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Nutritional Status of Adult People Living with HIV: A Narrative Review
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The Role of Cortisol and Dehydroepiandrosterone in Obesity, Pain, and Aging
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Oxidative Stress in Benign Prostatic Hyperplasia: Mechanisms, Clinical Relevance and Therapeutic Perspectives
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Managing Depressive Symptoms in Breast Cancer
Journal Description
Diseases
Diseases
is an international, peer-reviewed, open access, multidisciplinary journal which focuses on the latest and outstanding research on diseases and conditions published monthly online by MDPI. The first issue is released in 2013.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Medicine, Research and Experimental)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 21.4 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 8 topical sections.
Impact Factor:
3.0 (2024);
5-Year Impact Factor:
3.4 (2024)
Latest Articles
Atherogenic Risk in Shift Versus Non-Shift Workers: Associations with Sociodemographic and Lifestyle Factors
Diseases 2025, 13(6), 188; https://doi.org/10.3390/diseases13060188 - 18 Jun 2025
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Introduction. Atherosclerosis is the histopathological lesion underlying most cardiovascular diseases. Several scales assess the risk of developing atherosclerosis, with the most recognized being atherogenic dyslipidemia (AD) and atherogenic indices (AIs). The aim of this study is to assess the associations between shift work,
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Introduction. Atherosclerosis is the histopathological lesion underlying most cardiovascular diseases. Several scales assess the risk of developing atherosclerosis, with the most recognized being atherogenic dyslipidemia (AD) and atherogenic indices (AIs). The aim of this study is to assess the associations between shift work, sociodemographic variables, and lifestyle with atherogenic risk, as determined by atherogenic indices, atherogenic dyslipidemia, and the lipid triad. Material and Methods. This is a descriptive, cross-sectional study involving 53,053 workers (28,808 shift workers and 24,245 non-shift workers) from various autonomous communities in Spain and multiple occupational sectors. The association between sociodemographic variables such as age, sex, and socioeconomic status, health habits including tobacco and alcohol consumption, physical activity (PA), adherence to the Mediterranean diet (MD), and shift work with the presence of AD and high values of three AIs (Cholesterol/HDL-c, LDL-c/HDL-c, and Triglycerides/HDL-c) were assessed. Results. All variables analyzed were associated with AD and AIs values. Among the variables, the strongest associations were observed for physical activity, with odds ratios (ORs) ranging from 7.70 (95% CI: 6.86–8.55) for high LDL-c/HDL-c to 14.10 (95% CI: 9.05–14.16) for AD; adherence to the Mediterranean diet, with ORs ranging from 1.98 (95% CI: 1.60–2.37) for high LDL-c/HDL-c to 5.89 (95% CI: 4.92–6.86) for AD; and age, with ORs of 2.11 (95% CI: 1.84–2.38) for high Triglycerides/HDL-c and 4.66 (95% CI: 4.04–5.28) for high Total Cholesterol/HDL-c. Conclusions. The profile of a worker with the highest atherogenic risk in our study is a male, older in age, with low socioeconomic status, a smoker, a habitual alcohol consumer, physically inactive, with low adherence to the Mediterranean diet, and engaged in shift work.
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Open AccessArticle
Single-Port Laparoscopic Hepatectomy: Slovenian Single-Center Experience
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Jerica Novak, Miha Petrič, Blaž Trotovšek and Mihajlo Đokić
Diseases 2025, 13(6), 187; https://doi.org/10.3390/diseases13060187 - 18 Jun 2025
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Background: Single-port laparoscopic hepatectomy is a minimally invasive modality for the treatment of benign and malignant liver lesions. Due to the method’s technical challenges, it is suitable for experienced hepatobiliary surgeons and selected groups of patients. The aim of this study was to
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Background: Single-port laparoscopic hepatectomy is a minimally invasive modality for the treatment of benign and malignant liver lesions. Due to the method’s technical challenges, it is suitable for experienced hepatobiliary surgeons and selected groups of patients. The aim of this study was to evaluate the results of a single Slovenian center performing single-port laparoscopic hepatectomy with a literature overview. Methods: A single-center retrospective consecutive case series of the twenty-six patients with liver disease operated with the single-port technique from January 2018 to July 2024 at the Department of Abdominal Surgery at the University Medical Centre, Ljubljana, was performed. Lesions were located in easy-to-treat segments. Operative time, conversion rate, length of hospital stay, and surgical complications were recorded and evaluated. Results: We performed twenty-six single-port laparoscopic liver resections (median age 63.5, range 31 to 79 years). The mean operative time was 92 ± 31 min. None of the cases were converted to multi-port laparoscopic or open surgery. Safe resection margins were obtained in cases of malignant disease. The mean hospital stay was 4 days. The post-operative complication rate involving intervention was 7% (2/26). The incisional hernia rate was 11.5% (3/26). No life-threatening surgical complications or morbidity were noted. Conclusions: Single-port laparoscopic hepatectomy is a safe and feasible technique for the resection of benign and malignant liver lesions in the hands of skilled and well-trained hepatobiliary surgeons.
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Open AccessSystematic Review
The Impact of Preventive Protocols on Oral Health Outcomes in Cancer Patients Undergoing Chemotherapy or Radiotherapy: A Systematic Review and Meta-Analysis
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Carol Moussa, Laurent Estrade, Jeremy Glomet, Gael Y. Rochefort, Frédéric Denis and Maha H. Daou
Diseases 2025, 13(6), 186; https://doi.org/10.3390/diseases13060186 - 16 Jun 2025
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Background/Objectives: Cancer patients undergoing chemotherapy (CT) or radiotherapy (RT) are at increased risk of oral complications. Preventive dental care has been proposed to mitigate these risks, yet its effectiveness is not sufficiently evaluated. This systematic review and meta-analysis aimed to assess the
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Background/Objectives: Cancer patients undergoing chemotherapy (CT) or radiotherapy (RT) are at increased risk of oral complications. Preventive dental care has been proposed to mitigate these risks, yet its effectiveness is not sufficiently evaluated. This systematic review and meta-analysis aimed to assess the impact of preventive oral health interventions on key clinical outcomes in oncology patients. Methods: A systematic search of MEDLINE, Embase, and CENTRAL databases was conducted (March 2025), adhering to PRISMA guidelines with a PROSPERO-registered protocol (CRD 420251006799). Eligible studies included randomized trials, cohort studies, and pre–post intervention studies evaluating preventive dental care in patients receiving CT or RT. The outcomes included gingival index (GI), dental caries (DMFT), plaque levels, and periodontal health. Meta-analyses were performed on GI and DMFT outcomes using random-effects models. Results: Eleven studies were included in the qualitative synthesis and four in the meta-analyses. Preventive interventions, such as fluoride applications, oral hygiene education, and regular professional cleanings, were associated with stabilization or improvement of gingival health. The pooled estimate for GI showed no significant deterioration over time (MD = −0.05, 95% CI: −0.34 to 0.24, p = 0.72). For DMFT, a slight but significant increase was observed (MD = 1.07, 95% CI: 0.08 to 2.05, p = 0.03), suggesting a continued risk of caries despite intervention. Conclusions: Preventive dental care interventions appear to support the maintenance of gingival health in cancer patients undergoing CT or RT. However, despite these interventions, a slight increase in dental caries was still observed, indicating that preventive strategies may not fully eliminate the risk of caries. These findings highlight the importance of sustained and individualized oral health programs as part of comprehensive oncology care. Future studies using standardized protocols and longer follow-up periods are needed to better evaluate their long-term effectiveness across diverse cancer populations.
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(This article belongs to the Special Issue Oral Health and Care)
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Open AccessReview
Tumor Necrosis Factor-Alpha’s Role in the Pathophysiology of Colon Cancer
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Saleha Khan, Yara Aldawood, Ayesha Hanin Shaikh, Aleena Zobairi, Urwa Nabilah, H. M. Alqahtani and Mansoor-Ali Vaali-Mohammed
Diseases 2025, 13(6), 185; https://doi.org/10.3390/diseases13060185 - 15 Jun 2025
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Colon cancer remains a significant global health challenge, with inflammatory pathways such as TNF-α playing a central role in its progression. TNF-α, a key proinflammatory cytokine, is implicated in various stages of colon cancer development, including inflammation, tumor growth, and metastasis. This review
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Colon cancer remains a significant global health challenge, with inflammatory pathways such as TNF-α playing a central role in its progression. TNF-α, a key proinflammatory cytokine, is implicated in various stages of colon cancer development, including inflammation, tumor growth, and metastasis. This review provides a comprehensive overview of the molecular mechanisms through which TNF-α contributes to colon cancer progression, with a focus on its interaction with signaling pathways like NF-κB and the Wnt/β-catenin in humans. TNF-α’s involvement in promoting tumorigenesis and its complex role in the tumor microenvironment highlight its potential as both a therapeutic target and a challenge for effective treatment. This review explores the potential of anti-TNF-α therapies and the emerging role of combination strategies with immune checkpoint inhibitors. Despite promising preclinical findings, clinical application faces challenges due to the dual role of TNF-α in both promoting and inhibiting tumor progression. Future research should aim to overcome resistance mechanisms, develop personalized therapeutic strategies, and balance the effects of TNF-α in cancer therapy.
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Open AccessReview
Integration of AI and ML in Tuberculosis (TB) Management: From Diagnosis to Drug Discovery
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Sameeullah Memon, Shabana Bibi and Guozhong He
Diseases 2025, 13(6), 184; https://doi.org/10.3390/diseases13060184 - 11 Jun 2025
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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Despite the improvements in diagnostic techniques, the accuracy of TB diagnosis is still low. In recent years, the development of artificial intelligence (AI) has opened up new possibilities in diagnosing and treating TB
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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Despite the improvements in diagnostic techniques, the accuracy of TB diagnosis is still low. In recent years, the development of artificial intelligence (AI) has opened up new possibilities in diagnosing and treating TB with high accuracy compared to traditional methods. Traditional diagnostic techniques, such as sputum smear microscopy, culture tests, and chest X-rays, are time-consuming, with less sensitivity for the detection of TB in patients. Due to the new developments in AI, advanced diagnostic and treatment techniques have been developed with high accessibility, speed, and accuracy. AI, including various specific methodologies, is becoming vital in managing TB. Machine learning (ML) methodologies, such as support vector machines (SVMs) and random forests (RF), alongside deep learning (DL) technologies, particularly convolutional neural networks (CNNs) for image analysis, are employed to analyze diverse patient data, including medical images and biomarkers, to enhance the accuracy and speed of tuberculosis diagnosis. This study summarized the benefits and drawbacks of both traditional and AI-driven TB diagnosis, highlighting how AI can support traditional techniques to increase early detection, lower misdiagnosis, and strengthen international TB control initiatives.
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Open AccessReview
Supporting Post-ICU Recovery: A Narrative Review for General Practitioners
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Charikleia S. Vrettou and Athina G. Mantelou
Diseases 2025, 13(6), 183; https://doi.org/10.3390/diseases13060183 - 11 Jun 2025
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Survivors of intensive care unit (ICU) hospitalization often face persistent health challenges after discharge, collectively referred to as post-intensive care syndrome (PICS). This condition affects physical, cognitive, and mental health, significantly impacting patients’ quality of life and increasing their healthcare utilization. Additionally, caregivers
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Survivors of intensive care unit (ICU) hospitalization often face persistent health challenges after discharge, collectively referred to as post-intensive care syndrome (PICS). This condition affects physical, cognitive, and mental health, significantly impacting patients’ quality of life and increasing their healthcare utilization. Additionally, caregivers may develop PICS-F (PICS family), experiencing stress-related health burdens. Despite the growing awareness of these issues, structured post-ICU follow-up remains inconsistent, leaving a gap in care that general practitioners (GPs) must often fill. This review examines the role of GPs in managing post-ICU patients, outlining common complications, screening tools, rehabilitation strategies, and potential areas for improved collaboration between primary care and ICU teams. Emphasizing a multidisciplinary and proactive approach, we propose practical interventions that GPs can adopt to enhance long-term recovery outcomes for ICU survivors.
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(This article belongs to the Special Issue Care Integration for the Management of Chronic Diseases within Primary Health Care)
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Immune Response and Serum Biomarker Screening in Pregnant Women with Influenza A Virus Infection: Insight into Susceptibility and Disease Severity
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Suping Zhang, Jiarun Jiang, Rui Wang, Yuanyuan Zhang, Jinghui Sun, Wanting Hong, Likai Qi, Jia Zang, Zeyi Liu, Yu Xia, Haibing Yang and Liling Chen
Diseases 2025, 13(6), 182; https://doi.org/10.3390/diseases13060182 - 10 Jun 2025
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Background: Seasonal influenza infection poses substantial risks to pregnant women, yet the immunological mechanisms underlying their heightened disease susceptibility remain incompletely characterized. Methods: This study employed multiparametric immunophenotyping and metabolic profiling to investigate cellular immunity, cytokine dynamics, and serum biomarkers in pregnant women
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Background: Seasonal influenza infection poses substantial risks to pregnant women, yet the immunological mechanisms underlying their heightened disease susceptibility remain incompletely characterized. Methods: This study employed multiparametric immunophenotyping and metabolic profiling to investigate cellular immunity, cytokine dynamics, and serum biomarkers in pregnant women infected with H3N2 across gestational stages. Through integrated flow cytometric analysis of peripheral blood mononuclear cells (PBMCs), multiple cytokine quantification, and LC-MS-based serum metabolomics, we compared immunological parameters, serum cytokines, and metabolites across trimesters in pregnant women infected and not infected with H3N2. Results: The results revealed reduced CD4+/CD8+ T cell ratios, a diminished CD27+ memory B cell population in pregnant women infected with H3N2, and elevated NK cells and Th2-skewed cytokines (IL-4, IL-6, IL-10) in severe influenza cases. Metabolomic profiling identified the dysregulation of the tryptophan–kynurenine (Trp–Kyn) pathway, with a 15-fold increase in the Kyn/Trp ratio in severe influenza compared to a normal pregnancy as a potential biomarker. Conclusions: These results elucidate synergistic pathophysiological axes-immune dysregulation and tryptophan metabolism alteration that potentially drive adverse outcomes. The identified biomarker panel (CD4/CD8 ratio, IL-6, Kyn/Trp ratio) shows potential clinical promise for early risk stratification in high-risk pregnancies with influenza infection.
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(This article belongs to the Section Infectious Disease)
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A Potential Oncoprotective Role of Cytomegalovirus Against Breast Cancer: Worldwide Correlation and Survey of Evidence
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Marko Jankovic, Sofija Glumac, Aleksandra Knezevic, Ana Tomic, Danijela Miljanovic, Jovana Cupic, Ana Banko, Djurdjina Kablar, Ivana Celic, Sara Urosevic and Ivana Lazarevic
Diseases 2025, 13(6), 181; https://doi.org/10.3390/diseases13060181 - 9 Jun 2025
Abstract
Introduction: While not considered a genuine tumorigenic pathogen, the human cytomegalovirus (CMV) has been associated with a wide assortment of malignancies, including breast cancer (BC). In recent years, increasing evidence has been detailing the potential anti-oncogenic capabilities of CMV. Works in the literature
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Introduction: While not considered a genuine tumorigenic pathogen, the human cytomegalovirus (CMV) has been associated with a wide assortment of malignancies, including breast cancer (BC). In recent years, increasing evidence has been detailing the potential anti-oncogenic capabilities of CMV. Works in the literature addressing the issue are scarce, and a global approach elucidating the role of CMV in breast cancer is lacking. Aim: We inquired into the association between CMV and BC on a global level and surveyed the related literature. Material and Methods: Virus–tumor interaction was examined by correlating country-specific CMV seroprevalence and the age-standardized BC incidence rates for 73 countries, as provided by the International Agency for Research on Cancer (IARC). Statistical analysis was conducted using Spearman’s correlation, along with univariate and multivariate linear regression analysis. The literature review included works available in the PubMed® database until and including February 2025. Results: The worldwide incidence of BC correlated strongly and inversely with CMV prevalence the world over (p < 0.001, Spearman ρ = −0.553). This association was upheld after univariate and multivariate linear regression, extending to other tumors such as skin melanoma and kidney cancer (p < 0.001). Conclusions: In this study, we draw attention to a previously unexplored global inverse relationship between the prevalence of CMV and the incidence of BC, which suggests a potential oncoprotective role for this pathogen. Although the association itself does not imply causality, these data provide an intriguing possibility of observing CMV as a tentative factor of protection against this malignancy.
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(This article belongs to the Section Oncology)
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Open AccessReview
Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes
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Chiara Anna Fiasconaro, Alice Carbone, Silvia Giordano, Francesco Cavallo, Paolo Fava, Barbara Pasini, Yuliya Yakymiv, Sara Marchisio, Pietro Quaglino, Simone Ribero and Gabriele Roccuzzo
Diseases 2025, 13(6), 180; https://doi.org/10.3390/diseases13060180 - 9 Jun 2025
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The etiology of melanoma is multifactorial and arises from the interplay of genetic, phenotypic, and environmental factors. The genetic predisposition to melanoma is influenced by a complex interaction among genes exhibiting varying levels of penetrance (high, moderate, and low), each contributing differently to
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The etiology of melanoma is multifactorial and arises from the interplay of genetic, phenotypic, and environmental factors. The genetic predisposition to melanoma is influenced by a complex interaction among genes exhibiting varying levels of penetrance (high, moderate, and low), each contributing differently to the susceptibility of the disease. Furthermore, penetrance may vary based on the incidence of melanoma across diverse populations and geographical regions. Advances in genetic sequencing technologies have facilitated the identification of novel genes potentially associated with melanoma, as well as the characterization of relevant germline variants. While the most extensively researched variant is CDKN2A, recent studies have highlighted other variants unrelated to CDKN2A as significant areas of investigation. Among them, high-penetrance genes encompass CDK4, BAP1, POT1, TERT, ACD, and TERF2IP. In contrast, moderate-penetrance genes include MC1R, MITF, and SLC45A2, while low-penetrance genes consist of OCA2, TYRP1, and TYR. In addition to elevating the risk of melanoma, these genetic alterations may also predispose individuals to internal neoplasms. This review aims to provide a comprehensive overview of the definitions of sporadic, multiple primary, familial, and hereditary melanoma, with a particular emphasis on non-CDKN2A germline variants and their dermoscopic and phenotypic features.
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(This article belongs to the Special Issue Advances in Melanoma: From Basic Research to Clinical Management, and Future Horizons Exploitation)
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Open AccessReview
Renal Resistive Index from Renal Hemodynamics to Cardiovascular Risk: Diagnostic, Prognostic, and Therapeutic Implications
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Giulio Geraci, Pietro Ferrara, Luigi La Via, Alessandra Sorce, Vincenzo Calabrese, Giuseppe Cuttone, Valentina Paternò, Francesco Pallotti, Gianluca Sambataro, Luca Zanoli, Jacob George, Riccardo Polosa, Giuseppe Mulè and Caterina Carollo
Diseases 2025, 13(6), 178; https://doi.org/10.3390/diseases13060178 - 9 Jun 2025
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Duplex-Doppler ultrasonography has become an essential tool in the diagnosis and management of kidney diseases, allowing clinicians to assess renal hemodynamics, detect vascular abnormalities, and monitor disease progression. Among the various Doppler-derived parameters, the renal resistive index (RRI) has gained particular attention both
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Duplex-Doppler ultrasonography has become an essential tool in the diagnosis and management of kidney diseases, allowing clinicians to assess renal hemodynamics, detect vascular abnormalities, and monitor disease progression. Among the various Doppler-derived parameters, the renal resistive index (RRI) has gained particular attention both as a diagnostic tool and a prognostic marker in nephrology. Traditionally considered an indicator of parenchymal perfusion, recent evidence highlights its strong association with systemic hemodynamic factors, particularly arterial stiffness, positioning RRI as a valuable tool for evaluating patients with systemic vascular impairment, such as hypertension, diabetes mellitus, and atherosclerosis. RRI has been strongly linked to vascular damage, which in turn is influenced by inflammation and endothelial dysfunction, making it a reliable marker of cardiovascular damage and a potential predictor of cardiovascular risk. Furthermore, emerging studies suggest that RRI could serve as a dynamic parameter to monitor vascular changes induced by therapeutic interventions. This narrative review summarizes the classic and evolving applications of RRI, from its origin as a renal hemodynamic marker to its emerging role as a systemic vascular biomarker with diagnostic and prognostic significance in cardiovascular and metabolic diseases.
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(This article belongs to the Section Cardiology)
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Sex Differences in Immune Responses to Infectious Diseases: The Role of Genetics, Hormones, and Aging
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Pierluigi Rio, Mario Caldarelli, Edoardo Miccoli, Giulia Guazzarotti, Antonio Gasbarrini, Giovanni Gambassi and Rossella Cianci
Diseases 2025, 13(6), 179; https://doi.org/10.3390/diseases13060179 - 7 Jun 2025
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In recent years, gender medicine has emerged as a field of research analyzing sex-related differences in health and disease. Biological sex, depending on sex chromosome complement, sex steroid hormones, and reproductive organs, has been demonstrated to influence human susceptibility to infections, immune responses
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In recent years, gender medicine has emerged as a field of research analyzing sex-related differences in health and disease. Biological sex, depending on sex chromosome complement, sex steroid hormones, and reproductive organs, has been demonstrated to influence human susceptibility to infections, immune responses against pathogens, the clinical severity of infectious diseases, and responses to the available treatments. Men and women differ in their chromosome set, with men having one X chromosome (XY) and women two (XX). This different genetic composition results in a sex-dimorphic expression of genes and pathways involved in immune regulation, as well as in shaping immune responses to infectious agents. Moreover, estrogen, progesterone, and testosterone, impacting cells and pathways involved in both innate and adaptive immunity, have been shown to drive sex dimorphism in infectious diseases. This narrative review aims to explore the sex-related differences in responses to infections, specifically focusing on the underlying genetic and hormonal mechanisms. Hence, aging-related changes in the immune system and their potential impact on immune responses against pathogens will be discussed. Understanding sex differences and stratifying the population according to them will open the door to precision medicine and personalized patient care.
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(This article belongs to the Section Infectious Disease)
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Open AccessSystematic Review
Evaluation of Prognostic Factors in Myxoid Liposarcoma Treated with Combined Neoadjuvant Radiotherapy and Surgical Excision: Systematic Review
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Giuseppe Francesco Papalia, Giulia De Marco, Claudia Luciano, Luisana Sisca, Pasquale Farsetti, Bruno Vincenzi and Rocco Papalia
Diseases 2025, 13(6), 177; https://doi.org/10.3390/diseases13060177 - 6 Jun 2025
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Purpose: Myxoid liposarcoma (MLPS) is a malignant tumor that occurs predominantly in the deep soft tissues of the extremities. Preoperative radiotherapy (RT) is used to reduce tumor volume to achieve adequate surgical margins. This systematic review aims to evaluate the impact of preoperative
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Purpose: Myxoid liposarcoma (MLPS) is a malignant tumor that occurs predominantly in the deep soft tissues of the extremities. Preoperative radiotherapy (RT) is used to reduce tumor volume to achieve adequate surgical margins. This systematic review aims to evaluate the impact of preoperative RT on surgical margins, local recurrence (LR) rates, metastasis development, and overall survival in patients with MLPS and associated prognostic factors. Methods: A systematic literature search was conducted by two reviewers following PRISMA guidelines on PubMed, Scopus, and the Cochrane Library on 30 November 2024. We included prospective and retrospective cohort studies published in English that evaluate surgical margin status, LR and metastasis rates, and survival outcomes in patients undergoing surgical excision of MLPS following neoadjuvant radiotherapy. Two authors extracted tumor characteristics, percentage of round cells (RCs), change in tumor volume post-RT, surgical margins, postoperative complications, LR and metastasis rates, survival rates, and related prognostic factors. Results: The twelve studies included in this review involved 1483 patients with a mean age of 44.8 years. Tumors were mostly located in the lower limbs, deeply localized, and larger than 5 cm in most cases. The average LR and metastasis rates were 5.2% and 17%, respectively. The mean 5-year and 10-year overall survival rates were 87% and 74%, respectively. Poor prognosis was associated with >5% RC components, tumors larger than 15 cm, deep localization, and inadequate surgical margins. Conclusion: The management of MLPS requires a multidisciplinary approach. Preoperative radiotherapy offers several advantages in reducing tumor volume and facilitating the achievement of adequate surgical margins, finally improving local control and long-term outcomes.
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Open AccessReview
The Role of Targeted Microbiota Therapy in the Prevention and Management of Puerperal Mastitis
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Mariarosaria Matera, Chiara Maria Palazzi, Alexander Bertuccioli, Francesco Di Pierro, Nicola Zerbinati, Massimiliano Cazzaniga, Aurora Gregoretti and Ilaria Cavecchia
Diseases 2025, 13(6), 176; https://doi.org/10.3390/diseases13060176 - 5 Jun 2025
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Mastitis, an inflammatory condition of the breast, significantly affects breastfeeding women and can lead to the early cessation of lactation. This article explores the pathophysiology of mastitis, distinguishing between acute mastitis (AM) and subacute mastitis (SAM), with a focus on the microbial dynamics
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Mastitis, an inflammatory condition of the breast, significantly affects breastfeeding women and can lead to the early cessation of lactation. This article explores the pathophysiology of mastitis, distinguishing between acute mastitis (AM) and subacute mastitis (SAM), with a focus on the microbial dynamics involved. AM is primarily associated with Staphylococcus aureus, while SAM is linked to a dysbiotic milk microbiota characterized by an imbalance of microbial species, including increased levels of opportunistic pathogens. The role of inflammation and the gut–breast axis in the development of mastitis are discussed, emphasizing the importance of maintaining a healthy microbiota. Recent studies highlight the potential of probiotics as a preventive and therapeutic measure against mastitis, showing promising results in reducing incidence and recurrence. However, further research is necessary to optimize probiotic strains, dosages, and treatment protocols. This review underscores the need for a comprehensive understanding of the microbiological, immunological, and inflammatory factors involved in mastitis to develop effective prevention and treatment strategies.
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Open AccessArticle
Association of Mitochondrial DNA Copy Number Variations with Triple-Negative Breast Cancer: A Potential Biomarker Study
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Karin Manto, Sevdican Ustun Yilmaz, Zeliha Pala Kara, Halil Kara, Fatma Tokat, Cemaliye B. Akyerli, Cihan Uras, Meltem Muftuoglu and Ugur Özbek
Diseases 2025, 13(6), 175; https://doi.org/10.3390/diseases13060175 - 1 Jun 2025
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Background/Objectives: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options, and identifying reliable biomarkers for diagnosis and prognosis is crucial for improving patient outcomes. Mitochondrial DNA (mtDNA) copy number has been linked to an increased risk of developing various
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Background/Objectives: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options, and identifying reliable biomarkers for diagnosis and prognosis is crucial for improving patient outcomes. Mitochondrial DNA (mtDNA) copy number has been linked to an increased risk of developing various types of cancer, including breast cancer. However, there is a lack of understanding regarding how mtDNA copy number variations may influence the development and progression of TNBC. Methods: This study investigated mtDNA copy number in TNBC tumors and corresponding normal breast tissues from 23 TNBC patients who received neoadjuvant chemotherapy. The relative mtDNA copy number was estimated using quantitative PCR for the NADH dehydrogenase subunit 1 (ND1) and subunit 5 (ND5) regions. Results: The results showed a significant decrease in mtDNA copy number in TNBC tumor tissues compared to corresponding normal breast tissue. However, no significant correlation was found between mtDNA content and clinical parameters such as age, tumor size, or chemotherapy response. Conclusions: These results suggest that while mtDNA content decreases in TNBC tumors, it may not directly influence these clinical characteristics. Despite some inconsistencies in the literature regarding mtDNA dynamics in cancer, this study supports the potential of mtDNA as a biomarker for TNBC. Larger cohort studies are needed to further validate these results and explore the role of mtDNA in guiding personalized treatment strategies for TNBC patients.
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Open AccessArticle
The Relationship Between Non-Traumatic Fat Embolism and Fat Embolism Syndrome (FES) in Patients with Cancer
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Beáta Ágnes Borsay, Barbara Dóra Halasi, Zoltán Hendrik, Pórszász Kristóf Róbert, Katalin Károlyi, Teodóra Tóth and Péter Attila Gergely
Diseases 2025, 13(6), 174; https://doi.org/10.3390/diseases13060174 - 30 May 2025
Abstract
Background: Fat embolism and fat embolism syndrome are rare but well-known consequences of long bone fractures and orthopedic surgeries. These sources support the mechanical theory of their development. On the other hand, as an alternative pathway suggested by the biochemical theory, lipase activation
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Background: Fat embolism and fat embolism syndrome are rare but well-known consequences of long bone fractures and orthopedic surgeries. These sources support the mechanical theory of their development. On the other hand, as an alternative pathway suggested by the biochemical theory, lipase activation and fat breakdown are also a possible background for lipid droplets appearing in the vasculature. According to Hulman’s theory, elevated C-reactive protein levels can facilitate calcium-dependent agglutination of very low-density proteins and chylomicrons forming fat globules. The level of this acute-phase protein can increase mainly in advanced-stage cancers but also has predictive or indicative value in treatment success. Methods: This study focused on strictly selected patients with different histological types and origins of cancer, as well as advanced cancer in approximately 90% of the deceased. After collecting the tissue samples, the frozen sections were stained with Oil Red O to detect fat emboli. Results: Less than 50% of the cases showed punctiform, non-clinically relevant pulmonary fat embolism, and fat embolism syndrome was identified in none of the cases. In one, non-advanced cancer case, punctiform kidney fat embolism was observed. Conclusions: The end-of-life anergic state of patients may influence the procedure. In the case of osseous metastases, since the intramedullary sinuses are affected, both the mechanical and the biochemical backgrounds may prevail and mediate fat embolism formation.
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(This article belongs to the Section Oncology)
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Open AccessArticle
Prevalence and Associated Factors of Latent Tuberculosis Infection Among Healthcare Workers in a Mexican Tertiary Care Hospital
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José Ángel Hernández-Mariano, Mónica Alethia Cureño-Díaz, Verónica Fernández-Sánchez, Estibeyesbo Said Plascencia-Nieto, Dulce Milagros Razo-Blanco-Hernández, Claudia Vázquez-Zamora, Víctor Hugo Gutiérrez-Muñoz, Beatriz Leal-Escobar, Erika Gómez-Zamora and Yanelly Estrella Morales-Vargas
Diseases 2025, 13(6), 173; https://doi.org/10.3390/diseases13060173 - 30 May 2025
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Background/Objectives: Healthcare workers (HCWs) are globally recognized as a high-risk group for tuberculosis (TB) infection. However, limited data exist on the prevalence of latent TB infection (LTBI) and associated occupational risk factors in the Mexican context. Identifying the burden of LTBI is essential
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Background/Objectives: Healthcare workers (HCWs) are globally recognized as a high-risk group for tuberculosis (TB) infection. However, limited data exist on the prevalence of latent TB infection (LTBI) and associated occupational risk factors in the Mexican context. Identifying the burden of LTBI is essential for effective prevention. This study aimed to estimate the prevalence of LTBI among HCWs in a tertiary care hospital in Mexico and to explore associated risk factors. Methods: An analytical cross-sectional study was conducted among 300 HCWs (including physicians, nurses, and stretcher-bearers) at a tertiary-level hospital in Mexico. Sociodemographic and occupational data were collected through a structured questionnaire. LTBI screening was performed using the tuberculin skin test (TST), with positive results confirmed via the QuantiFERON-TB Gold assay. Associations between relevant variables and LTBI were assessed using logistic regression models, adjusted for potential confounders. Results: The prevalence of LTBI was 16.7%. After adjusting for confounders, male HCWs had significantly higher odds of LTBI compared to females (adjusted odds ratio [aOR] = 2.02; 95% confidence interval [CI]: 1.06–3.80). Although elevated odds of LTBI were also observed among physicians, stretcher-bearers, and those with direct contact with TB patients, these associations were not statistically significant. Conclusion: LTBI represents a relevant occupational health issue among HCWs, with nearly one in six workers affected. Early detection and prevention of TB in healthcare settings are critical to protecting individual workers and public health. These findings highlight the need to strengthen occupational TB surveillance and prevention strategies in similar healthcare environments.
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Open AccessArticle
The Overlapping Burdens of Fatigue and Daytime Sleepiness: Gender-Specific Impacts on Life Quality in Patients with Sleep Disorders
by
Bianca Temporini, Dario Bottignole, Giulia Balella, Giorgio Ughetti, Irene Pollara, Margherita Soglia, Francesco Rausa, Ylenia Ciuro, Christian Franceschini, Marcello Giuseppe Maggio, Liborio Parrino and Carlotta Mutti
Diseases 2025, 13(6), 172; https://doi.org/10.3390/diseases13060172 - 29 May 2025
Abstract
Background: Excessive daytime sleepiness (EDS) and fatigue are two impactful symptoms, frequently associated with sleep disorders, which can worsen the quality of life. Due to overlapping features and patient-report ambiguity a clear-cut distinction between EDS and fatigue can become a challenging issue. We
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Background: Excessive daytime sleepiness (EDS) and fatigue are two impactful symptoms, frequently associated with sleep disorders, which can worsen the quality of life. Due to overlapping features and patient-report ambiguity a clear-cut distinction between EDS and fatigue can become a challenging issue. We aimed to investigate the prevalence and consequences of these two conditions in several sleep pathologies, examining their social, psychological, and dietary impact, with a focus on gender-related differences and occupational status. Methods: We prospectively recruited for an online survey 136 adult outpatients (60 females) affected by various sleep disorders and admitted to our Sleep Disorders Center in Parma, Italy. Patients were asked to complete the following tests: Epworth Sleepiness Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Difficulties in Emotion Regulation Scale, Depression Anxiety Stress Scale-21, Hyperarousal Scale, the Addiction-like Eating Behaviors Scale, Work Productivity and Activity Impairment Questionnaire, MEDI-Lite, and EQ-5D Health Questionnaire. Results:Fatigue was the primary daily symptom leading to serious repercussions on social/emotional and psychological well-being, while daytime sleepiness showed a less relevant role. Women reported higher levels of fatigue, sleep disturbances, emotional dysregulation, hyperarousal, and work productivity impairments. Unemployed people experienced a higher degree of fatigue, with multi-level negative consequences. Conclusions: We suggest sleep clinicians place a greater emphasis on the assessment of fatigue during clinical interviews, keeping in mind the greater vulnerability of females, experiencing disproportionate consequences. Further studies should expand our findings, exploring a wider range of gender identities and recruiting larger samples of patients.
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(This article belongs to the Special Issue Mental Health Across the Lifespan: Integrating Multidisciplinary Perspectives)
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Open AccessArticle
Plasma Matrix Metalloproteinases Signature as Biomarkers for Pediatric Tuberculosis Diagnosis: A Prospective Case–Control Study
by
Nathella Pavan Kumar, Syed Hissar, Arul Nancy, Kannan Thiruvengadam, Velayuthum V. Banurekha, Sarath Balaji, S. Elilarasi, N. S. Gomathi, J. Ganesh, M. A. Aravind, Dhanaraj Baskaran, Soumya Swaminathan and Subash Babu
Diseases 2025, 13(6), 171; https://doi.org/10.3390/diseases13060171 - 27 May 2025
Abstract
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Diagnosing tuberculosis (TB) in children presents significant challenges, necessitating the identification of reliable biomarkers for accurate diagnosis. In this study, we investigated plasma matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as potential diagnostic markers. A prospective case–control study involved 167 children
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Diagnosing tuberculosis (TB) in children presents significant challenges, necessitating the identification of reliable biomarkers for accurate diagnosis. In this study, we investigated plasma matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as potential diagnostic markers. A prospective case–control study involved 167 children classified into confirmed TB, unconfirmed TB, and unlikely TB control groups. Plasma levels of MMPs (MMP 1, 2, 3, 7, 8, 9, 12, and 13) and TIMPs (TIMP 1, 2, 3, and 4) were measured using multiplex assays. Elevated baseline levels of MMP-1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 were observed in active TB cases compared to unlikely TB controls. Receiver operating characteristics (ROC) analysis identified MMP-1, MMP-2, MMP-9, and TIMP-1 as potential biomarkers with over 80% sensitivity and specificity. A three-MMP signature (MMP-1, MMP-2, and MMP-9) demonstrated 100% sensitivity and specificity. The findings suggest that a baseline MMP signature could serve as an accurate biomarker for diagnosing pediatric TB, enabling early intervention and effective management.
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Open AccessCase Report
Intraosseous Pneumatocysts of the Scapula Mimicking Bone Tumors: A Report of Two Rare Cases Along with Elucidation of Their Etiology
by
Jiro Ichikawa, Masanori Wako, Tomonori Kawasaki, Satoshi Ochiai, Tetsuo Hagino, Naofumi Taniguchi, Kouhei Mitsui and Kojiro Onohara
Diseases 2025, 13(6), 170; https://doi.org/10.3390/diseases13060170 - 27 May 2025
Abstract
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Background/Objectives: Pneumatocysts, characterized by gas-filled cavities, are commonly found in the spine and pelvis but are rarely observed in the scapula. In this report, we describe two rare cases of scapular pneumatocysts mimicking bone tumors and exhibiting different image findings. Case Report: Case
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Background/Objectives: Pneumatocysts, characterized by gas-filled cavities, are commonly found in the spine and pelvis but are rarely observed in the scapula. In this report, we describe two rare cases of scapular pneumatocysts mimicking bone tumors and exhibiting different image findings. Case Report: Case 1. A 47-year-old man who presented with neck pain underwent radiography, followed by magnetic resonance imaging (MRI). MRI showed heterogeneity with low and high signals on fat-suppressed T2-weighted images, suggestive of enchondroma or fibrous dysplasia (FD). However, preoperative computed tomography (CT) revealed gas-filled cavities within the tumor, in continuity with the shoulder joint, confirming the diagnosis of a pneumatocyst. Case 2. A 58-year-old woman who presented with neck pain underwent similar examinations to Case 1. MRI showed homogeneity with high signals on fat-suppressed T2-weighted images, leading to a suspicion of solitary bone cysts and FD. Preoperative CT revealed gas-filled cavities within the tumor, but no continuity with the joint, leading to the diagnosis of a pneumatocyst. While the exact etiology of pneumatocysts remains unclear, two potential causes are as follows: (i) gas migration from the joint to the bone, and (ii) gas replacement in cystic tumors. Thus, CT is particularly valuable in confirming the presence of gas-filled cavities and aiding in diagnosis. Conclusions: This report highlights two extremely rare cases of scapular pneumatocysts, reflecting two potential etiologies. The utility of CT in the diagnosis of pneumatocyst has been clarified.
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Open AccessArticle
A Study of Adrenal Incidentaloma-Related Hormonal Assays After First Integration of the Diagnosis Within Primary Healthcare
by
Oana-Claudia Sima, Mihai Costachescu, Ana Valea, Mihaela Stanciu, Ioana Codruta Lebada, Tiberiu Vasile Ioan Nistor, Mihai-Lucian Ciobica, Claudiu Nistor and Mara Carsote
Diseases 2025, 13(6), 169; https://doi.org/10.3390/diseases13060169 - 26 May 2025
Abstract
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Background: Adrenal incidentalomas are detected in various medical and surgical healthcare departments, including primary healthcare. One up to three out of ten individuals confirmed with nonfunctioning adrenal incidentalomas (NFAs) actually present a mild autonomous cortisol secretion (MACS), which is distinct from Cushing’s syndrome.
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Background: Adrenal incidentalomas are detected in various medical and surgical healthcare departments, including primary healthcare. One up to three out of ten individuals confirmed with nonfunctioning adrenal incidentalomas (NFAs) actually present a mild autonomous cortisol secretion (MACS), which is distinct from Cushing’s syndrome. Objective: We aimed to assess the cortisol secretion in newly detected adrenal incidentalomas in patients who were referred by their primary healthcare physician upon accidental detection of an adrenal tumor at abdominal computed tomography (CT) scan that was performed for unrelated (non-endocrine) purposes. Methods: This retrospective study included adults diagnosed with an adrenal incidentaloma via CT during the previous 3 months. Inclusion criteria: age ≥ 40 years (y). A triple stratification of exclusion criteria involved: (1) Clinical aspects and medical records such as active malignancies or malignancies under surveillance protocols, subjects under exogenous glucocorticoid exposure (current or during the previous year), or suggestive endocrine phenotypes for any hormonal ailment; (2) Radiological appearance of suspected/confirmed (primary or secondary) adrenal malignancy, adrenal cysts, or myelolipomas; (3) Endocrine assays consistent with active endocrine tumors. Protocol of assessment included baseline ACTH, morning plasma cortisol (C-B), cortisol at 6 p.m. (C-6 pm), and after 1 mg dexamethasone suppression testing (C-1 mg-DST), 24-h urinary free cortisol (UFC), and a second opinion for all CT scans. MACS were defined based on C-1 mg-DST ≥ 1.8 and <5 µg/dL (non-MACS: C-1 mg-DST < 1.8 µg/dL). Results: The cohort (N = 60, 78.33% female; 60.72 ± 10.62 y) associated high blood pressure (HBP) in 66.67%, respectively, type 2 diabetes (T2D) in 28.37% of the patients. Females were statistically significantly older than males (62.40 ± 10.47 vs. 54.62 ± 9.11 y, p = 0.018), while subjects with unilateral vs. bilateral tumors (affecting 26.67% of the individuals) and those with MACS-positive vs. MACS-negative profile had a similar age. Body mass index (BMI) was similar between patients with unilateral vs. bilateral incidentalomas, regardless of MACS. Patients were divided into five age groups (decades); most of them were found between 60 and 69 years (40%). Left-gland involvement was found in 43.33% of all cases. The mean largest tumor diameter was 26.08 ± 8.78 mm. The highest rate of bilateral tumors was 46.67% in the 50–59 y decade. The rate of unilateral/bilateral and tumor diameters was similar in females vs. males. The MACS-positive rate was similar in females vs. males (23.40% vs. 23.08%). A statistically significant negative correlation (N = 60) was found between BMI and C-B (r = −0.193, p = 0.03) and BMI and UFC (r = −0.185, p = 0.038), and a positive correlation was found between C-B and C-6 pm (r = 0.32, p < 0.001), C-B and UFC (r = 0.226, p = 0.011), and C-6 pm and C-1 mg-DST (r = 0.229, p = 0.010), and the largest tumor diameter and C-1 mg-DST (r = 0.241, p = 0.007). Conclusions: Adrenal incidentalomas belong to a complex scenario of detection in the modern medical era, requiring a multidisciplinary collaboration since the patients might be initially detected in different departments (as seen in the current study) and then referred to primary healthcare for further decision. In these consecutive patients, we found a higher female prevalence, a MACS rate of 23.33%, regardless of uni/bilateral involvement or gender distribution, and a relatively high rate (than expected from general data) of bilateral involvement of 26.67%. The MACS-positive profile adds to the disease burden and might require additional assessments during follow-up and a protocol of surveillance, including a tailored decision of tumor removal. The identification of an adrenal incidentaloma at CT and its hormonal characterization needs to be integrated into the panel of various chronic disorders of one patient. The collaboration between endocrinologists and primary healthcare physicians might improve the overall long-term outcomes.
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