of teaching, research, mentorship, professional development, and service all impact the mental health and overall well-being of faculty. Higher education institutions have structurally changed as has the research landscape. These changes as well as faculty-specific and student-specific factors coupled to the effect of the COVID-19 pandemic have led to profound effects on the mental health of academics. This paper is a narrative review of the pertinent literature describing faculty mental health and well-being. It summarizes the available evidence on factors influencing faculty mental health and shows the prevalence of anxiety, depression, stress, and burnout among faculty from various academic fields and along the whole academic ladder. Using a…

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    Noise-Induced Hearing Loss

    Nirvikalpa Natarajan, Shelley A. Batts, Konstantina M. Stanković

    258 citationsOpen access (CC-BY)doi:10.3390/jcm12062347OpenAlex

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    Noise-induced hearing loss (NIHL) is the second most common cause of sensorineural hearing loss, after age-related hearing loss, and affects approximately 5% of the world's population. NIHL is associated with substantial physical, mental, social, and economic impacts at the patient and societal levels. Stress and social isolation in patients' workplace and personal lives contribute to quality-of-life decrements which may often go undetected. The pathophysiology of NIHL is multifactorial and complex, encompassing genetic and environmental factors with substantial occupational contributions. The diagnosis and screening of NIHL are conducted by reviewing a patient's history of noise exposure, audiograms, speech-in-noise test results, and measurements of distortion product otoacoustic emissions and auditory brainstem response. Essential aspects of decreasing the burden of NIHL are prevention and early detection, such as implementation of educational and screening programs in routine primary care and specialty clinics. Additionally, current research on the pharmacological treatment of…

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    Acute Kidney Injury: Medical Causes and Pathogenesis

    Faruk Hilmi Turgut, Alaa S. Awad, Emaad M. Abdel‐Rahman

    211 citationsOpen access (CC-BY)doi:10.3390/jcm12010375OpenAlex

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    Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI.

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    Chronic Low Back Pain: A Narrative Review of Recent International Guidelines for Diagnosis and Conservative Treatment

    Vanina Nicol, Claire Verdaguer, Camille Daste, H. Bisseriex, Eric Lapeyre and 5 more

    201 citationsOpen access (CC-BY)doi:10.3390/jcm12041685OpenAlex

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    Chronic low back pain (cLBP) is a public and occupational health problem that is a major professional, economic and social burden. We aimed to provide a critical overview of current international recommendations regarding the management of non-specific cLBP. We conducted a narrative review of international guidelines for the diagnosis and conservative treatment of people with non-specific cLBP. Our literature search yielded five reviews of guidelines published between 2018 and 2021. In these five reviews, we identified eight international guidelines that fulfilled our selection criteria. We added the 2021 French guidelines into our analysis. Regarding diagnosis, most international guidelines recommend searching for so-called yellow, blue and black flags, in order to stratify the risk of chronicity and/or persistent disability. The relevance of clinical examination and imaging are under debate. Regarding management, most international guidelines recommend non-pharmacological treatments, including exercise therapy, physical activity, physiotherapy and education; however,…

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    Serum Albumin Levels: A Biomarker to Be Repurposed in Different Disease Settings in Clinical Practice

    Elisa Gremese, Dario Bruno, Valentina Varriano, Simone Perniola, Luca Petricca and 1 more

    200 citationsOpen access (CC-BY)doi:10.3390/jcm12186017OpenAlex

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    Serum albumin (ALB), one of the most important proteins in human physiology, has the main functions of maintaining plasma oncotic pressure and plasma volume, transporting hormones, vitamins, oligominerals and drugs, and exerting a powerful antioxidant-anti-inflammatory role. Its prognostic value in liver and malabsorption syndromes is well known. In this narrative review, an analysis of the most important studies evaluating the prognostic significance of low serum ALB levels in hospitalized patients was performed. Specifically, the risk in emergency medicine, cardiovascular diseases, Coronavirus Disease 19 (COVID-19) infection, nephrology, oncology, and autoimmune rheumatic diseases has been examined to fully explore its clinical value. ALB is a negative acute-phase reactant and the reduction in its serum levels represents a threatening parameter for long-term survival in several clinical settings, and a strong biomarker for a poor prognosis in most diseases. Therefore, clinicians should consider serum ALB as a valuable tool to assess the efficacy of specific therapies, both in…

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    Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

    Akbayan Turesheva, Gulzhanat Nuratdinovna Aimagambetova, Talshyn Ukybassova, Аizada Marat, Perizat Kanabekova and 8 more

    175 citationsOpen access (CC-BY)doi:10.3390/jcm12124074OpenAlex

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    Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their…

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    Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss

    Nicole Natarelli, Nimrit Gahoonia, Raja K. Sivamani

    173 citationsOpen access (CC-BY)doi:10.3390/jcm12030893OpenAlex

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    The hair cycle is composed of four primary phases: anagen, catagen, telogen, and exogen. Anagen is a highly mitotic phase characterized by the production of a hair shaft from the hair follicle, whereas catagen and telogen describe regression and the resting phase of the follicle, respectively, ultimately resulting in hair shedding. While 9% of hair follicles reside in telogen at any time, a variety of factors promote anagen to telogen transition, including inflammation, hormones, stress, nutritional deficiency, poor sleep quality, and cellular division inhibiting medication. Conversely, increased blood flow, direct stimulation of the hair follicle, and growth factors promote telogen to anagen transition and subsequent hair growth. This review seeks to comprehensively describe the hair cycle, anagen and telogen balance, factors that promote anagen to telogen transition and vice versa, and the clinical utility of a variety of lab testing and evaluations. Ultimately, a variety of factors impact the hair cycle, necessitating a holistic approach to hair loss.

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    Advances in Neurodegenerative Diseases

    Jeroen Van Schependom, Miguel D’haeseleer

    166 citationsOpen access (CC-BY)doi:10.3390/jcm12051709OpenAlex

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    Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population [...].

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    Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

    Gian Marco Leone, Katia Mangano, Maria Cristina Petralia, Ferdinando Nicoletti, Paolo Fagone

    162 citationsOpen access (CC-BY)doi:10.3390/jcm12041630OpenAlex

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    Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

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    The Global Burden of Valvular Heart Disease: From Clinical Epidemiology to Management

    Gloria Santangelo, Francesca Bursi, Andrea Faggiano, Silvia Moscardelli, Pasquale Simone Simeoli and 4 more

    158 citationsOpen access (CC-BY)doi:10.3390/jcm12062178OpenAlex

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    Valvular heart disease is a leading cause of cardiovascular morbidity and mortality and a major contributor of symptoms and functional disability. Knowledge of valvular heart disease epidemiology and a deep comprehension of the geographical and temporal trends are crucial for clinical advances and the formulation of effective health policy for primary and secondary prevention. This review mainly focuses on the epidemiology of primary (organic, related to the valve itself) valvular disease and its management, especially emphasizing the importance of heart valve centers in ensuring the best care of patients through a multidisciplinary team.

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    Correlation between Temporomandibular Disorders (TMD) and Posture Evaluated trough the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD): A Systematic Review with Meta-Analysis

    Giuseppe Minervini, Rocco Franco, Maria Maddalena Marrapodi, Salvatore Crimi, Almir Badnjević and 3 more

    155 citationsOpen access (CC-BY)doi:10.3390/jcm12072652OpenAlex

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    BACKGROUND: Temporomandibular disorders (TMDs) are a series of disorders that affect the muscles and joint. Symptoms include joint pain, muscle pain, and limitation of mouth opening. One of several multifactorial diseases, temporomandibular dysfunction has mostly been linked to five etiological factors: occlusion, trauma, severe pain stimuli, parafunctional activities, and psychological elements, including stress, anxiety, and depression. The position of the human body as it is displayed in space is referred to as posture. Several nerve pathways regulate posture, and through ligaments, TMD and posture affect each other. The purpose of this study is to evaluate the possible correlation between posture and TMD through a meta-analysis of the literature; Methods: A literature search was performed on PubMed, Lilacs, and Web of science, and articles published from 2000 to 31 December 2022 were considered, according to the keywords entered. The term "temporomandibular disorders" has been combined with "posture", using the Boolean connector AND; Results: At the end of the research, 896…

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    Irritable Bowel Syndrome and the Gut Microbiome: A Comprehensive Review

    Sofia D. Shaikh, Natalie Z. Sun, Andrew Canakis, William Y. Park, Horst Christian Weber

    142 citationsOpen access (CC-BY)doi:10.3390/jcm12072558OpenAlex

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    Irritable Bowel Syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal pain and altered bowel habits. It has a prevalence of 10 to 25% in the United States and has a high disease burden, as evidenced by reduced quality of life, decreased work productivity and increased healthcare utilization and costs. IBS has been associated with several intra-intestinal and extra-intestinal conditions, including psychiatric comorbidities. Although the pathophysiology of IBS has not been fully elucidated, it involves dysregulation of communication between the brain and gut (brain-gut axis) which is associated with alterations in intestinal motility, gut permeability, visceral hypersensitivity and gut microbiota composition. The purpose of this article is to review the role the gut microbiota plays in the pathophysiology of IBS, understand factors that affect the gut microbiome and explore the microbiome as a target of treatment.

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    Prevalence of Overweight and Obesity in France: The 2020 Obepi-Roche Study by the “Ligue Contre l’Obésité”

    Annick Fontbonne, Andrew Currie, Patrick Tounian, Marie‐Christine Picot, Olivier Foulatier and 2 more

    141 citationsOpen access (CC-BY)doi:10.3390/jcm12030925OpenAlex

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    Obepi-Roche 2020 by the “Ligue Contre l’Obésité” (League Against Obesity) estimated overweight and obesity prevalence in France. The adopted methodology was chosen to be as similar as possible to that of a series of quota-based surveys conducted every three years from 1997 to 2012 (Obepi-Roche studies). The 2020 survey was conducted online from 24th September to 5th October 2020 by the Odoxa polling institute on a sample of metropolitan French subjects aged 18 years or over. Participants (n = 9598) self-measured their height and weight according to detailed instructions. Prevalence estimates were produced for all categories of body mass index. The prevalence of excess weight was 47.3% (17.0% of subjects with obesity), with higher values in the north and east of France. When comparing these 2020 estimates to previous Obepi-Roche estimates in order to visualize trends since 1997, it appeared that overweight fluctuated around 30%, and obesity prevalence increased steadily at a rapid pace. The increase was even steeper in the youngest age groups and for severe and complex obesity. Given…

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    Dyslipidemia and Cardiovascular Disease: Current Knowledge, Existing Challenges, and New Opportunities for Management Strategies

    Zhiyong Du, Yanwen Qin

    139 citationsOpen access (CC-BY)doi:10.3390/jcm12010363OpenAlex

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    Cardiovascular disease is the leading cause of morbidity and mortality worldwide, and dyslipidemia is one of the major risk factors [...].

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    The Firmicutes/Bacteroidetes Ratio as a Risk Factor of Breast Cancer

    Jeongshin An, Hyungju Kwon, Young Ju Kim

    138 citationsOpen access (CC-BY)doi:10.3390/jcm12062216OpenAlex

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    The gut microbiome can reflect the health condition of the entire body. Firmicutes and Bacteroidetes, the major phyla of the colon, can influence diseases related to obesity which are also risk factors for breast cancer. Therefore, the Firmicutes/Bacteroidetes (F/B) ratio was analyzed in patients with breast cancer. Bacterial extracellular vesicles were extracted from the serum of patients with breast cancer and healthy controls. Phyla Firmicutes and Bacteroidetes were analyzed using microbiome sequencing. Prognostic factors for breast cancer and serological test results were analyzed for correlations with the F/B ratio. The F/B ratio was three times lower in patients with breast cancer than in healthy controls. In addition, the risk factor for breast cancer, such as fasting serum glucose, was found to be related to the F/B ratio. The F/B ratio can be used as a risk factor of breast cancer and as a clue to explain underlying mechanisms affecting the development of breast cancer.

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    Current Treatment Landscape for Early Triple-Negative Breast Cancer (TNBC)

    Jieun Lee

    136 citationsOpen access (CC-BY)doi:10.3390/jcm12041524OpenAlex

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    Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and is characterized by an aggressive nature and a high rate of recurrence despite neoadjuvant and adjuvant chemotherapy. Although novel agents are constantly being introduced for the treatment of breast cancer, conventional cytotoxic chemotherapy based on anthracyclines and taxanes is the mainstay treatment option for TNBC. Based on CTNeoBC pooled analysis data, the achievement of pathologic CR (pCR) in TNBC is directly linked to improved survival outcomes. Therefore, the treatment paradigm for early TNBC has shifted to neoadjuvant treatment, and the escalation of neoadjuvant chemotherapy to improve the pCR rate and the addition of post-neoadjuvant chemotherapy to control the residual disease have been investigated. In this article, we review the current treatment landscape for early TNBC, from standard cytotoxic chemotherapy to recent data on immune checkpoint inhibitors, capecitabine, and olaparib.

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    The Burden of Rheumatoid Arthritis: Findings from the 2019 Global Burden of Diseases Study and Forecasts for 2030 by Bayesian Age-Period-Cohort Analysis

    Yuanqing Cai, Jianan Zhang, Jialin Liang, Mofan Xiao, Guangyang Zhang and 4 more

    134 citationsOpen access (CC-BY)doi:10.3390/jcm12041291OpenAlex

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    BACKGROUND: Rheumatoid arthritis (RA) is a key health issue worldwide. Due to early identification and effective treatment strategies, the disease pattern of RA has also changed. However, the most comprehensive and up-to-date information about the burden of RA and its trends in subsequent years is lacking. OBJECTIVE: this study aimed to report the global burden of RA by sex, age, region, and forecast for 2030. METHOD: Publicly available data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used in this study. The trends in the prevalence, incidence, and disability-adjusted life years (DALYs) of RA from 1990 to 2019 were reported. The global burden of RA in 2019 was reported by a sex, age, and sociodemographic index (SDI). Finally, the trends in the following years were predicted by Bayesian age-period-cohort (BAPC) models. RESULTS: Globally, the age-standardized prevalence rate increased from 207.46 (95% UI:189.99 to 226.95) in 1990 to 224.25 (95% UI: 204.94 to 245.99) in 2019, with an estimated annual percent change (EAPC) of 0.37% (95% CI: 0.32…

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    A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management

    Qamar Sultana, Jill Kar, Amogh Verma, Shreya Sanghvi, Nirja Kaka and 5 more

    130 citationsOpen access (CC-BY)doi:10.3390/jcm12155138OpenAlex

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    Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs-both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)-have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide…

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    Oral Cavity Squamous Cell Carcinoma Risk Factors: State of the Art

    Lara Nokovitch, Charles Maquet, Frédéric Crampon, Ihsène Taïhi, Lise‐Marie Roussel and 4 more

    128 citationsOpen access (CC-BY)doi:10.3390/jcm12093264OpenAlex

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    Head and neck (HN) squamous cell carcinomas (SCCs) originate from the epithelial cells of the mucosal linings of the upper aerodigestive tract, which includes the oral cavity, the pharynx, the larynx, and the sinonasal cavities. There are many associated risk factors, including alcohol drinking coupled with tobacco use, which accounts for 70% to 80% of HNSCCs. Human papilloma virus (HPV) is another independent risk factor for oropharyngeal SCC, but it is only a minor contributor to oral cavity SCC (OSCC). Betel quid chewing is also an established risk factor in southeast Asian countries. However, OSCC, and especially oral tongue cancer, incidence has been reported to be increasing in several countries, suggesting risk factors that have not been identified yet. This review summarizes the established risk factors for oral cavity squamous cell carcinomas and examines other undemonstrated risk factors for HNSCC.

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    Colorectal Cancer: Current Updates and Future Perspectives

    Rosa Marcellinaro, Domenico Spoletini, Michele Grieco, Pasquale Avella, Micaela Cappuccio and 4 more

    125 citationsOpen access (CC-BY)doi:10.3390/jcm13010040OpenAlex

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    Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In recent years, the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques, and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality, and survival rate for CRC.

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    Association between the Prognostic Nutritional Index and Chronic Microvascular Complications in Patients with Type 2 Diabetes Mellitus

    Gülali Aktaş

    125 citationsOpen access (CC-BY)doi:10.3390/jcm12185952OpenAlex

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    The prognostic nutritional index (PNI) is associated with inflammatory conditions. Since type 2 diabetes mellitus (T2DM) and its microvascular complications produce a significant inflammatory burden, we aimed to compare the PNI levels of the subjects with T2DM to those of healthy individuals. Furthermore, we aimed to compare the PNI levels of the diabetic subjects, with and without microvascular complications. The study cohort consisted of T2DM patients and healthy volunteers. The general characteristics, laboratory data, and PNI of the T2DM and control groups were compared. We further compared the PNI levels of the diabetic patients, with and without diabetic microvascular complications. The PNI levels of the T2DM patients and the control group were 51.6 (30.1–73.8)% and 64.8 (49.4–76)%, respectively (p < 0.001). Subgroup analyses revealed that the PNI was lower in the diabetic subjects with diabetic microvascular complications than in the diabetic patients without microvascular complications (p < 0.001), in patients with diabetic nephropathy compared to those without nephropathy…

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    Bronchopulmonary Dysplasia: Pathogenesis and Pathophysiology

    Nilesh Dankhara, Ira Holla, Sumana M. Ramarao, Renjithkumar Kalikkot Thekkeveedu

    123 citationsOpen access (CC-BY)doi:10.3390/jcm12134207OpenAlex

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    Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "classic" BPD, as per the original description, is less common now. "New BPD", which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving because of medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

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    Chondrosarcoma: A Clinical Review

    Aaron Gazendam, Snežana Popović, Naveen Parasu, Michelle A. Ghert

    122 citationsOpen access (CC-BY)doi:10.3390/jcm12072506OpenAlex

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    Chondrosarcomas are a diverse group of malignant cartilaginous matrix-producing neoplasms. Conventional chondrosarcomas are a continuum of disease based on the biologic activity of the tumor. The tumors range from the relatively biologically benign low-grade tumors or intermediate atypical cartilaginous tumors (ACTs), to malignant, aggressive high-grade tumors. The clinical presentation, radiographic and pathologic findings, treatments and outcomes vary significantly based on the histologic grade of the tumor. Chondrosarcomas present a diagnostic dilemma, particularly in the differentiation between high- and intermediate-grade tumors and that of low-grade tumors from benign enchondromas. A multidisciplinary team at a tertiary sarcoma centre allows for optimal care of these patients.

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    Stage IV Colorectal Cancer Management and Treatment

    Oscar Hernandez Dominguez, Sümeyye Yılmaz, Scott R. Steele

    121 citationsOpen access (CC-BY)doi:10.3390/jcm12052072OpenAlex

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    (1) Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. Up to 50% of patients with CRC develop metastatic CRC (mCRC). Surgical and systemic therapy advances can now offer significant survival advantages. Understanding the evolving treatment options is essential for decreasing mCRC mortality. We aim to summarize current evidence and guidelines regarding the management of mCRC to provide utility when making a treatment plan for the heterogenous spectrum of mCRC. (2) Methods: A comprehensive literature search of PubMed and current guidelines written by major cancer and surgical societies were reviewed. The references of the included studies were screened to identify additional studies that were incorporated as appropriate. (3) Results: The standard of care for mCRC primarily consists of surgical resection and systemic therapy. Complete resection of liver, lung, and peritoneal metastases is associated with better disease control and survival. Systemic therapy now includes chemotherapy, targeted therapy,…

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    Precision Medicine and the future of Cardiovascular Diseases: A Clinically Oriented Comprehensive Review

    Yashendra Sethi, Neil Patel, Nirja Kaka, Oroshay Kaiwan, Jill Kar and 4 more

    121 citationsOpen access (CC-BY)doi:10.3390/jcm12051799OpenAlex

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    Cardiac diseases form the lion's share of the global disease burden, owing to the paradigm shift to non-infectious diseases from infectious ones. The prevalence of CVDs has nearly doubled, increasing from 271 million in 1990 to 523 million in 2019. Additionally, the global trend for the years lived with disability has doubled, increasing from 17.7 million to 34.4 million over the same period. The advent of precision medicine in cardiology has ignited new possibilities for individually personalized, integrative, and patient-centric approaches to disease prevention and treatment, incorporating the standard clinical data with advanced "omics". These data help with the phenotypically adjudicated individualization of treatment. The major objective of this review was to compile the evolving clinically relevant tools of precision medicine that can help with the evidence-based precise individualized management of cardiac diseases with the highest DALY. The field of cardiology is evolving to provide targeted therapy, which is crafted as per the "omics", involving genomics, transcriptomics,…

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    Machine Learning-Based Early Prediction of Sepsis Using Electronic Health Records: A Systematic Review

    Khandaker Reajul Islam, Johayra Prithula, Jaya Kumar, Toh Leong Tan, Mamun Bin Ibne Reaz and 2 more

    119 citationsOpen access (CC-BY)doi:10.3390/jcm12175658OpenAlex

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    BACKGROUND: Sepsis, a life-threatening infection-induced inflammatory condition, has significant global health impacts. Timely detection is crucial for improving patient outcomes as sepsis can rapidly progress to severe forms. The application of machine learning (ML) and deep learning (DL) to predict sepsis using electronic health records (EHRs) has gained considerable attention for timely intervention. METHODS: PubMed, IEEE Xplore, Google Scholar, and Scopus were searched for relevant studies. All studies that used ML/DL to detect or early-predict the onset of sepsis in the adult population using EHRs were considered. Data were extracted and analyzed from all studies that met the criteria and were also evaluated for their quality. RESULTS: This systematic review examined 1942 articles, selecting 42 studies while adhering to strict criteria. The chosen studies were predominantly retrospective (n = 38) and spanned diverse geographic settings, with a focus on the United States. Different datasets, sepsis definitions, and prevalence rates were employed, necessitating data augmentation.…

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    Cellular and Molecular Players in the Tumor Microenvironment of Renal Cell Carcinoma

    Francesco M. Lasorsa, Monica Rutigliano, Martina Milella, Matteo Ferro, Savio Domenico Pandolfo and 6 more

    119 citationsOpen access (CC-BY)doi:10.3390/jcm12123888OpenAlex

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    Globally, clear-cell renal cell carcinoma (ccRCC) represents the most prevalent type of kidney cancer. Surgery plays a key role in the treatment of this cancer, although one third of patients are diagnosed with metastatic ccRCC and about 25% of patients will develop a recurrence after nephrectomy with curative intent. Molecular-target-based agents, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), are recommended for advanced cancers. In addition to cancer cells, the tumor microenvironment (TME) includes non-malignant cell types embedded in an altered extracellular matrix (ECM). The evidence confirms that interactions among cancer cells and TME elements exist and are thought to play crucial roles in the development of cancer, making them promising therapeutic targets. In the TME, an unfavorable pH, waste product accumulation, and competition for nutrients between cancer and immune cells may be regarded as further possible mechanisms of immune escape. To enhance immunotherapies and reduce resistance, it is crucial first to understand how the immune…

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    Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment

    Norah A. Alturki

    118 citationsOpen access (CC-BY)doi:10.3390/jcm12134301OpenAlex

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    Checkpoint proteins are an integral part of the immune system and are used by the tumor cells to evade immune response, which helps them grow uncontrollably. By blocking these proteins, immune checkpoint inhibitors can restore the capability of the immune system to attack cancer cells and stop their growth. These findings are backed by adequate clinical trial data and presently, several FDA-approved immune checkpoint inhibitors exist in the market for treating various types of cancers, including melanoma, hepatocellular, endometrial, lung, kidney and others. Their mode of action is inhibition by targeting the checkpoint proteins CTLA-4, PD-1, PD-L1, etc. They can be used alone as well as in amalgamation with other cancer treatments, like surgery, radiation or chemotherapy. Since these drugs target only specific immune system proteins, their side effects are reduced in comparison with the traditional chemotherapy drugs, but may still cause a few affects like fatigue, skin rashes, and fever. In rare cases, these inhibitors are known to have caused more serious side effects, such as…

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    Classification of Skin Cancer Using Novel Hyperspectral Imaging Engineering via YOLOv5

    Hung‐Yi Huang, Yu‐Ping Hsiao, Arvind Mukundan, Yu-Ming Tsao, Wen‐Yen Chang and 1 more

    115 citationsOpen access (CC-BY)doi:10.3390/jcm12031134OpenAlex

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    Many studies have recently used several deep learning methods for detecting skin cancer. However, hyperspectral imaging (HSI) is a noninvasive optics system that can obtain wavelength information on the location of skin cancer lesions and requires further investigation. Hyperspectral technology can capture hundreds of narrow bands of the electromagnetic spectrum both within and outside the visible wavelength range as well as bands that enhance the distinction of image features. The dataset from the ISIC library was used in this study to detect and classify skin cancer on the basis of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and seborrheic keratosis (SK). The dataset was divided into training and test sets, and you only look once (YOLO) version 5 was applied to train the model. The model performance was judged according to the generated confusion matrix and five indicating parameters, including precision, recall, specificity, accuracy, and the F1-score of the trained model. Two models, namely, hyperspectral narrowband image (HSI-NBI) and RGB classification, were…

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    Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: The Patient and Physician Perspective

    Wayne Eskridge, Donna R. H. Cryer, Jörn Markus Schattenberg, Amalia Gastaldelli, Harmeet Malhi and 3 more

    113 citationsOpen access (CC-BY)doi:10.3390/jcm12196216OpenAlex

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    Diagnosing and managing metabolic dysfunction-associated steatotic liver disease (MASLD) remains a major challenge in primary care due to lack of agreement on diagnostic tools, difficulty in identifying symptoms and determining their cause, absence of approved pharmacological treatments, and limited awareness of the disease. However, prompt diagnosis and management are critical to preventing MASLD from progressing to more severe forms of liver disease. This highlights the need to raise awareness and improve understanding of MASLD among both patients and physicians. The patient perspective is invaluable to advancing our knowledge of this disease and how to manage it, as their perspectives have led to the growing recognition that patients experience subtle symptoms and that patient-reported outcomes should be incorporated into drug development. This review and expert opinion examine MASLD and metabolic dysfunction-associated steatohepatitis from the patient and physician perspective from pre-diagnosis to diagnosis and early care, through to progression to advanced liver damage.…

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    Overview of Artificial Intelligence in Breast Cancer Medical Imaging

    Dan Zheng, Xiujing He, Jing Jing

    113 citationsOpen access (CC-BY)doi:10.3390/jcm12020419OpenAlex

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    The heavy global burden and mortality of breast cancer emphasize the importance of early diagnosis and treatment. Imaging detection is one of the main tools used in clinical practice for screening, diagnosis, and treatment efficacy evaluation, and can visualize changes in tumor size and texture before and after treatment. The overwhelming number of images, which lead to a heavy workload for radiologists and a sluggish reporting period, suggests the need for computer-aid detection techniques and platform. In addition, complex and changeable image features, heterogeneous quality of images, and inconsistent interpretation by different radiologists and medical institutions constitute the primary difficulties in breast cancer screening and imaging diagnosis. The advancement of imaging-based artificial intelligence (AI)-assisted tumor diagnosis is an ideal strategy for improving imaging diagnosis efficient and accuracy. By learning from image data input and constructing algorithm models, AI is able to recognize, segment, and diagnose tumor lesion automatically, showing promising…

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    Stroke in Young Adults

    Syed Bukhari, Shadi R. Yaghi, Zubair Shahid Bashir

    112 citationsOpen access (CC-BY)doi:10.3390/jcm12154999OpenAlex

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    Stroke in young adults is associated with significant morbidity, and its prevalence is rising in the United States. This is partly attributed to a rise in the prevalence of traditional risk factors including hypertension, hypercholesterolemia, obesity, diabetes mellitus, smoking and heart disease. In addition, there are non-modifiable risk factors comprising migraine, pregnancy and postpartum state, illicit drug use, oral contraceptives and hypercoagulable state. The mechanisms causing stroke in young adults are unique and include cervical dissection, cardioembolic phenomenon, vasculitis and vasculopathy, connective tissue disease, patent foramen ovale and cerebral venous thrombosis. The diagnosis of stroke in the young population can be challenging given its myriad clinical presentations. In this document, we provide an overview of the epidemiology of stroke in young adults, explore mechanisms that may explain increasing rates of stroke in this population, and provide a critical updated overview of the existing literature on the management and prevention of stroke in young adults.

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    Inferior Vena Cava Ultrasonography for Volume Status Evaluation: An Intriguing Promise Never Fulfilled

    Pierpaolo Di Nicolò, Guido Tavazzi, Luca Nannoni, Francesco Corradi

    111 citationsOpen access (CC-BY)doi:10.3390/jcm12062217OpenAlex

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    The correct determination of volume status is a fundamental component of clinical evaluation as both hypovolaemia (with hypoperfusion) and hypervolaemia (with fluid overload) increase morbidity and mortality in critically ill patients. As inferior vena cava (IVC) accounts for two-thirds of systemic venous return, it has been proposed as a marker of volaemic status by indirect assessment of central venous pressure or fluid responsiveness. Although ultrasonographic evaluation of IVC is relatively easy to perform, correct interpretation of the results may not be that simple and multiple pitfalls hamper its wider application in the clinical setting. In the present review, the basic elements of the pathophysiology of IVC behaviour, potential applications and limitations of its evaluation are discussed.

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    The Impact of Microbiota on the Gut–Brain Axis: Examining the Complex Interplay and Implications

    Tuba Shahid Chaudhry, Sidhartha Gautam Senapati, Srikanth Gadam, Hari Priya Sri Sai Mannam, Hima Varsha Voruganti and 6 more

    100 citationsOpen access (CC-BY)doi:10.3390/jcm12165231OpenAlex

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    The association and interaction between the central nervous system (CNS) and enteric nervous system (ENS) is well established. Essentially ENS is the second brain, as we call it. We tried to understand the structure and function, to throw light on the functional aspect of neurons, and address various disease manifestations. We summarized how various neurological disorders influence the gut via the enteric nervous system and/or bring anatomical or physiological changes in the enteric nervous system or the gut and vice versa. It is known that stress has an effect on Gastrointestinal (GI) motility and causes mucosal erosions. In our literature review, we found that stress can also affect sensory perception in the central nervous system. Interestingly, we found that mutations in the neurohormone, serotonin (5-HT), would result in dysfunctional organ development and further affect mood and behavior. We focused on the developmental aspects of neurons and cognition and their relation to nutritional absorption via the gastrointestinal tract, the development of neurodegenerative disorders in…

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    Role of Gut Microbiota in Neurological Disorders and Its Therapeutic Significance

    Prabhakar Tiwari, Rekha Dwivedi, Manisha Bansal, Manjari Tripathi, Rima Dada

    100 citationsOpen access (CC-BY)doi:10.3390/jcm12041650OpenAlex

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    In humans, the gut microbiota (GM) are known to play a significant role in the metabolism of nutrients and drugs, immunomodulation, and pathogen defense by inhabiting the gastrointestinal tract (GIT). The role of the GM in the gut-brain axis (GBA) has been documented for different regulatory mechanisms and associated pathways and it shows different behaviors with individualized bacteria. In addition, the GM are known as susceptibility factor for neurological disorders in the central nervous system (CNS), regulating disease progression and being amenable to intervention. Bidirectional transmission between the brain and the GM occurs in the GBA, implying that it performs a significant role in neurocrine, endocrine, and immune-mediated signaling pathways. The GM regulates multiple neurological disorders by supplementing them with prebiotics, probiotics, postbiotics, synbiotics, fecal transplantations, and/or antibiotics. A well-balanced diet is critically important for establishing healthy GM, which can alter the enteric nervous system (ENS) and regulate multiple neurological…

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    Renal Biopsy for Diagnosis in Kidney Disease: Indication, Technique, and Safety

    Peter Schnuelle

    98 citationsOpen access (CC-BY)doi:10.3390/jcm12196424OpenAlex

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    Renal biopsies are the gold standard for diagnosis, staging, and prognosis of underlying parenchymal kidney disease. This article provides an overview of the current indications and highlights ways to reduce bleeding complications in order to achieve optimal diagnostic yield with minimal risk to the patient. Novel indications have emerged from the increasing use of new molecularly targeted oncologic therapies in recent years, which often induce immune-mediated renal disease. On the other hand, the detection of specific antibodies against target antigens on podocytes in the sera of patients with new-onset nephrotic syndrome has now relativized the indication for biopsy in membranous nephropathy. The use of semi-automatic spring-loaded biopsy devices and real-time ultrasound considerably declined the complication rate and is the current standard. Percutaneous renal biopsies are overall a safe procedure if contraindications are considered. A coagulation disorder needs to be excluded beforehand, and an elevated blood pressure must be reduced to the normotensive range with medications. A…

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    Marginal Ulcers after Roux-en-Y Gastric Bypass: Etiology, Diagnosis, and Management

    Marita Salame, Noura Jawhar, Amanda Belluzzi, Mohammad Al-Kordi, Andrew C. Storm and 2 more

    96 citationsOpen access (CC-BY)doi:10.3390/jcm12134336OpenAlex

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    Marginal ulcer (MU) is a potential complication following Roux-en-Y gastric bypass (RYGB), with a mean prevalence of 4.6%. Early identification and prompt intervention are crucial to mitigating further complications. The pathophysiology of MU is complex and involves multiple factors, including smoking, Helicobacter pylori infection, non-steroidal anti-inflammatory drug (NSAID) use, and larger pouch size. Patients with MU may experience acute or chronic abdominal pain. Rarely, they may present with a complication from the ulceration, such as bleeding, perforation, or strictures. Following diagnosis by endoscopy, management of MU typically involves modification of risk factors and medical therapy focused on proton pump inhibitors. In case of complicated ulcers, surgical intervention is often required for the repair of the perforation or resection of the stricture. For recurrent or recalcitrant ulcers, endoscopic coverage of the ulcer bed, resection of the anastomosis, and abdominal or thoracoscopic truncal vagotomy may be considered. This review aims at providing an overview of the…

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    Clinical Usefulness of Right Ventricle–Pulmonary Artery Coupling in Cardiovascular Disease

    Qing He, Yixia Lin, Ye Chao Zhu, Lang Gao, Mengmeng Ji and 3 more

    96 citationsOpen access (CC-BY)doi:10.3390/jcm12072526OpenAlex

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    Right ventricular-pulmonary artery coupling (RV-PA coupling) refers to the relationship between RV contractility and RV afterload. Normal RV-PA coupling is maintained only when RV function and pulmonary vascular resistance are appropriately matched. RV-PA uncoupling occurs when RV contractility cannot increase to match RV afterload, resulting in RV dysfunction and right heart failure. RV-PA coupling plays an important role in the pathophysiology and progression of cardiovascular diseases. Therefore, early and accurate evaluation of RV-PA coupling is of great significance for a patient's condition assessment, clinical decision making, risk stratification, and prognosis judgment. RV-PA coupling can be assessed by using invasive or noninvasive approaches. The aim of this review was to summarize the pathological mechanism and evaluation methods of RV-PA coupling, the advantages and disadvantages of each method, and the application value of RV-PA coupling in various cardiovascular diseases.

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    Machine Learning in Dentistry: A Scoping Review

    Lubaina T. Arsiwala-Scheppach, Akhilanand Chaurasia, Anne Müller, Joachim Krois, Falk Schwendicke

    96 citationsOpen access (CC-BY)doi:10.3390/jcm12030937OpenAlex

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    Machine learning (ML) is being increasingly employed in dental research and application. We aimed to systematically compile studies using ML in dentistry and assess their methodological quality, including the risk of bias and reporting standards. We evaluated studies employing ML in dentistry published from 1 January 2015 to 31 May 2021 on MEDLINE, IEEE Xplore, and arXiv. We assessed publication trends and the distribution of ML tasks (classification, object detection, semantic segmentation, instance segmentation, and generation) in different clinical fields. We appraised the risk of bias and adherence to reporting standards, using the QUADAS-2 and TRIPOD checklists, respectively. Out of 183 identified studies, 168 were included, focusing on various ML tasks and employing a broad range of ML models, input data, data sources, strategies to generate reference tests, and performance metrics. Classification tasks were most common. Forty-two different metrics were used to evaluate model performances, with accuracy, sensitivity, precision, and intersection-over-union being the most…

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    Tinnitus and Its Relation to Depression, Anxiety, and Stress—A Population-Based Cohort Study

    Berit Hackenberg, Julia Döge, Karoline O’Brien, Andrea Bohnert, Karl Johannes Lackner and 9 more

    95 citationsOpen access (CC-BY)doi:10.3390/jcm12031169OpenAlex

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    Tinnitus is a common symptom reported in otolaryngologic practice. Although the pathophysiology of tinnitus has not been fully understood, clinical studies suggest that psychological symptoms of depression, anxiety, and somatization are increased in tinnitus patients. However, patients seeking medical treatment for tinnitus may be especially vulnerable. Population-based studies reporting on the association between tinnitus and psychological distress are still lacking. The aim of this study was to investigate the correlation of tinnitus with depression, anxiety, or somatization in a large population-based cohort. The Gutenberg Health Study is a population-based cohort study. Participants were asked about the occurrence of tinnitus (yes/no) and how much they were bothered by it. In addition, they completed the PHQ-9, GAD-7, and SSS-8 questionnaires to assess depressive symptoms, anxiety, and somatic symptom disorders. A total of 8539 participants were included in the study cohort. Tinnitus prevalence was 28.0% (2387). The prevalence of depression/anxiety/somatic symptom disorders was…

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    Three Types of Endometriosis: Pathogenesis, Diagnosis and Treatment. State of the Art

    Ludovica Imperiale, Michelle Nisolle, Jean‐Christophe Noël, Maxime Fastrez

    93 citationsOpen access (CC-BY)doi:10.3390/jcm12030994OpenAlex

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    At present, there is no curative treatment for endometriosis. Medical management and surgical treatment do not provide long-term relief. A detailed understanding of its pathophysiology is mandatory in order to facilitate both the diagnosis and treatment. The delay that typically precedes proper diagnosis (6 to 7 years) is probably one of the most challenging aspects of endometriosis management. In 2012, the total cost per woman due to endometriosis was estimated to be 9579€ per year in a multicenter study across the USA and Europe. According to their physiopathology and their localization, ectopic endometrial lesions, consisting of endometrial glands and stroma, can be divided into three different types: superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The following paper aims to review the available data in the literature on the pathogenesis, diagnosis, and treatment of different types of endometriosis.

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    Face the Future—Artificial Intelligence in Oral and Maxillofacial Surgery

    Maximilian F. Miragall, Samuel A. Knoedler, Martin Kauke‐Navarro, Rakan Saadoun, Alex Grabenhorst and 5 more

    92 citationsOpen access (CC-BY)doi:10.3390/jcm12216843OpenAlex

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    Artificial intelligence (AI) has emerged as a versatile health-technology tool revolutionizing medical services through the implementation of predictive, preventative, individualized, and participatory approaches. AI encompasses different computational concepts such as machine learning, deep learning techniques, and neural networks. AI also presents a broad platform for improving preoperative planning, intraoperative workflow, and postoperative patient outcomes in the field of oral and maxillofacial surgery (OMFS). The purpose of this review is to present a comprehensive summary of the existing scientific knowledge. The authors thoroughly reviewed English-language PubMed/MEDLINE and Embase papers from their establishment to 1 December 2022. The search terms were (1) "OMFS" OR "oral and maxillofacial" OR "oral and maxillofacial surgery" OR "oral surgery" AND (2) "AI" OR "artificial intelligence". The search format was tailored to each database's syntax. To find pertinent material, each retrieved article and systematic review's reference list was thoroughly examined. According to the…

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    Cardiometabolic Index (CMI) and Visceral Adiposity Index (VAI) Highlight a Higher Risk of Metabolic Syndrome in Women with Severe Obesity

    Stefano Lazzer, Mattia D’Alleva, Miriam Isola, Maria De Martino, Diana Caroli and 3 more

    92 citationsOpen access (CC-BY)doi:10.3390/jcm12093055OpenAlex

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    Recent evidence shows that simple and inexpensive anthropometric measurements can be used to identify, at an early stage, women with obesity at increased risk of developing metabolic syndrome (MetS). Thus, the aim of this study was to compare the accuracy of five different indexes of adiposity and/or body composition in identifying MetS in a group of 876 women (mean age ± SD: 52.1 ± 13.8 years; body mass index (BMI): 43.6 ± 6.1 kg m−2). The following indexes were determined for each subject: waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), body mass fat index (BMFI), visceral adiposity index (VAI), and cardiometabolic index (CMI). Overall, the presence of MetS was detected in 544 patients (62%). Pearson correlation coefficients were calculated to evaluate the relationships between body composition indexes and metabolic characteristics of the women. Receiver operating characteristic (ROC) analysis was used to determine the best predictor for each adiposity index among metabolic risk factors. The ROC analysis showed VAI (AUC = 0.84) and CMI (AUC = 0.86) showed the best…

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    The Global Burden of Glaucoma: Findings from the Global Burden of Disease 2019 Study and Predictions by Bayesian Age–Period–Cohort Analysis

    Yi Lin, Bingcai Jiang, Yuanqing Cai, Wangdu Luo, Xiaomin Zhu and 4 more

    91 citationsOpen access (CC-BY)doi:10.3390/jcm12051828OpenAlex

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    This study aims to report the most up-to-date information about the global disease burden of glaucoma from 1990 to 2019 and to forecast trends in the next few years. Publicly available data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used in this study. The prevalence and disability-adjusted life years (DALYs) of glaucoma from 1990 to 2019 were reported. Finally, trends in the years following 2019 were predicted by Bayesian age-period-cohort (BAPC) models. We showed that, globally, the number of prevalent cases was 3,881,624 [95% uncertainty interval (UI): 3,301,963 to 4,535,045] in 1990 and increased to 7,473,400 (95% UI: 6,347,183 to 8,769,520) in 2019, while the age-standardized prevalence rate decreased from 111.92 [95% uncertainty interval (UI): 94.76 to 130.28 per 100,000] in 1990 to 94.68 (95% UI: 80.42 to 110.87 per 100,000) in 2019. The DALY number of glaucoma increased between 1990 and 2019, from 442,182 (95% UI: 301,827 to 626,486) in 1990 to 748,308 (95% UI: 515,636 to 1,044,667) in 2019. There was a significantly negative…

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    Pathomechanisms of Diabetic Kidney Disease

    Satyesh K. Sinha, Susanne B. Nicholas

    89 citationsOpen access (CC-BY)doi:10.3390/jcm12237349OpenAlex

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    The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population of individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. The pathogenesis of DKD is intricate, originating with hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, and fibrotic which ultimately lead to renal damage. Within each pathway, several mediators contribute to the development of renal structural and functional changes. Some of these mediators, such as inflammatory cytokines, reactive oxygen species, and transforming growth factor β are shared among the different pathways, leading to significant overlap and interaction between them. While current treatment options for DKD have shown advancement over previous strategies, their effectiveness remains somewhat constrained as patients still experience residual risk of disease progression. Therefore, a comprehensive…

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    Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy

    Amaresh Kumar Ranjan, Anil Gulati

    89 citationsOpen access (CC-BY)doi:10.3390/jcm12206653OpenAlex

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    Neonatal hypoxic-ischemic encephalopathy (HIE) is a condition that results in brain damage in newborns due to insufficient blood and oxygen supply during or after birth. HIE is a major cause of neurological disability and mortality in newborns, with over one million neonatal deaths occurring annually worldwide. The severity of brain injury and the outcome of HIE depend on several factors, including the cause of oxygen deprivation, brain maturity, regional blood flow, and maternal health conditions. HIE is classified into mild, moderate, and severe categories based on the extent of brain damage and resulting neurological issues. The pathophysiology of HIE involves different phases, including the primary phase, latent phase, secondary phase, and tertiary phase. The primary and secondary phases are characterized by episodes of energy and cell metabolism failures, increased cytotoxicity and apoptosis, and activated microglia and inflammation in the brain. A tertiary phase occurs if the brain injury persists, characterized by reduced neural plasticity and neuronal loss. Understanding the…

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    Human Digital Twin for Personalized Elderly Type 2 Diabetes Management

    Padmapritha Thamotharan, Seshadhri Srinivasan, Jothydev Kesavadev, Gopika Krishnan, Viswanathan Mohan and 3 more

    89 citationsOpen access (CC-BY)doi:10.3390/jcm12062094OpenAlex

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    Managing Elderly type 2 diabetes (E-T2D) is challenging due to geriatric conditions (e.g., co-morbidity, multiple drug intake, etc.), and personalization becomes paramount for precision medicine. This paper presents a human digital twin (HDT) framework to manage E-T2D that exploits various patient-specific data and builds a suite of models exploiting the data for prediction and management to personalize diabetes treatment in E-T2D patients. These models include mathematical and deep-learning ones that capture different patient aspects. Consequently, the HDT virtualizes the patient from different viewpoints using an HDT that mimics the patient and has interfaces to update the virtual models simultaneously from measurements. Using these models the HDT obtains deeper insights about the patient. Further, an adaptive patient model fusing this information and a learning-based model predictive control (LB-MPC) algorithm are proposed. The geriatric conditions are captured as model parameters and constraints while solving the LB-MPC to personalize the insulin infusion for E-T2D management.…

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    Adherence to Oral Antidiabetic Drugs in Patients with Type 2 Diabetes: Systematic Review and Meta-Analysis

    Eugenia Piragine, Davide Petri, Alma Martelli, Vincenzo Calderone, Ersilia Lucenteforte

    89 citationsOpen access (CC-BY)doi:10.3390/jcm12051981OpenAlex

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    Poor adherence to oral antidiabetic drugs (OADs) in patients with type 2 diabetes (T2D) can lead to therapy failure and risk of complications. The aim of this study was to produce an adherence proportion to OADs and estimate the association between good adherence and good glycemic control in patients with T2D. We searched in MEDLINE, Scopus, and CENTRAL databases to find observational studies on therapeutic adherence in OAD users. We calculated the proportion of adherent patients to the total number of participants for each study and pooled study-specific adherence proportions using random effect models with Freeman-Tukey transformation. We also calculated the odds ratio (OR) of having good glycemic control and good adherence and pooled study-specific OR with the generic inverse variance method. A total of 156 studies (10,041,928 patients) were included in the systematic review and meta-analysis. The pooled proportion of adherent patients was 54% (95% confidence interval, CI: 51-58%). We observed a significant association between good glycemic control and good adherence (OR: 1.33;…

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    Challenges in ARDS Definition, Management, and Identification of Effective Personalized Therapies

    Denise Battaglini, Brigitta Fazzini, Pedro Leme Silva, Fernanda Ferreira Cruz, Lorenzo Ball and 3 more

    88 citationsOpen access (CC-BY)doi:10.3390/jcm12041381OpenAlex

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    Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of low tidal volume (VT) 4–6 mL/kg of predicted body weight, plateau pressure (PPLAT) < 30 cmH2O, and driving pressure (∆P) < 14 cmH2O. Moreover, positive end-expiratory pressure should be individualized. Recently, variables such as mechanical power and transpulmonary pressure seem promising for limiting ventilator-induced lung injury and optimizing ventilator settings. Rescue therapies such as recruitment maneuvers, vasodilators, prone positioning, extracorporeal membrane oxygenation, and extracorporeal carbon dioxide removal have been considered for patients with severe ARDS. Regarding pharmacotherapies, despite more than 50 years of research, no effective treatment has yet been found. However, the identification of ARDS sub-phenotypes has revealed that some…

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    Current Trends in Volume and Surgical Outcomes in Gastric Cancer

    Luigi Marano, Luigi Verre, Ludovico Carbone, Gianmario Edoardo Poto, Daniele Fusario and 8 more

    87 citationsOpen access (CC-BY)doi:10.3390/jcm12072708OpenAlex

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    Gastric cancer is ranked as the fifth most frequently diagnosed type of cancer. Complete resection with adequate lymphadenectomy represents the goal of treatment with curative intent. Quality assurance is a crucial factor in the evaluation of oncological surgical care, and centralization of healthcare in referral hospitals has been proposed in several countries. However, an international agreement about the setting of “high-volume hospitals” as well as “minimum volume standards” has not yet been clearly established. Despite the clear postoperative mortality benefits that have been described for gastric cancer surgery conducted by high-volume surgeons in high-volume hospitals, many authors have highlighted the limitations of a non-composite variable to define the ideal postoperative period. The textbook outcome represents a multidimensional measure assessing the quality of care for cancer patients. Transparent and easily available hospital data will increase patients’ awareness, providing suitable elements for a more informed hospital choice.

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    Treatment of Vulvovaginal Candidiasis—An Overview of Guidelines and the Latest Treatment Methods

    Małgorzata Satora, Arkadiusz Grunwald, Bartłomiej Zaremba, Karolina Frankowska, Klaudia Żak and 2 more

    84 citationsOpen access (CC-BY)doi:10.3390/jcm12165376OpenAlex

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    Vulvovaginal candidiasis (VVC) is a common condition associated with discomfort in affected women. Due to the presence of different forms of the disease, diverse treatment regimens are developed; the newest ones include oteseconazole and ibrexafungerp. Here, we focus on the most up-to-date recommendations regarding VVC treatment, as well as novel treatment options. Topical and oral azoles are the drugs of choice in uncomplicated mycosis. The efficacy of probiotics and substances such as TOL-463 and chlorhexidine is indicated as satisfactory; however, there are no relevant guidelines. Although the majority of researchers agree that the treatment of non-albicans VVC should be long-lasting, the recommendations are inconsistent. Another clinical problem is the treatment of VVC with azole intolerance or resistance, for which literature proposes the use of several drugs including oteseconazole, ibrexafungerp, and voriconazole. The treatment schedules for recurrent VVC include mainly fluconazole; however, alternative options such as immunotherapeutic vaccine (NDV-3A) or designed…

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    Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy

    Tiantian Zhang, Tony Hong‐Ting Jou, Jerline Hsin, Zhe Wang, Kelly X. Huang and 3 more

    83 citationsOpen access (CC-BY)doi:10.3390/jcm12031098OpenAlex

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    The landscape of melanoma treatment has undergone a dramatic revolution in the past decade. The use of oncolytic viruses (OVs) represents a novel therapeutic approach that can selectively infect and lyse tumor cells and induce local and systemic antitumor immune responses. As the first OV approved by the Food and Drug Administration (FDA) for melanoma treatment, talimogene laherparepvec (T-VEC), a genetically modified herpes simplex virus (HSV), has shown promising therapeutic effects in the treatment of advanced melanoma, both as a monotherapy or in combination with other immunotherapies, such as the immune checkpoint inhibitors (ICIs). With proven efficacy, T-VEC has been evaluated against a variety of other cancer types in a clinical trial setting. In this article, we will provide a review on OVs and the application of T-VEC in melanoma monotherapy and combination therapy. In addition, we will review the recent progress of T-VEC application in other cutaneous cancer types. Moreover, we will briefly describe our experience of T-VEC therapy at City of Hope, aiming to provide more…

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    Do GLP-1 Analogs Have a Place in the Treatment of PCOS? New Insights and Promising Therapies

    Aleksandra Szczęsnowicz, Anna Szeliga, Olga Niwczyk, Gregory Bala, Błażej Męczekalski

    82 citationsOpen access (CC-BY)doi:10.3390/jcm12185915OpenAlex

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    Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo- or anovulation. PCOS patients often present comorbidities such as obesity, insulin resistance, impaired glucose metabolism, dyslipidemia, hypertension, metabolic syndrome, and an increased risk of diabetes. Given the profound implications of metabolic impairment in PCOS, the accurate diagnosis and management of these facets are imperative. The first-line approach to treatment involves lifestyle modifications, including dietary adjustments and exercise aimed at achieving weight loss, a strategy consistently emphasized across the literature. Supplementation with probiotics, vitamin D, and L-carnitine have also provided additional benefits to patients. In select cases, pharmacological interventions are needed for optimal therapeutic results. The most common medications used in PCOS include metformin, thiazolidinediones, inositols, and two classes of antidiabetic agents: dipeptidyl peptidase-IV (DPP-IV) inhibitors, and…

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    Levodopa-Induced Dyskinesias in Parkinson’s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions

    Lazzaro di Biase, Pasquale Maria Pecoraro, Simona Paola Carbone, Maria Letizia Caminiti, Vincenzo Di Lazzaro

    80 citationsOpen access (CC-BY)doi:10.3390/jcm12134427OpenAlex

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    Since its first introduction, levodopa has become the cornerstone for the treatment of Parkinson's disease and remains the leading therapeutic choice for motor control therapy so far. Unfortunately, the subsequent appearance of abnormal involuntary movements, known as dyskinesias, is a frequent drawback. Despite the deep knowledge of this complication, in terms of clinical phenomenology and the temporal relationship during a levodopa regimen, less is clear about the pathophysiological mechanisms underpinning it. As the disease progresses, specific oscillatory activities of both motor cortical and basal ganglia neurons and variation in levodopa metabolism, in terms of the dopamine receptor stimulation pattern and turnover rate, underlie dyskinesia onset. This review aims to provide a global overview on levodopa-induced dyskinesias, focusing on pathophysiology, clinical manifestations, therapy management strategies and future directions.

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    The Biology of Stress Intolerance in Patients with Chronic Pain—State of the Art and Future Directions

    Arne Wyns, Jolien Hendrix, Astrid Lahousse, Elke De Bruyne, Jo Nijs and 2 more

    80 citationsOpen access (CC-BY)doi:10.3390/jcm12062245OpenAlex

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    Stress has been consistently linked to negative impacts on physical and mental health. More specifically, patients with chronic pain experience stress intolerance, which is an exacerbation or occurrence of symptoms in response to any type of stress. The pathophysiological mechanisms underlying this phenomenon remain unsolved. In this state-of-the-art paper, we summarised the role of the autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis, the two major stress response systems in stress intolerance. We provided insights into such mechanisms based on evidence from clinical studies in both patients with chronic pain, showing dysregulated stress systems, and healthy controls supported by preclinical studies, highlighting the link between these systems and symptoms of stress intolerance. Furthermore, we explored the possible regulating role for (epi)genetic mechanisms influencing the ANS and HPA axis. The link between stress and chronic pain has become an important area of research as it has the potential to inform the development of interventions to improve the…

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    Cardiovascular Disease in Diabetes and Chronic Kidney Disease

    Sowmya Swamy, Sahibzadi Mahrukh Noor, Roy O. Mathew

    78 citationsOpen access (CC-BY)doi:10.3390/jcm12226984OpenAlex

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    Chronic kidney disease (CKD) is a common occurrence in patients with diabetes mellitus (DM), occurring in approximately 40% of cases. DM is also an important risk factor for cardiovascular disease (CVD), but CKD is an important mediator of this risk. Multiple CVD outcomes trials have revealed a greater risk for CVD events in patients with diabetes with CKD versus those without. Thus, reducing the risk of CKD in diabetes should result in improved CVD outcomes. To date, of blood pressure (BP) control, glycemic control, and inhibition of the renin-angiotensin system (RASI), glycemic control appears to have the best evidence for preventing CKD development. In established CKD, especially with albuminuria, RASI slows the progression of CKD. More recently, sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1RA) have revolutionized the care of patients with diabetes with and without CKD. SGLT2i and GLP1RA have proven to reduce mortality, heart failure (HF) hospitalizations, and worsening CKD in patients with diabetes with and without existing…

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    Role of Cardiovascular Imaging in Risk Assessment: Recent Advances, Gaps in Evidence, and Future Directions

    Francesco Perone, Marco Bernardi, Alban B. Redheuil, Dario Mafrica, Edoardo Conte and 14 more

    78 citationsOpen access (CC-BY)doi:10.3390/jcm12175563OpenAlex

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    Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular…

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    Overview of Atopic Dermatitis in Different Ethnic Groups

    Andrea Chiricozzi, Martina Maurelli, Laura Calabrese, Ketty Peris, Giampiero Girolomoni

    78 citationsOpen access (CC-BY)doi:10.3390/jcm12072701OpenAlex

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    Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a high prevalence worldwide, including countries from Asia, Africa, and Latin America, and in different ethnic groups. In recent years, more attention has been placed on the heterogeneity of AD associated with multiple factors, including a patient's ethnic background, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineates differences in AD among racial groups. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, but very rarely in Africans. Th2 hyperactivation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal, whereas African Americans show a strong Th2/Th22 signature and an absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity of AD may hold important therapeutic implications as a patient's genetic predisposition may affect treatment response and,…

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    Effects of Preoperative Anxiety on Postoperative Outcomes and Sleep Quality in Patients Undergoing Laparoscopic Gynecological Surgery

    Xiangyi Gu, Yufei Zhang, Wenxin Wei, Junchao Zhu

    78 citationsOpen access (CC-BY)doi:10.3390/jcm12051835OpenAlex

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    OBJECTIVE: Preoperative anxiety is a psychological state that commonly occurs before surgery and may have a negative impact on postoperative outcomes. This study aimed to investigate the effects of preoperative anxiety on postoperative sleep quality and recovery outcomes among patients undergoing laparoscopic gynecological surgery. METHODS: The study was conducted as a prospective cohort study. A total of 330 patients were enrolled and underwent laparoscopic gynecological surgery. After assessing the patient's preoperative anxiety score on the APAIS scale, 100 patients were classified into the preoperative anxiety (PA) group (preoperative anxiety score > 10) and 230 patients into the non-preoperative-anxiety (NPA) group (preoperative anxiety score ≤ 10). The Athens Insomnia Scale (AIS) was assessed on the night before surgery (Sleep Pre 1), the first night after surgery (Sleep POD 1), the second night after surgery (Sleep POD2), and the third night after surgery (Sleep POD 3). Postoperative pain was evaluated by the Visual Analog Scale (VAS), and the postoperative recovery outcomes…

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    KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration

    Yunkai Yang, Huan Zhang, Shanshan Huang, Qian Chu

    78 citationsOpen access (CC-BY)doi:10.3390/jcm12020709OpenAlex

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    Kristen rat sarcoma (KRAS) gene is one of the most common mutated oncogenes in solid tumors. Yet, KRAS inhibitors did not follow suit with the development of targeted therapy, for the structure of KRAS has been considered as being implausible to target for decades. Chemotherapy was the initial recommended therapy for KRAS-mutant cancer patients, which was then replaced by or combined with immunotherapy. KRAS G12C inhibitors became the most recent breakthrough in targeted therapy, with Sotorasib being approved by the Food and Drug Administration (FDA) based on its significant efficacy in multiple clinical studies. However, the subtypes of the KRAS mutations are complex, and the development of inhibitors targeting non-G12C subtypes is still at a relatively early stage. In addition, the monotherapy of KRAS inhibitors has accumulated possible resistance, acquiring the exploration of combination therapies or next-generation KRAS inhibitors. Thus, other non-target, conventional therapies have also been considered as being promising. Here in this review, we went through the characteristics…

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    Epicardial and Pericoronary Adipose Tissue, Coronary Inflammation, and Acute Coronary Syndromes

    Gianluigi Napoli, Valeria Pergola, Paolo Basile, Daniele De Feo, Fulvio Bertrandino and 10 more

    77 citationsOpen access (CC-BY)doi:10.3390/jcm12237212OpenAlex

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    Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcification, inflammation, and plaque vulnerability. They also participate in the vascular response during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evaluation of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant attention. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognostic value in coronary artery disease (CAD), being associated with plaque development,…

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    Exploring CAR-T Cell Therapy Side Effects: Mechanisms and Management Strategies

    Yugu Zhang, Diyuan Qin, Arthur Shou, Yanbin Liu, Yongsheng Wang and 1 more

    77 citationsOpen access (CC-BY)doi:10.3390/jcm12196124OpenAlex

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    Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of malignancies, especially hematological tumors, but toxicities have tempered its success. The main impediments to the development of CAR-T cell therapies are the following: cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and on-target/off-tumor toxicity (OTOT). This review summarizes these side effects' underlying mechanisms and manifestations over time. It provides potential prevention and treatment according to the consensus grading, stressing the significance of establishing strategies that anticipate, reduce, and navigate the beginning of these side effects. It is essential to fully comprehend the mechanisms underlying these toxicities to create efficient treatment and preventive approaches.

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    From Innate Immunity to Metabolic Disorder: A Review of the NLRP3 Inflammasome in Diabetes Mellitus

    Iris Maria Nițulescu, George Ciulei, Angela Cozma, Lucia Maria Procopciuc, Olga Hilda Orasan

    77 citationsOpen access (CC-BY)doi:10.3390/jcm12186022OpenAlex

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    The role of the NLRP3 inflammasome is pivotal in the pathophysiology and progression of diabetes mellitus (DM), encompassing both type 1 (T1D), or type 2 (T2D). As part of the innate immune system, NLRP3 is also responsible for the chronic inflammation triggered by hyperglycemia. In both conditions, NLRP3 facilitates the release of interleukin-1β and interleukin-18. For T1D, NLRP3 perpetuates the autoimmune cascade, leading to the destruction of pancreatic islet cells. In T2D, its activation is associated with the presence of insulin resistance. NLRP3 activation is also instrumental for the presence of numerous complications associated with DM, microvascular and macrovascular. A considerable number of anti-diabetic drugs have demonstrated the ability to inhibit the NLRP3 inflammasome.

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    Non-Pharmacological Pain Management in Labor: A Systematic Review

    Wassan Nori, Mustafa Ali Kassim Kassim, Zeena Raad Helmi, Alexandru Cosmin Pantazi, Dragoș Brezeanu and 3 more

    76 citationsOpen access (CC-BY)doi:10.3390/jcm12237203OpenAlex

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    Childbirth is a remarkable, life-changing process and is frequently regarded as an excruciating, physically and emotionally demanding experience that women endure. Labor pain management poses a significant challenge for obstetricians and expectant mothers. Although pharmacological pain management is the gold standard, it still imposes risks on the mother and baby. Recently, non-pharmacological pain management (NPPM) has emerged as a safe, effective option. Six databases were searched for articles published up to 2023 using specific related keywords and defined inclusion and exclusion criteria. The extraction and gathering of data was made so as to be categorized into physical, psychological, and complementary NPPM techniques. In light of the enormous development and diversity of NPPM techniques, the present review aims to examine contemporary NPPM knowledge and application, discussing efficacy, advantages, limitations, and potential adverse effects, with a specific focus on women's individual requirements, to strengthen obstetricians' knowledge in guiding decision-making for women…

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    The Role of Back Muscle Dysfunctions in Chronic Low Back Pain: State-of-the-Art and Clinical Implications

    Thomas Matheve, Paul W. Hodges, Lieven A. Danneels

    76 citationsOpen access (CC-BY)doi:10.3390/jcm12175510OpenAlex

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    Changes in back muscle function and structure are highly prevalent in patients with chronic low back pain (CLBP). Since large heterogeneity in clinical presentation and back muscle dysfunctions exists within this population, the potential role of back muscle dysfunctions in the persistence of low back pain differs between individuals. Consequently, interventions should be tailored to the individual patient and be based on a thorough clinical examination taking into account the multidimensional nature of CLBP. Considering the complexity of this process, we will provide a state-of-the-art update on back muscle dysfunctions in patients with CLBP and their implications for treatment. To this end, we will first give an overview of (1) dysfunctions in back muscle structure and function, (2) the potential of exercise therapy to address these dysfunctions, and (3) the relationship between changes in back muscle dysfunctions and clinical parameters. In a second part, we will describe a framework for an individualised approach for back muscle training in patients with CLBP.

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    The Protective Role of Cognitive Reserve in Mild Cognitive Impairment: A Systematic Review

    Ilaria Corbo, Giulia Marselli, Valerio Di Ciero, Maria Casagrande

    76 citationsOpen access (CC-BY)doi:10.3390/jcm12051759OpenAlex

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    Cognitive reserve (CR) represents the ability to optimize performance and functioning to cope with brain damage or disease. CR reflects the capability to adaptively and flexibly use cognitive processes and brain networks to compensate for the deterioration typical of aging. Several studies have investigated the potential role of CR in aging, especially from the perspective of preventing and protecting against dementia and Mild Cognitive Impairment (MCI). This systematic literature review aimed to investigate the role of CR as a protective factor against MCI and associated cognitive decline. The review process was conducted according to the PRISMA statement. For this purpose, ten studies were analyzed. The results of this review show that high CR is significantly associated with a reduced risk of MCI. In addition, a significant positive relationship between CR and cognitive functioning is observed when comparing subjects with MCI and healthy subjects and within people with MCI. Thus, the results confirm the positive role of cognitive reserve in mitigating cognitive impairment. The…

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    Epidemiology of Inflammatory Bowel Diseases: A Population Study in a Healthcare District of North-West Italy

    Gian Paolo Caviglia, Angela Garrone, Chiara Bertolino, Riccardo Vanni, Elisabetta Bretto and 8 more

    76 citationsOpen access (CC-BY)doi:10.3390/jcm12020641OpenAlex

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    The burden of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. The aim of the present study was to investigate the clinical characteristics and the changing in epidemiology of IBD in the Healthcare District Bra, an area of North-West Italy accounting for 57,615 inhabitants as of 31 December 2021. Clinical and demographic data were retrieved from administrative databases and the medical records of general practitioners (n = 39) at Verduno Hospital. Prevalence and incidence rates were calculated for the time span 2016–2021 and compared to the 2001–2006 period. IBD prevalence was 321.2 per 100,000 population in 2021 and, compared with 2006 (200 per 100,000 population), the prevalence has increased at a rate of +46%. Similarly, the average incidence has increased from the period 2001–2006 (6.7 per 100,000 population/year) to the period 2016–2021 (18.0 per 100,000 population/year) at a rate of +169%; such an increase was greater for CD than UC. In the 2016–2021 period, the mean age at diagnosis was 42.0 ± 17.4 years…

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    Risk Factors for Myopia: A Review

    Noelia Martínez-Albert, Inmaculada Bueno-Gimeno, Andrés Gené‐Sampedro

    75 citationsOpen access (CC-BY)doi:10.3390/jcm12186062OpenAlex

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    Due to the myopia prevalence increase worldwide, this study aims to establish the most relevant risk factors associated with its development and progression. A review search was carried out using PubMed, Web of Science, and Scopus databases to identify the main myopia risk factors. The inclusion criteria for the articles were those related to the topic, carried out in subjects from 5 to 30 years, published between January 2000 and May 2023, in English, and with the full text available. Myopia etiology has proven to be associated with both genetic and environmental factors as well as with gene-environment interaction. The risk of developing myopia increases in children with myopic parents (one parent ×2 times, two parents ×5 times). Regarding environmental factors, education is the main risk factor correlated with myopia prevalence increase. Further, several studies found that shorter distance (<30 cm) and longer time spent (>30 min) for near work increase the risk of myopia. Meanwhile, increased outdoor activity (>40 min/day) has been shown to be a key factor in reducing myopia…

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    A Review of FLT3 Kinase Inhibitors in AML

    Cristina Negotei, Andrei Coliţă, Iuliana Mitu, Anca Roxana Lupu, Mihai-Emilian Lapadat and 4 more

    74 citationsOpen access (CC-BY)doi:10.3390/jcm12206429OpenAlex

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    Acute myeloid leukemia (AML) is a highly aggressive illness distinguished by the accumulation of abnormal hematopoietic precursors in both the bone marrow and peripheral blood. The prevalence of FLT3 gene mutations is high and escalates the probability of relapse and mortality. The survival rates for AML patients, particularly those over 65, are low. FLT3 mutation screening at diagnosis is mandatory, and FLT3 inhibitors are crucial in treating AML patients with mutations. There are two categories of FLT3 mutations: FLT3-ITD located in the juxtamembrane domain and FLT3-TKD in the tyrosine kinase domain. FLT3-ITD is the most common type, affecting nearly a quarter of patients, whereas FLT3-TKD only affects 6-8% of patients. FLT3 inhibitors are now crucial in treating AML patients with FLT3 mutations. When dealing with FLT3-mutated AML, the recommended course of treatment typically involves chemotherapy and midostaurin, followed by allogeneic hematopoietic cell transplantation (HCT) to maximize the likelihood of success. Maintenance therapy can lower the risk of relapse, and…

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    Adenomyosis: An Updated Review on Diagnosis and Classification

    Gaby Moawad, Arrigo Fruscalzo, Youssef Youssef, Mira H. Kheil, Tala Tawil and 6 more

    74 citationsOpen access (CC-BY)doi:10.3390/jcm12144828OpenAlex

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    Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths…

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    How Radiomics Can Improve Breast Cancer Diagnosis and Treatment

    Filippo Pesapane, P. De Marco, Anna Rapino, Eleonora Lombardo, Luca Nicosia and 14 more

    74 citationsOpen access (CC-BY)doi:10.3390/jcm12041372OpenAlex

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    Recent technological advances in the field of artificial intelligence hold promise in addressing medical challenges in breast cancer care, such as early diagnosis, cancer subtype determination and molecular profiling, prediction of lymph node metastases, and prognostication of treatment response and probability of recurrence. Radiomics is a quantitative approach to medical imaging, which aims to enhance the existing data available to clinicians by means of advanced mathematical analysis using artificial intelligence. Various published studies from different fields in imaging have highlighted the potential of radiomics to enhance clinical decision making. In this review, we describe the evolution of AI in breast imaging and its frontiers, focusing on handcrafted and deep learning radiomics. We present a typical workflow of a radiomics analysis and a practical "how-to" guide. Finally, we summarize the methodology and implementation of radiomics in breast cancer, based on the most recent scientific literature to help researchers and clinicians gain fundamental knowledge of this…

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    Latest Evidence on Post-Prostatectomy Urinary Incontinence

    Mauro Gacci, Cosimo De Nunzio, Vasileios I. Sakalis, Malte Rieken, Jean‐Nicolas Cornu and 1 more

    74 citationsOpen access (CC-BY)doi:10.3390/jcm12031190OpenAlex

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    A radical prostatectomy is frequently used as the first-line treatment for men with prostate cancer. Persistent urinary incontinence after surgery is one of the most severe adverse events. We report the results of a comprehensive literature search focused on post-prostatectomy urinary incontinence (PPI), performed by a panel of experts on non-neurogenic lower urinary tract symptoms. The data on the prevalence and timing of PPI are very heterogeneous. The etiology of PPI can be multifactorial and mainly dependent on patient characteristics, lower urinary tract function or surgical issues. The medical history with a physical examination, the use of validated questionnaires with a voiding diary and pad tests are determinants in identifying the contributing factors and choosing the right treatment. Lifestyle intervention and urinary containment are the most frequently used strategies for the conservative management of PPI, while antimuscarinics, beta-3 agonists and duloxetine (off-label) are drugs indicated to manage PPI with a concomitant overactive bladder. Surgical therapies for the…

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    The Performance of GALAD Score for Diagnosing Hepatocellular Carcinoma in Patients with Chronic Liver Diseases: A Systematic Review and Meta-Analysis

    Ming‐Cheng Guan, Shiyu Zhang, Qian Ding, Na Li, Tingting Fu and 5 more

    73 citationsOpen access (CC-BY)doi:10.3390/jcm12030949OpenAlex

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    Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78–0.85), 0.89 (95%CI: 0.85–0.91), and 0.92 (95%CI: 0.89–0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona…

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    Introducing Machine Perfusion into Routine Clinical Practice for Liver Transplantation in the United States: The Moment Has Finally Come

    Kristopher P. Croome

    73 citationsOpen access (CC-BY)doi:10.3390/jcm12030909OpenAlex

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    While adoption of machine perfusion technologies into clinical practice in the United States has been much slower than in Europe, recent changes in the transplant landscape as well as device availability following FDA approval have paved the way for rapid growth. Machine perfusion may provide one mechanism to maximize the utilization of potential donor liver grafts. Indeed, multiple studies have shown increased organ utilization with the implementation of technologies such as ex-situ normothermic machine perfusion (NMP), ex-situ hypothermic machine perfusion (HMP) and in-situ normothermic regional perfusion (NRP). The current review describes the history and development of machine perfusion utilization in the Unites States along with future directions. It also describes the differences in landscape between Europe and the United States and how this has shaped clinical application of these technologies.

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    Review of Osteoradionecrosis of the Jaw: Radiotherapy Modality, Technique, and Dose as Risk Factors

    Erkan Topkan, Ahmet Küçük, Efsun Somay, Busra Nur Gokkurt Yilmaz, Berrin Pehlivan and 1 more

    72 citationsOpen access (CC-BY)doi:10.3390/jcm12083025OpenAlex

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    Radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) is the cornerstone of organ-sparing or adjuvant therapy for nearly all head and neck cancers. Unfortunately, aggressive RT or CCRT can result in severe late toxicities, such as osteoradionecrosis of the jaws (ORNJ). The incidence of ORNJ is currently less than 5-6% due to advances in dental preventive care programs, RT planning systems, and RT techniques. Although numerous patient-, tumor-, and treatment-related factors may influence the incidence rates of ORNJ, RT modality (equipment), technique, and dose-volume-related factors are three of the most influential factors. This is mainly because different RT equipment and techniques have different levels of success at delivering the prescribed dose to the focal volume of the treatment while keeping the "organ at risk" safe. ORNJ risk is ultimately determined by mandibular dose, despite the RT technique and method being known predictors. Regardless of the photon delivery method, the radiobiological effects will be identical if the total dose, dose per fraction, and dose…

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    Prevalence of Sarcopenia in Knee Osteoarthritis: A Systematic Review and Meta-Analysis

    Francesco Pegreffi, Alice Balestra, Orazio De Lucia, Lee Smith, Mario Barbagallo and 1 more

    72 citationsOpen access (CC-BY)doi:10.3390/jcm12041532OpenAlex

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    An association between knee osteoarthritis (OA) and sarcopenia has been proposed, but the evidence is controversial, with the recent literature showing disparate results. Therefore, we aimed to perform a systematic review and meta-analysis to evaluate the prevalence of sarcopenia in knee OA patients compared to people not affected by this condition. We searched several databases until 22 February 2022. The data regarding prevalence were summarized using odds ratios (ORs) with their 95% confidence intervals (CIs). Among the 504 papers initially screened, 4 were included for a total of 7495 participants with a mean age of 68.4 years, who were mainly females (72.4%). The prevalence of sarcopenia in people with knee OA was 45.2%, whilst, in the controls, it was 31.2%. Pooling the data of the studies included that the prevalence of sarcopenia in knee OA was more than two times higher than in the control group (OR = 2.07; 95%CI: 1.43–3.00; I2 = 85%). This outcome did not suffer any publication bias. However, after removing an outlier study, the recalculated OR was 1.88. In conclusion, the…

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    Clinical Potential of Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration

    Bárbara Torrecillas-Baena, Victoria Pulido-Escribano, Gabriel Dorado, María Ángeles Gálvez-Moreno, Marta Camacho-Cardeñosa and 1 more

    71 citationsOpen access (CC-BY)doi:10.3390/jcm12134385OpenAlex

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    Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, and traumatic fractures require effective treatments that favor bone formation and regeneration. Among these, cell therapy based on mesenchymal stem cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part on their paracrine properties. These are mainly mediated by extracellular vesicle (EV) secretion. EV modulates regenerative processes such as inflammation, angiogenesis, cell proliferation, migration, and differentiation. Thus, MSC-EV are currently an important tool for the development of cell-free therapies in regenerative medicine. This review describes the current knowledge of the effects of MSC-EV in the different phases of bone regeneration. MSC-EV has been used by intravenous injection, directly or in combination with different types of biomaterials, in preclinical models of bone diseases. They have shown great clinical potential in regenerative medicine applied to bone. These…

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    Application and Progress of Artificial Intelligence in Fetal Ultrasound

    Sushan Xiao, Junmin Zhang, Ye Chao Zhu, Zisang Zhang, Haiyan Cao and 2 more

    70 citationsOpen access (CC-BY)doi:10.3390/jcm12093298OpenAlex

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    Prenatal ultrasonography is the most crucial imaging modality during pregnancy. However, problems such as high fetal mobility, excessive maternal abdominal wall thickness, and inter-observer variability limit the development of traditional ultrasound in clinical applications. The combination of artificial intelligence (AI) and obstetric ultrasound may help optimize fetal ultrasound examination by shortening the examination time, reducing the physician's workload, and improving diagnostic accuracy. AI has been successfully applied to automatic fetal ultrasound standard plane detection, biometric parameter measurement, and disease diagnosis to facilitate conventional imaging approaches. In this review, we attempt to thoroughly review the applications and advantages of AI in prenatal fetal ultrasound and discuss the challenges and promises of this new field.

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    Gut Microbiota in Chronic Kidney Disease: From Composition to Modulation towards Better Outcomes—A Systematic Review

    Luminita E. Voroneanu, Alexandru Burlacu, Crischentian Brinza, Andreea Simona Covic, Gheorghe Gh Bălan and 4 more

    70 citationsOpen access (CC-BY)doi:10.3390/jcm12051948OpenAlex

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    Background: A bidirectional kidney–gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. Materials and methods: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. Results: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls…

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    Stent Thrombosis and Restenosis with Contemporary Drug-Eluting Stents: Predictors and Current Evidence

    Francesco Condello, Carmen Spaccarotella, Sabato Sorrentino, Ciro Indolfi, Giulio Giuseppe Stefanini and 1 more

    70 citationsOpen access (CC-BY)doi:10.3390/jcm12031238OpenAlex

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    Iterations in stent technologies, advances in pharmacotherapy, and awareness of the implications of implantation techniques have markedly reduced the risk of stent failure, both in the form of stent thrombosis (ST) and in-stent restenosis (ISR). However, given the number of percutaneous coronary interventions (PCI) performed worldwide every year, ST and ISR, albeit occurring at a fairly low rate, represent a public health problem even with contemporary DES platforms. The understanding of mechanisms and risk factors for these two PCI complications has been of fundamental importance for the parallel evolution of stent technologies. Risk factors associated with ST and ISR are usually divided into patient-, lesion-, device- and procedure-related. A number of studies have shown how certain risk factors are related to early (1 month) versus late/very late ST (between 1 month and 1 year and >1 year, respectively). However, more research is required to conclusively show the role of time-dependence of risk factors also in the incidence of ISR (early [1 year] or late [>1 year]). A thorough…

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    Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs

    Enrico Carmina, Rosa Alba Longo

    69 citationsOpen access (CC-BY)doi:10.3390/jcm12185921OpenAlex

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    In spite of the widespread use of lifestyle modifications programs, many patients with PCOS are obese and prevalence of obesity in PCOS remains high. In this study, we present the data on the use of semaglutide, an incretin mimetic drug, in obese PCOS patients who were unresponsive to a lifestyle modification program. Twenty-seven obese patients with a diagnosis of PCOS, who did not reduce their body weight by a lifestyle modification program, were included in this study and treated by semaglutide, 0.5 mg subcutaneously once a week. After three months of treatment, an improvement in body weight with a mean decrease in body weight of 7.6 kg and a mean BMI loss of 3.1 was observed, while very few side effects were reported. Almost 80% of the studied obese PCOS patients obtained at least a 5% decrease in their body weight. Only a few patients (22%) obtained a decrease in body weight lower than 5% and were considered non-responsive to semaglutide, at least at the used doses. These patients presented a more severe obesity than responsive patients. Independently of results on body weight,…

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    Associations between Stress, Anxiety, Depression and Sleep Quality among Healthcare Students

    Monira Alwhaibi, Noha Abdullah Al Aloola

    69 citationsOpen access (CC-BY)doi:10.3390/jcm12134340OpenAlex

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    OBJECTIVES: Stress, anxiety, and depression among students have many negative health consequences and may predispose students to poor sleep quality; therefore, this research aimed to investigate the perceived stress, anxiety, and depression and their relation to the level of sleep quality among healthcare students. METHODS: A cross-sectional study using a validated survey was conducted among Saudi healthcare students from different regions during the period from 26 September 2022 to 30 October 2022. The Pittsburgh Sleep Quality Index (PSQI) was utilized to assess sleep quality. PSPP Statistical Analysis Software version 1.2.0 was used for all statistical analyses. RESULTS: 701 respondents participated in this research; the response rate was 73.8%. About 60% of the study sample was female, and the average age was 20.9 years. 80.3% of students have poor sleep quality; the participants' mean sleeping hours per night was 6.81 ± 1.88 h. About three-quarters of students (72.9%) perceive themselves as stressed. A significant positive correlation was observed between sleep quality and…

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    Narrative Review: Low-Dose Ketamine for Pain Management

    Alessandro Riccardi, Mario Guarino, Sossio Serra, Michele Domenico Spampinato, Simone Vanni and 4 more

    69 citationsOpen access (CC-BY)doi:10.3390/jcm12093256OpenAlex

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    Pain is the leading cause of medical consultations and occurs in 50-70% of emergency department visits. To date, several drugs have been used to manage pain. The clinical use of ketamine began in the 1960s and it immediately emerged as a manageable and safe drug for sedation and anesthesia. The analgesic properties of this drug were first reported shortly after its use; however, its psychomimetic effects have limited its use in emergency departments. Owing to the misuse and abuse of opioids in some countries worldwide, ketamine has become a versatile tool for sedation and analgesia. In this narrative review, ketamine's role as an analgesic is discussed, with both known and new applications in various contexts (acute, chronic, and neuropathic pain), along with its strengths and weaknesses, especially in terms of psychomimetic, cardiovascular, and hepatic effects. Moreover, new scientific evidence has been reviewed on the use of additional drugs with ketamine, such as magnesium infusion for improving analgesia and clonidine for treating psychomimetic symptoms. Finally, this narrative…

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    Tinnitus Guidelines and Their Evidence Base

    Berthold Langguth, Tobias Kleinjung, Winfried Schlee, Sven Vanneste, Dirk De Ridder

    69 citationsOpen access (CC-BY)doi:10.3390/jcm12093087OpenAlex

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    Evidence-based medicine (EBM) is generally accepted as the gold standard for high-quality medicine and, thus, for managing patients with tinnitus. EBM integrates the best available scientific information with clinical experience and patient values to guide decision-making about clinical management. To help health care providers and clinicians, the available evidence is commonly translated into medical or clinical guidelines based on a consensus. These involve a systematic review of the literature and meta-analytic aggregation of research findings followed by the formulation of clinical recommendations. However, this approach also has limitations, which include a lack of consideration of individual patient characteristics, the susceptibility of guideline recommendations to material and immaterial conflicts of interest of guideline authors and long latencies till new knowledge is implemented in guidelines. A further important aspect in interpreting the existing literature is that the absence of evidence is not evidence of absence. These circumstances could result in the decoupling of…

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    Effects of Multidisciplinary Rehabilitation Program in Patients with Long COVID-19: Post-COVID-19 Rehabilitation (PCR SIRIO 8) Study

    Małgorzata Ostrowska, Alicja Rzepka-Cholasińska, Łukasz Pietrzykowski, Piotr Michalski, Agata Kosobucka and 4 more

    69 citationsOpen access (CC-BY)doi:10.3390/jcm12020420OpenAlex

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    Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients’ physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m (p < 0.0001), the number of repetitions in the 30 s Chair Stand Test improved from 13 to 16 (p < 0.0001), as well as physical fitness in the Short Physical Performance Battery Test from 14 to 16 (p < 0.0001). The impact of fatigue on everyday…

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    Coronary No-Reflow after Primary Percutaneous Coronary Intervention—Current Knowledge on Pathophysiology, Diagnosis, Clinical Impact and Therapy

    Gjin Ndrepepa, Adnan Kastrati

    68 citationsOpen access (CC-BY)doi:10.3390/jcm12175592OpenAlex

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    Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to…

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    The Effect of High-Intensity Interval Training Type on Body Fat Percentage, Fat and Fat-Free Mass: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

    Fatemeh Khodadadi, Reza Bagheri, Raoof Negaresh, Sajjad Moradi, Michael Nordvall and 3 more

    68 citationsOpen access (CC-BY)doi:10.3390/jcm12062291OpenAlex

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    This systematic review and meta-analysis of randomized controlled trials (RCTs) compared body compositional changes, including fat mass (FM), body fat percentage (BF%), and fat-free mass (FFM), between different types of high-intensity interval training (HIIT) (cycling vs. overground running vs. treadmill running) as well as to a control (i.e., no exercise) condition. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCTs. Thirty-six RCTs lasting between 3 to 15 weeks were included in the current systematic review and meta-analysis. RCTs that examined the effect of HIIT type on FM, BF%, and FFM were sourced from online databases including PubMed, Scopus, Web of Science, and Google Scholar up to 21 June 2022. HIIT (all modalities combined) induced a significant reduction in FM (weighted mean difference [WMD]: −1.86 kg, 95% CI: −2.55 to −1.18, p = 0.001) despite a medium between-study heterogeneity (I2 = 63.3, p = 0.001). Subgroup analyses revealed cycling and overground running reduced FM (WMD: −1.72 kg, 95% CI: −2.41 to…

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    Surgical Management of Ovarian Endometrioma: Impact on Ovarian Reserve Parameters and Reproductive Outcomes

    Angelos Danilidis, Georgios Grigoriadis, Dimitrios Rafail Kalaitzopoulos, Stefano L. Angioni, Üzeyir Kalkan and 3 more

    67 citationsOpen access (CC-BY)doi:10.3390/jcm12165324OpenAlex

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    Ovarian endometriomas have a negative impact on a patient's reproductive potential and are likely to cause a reduction in ovarian reserve. The most commonly employed ovarian reserve parameters are anti-Müllerian hormone (AMH) and antral follicular count (AFC). Surgical management options of endometrioma include cystectomy, ablative methods, ethanol sclerotherapy and combined techniques. The optimal surgical approach remains a matter of debate. Our review aimed to summarize the literature on the impact of surgical management of endometrioma on AMH, AFC and fertility outcomes. Cystectomy may reduce recurrence rates and increase chances of spontaneous conception. However, a postoperative reduction in AMH is to be anticipated, despite there being evidence of recovery during follow-up. The reduction in ovarian reserve is likely multi-factorial. Cystectomy does not appear to significantly reduce, and may even increase, AFC. Ablative methods achieve an ovarian-tissue-sparing effect, and improved ovarian reserve, compared to cystectomy, has been demonstrated. A single study reported on AMH…

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    Management of Coronary Artery Disease in Older Adults: Recent Advances and Gaps in Evidence

    Stefano Cacciatore, Luigi Spadafora, Marco Bernardi, Mattía Galli, Matteo Betti and 10 more

    67 citationsOpen access (CC-BY)doi:10.3390/jcm12165233OpenAlex

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    Coronary artery disease (CAD) is highly prevalent in older adults, yet its management remains challenging. Treatment choices are made complex by the frailty burden of older patients, a high prevalence of comorbidities and body composition abnormalities (e.g., sarcopenia), the complexity of coronary anatomy, and the frequent presence of multivessel disease, as well as the coexistence of major ischemic and bleeding risk factors. Recent randomized clinical trials and epidemiological studies have provided new data on optimal management of complex patients with CAD. However, frail older adults are still underrepresented in the literature. This narrative review aims to highlight the importance of assessing frailty as an aid to guide therapeutic decision-making and tailor CAD management to the specific needs of older adults, taking into account age-related pharmacokinetic and pharmacodynamic changes, polypharmacy, and potential drug interactions. We also discuss gaps in the evidence and offer perspectives on how best in the future to optimize the global strategy of CAD management in older…

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    Osteosarcoma: Current Concepts and Evolutions in Management Principles

    Pampina Pilavaki, Amir Hossain Gahanbani Ardakani, Panagiotis D. Gikas, Anastasia Constantinidou

    67 citationsOpen access (CC-BY)doi:10.3390/jcm12082785OpenAlex

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    Osteosarcoma is a rare malignancy arising from mesenchymal tissue, and represents the most common bone sarcoma. The management of osteosarcoma is challenging, and requires a multidisciplinary approach. In daily clinical practice, surgery, radiotherapy, and conventional chemotherapy constitute the therapeutic armamentarium against the disease. However, a significant number of patients with initially localized osteosarcoma will experience local or distant recurrence, and the prognosis for metastatic disease remains dismal. There is a pressing need to identify novel therapeutic strategies to better manage osteosarcoma and improve survival outcomes. In this study, we present recent advances in the therapeutic management of osteosarcoma, including surgical and medical advances. The role of immunotherapy (immune checkpoint inhibitors, adoptive cellular therapy, cancer vaccines) and other targeted therapies including tyrosine kinase inhibitors is discussed; however, additional studies are required to delineate their roles in clinical practice.

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    Limb–Girdle Muscular Dystrophies Classification and Therapies

    Camille Bouchard, Jacques P. Tremblay

    66 citationsOpen access (CC-BY)doi:10.3390/jcm12144769OpenAlex

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    Limb-girdle muscular dystrophies (LGMDs) are caused by mutations in multiple genes. This review article presents 39 genes associated with LGMDs. Some forms are inherited in a dominant fashion, while for others this occurs recessively. The classification of LGMDs has evolved through time. Lately, to be considered an LGMD, the mutation has to cause a predominant proximal muscle weakness and must be found in two or more unrelated families. This article also presents therapies for LGMDs, examining both available treatments and those in development. For now, only symptomatic treatments are available for patients. The goal is now to solve the problem at the root of LGMDs instead of treating each symptom individually. In the last decade, multiple other potential treatments were developed and studied, such as stem-cell transplantation, exon skipping, gene delivery, RNAi, and gene editing.

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    The Biology of Placebo and Nocebo Effects on Experimental and Chronic Pain: State of the Art

    Giacomo Rossettini, Francesco Campaci, Joel E. Bialosky, Eva Huysmans, Lene Vase and 1 more

    66 citationsOpen access (CC-BY)doi:10.3390/jcm12124113OpenAlex

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    (1) Background: In recent years, placebo and nocebo effects have been extensively documented in different medical conditions, including pain. The scientific literature has provided strong evidence of how the psychosocial context accompanying the treatment administration can influence the therapeutic outcome positively (placebo effects) or negatively (nocebo effects). (2) Methods: This state-of-the-art paper aims to provide an updated overview of placebo and nocebo effects on pain. (3) Results: The most common study designs, the psychological mechanisms, and neurobiological/genetic determinants of these phenomena are discussed, focusing on the differences between positive and negative context effects on pain in experimental settings on healthy volunteers and in clinical settings on chronic pain patients. Finally, the last section describes the implications for clinical and research practice to maximize the medical and scientific routine and correctly interpret the results of research studies on placebo and nocebo effects. (4) Conclusions: While studies on healthy participants seem…

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    Delirium in Medically Hospitalized Patients: Prevalence, Recognition and Risk Factors: A Prospective Cohort Study

    Rajaa Saleh Al Farsi, Abdullah Mohammed Al Alawi, Aisha Ramadhan Al Huraizi, Taif Al-Saadi, Noof Al-Hamadani and 2 more

    66 citationsOpen access (CC-BY)doi:10.3390/jcm12123897OpenAlex

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    BACKGROUND: Delirium is a common neuropsychiatric syndrome in hospitalized elderly patients and is associated with poor clinical outcomes. We aimed to determine the prevalence, recognition, risk factors, and course of delirium among hospitalized elderly (65 years of age or older) patients at Sultan Qaboos University Hospital (SQUH). METHODS: A prospective cohort study included 327 elderly patients (65 years of age or older) admitted to the medical wards at SQUH. Patients were screened for delirium using the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM). Additionally, medical records were reviewed to identify possible associated factors. RESULTS: The prevalence of delirium was 55.4% (95% CI 49.9-60.7), and 35.4% of patients with delirium were not recognized by the treating team. Hypoactive delirium is the most common type of delirium. The logistic regression analyzes demonstrated that pre-existing cognitive impairment (OR = 4.0); poor functional status (OR = 1.9); the use of medications that are known to precipitate delirium (OR = 2.3); polypharmacy (OR = 5.7); urinary…

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    The Pain Management of Trauma Patients in the Emergency Department

    Andrea Fabbri, Antonio Voza, Alessandro Riccardi, Sossio Serra, Fabio De Iaco

    66 citationsOpen access (CC-BY)doi:10.3390/jcm12093289OpenAlex

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    The vast majority of injured patients suffer from pain. Systematic assessment of pain on admission to the emergency department (ED) is a cornerstone of translating the best treatment strategies for patient care into practice. Pain must be measured with severity scales that are validated in clinical practice, including for specific populations (such as children and older adults). Although primary care ED of trauma patients focuses on resuscitation, diagnosis and treatment, pain assessment and management remains a critical element as professionals are not prepared to provide effective and early therapy. To date, most EDs have pain assessment and management protocols that take into account the patient's hemodynamic status and clinical condition and give preference to non-pharmacological approaches where possible. When selecting medications, the focus is on those that are least disruptive to hemodynamic status. Pain relief may still be necessary in hemodynamically unstable patients, but caution should be exercised, especially when using opioids, as absorption may be impaired or shock…

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    Impact of Dental Anxiety on Dental Care Routine and Oral-Health-Related Quality of Life in a German Adult Population—A Cross-Sectional Study

    Christian H. Winkler, Monika Bjelopavlovic, Karl Martin Lehmann, Katja Petrowski, Lisa Irmscher and 1 more

    65 citationsOpen access (CC-BY)doi:10.3390/jcm12165291OpenAlex

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    The interaction between dental anxiety and the establishment of a consistent dental care routine has been an ongoing challenge. Unfortunately, there is limited available data concerning the detailed dental care practices of individuals with dental anxiety. Therefore, this study aims to explore how dental anxiety influences dental care habits and oral-health-related quality of life within an adult population. By utilizing the Dental Anxiety Scale (DAS) and the German Oral Health Impact Profile (OHIP-G5), we assessed their extent. To evaluate the differences, we performed analyses of variance (Anova), an independent t-test and rank correlation. The findings of this study unveil a significant correlation between elevated DAS scores and reduced frequency of tooth brushing; calculus removal and appointments for professional teeth cleaning. Interestingly; the use of dental floss and mouthwash solution as well as toothbrush hardness appeared to be not significantly affected by dental fear. Moreover, individuals with dental anxiety demonstrated a preference for manual toothbrushes over…

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    Novel Biomarkers of Gastric Cancer: Current Research and Future Perspectives

    Yasushi Sato, Koichi Okamoto, Yutaka Kawano, Akinari Kasai, Tomoyuki Kawaguchi and 4 more

    65 citationsOpen access (CC-BY)doi:10.3390/jcm12144646OpenAlex

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    Gastric cancer is a heterogeneous disease with diverse histological and genomic subtypes, making it difficult to demonstrate treatment efficacy in clinical trials. However, recent efforts have been made to identify molecular biomarkers with prognostic and predictive implications to better understand the broad heterogeneity of gastric cancer and develop effective targeted therapies for it. HER2 overexpression, HER2/neu amplification, MSI-H, and PD-L1+ are predictive biomarkers in gastric cancer, and a growing number of clinical trials based on novel biomarkers have demonstrated the efficacy of targeted therapies alone or in combination with conventional chemotherapy. Enrichment design clinical trials of targeted therapies against FGFR2b and claudin 18.2 have demonstrated efficacy in unresectable advanced gastric cancer. Nonetheless, it is essential to continuously validate promising molecular biomarkers and introduce them into clinical practice to optimize treatment selection and improve patient outcomes. In this review, we focused on established (PD-L1, HER2, MSI) and emerging…

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    Systemic Anti-Inflammatory Effects of Intravenous Lidocaine in Surgical Patients: A Systematic Review and Meta-Analysis

    Irene Castro, Pedro Carvalho, Nuno Vale, Teresa Monjardino, Joana Irene de Barros Mourão

    65 citationsOpen access (CC-BY)doi:10.3390/jcm12113772OpenAlex

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    There has recently been increasing evidence that the use of perioperative intravenous lidocaine infusion possesses analgesic, opioid-sparing and anti-inflammatory effects in surgical patients. Although opioid-sparing and analgesic properties have been strongly supported, the anti-inflammatory features are not well established in elective surgery. Therefore, the aim of this systematic review is to examine the effect of perioperative intravenous lidocaine infusion on postoperative anti-inflammatory status in patients undergoing elective surgery. A search strategy was created to identify suitable randomised clinical trials (RCTs) in PubMed, Scopus, Web of Science and Clinicaltrials.gov databases until January 2023. RCTs that evaluated the effect of intravenous lidocaine infusion, compared with placebo, on adult patients who underwent elective surgery, in inflammatory markers response were included. Exclusion criteria consisted of paediatric patients, animal studies, non-RCT methodology, intervention without intravenous lidocaine, inadequate control group, duplicated samples, ongoing…

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The cohort is every article, review and book chapter OpenAlex attributes to Journal of Clinical Medicine with publication year 2023, excluding retracted works and paratext such as editorials and errata. The top 100 by citation count are listed; the percentile is the rank divided by the cohort size. 100 of the 100 entries have an abstract in OpenAlex. Counts were read on 29 October 2026 and will not be updated on this page, so a quoted rank stays verifiable. Full rules on the methodology page.

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