Diseases

16 pages, 757 KB

Open AccessSystematic Review

Targeting Myocardial Mechanics in Children and Adolescents with Obesity and Non-Elevated Blood Pressure: A Meta-Regression Study

by Andrea Faggiano, Elisa Gherbesi, Carla Sala, Stefano Carugo, Guido Grassi, Marijana Tadic and Cesare Cuspidi

Diseases 2025, 13(9), 301; https://doi.org/10.3390/diseases13090301 - 11 Sep 2025

Abstract

Background/Objectives: Although global longitudinal strain (GLS) appears more sensitive than the ejection fraction in uncovering subtle left ventricular (LV) dysfunction, evidence of impaired LV mechanics in children/adolescents with obesity, independent of comorbidities, remains limited. The aim of the present study was to provide [...] Read more.

Background/Objectives: Although global longitudinal strain (GLS) appears more sensitive than the ejection fraction in uncovering subtle left ventricular (LV) dysfunction, evidence of impaired LV mechanics in children/adolescents with obesity, independent of comorbidities, remains limited. The aim of the present study was to provide new information on clinical and echocardiographic correlates associated with LV mechanics in normotensive children/adolescents with obesity and without comorbidities. Methods: The Pub-Med, Ovid MEDLINE, Ovid EMBASE, and Cochrane databases were searched to identify eligible studies from inception up to 31 March 2025. Studies reporting data on LV mechanics (i.e., GLS, global circumferential strain [GCS]) in children/adolescents with obesity were included. Meta-regression analyses between GLS, GCS, and several clinical, laboratory, and echocardiographic parameters were performed using a random-effect model. Results: Twenty-seven studies including 1398 normotensive children/adolescents with obesity (mean age 12.6 ± 1.8 years) were considered. There was a significant inverse relationship between GLS and body mass index (BMI) (coefficient = −0.33 ± 0.11, p = 0.003) and fat mass (coefficient = −0.19 ± 0.07, p = 0.005); this was not the case for GCS. Notably, both GLS and GCS were unrelated to several clinical/laboratory variables such as blood pressure, metabolic parameters, LV mass, and LV diastolic function indices. Conclusions: Our findings suggest that increasing BMI and fat mass are the only key factors associated with reduced longitudinal myocardial deformation in pediatric obesity. GLS, unlike GCS, can be regarded as an early marker of subclinical organ damage in this setting and should be assessed to optimize cardiovascular prevention strategies in children/adolescents with obesity regardless of hypertension or comorbidities. Full article

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24 pages, 3144 KB

Open AccessSystematic Review

Fluid Resuscitation with Lactated Ringer vs. Normal Saline in Acute Pancreatitis: A Systematic Review and Meta-Analysis of Clinical Trials

by Freiser Eceomo Cruz Mosquera, Elizabeth Camacho Benítez, Mariatta Catalina Ceballos Benavides, Julián Esteban Castillo Muñoz, Carlos Andrés Castañeda and Yamil Liscano

Diseases 2025, 13(9), 300; https://doi.org/10.3390/diseases13090300 - 10 Sep 2025

Abstract

Background: Initial fluid therapy in acute pancreatitis is critical for modulating the systemic inflammatory response. The choice between Lactated Ringer and normal saline remains debated, given their potentially divergent impacts on disease progression and clinically relevant outcomes. The objective of this meta-analysis is [...] Read more.

Background: Initial fluid therapy in acute pancreatitis is critical for modulating the systemic inflammatory response. The choice between Lactated Ringer and normal saline remains debated, given their potentially divergent impacts on disease progression and clinically relevant outcomes. The objective of this meta-analysis is to determine the effectiveness of one solution versus the other in patients with AP. Methods: A systematic review of randomized clinical trials published between 2000 and 2024 was conducted through an exhaustive search in databases such as PubMed, ScienceDirect, LILACS, SCOPUS, Web of Science, Springer, Scielo, and Cochrane. The review protocol adhered to the recommendations established by PRISMA. The methodological quality of the selected studies was assessed using the Jadad scale, while statistical analyses were performed with RevMan 5.4^® and Jamovi 2.3.28^® software. Results: Five trials with 299 patients showed that, in patients with AP, Lactated Ringer significantly reduced ICU admission (RR: 0.39; 95% CI: 0.18–0.85; p = 0.02) and the progression of pancreatitis (RR: 0.63; 95% CI: 0.40–0.98; p = 0.04). There was no significant difference in mortality or hospital stay (SMD: −0.89; 95% CI: −2.26 to 0.48; p = 0.23). No clear effects were observed on SIRS at 24, 48, and 72 h. CRP at 48 h was significantly lower with lactate (SMD: −3.91; 95% CI: −4.66 to −3.17; p < 0.00001), but not at 72 h. Conclusions: The administration of Lactated Ringer in acute pancreatitis shows clinical and anti-inflammatory benefits, but the evidence is mostly of low quality. Full article

(This article belongs to the Section Gastroenterology)

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15 pages, 613 KB

Open AccessSystematic Review

Gut Microbiota in Adults with Chronic Widespread Pain: A Systematic Review

by Pui-Ying Leong and Lin-Hong Shi

Diseases 2025, 13(9), 299; https://doi.org/10.3390/diseases13090299 - 9 Sep 2025

Abstract

Background/Objectives: Chronic widespread pain (CWP), a key feature of fibromyalgia (FM), has been increasingly associated with gut microbiota alterations, yet the specific changes in microbial composition and the therapeutic potential of probiotics or prebiotics in these patients remain unclear. This systematic review aimed [...] Read more.

Background/Objectives: Chronic widespread pain (CWP), a key feature of fibromyalgia (FM), has been increasingly associated with gut microbiota alterations, yet the specific changes in microbial composition and the therapeutic potential of probiotics or prebiotics in these patients remain unclear. This systematic review aimed to synthesize current evidence regarding gut microbiota alterations and the effects of microbiota-targeted interventions in individuals with CWP/FM. Methods: A comprehensive search across multiple databases, including PubMed, Web of Science, Cochrane Library, Ovid Embase, Medline, Ovid AMED, and Global Health. These studies were categorized into two primary themes: changes in gut microbiota composition at various taxonomic levels and the therapeutic impact of microbiota-involved treatments in patients with CWP/FM. Results: We finally identified 432 studies, of which 11 met the inclusion criteria. The findings indicate that while alterations in the gut microbiota have been observed in CWP patients, the evidence remains limited and heterogeneous. Conclusions: Preliminary indications suggest a potential role of dysbiosis in the pathophysiology of CWP, but further rigorously designed studies are needed to clarify the therapeutic efficacy of microbiota-based interventions in this patient population. Full article

(This article belongs to the Special Issue Microbiota in Human Disease)

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17 pages, 1396 KB

Open AccessReview

Paroxysmal Nocturnal Hemoglobinuria: Unraveling Its Molecular Pathogenesis and Advancing Targeted Therapeutic Strategies

by Elisavet Apostolidou, Vasileios Georgoulis, Dimitrios Leonardos, Eleni Kapsali and Eleftheria Hatzimichael

Diseases 2025, 13(9), 298; https://doi.org/10.3390/diseases13090298 - 9 Sep 2025

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematologic disorder caused by somatic mutations in the PIGA gene of hematopoietic stem cells, leading to the absence of GPI-anchored proteins, including the complement regulators CD55 and CD59. This deficiency results in uncontrolled complement [...] Read more.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematologic disorder caused by somatic mutations in the PIGA gene of hematopoietic stem cells, leading to the absence of GPI-anchored proteins, including the complement regulators CD55 and CD59. This deficiency results in uncontrolled complement activation, causing intravascular and extravascular hemolysis, thrombosis, and bone marrow failure. Historically associated with substantial morbidity, PNH management has been transformed by the advent of complement inhibitors. Eculizumab, the first approved C5 inhibitor, significantly reduced thrombotic risk and improved survival but did not eliminate anemia due to extravascular hemolysis. Newer agents now target proximal complement components, offering broader control and improved convenience. This review summarizes the pathophysiology of PNH, evaluates established and emerging complement inhibitors, and discusses ongoing therapeutic challenges and future directions. Full article

(This article belongs to the Section Oncology)

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Graphical abstract

13 pages, 236 KB

Open AccessArticle

Impact of BRCA Status on Reproductive Outcomes in Breast Cancer Patients in Romania: A Retrospective Study

by Cristina Tanase-Damian, Diana Loreta Paun, Nicoleta Zenovia Antone, Alexandru Eniu, Carina Crisan, Eliza Belea, Anca-Magdalena Coricovac, Ioan Tanase, Patriciu Andrei Achimas-Cadariu and Alexandru Blidaru

Diseases 2025, 13(9), 297; https://doi.org/10.3390/diseases13090297 - 8 Sep 2025

Abstract

Background: Breast cancer is the most frequently diagnosed cancer in women, and advances in genetic screening have led to a growing number of patients being identified as BRCA mutation carriers. For these women, the safety of pregnancy following cancer treatment remains insufficiently studied, [...] Read more.

Background: Breast cancer is the most frequently diagnosed cancer in women, and advances in genetic screening have led to a growing number of patients being identified as BRCA mutation carriers. For these women, the safety of pregnancy following cancer treatment remains insufficiently studied, and possible biological mechanisms—including defective DNA repair pathways and accelerated depletion of the ovarian reserve—may influence fertility potential and pregnancy outcomes. This exploratory research set out to examine whether BRCA status impacts reproductive outcomes in breast cancer survivors, while also considering underlying biological explanations for any observed differences. Methods: We performed a retrospective, single-institution cohort study involving young women with non-metastatic breast cancer who had undergone BRCA testing over a 17-year period. Clinical, oncologic, and reproductive data were collected and patients were followed longitudinally. Results: Of the 117 women who met eligibility criteria, 15 conceived at least once after cancer therapy; 11 carried no BRCA mutation, and 4 were BRCA-positive (2 with BRCA1 and 2 with BRCA2 variants). While the overall cohorts were broadly comparable, significant differences emerged in terms of tumor grade, hormone receptor status, HER2 expression, and treatment modalities. BRCA mutation status did not appear to influence reproductive outcomes, and all pregnancies in both groups progressed to full-term delivery without major obstetric complications or congenital anomalies. Conclusions: Within the limitations of a small, retrospective, single-center dataset without adjustment for confounding variables, these preliminary findings suggest that pregnancy after breast cancer may be safe for BRCA mutation carriers, with no apparent adverse effect on maternal prognosis or birth outcomes. Confirmation from larger, prospective, multicenter studies is essential to validate these results, clarify possible biological mechanisms, and inform evidence-based fertility counseling and survivorship planning for this patient population. Full article

23 pages, 638 KB

Open AccessReview

Matrix Metalloproteinase Inhibitors and Their Potential Clinical Application in Periodontitis

by Daniela Mendoza-Juárez, Manuel Sánchez-Gutiérrez, Aleli Julieta Izquierdo-Vega, Eduardo Osiris Madrigal-Santillán, Claudia Velázquez-González and Jeannett Alejandra Izquierdo-Vega

Diseases 2025, 13(9), 296; https://doi.org/10.3390/diseases13090296 - 6 Sep 2025

Abstract

Matrix metalloproteinases (MMPs) are a family of endopeptidases recognized for their involvement in the degradation of the extracellular matrix and their important role in the pathogenesis of periodontitis. This chronic inflammatory condition causes the degradation of dental supporting tissues, resulting in bone loss. [...] Read more.

Matrix metalloproteinases (MMPs) are a family of endopeptidases recognized for their involvement in the degradation of the extracellular matrix and their important role in the pathogenesis of periodontitis. This chronic inflammatory condition causes the degradation of dental supporting tissues, resulting in bone loss. In patients with periodontitis, the expression and activation of MMPs, especially MMP-8 and MMP-9, significantly influence tissue degradation. In periodontitis treatment, various natural or synthetic metalloproteinase inhibitors (MMPIs) and antibiotics are used in sub-antimicrobial doses. However, while the evidence supports a role for MMPIs in reducing inflammation, preserving connective tissue, and improving the results of conventional periodontitis treatment, their clinical application is limited. In this review, we summarize MMPIs, their characteristics, and the mechanisms of action that may support their use in the treatment of periodontitis. In conclusion, MMPIs are a therapeutic alternative with great potential in the management of periodontitis, especially when combined with mechanical treatments, although further research is needed to optimize their clinical use. Full article

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16 pages, 297 KB

Open AccessReview

Prevention and Management of Perioperative Acute Kidney Injury: A Narrative Review

by Mary O’Dell Duplechin, Garrett T. Folds, Drake P. Duplechin, Shahab Ahmadzadeh, Sarah H. Myers, Sahar Shekoohi and Alan D. Kaye

Diseases 2025, 13(9), 295; https://doi.org/10.3390/diseases13090295 - 5 Sep 2025

Abstract

Acute kidney injury is a common complication in the perioperative setting, especially among patients undergoing high-risk surgeries such as cardiac, abdominal, or orthopedic procedures. Characterized by a sudden decline in renal function, perioperative acute kidney injury is typically diagnosed based on rising serum [...] Read more.

Acute kidney injury is a common complication in the perioperative setting, especially among patients undergoing high-risk surgeries such as cardiac, abdominal, or orthopedic procedures. Characterized by a sudden decline in renal function, perioperative acute kidney injury is typically diagnosed based on rising serum creatinine or reduced urine output. Its incidence varies depending on the surgical type and patient risk factors, but even mild cases are linked to significant consequences, including prolonged hospital stays, enhanced healthcare costs, and higher mortality rates. Despite advances in surgical and anesthetic care, acute kidney injury remains a major cause of morbidity. The development of acute kidney injury in the perioperative period often results from a complex interplay of hypoperfusion, ischemia–reperfusion injury, inflammation, and exposure to nephrotoxic agents. While some predictive models and biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), have shown promise in identifying patients at risk, widespread adoption remains inconsistent, and standardized prevention protocols are lacking. This narrative review synthesizes current evidence on the pathophysiology, risk factors, and prevention strategies for perioperative acute kidney injury. It explores emerging tools for risk stratification and early diagnosis, including novel biomarkers and learning-based models. Additionally, it highlights pharmacologic and non-pharmacologic measures to reduce acute kidney injury incidence, such as balanced fluid management, renal-protective anesthetic strategies, and bundle-based care approaches. Emphasizing a multidisciplinary and personalized model of care, this review highlights the need for coordinated efforts between anesthesiologists, surgeons, and nephrologists to identify modifiable risks and improve outcomes. Reducing the incidence of perioperative acute kidney injury has the potential to enhance recovery, preserve long-term kidney function, and ultimately improve surgical safety. Full article

17 pages, 623 KB

Open AccessReview

Decoding Microbiome’s Role in Prostate Cancer Progression and Treatment Response

by Minas Sakellakis, Panagiota Resta, Evangelia Papagianni, Kassandra A. Procter, Irene Belouka, Katerina Gioti, Fragkiski Anthouli-Anagnostopoulou, Dimitrios Chaniotis and Apostolos Beloukas

Diseases 2025, 13(9), 294; https://doi.org/10.3390/diseases13090294 - 5 Sep 2025

Abstract

Prostate cancer (PCa) is the most common genitourinary malignancy in men, with a multifactorial etiology influenced by genetic, environmental, and microbial determinants. Although the prostate was traditionally considered sterile, advances in microbiome research have challenged this view, revealing potential links between microbial communities [...] Read more.

Prostate cancer (PCa) is the most common genitourinary malignancy in men, with a multifactorial etiology influenced by genetic, environmental, and microbial determinants. Although the prostate was traditionally considered sterile, advances in microbiome research have challenged this view, revealing potential links between microbial communities and PCa development, progression, and treatment response. This review synthesizes evidence on the gut, urinary, seminal fluid, and prostatic microbiomes, highlighting their potential contributions to PCa pathogenesis and therapeutic outcomes. Key studies utilizing next-generation sequencing (NGS), whole-genome sequencing (WGS), PCR, and metagenomic analyses have identified specific bacterial and fungal taxa associated with Pca; however, findings remain inconsistent across methodologies and cohorts. Microorganisms such as Propionibacterium acnes and Pseudomonas spp. may modulate inflammation, immune responses, and resistance to androgen-deprivation therapy. Further research is required to determine whether microbial signatures can serve as reliable biomarkers for early detection, prognosis, or novel therapeutic strategies in PCa management. Full article

(This article belongs to the Section Oncology)

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18 pages, 1078 KB

Open AccessArticle

Epidemiological Patterns of Genital Ulcer Disease and Human Immunodeficiency Virus Among Public Clinic Attendees in Mthatha, Eastern Cape, South Africa

by Thembisa R. Tshaka, Lindiwe M. Faye, Teke R. Apalata and Zizipho Z. A. Mbulawa

Diseases 2025, 13(9), 293; https://doi.org/10.3390/diseases13090293 - 5 Sep 2025

Abstract

Background: Sexually transmitted infections (STIs) are common globally, posing significant public health challenges and financial strain, especially in low- and middle-income countries. Sub-Saharan Africa (SSA) accounts for 40% of global STI prevalence, with South Africa having the highest rates of curable STIs and [...] Read more.

Background: Sexually transmitted infections (STIs) are common globally, posing significant public health challenges and financial strain, especially in low- and middle-income countries. Sub-Saharan Africa (SSA) accounts for 40% of global STI prevalence, with South Africa having the highest rates of curable STIs and human immunodeficiency virus (HIV), both of which are closely linked to increasing HIV transmission risk and other STIs. Genital ulcer disease (GUD), primarily caused by HSV-1, HSV-2, and Treponema pallidum, and less frequently by Haemophilus ducreyi, Klebsiella granulomatis, and Chlamydia trachomatis, exemplifies the complex interplay of STIs. Methods: This study analyzed GUD and co-infection with HIV, testing patterns, and co-occurrence trends among public clinic attendees in Mthatha, South Africa, to identify demographic, behavioral, and occupational disparities. Results: Sex-specific analysis revealed higher HIV prevalence among female attendees (47.00%) compared to male attendees (22.00%), alongside notable testing gaps and disparities in diseases such as syphilis, genital herpes, and lymphogranuloma venereum (LGV). Age-specific trends indicated the highest HIV prevalence in individuals aged 30–49, with peaks at 66.67% (30–39) and 76.47% (40–49). Treponema pallidum and HSV-2 prevalence were most pronounced in younger age groups (<20 and 20–29), while older demographics (50+) exhibited significant diagnostic gaps. Occupation-based analysis highlighted elevated HIV (65.91%) and HSV-2 (19.61%) prevalence among unemployed individuals, reflecting socioeconomic vulnerabilities. Co-occurrence analysis revealed notable overlaps, such as HIV and HSV-2 (6.67%) and Chlamydia trachomatis with HSV-1 (5.71%) and HSV-2 (4.76%), driven by shared risk factors. Correlation analysis identified strong links between HSV-1 and Haemophilus ducreyi (0.64) and between Chlamydia trachomatis and HSV-1 (0.56), underscoring the potential for integrated diagnostic strategies. Conclusion: These findings emphasize the need for targeted public health interventions addressing sex, age, and occupational disparities while improving diagnostic coverage and prevention efforts for co-occurring infections. Full article

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11 pages, 399 KB

Open AccessArticle

Utilization Pattern of Acupuncture and Its Associated Predictors for Cancer Pain in South Korea: A Cross-Sectional Study

by Eunbin Kwag, Haneum Joo, Soo-Dam Kim, So Jung Park, Jung Hyo Cho, Nam Hun Lee, Jong Cheon Joo, Myung Han Hyun, Susan Chimonas, Ting Bao, Jun J. Mao, Jee Young Lee and Hwaseung Yoo

Diseases 2025, 13(9), 292; https://doi.org/10.3390/diseases13090292 - 2 Sep 2025

Abstract

Background: Cancer-related pain is a common and distressing symptom among patients with cancer. Although acupuncture is widely used and supported by growing evidence, its real-world use and related patient attitudes remain underexplored in South Korea. This study aimed to investigate patterns of acupuncture [...] Read more.

Background: Cancer-related pain is a common and distressing symptom among patients with cancer. Although acupuncture is widely used and supported by growing evidence, its real-world use and related patient attitudes remain underexplored in South Korea. This study aimed to investigate patterns of acupuncture use and identify factors influencing its use among Korean cancer patients experiencing pain. Methods: A cross-sectional survey was conducted from October 2023 to May 2024 at six Korean medicine hospitals. A total of 201 cancer patients with pain completed a questionnaire assessing acupuncture use, pain severity and interference, and beliefs using a modified version of the ABCAM (Attitudes and Beliefs about Complementary and Alternative Medicine) instrument. Treatment concerns, logistical barriers, and social norms were analyzed. Results: Of the 201 participants, 80.6% reported using acupuncture for cancer-related pain. Pain severity was the only significant predictor of acupuncture use (OR = 1.53, 95% CI: 1.10–2.12, p = 0.01). Acupuncture users reported fewer concerns about safety and side effects, fewer logistical barriers, and stronger encouragement from family, healthcare providers, and peers. Conclusions: This is the first study to explore real-world use of acupuncture for cancer pain in South Korea. Greater pain severity, perceived safety, ease of access, and social support were associated with higher acupuncture use. These findings suggest that improved patient education and integration of acupuncture into cancer care may enhance pain management for Korean patients. Full article

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15 pages, 742 KB

Open AccessArticle

Assessment of the Impact of Chronic Pain on the Prevalence of Depressive Disorders in Patients with Endometriosis

by Edyta Rysiak, Anna Grajewska, Anna Łońska, Jakub Tomaszewski, Karolina Kymona and Joanna Rostkowska

Diseases 2025, 13(9), 291; https://doi.org/10.3390/diseases13090291 - 2 Sep 2025

Abstract

Background: Endometriosis is a chronic, estrogen-dependent inflammatory and immunological disease, with chronic pain being its predominant clinical manifestation. This condition significantly impairs quality of life and is frequently associated with depressive and anxiety symptoms, further exacerbating social and occupational dysfunction in affected women. [...] Read more.

Background: Endometriosis is a chronic, estrogen-dependent inflammatory and immunological disease, with chronic pain being its predominant clinical manifestation. This condition significantly impairs quality of life and is frequently associated with depressive and anxiety symptoms, further exacerbating social and occupational dysfunction in affected women. The aim of this study was to assess the relationship between chronic pain in patients with endometriosis and the severity of depressive symptoms. Methods: A retrospective analysis was conducted on the medical records of 60 women of reproductive age treated at the Tomaszewski Medical Center in Białystok between 2023 and 2024. Pain intensity was evaluated using the Visual Analogue Scale (VAS) and the McGill Pain Questionnaire, while depressive symptoms were assessed with the Beck Depression Inventory (BDI). Results: Statistical analyses included the Student t-test, Wilcoxon signed-rank test, chi-square test, and Shapiro–Wilk test, with significance set at p < 0.05. Pain intensity was significantly higher during menstruation (M = 7.23) compared to non-menstrual phases of the cycle (M = 4.55; p < 0.001). Accompanying symptoms included sleep disturbances, reduced activity, and gastrointestinal complaints. Depressive symptoms were also more severe during menstruation (M = 30.12) than during the rest of the cycle (M = 22.15; p < 0.001). A significant association between pain severity and depressive symptoms was observed during menstruation (χ²(4) = 12.89; p = 0.012), but not outside this phase. Conclusions: (1) Pain in endometriosis is chronic and cyclic in nature. (2) Depressive symptoms are common but may be masked by nonspecific somatic complaints. (3) Pain intensity strongly correlates with the severity of depressive disorders, particularly during menstruation. (4) The coexistence of depression significantly impairs patient functioning. (5) Effective management of endometriosis should integrate gynecological treatment with psychological support and psychiatric care when necessary. Full article

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11 pages, 243 KB

Open AccessReview

Emerging Clinical Role of Tavapadon, a Novel Dopamine Partial Agonist, in the Treatment of Parkinson’s Disease

by Alan D. Kaye, Bennett M. Ford, Brennan M. Abbott, Kalob M. Broocks, Sofia Novacic and Sahar Shekoohi

Diseases 2025, 13(9), 290; https://doi.org/10.3390/diseases13090290 - 2 Sep 2025

Abstract

Tavapadon, a novel oral dopamine-D1R/D5R partial agonist, has been studied in recent years for the treatment of late-stage development Parkinson’s disease (PD). Levodopa, a dopamine precursor that currently remains the gold-standard first-line therapy for PD motor symptoms, serves as a benchmark against emerging [...] Read more.

Tavapadon, a novel oral dopamine-D1R/D5R partial agonist, has been studied in recent years for the treatment of late-stage development Parkinson’s disease (PD). Levodopa, a dopamine precursor that currently remains the gold-standard first-line therapy for PD motor symptoms, serves as a benchmark against emerging dopaminergic agents. By selectively activating D1-family receptors on direct-pathway medium neurons, Tavapadon differs in that it delivers levodopa-level motor benefit while avoiding its many D2R/D3R-mediated adverse effects. In placebo-controlled trials, Tavapadon produced clear, clinically meaningful gains in motor function and day-to-day activities, as captured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Recent late-stage results have revealed that Tavapadon maintains superior UPDRS outcomes in de novo patients and, when added to levodopa, extended “ON” time periods of reliable motor control free of troublesome dyskinesia, without introducing new safety concerns. In studies, nausea, headache, and somnolence were the most frequent adverse events. Hallucinations, orthostatic hypotension, and impulse-control disorders remained comparable to placebo, reflecting minimal D2R/D3R-mediated effects. Preclinical primate studies have demonstrated levodopa-like motor rescue with markedly less dyskinesia, a pattern mirrored in clinical add-on trials. Collectively, evidence indicates that Tavapadon can match levodopa-mediated symptomatic efficacy, lower dyskinesia liability compared with levodopa or earlier full D1 receptor (D1R) agonists, and offer the convenience of once-daily dosing characteristics, which may bridge the therapeutic gap between levodopa and the current D2R/D3R agonists in PD management. In the present investigation, the emerging clinical role for Tavapadon is described, along with the mechanism of action, clinical efficacy, safety, and future directions. Full article

21 pages, 1666 KB

Open AccessReview

Angiotensin-Converting Enzyme Gene Polymorphisms and Diabetic Neuropathy: Insights from a Scoping Review and Scientometric Analysis

by Rafaela Cirillo de Melo, Paula Rothbarth Silva, Nathalia Marçallo Peixoto Souza, Mateus Santana Lopes, Wellington Martins de Carvalho Ragassi, Luana Mota Ferreira, Fabiane Gomes de Moraes Rego and Marcel Henrique Marcondes Sari

Diseases 2025, 13(9), 289; https://doi.org/10.3390/diseases13090289 - 1 Sep 2025

Abstract

Background/Objectives: Diabetic neuropathy (DN) is one of the most common and disabling complications of diabetes mellitus (DM), affecting motor, sensory, and autonomic nerves. Genetic factors, particularly polymorphisms in the Angiotensin-converting enzyme (ACE) gene, have been proposed as contributors to DN susceptibility. [...] Read more.

Background/Objectives: Diabetic neuropathy (DN) is one of the most common and disabling complications of diabetes mellitus (DM), affecting motor, sensory, and autonomic nerves. Genetic factors, particularly polymorphisms in the Angiotensin-converting enzyme (ACE) gene, have been proposed as contributors to DN susceptibility. This study aimed to synthesize the scientific evidence on ACE gene polymorphisms and their association with DN through a scoping review combined with scientometric analysis. Methods: A comprehensive search of PubMed, Scopus, and Web of Science was performed in February 2025, following JBI and PRISMA-ScR guidelines. Observational studies involving individuals with DN and the genotyping of ACE polymorphisms were included. Scientometric mapping was conducted using the Bibliometrix package in RStudio to identify publication trends and key thematic terms. Results: From 100 screened articles, 11 met the inclusion criteria. Most studies (72.7%) addressed diabetic peripheral neuropathy, while 27.3% investigated cardiac autonomic neuropathy. All studies analyzed the I/D polymorphism in intron 16 of the ACE gene. The D allele and DD genotype were associated with increased susceptibility to DN in over half of the studies (6/11), while the II genotype was reported as protective in 3/11. Findings varied by ethnicity and study design. The scientometric analysis identified ‘peripheral diabetic neuropathy’, type 2 diabetes’, and ‘ACE gene polymorphism’ as the most frequently co-occurring terms, indicating that research on this topic has been concentrated around these themes, while showing limited diversity in geographic origin and scope. Conclusions: ACE I/D polymorphism appears to modulate susceptibility to DN, though interethnic variability and methodological heterogeneity challenge definitive conclusions. Broader, standardized studies are needed to validate its utility as a predictive biomarker. Full article

(This article belongs to the Special Issue From Monitoring to Management: Addressing Challenges in Type 1 and Type 2 Diabetes Care)

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12 pages, 874 KB

Open AccessArticle

Surveillance of Mpox Cases in Mexico: Epidemiological Patterns During the 2022–2023 National Outbreak

by Juan M. Bello-López, Dulce M. Razo Blanco-Hernández, Miguel Á. Loyola-Cruz, Clemente Cruz-Cruz, Oscar Sosa-Hernández, Nayeli G. Nieto-Velázquez, Georgina Victoria-Acosta, Adriana Jiménez, Laura Delgado-Balbuena, Luis G. Zárate-Sánchez, Paulina Carpinteyro-Espín, Enzo Vásquez-Jiménez, Adolfo López-Ornelas, Graciela Castro-Escarpulli, Araceli Rojas-Bernabé, María C. Tamayo-Ordóñez, Yahaira de J. Tamayo-Ordóñez, Francisco A. Tamayo-Ordóñez, Benjamín A. Ayil-Gutiérrez, Omar A. García-Hernández, Benito Hernández-Castellanos, Julio C. Castañeda-Ortega, Claudia C. Calzada-Mendoza and Emilio M. Durán-Manuel Show full author list Hide full author list

Diseases 2025, 13(9), 288; https://doi.org/10.3390/diseases13090288 - 1 Sep 2025

Abstract

Background: Mpox is an emerging zoonotic disease, caused by the monkeypox virus (MPXV). Since its discovery, it has been considered endemic in Central and West Africa. Mpox is of global significance as of May 2022, due to the report of simultaneous outbreaks in [...] Read more.

Background: Mpox is an emerging zoonotic disease, caused by the monkeypox virus (MPXV). Since its discovery, it has been considered endemic in Central and West Africa. Mpox is of global significance as of May 2022, due to the report of simultaneous outbreaks in more than 70 countries where the disease was not endemic. The global spread of mpox has shown the importance of maintaining active surveillance for emerging zoonotic diseases, many of which can cross borders. Objective: The aim of this study was to analyse mpox cases and national incidence in Mexico related to the global outbreak. Methods: Epidemiological data (confirmed cases and incidence of MPXV infection) were obtained from the morbidity yearbook of the General Directorate of Epidemiology of the Mexican Ministry of Health. The information was analysed for the construction of epidemic curves, distribution of cases by age and sex and quartiles of geographical incidence. Results: A total of 4081 cumulative confirmed cases were recorded with a peak and national incidence of 1191 and 1.87, respectively, in September 2022. The distribution of cases by age and sex showed that males were more prevalent (above 95%) in the 25–44 years age group compared to females. Finally, geographical analysis showed that cosmopolitan and population-concentrated states had the highest incidence, clustered in the top quartile. The 2022 mpox outbreak in Mexico was consistent with other countries as reported in the international literature, with most cases occurring among exposed individuals in cosmopolitan cities. Conclusions: The need for active surveillance of emerging diseases, access to specific diagnostics and implementation of vaccination strategies is analysed and discussed. Full article

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16 pages, 2426 KB

Open AccessArticle

The Role of Interleukin-13 in Chronic Airway Diseases: A Cross-Sectional Study in COPD and Asthma–COPD Overlap

by Marina Perković, Vesna Vukičević Lazarević, Pavo Perković, Tomislav Perković, Vanja Dolenec, Ana Hađak, Vesna Šupak Smolčić and Ljiljana Bulat Kardum

Diseases 2025, 13(9), 287; https://doi.org/10.3390/diseases13090287 - 1 Sep 2025

Abstract

Background: Distinguishing chronic obstructive pulmonary disease (COPD) from asthma–COPD overlap (ACO) remains challenging due to shared clinical and inflammatory features. Interleukin-13 (IL-13) is implicated in airway inflammation and remodeling and may represent a potential treatable trait. This study aimed to evaluate whether serum [...] Read more.

Background: Distinguishing chronic obstructive pulmonary disease (COPD) from asthma–COPD overlap (ACO) remains challenging due to shared clinical and inflammatory features. Interleukin-13 (IL-13) is implicated in airway inflammation and remodeling and may represent a potential treatable trait. This study aimed to evaluate whether serum IL-13 could differentiate between COPD and ACO or define ACO subtypes and to explore its relationship with clinical and phenotype parameters. Materials and Methods: We conducted a cross-sectional bicentric study in 215 COPD and ACO patients recruited from outpatient clinics. The study measured blood IL-13 levels in COPD vs. ACO patients, across five ACO subtypes, and evaluated IL-13’s ability to predict ACO. Additionally, correlations were explored among endotype (IL-13) and different phenotype traits (e.g., fractional exhaled nitric oxide (FeNO), sputum eosinophilia, serum total immunoglobulin E (tIgE) levels, blood eosinophilia, and neutrophilia) and clinical outcomes (annualized exacerbation rate, symptom scores, and pulmonary function parameters). Results: No significant differences in IL-13 levels were found between COPD and ACO patients or among ACO subtypes. IL-13 did not predict ACO occurrence. We observed a weak correlation between IL-13 and tIgE levels in the entire cohort. Additionally, there was a weak correlation between IL-13 and FeNO in patients with eosinophil counts exceeding 300 cells/μL, as well as between IL-13 and age in the COPD cohort. No correlation was found between IL-13 and other phenotypic features or clinical outcomes in the overall cohort, including within both COPD and ACO groups. Conclusions: IL-13 cannot differentiate between COPD and ACO or ACO’s subtypes. Full article

(This article belongs to the Section Respiratory Diseases)

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13 pages, 2559 KB

Open AccessArticle

Artificial Intelligence Versus Professional Standards: A Cross-Sectional Comparative Study of GPT, Gemini, and ENT UK in Delivering Patient Information on ENT Conditions

by Ali Alabdalhussein, Nehal Singhania, Shazaan Nadeem, Mohammed Talib, Derar Al-Domaidat, Ibrahim Jimoh, Waleed Khan and Manish Mair

Diseases 2025, 13(9), 286; https://doi.org/10.3390/diseases13090286 - 1 Sep 2025

Abstract

Objective: Patient information materials are sensitive and, if poorly written, can cause misunderstanding. This study evaluated and compared the readability, actionability, and quality of patient education materials on laryngology topics generated by ChatGPT, Google Gemini, and ENT UK. Methods: We obtained patient information [...] Read more.

Objective: Patient information materials are sensitive and, if poorly written, can cause misunderstanding. This study evaluated and compared the readability, actionability, and quality of patient education materials on laryngology topics generated by ChatGPT, Google Gemini, and ENT UK. Methods: We obtained patient information from ENT UK and generated equivalent content with ChatGPT-4-turbo and Google Gemini 2.5 Pro for six laryngology conditions. We assessed readability (Flesch–Kincaid Grade Level, FKGL; Flesch Reading Ease, FRE), quality (DISCERN), and patient engagement (PEMAT-P for understandability and actionability). Statistical comparisons involved using ANOVA, Tukey’s HSD, and Kruskal–Wallis tests. Results: ENT UK showed the highest readability (FRE: 64.6 ± 8.4) and lowest grade level (FKGL: 7.4 ± 1.5), significantly better than that of ChatGPT (FRE: 38.8 ± 10.5, FKGL: 11.0 ± 1.5) and Gemini (FRE: 38.3 ± 8.5, FKGL: 11.9 ± 1.2) (all p < 0.001). DISCERN scores did not differ significantly (ENT UK: 21.3 ± 7.5, GPT: 24.7 ± 9.1, Gemini: 29.5 ± 4.6; p > 0.05). PEMAT-P understandability results were similar (ENT UK: 72.7 ± 8.3%, GPT: 79.1 ± 5.8%, Gemini: 78.5 ± 13.1%), except for lower GPT scores on vocal cord paralysis (p < 0.05). Actionability was also comparable (ENT UK: 46.7 ± 16.3%, GPT: 41.1 ± 24.0%, Gemini: 36.7 ± 19.7%). Conclusion: GPT and Gemini produce patient information of comparable quality and engagement to ENT UK but require higher reading levels and fall short of recommended literacy standards. Full article

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30 pages, 1153 KB

Open AccessReview

A Review of the Mechanisms and Risks of Panax ginseng in the Treatment of Alcohol Use Disorder

by Eli Frazer, Candi Zhao, Jacky Lee, Jonathan Shaw, Charles Lai, Peter Bota and Tina Allee

Diseases 2025, 13(9), 285; https://doi.org/10.3390/diseases13090285 - 1 Sep 2025

Abstract

Alcohol use disorder (AUD) is a widespread, multifaceted disorder involving overproduction of pro-inflammatory cytokines, oxidative liver injury, and dysfunction of the brain’s dopaminergic reward circuits. Korean red ginseng (KRG), an herbal supplement derived from Panax ginseng, has demonstrated qualities potentially useful to [...] Read more.

Alcohol use disorder (AUD) is a widespread, multifaceted disorder involving overproduction of pro-inflammatory cytokines, oxidative liver injury, and dysfunction of the brain’s dopaminergic reward circuits. Korean red ginseng (KRG), an herbal supplement derived from Panax ginseng, has demonstrated qualities potentially useful to the treatment of AUD, including antioxidative, anti-inflammatory, neuroprotective, and anxiolytic effects. This review examines active constituents of KRG, their pharmacological actions, and evidence supporting KRG’s therapeutic potential in the context of AUD, while also assessing its safety profile, adverse effects, and potential drug interactions. KRG’s main bioactive constituents, ginsenosides, appear to have roles in modulating alcohol-metabolizing enzymes, ethanol-activated inflammatory cytokine cascades, and neurological systems disrupted by AUD, including GABAergic and dopaminergic pathways. Evidence from animal models and limited small-scale human trials suggests KRG may alleviate symptoms of alcohol withdrawal, enhance cognitive performance, and attenuate anxiety through these pathways. While generally safe for consumption, several case reports and animal studies have indicated KRG’s potential to pose a variety of risks in vulnerable populations at high, prolonged doses, including hepatotoxicity, cardiovascular changes, mood disturbances, and hormonal effects. Furthermore, KRG’s neuromodulating role and influence on cytochrome P450 enzymes make it liable to interact with several medications, including warfarin, midazolam, selegiline, and serotonergic agents. Overall, KRG shows promise as a complementary supplement in managing aspects of AUD, though current evidence is limited by low sample sizes, inconsistent reports regarding nuances of ginsenosides’ mechanisms, and a low number of human trials. Further human-focused research is needed to elucidate its safety, efficacy, and mechanism. Full article

(This article belongs to the Section Neuro-psychiatric Disorders)

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15 pages, 975 KB

Open AccessBrief Report

Immunoblotting Analysis of Fruit Proteins in Mexican Pediatric Patients Suggests the Existence of New Allergens

by Angélica Torres-Arroyo, Maidelen Suárez-Gutiérrez, Andrea Iglesias-Amaya, Aramiz López-Durán, Luisa Díaz-García, Horacio Reyes-Vivas and David Alejandro Mendoza-Hernández

Diseases 2025, 13(9), 284; https://doi.org/10.3390/diseases13090284 - 1 Sep 2025

Abstract

Background: Food allergies are chronic diseases that compromise quality of life and can be potentially fatal due to anaphylaxis. The WHO estimates a 1–11% global prevalence, which has been increasing in recent years. They are considered, along with obesity, to be the two [...] Read more.

Background: Food allergies are chronic diseases that compromise quality of life and can be potentially fatal due to anaphylaxis. The WHO estimates a 1–11% global prevalence, which has been increasing in recent years. They are considered, along with obesity, to be the two noninfectious pandemics. The WHO databases (WHO/IUIS) contain 403 food allergens, most of which have been reported from North America (Canada and the USA), Europe, and Asia, while reports of allergens from Latin America are scarce. Allergies have population and geographical specificities; therefore, identifying the main clinically relevant food allergens and potential new, undescribed components affecting Latin America is essential. This work aims to contribute to this field. Methods: we gathered data from 16 allergic Mexican pediatric patients to fruits from the Rosaceae (pear and peach) and Musaceae (banana) families, as well as an allergic adult to Lauraceae (avocado). These fruits are prevalent allergens in Latin America. Results: the data suggest that patients reacted to 20 different allergenic proteins reported in different allergen databases. Furthermore, we identified 16 previously unreported immunoreactive proteins, suggesting their potential role as new allergens. Conclusion: this preliminary work is particularly relevant, as it can influence the specific diagnosis of allergens most frequently affecting the pediatric population. Full article

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11 pages, 1007 KB

Open AccessArticle

Detection of Serum Levels of Interleukins-17, 21, 6 and Tumor Necrosis Factor-α in Patients with Patchy Alopecia Areata and Their Association with Disease Severity

by Abeer Khaled Abu-El-Azayem, Zinab Alatawi, Helal F. Hetta, Ayman Salama, Nizar Sirag, Eid Alatwi, Rehab Mohamed Naguib, Randa Erfan, Haitham Abdelhamid, Abeer El-Dessouki El Sayed and Mera Mohamed Galal Anan

Diseases 2025, 13(9), 283; https://doi.org/10.3390/diseases13090283 - 1 Sep 2025

Abstract

Background/Objectives: Alopecia areata (AA) is a common autoimmune disorder characterized by non-scarring hair loss. The destruction of hair follicle cells is mediated by cytotoxic T cells, which release cytokines that contribute to tissue damage. Among these, Th17 cells produce key inflammatory mediators, [...] Read more.

Background/Objectives: Alopecia areata (AA) is a common autoimmune disorder characterized by non-scarring hair loss. The destruction of hair follicle cells is mediated by cytotoxic T cells, which release cytokines that contribute to tissue damage. Among these, Th17 cells produce key inflammatory mediators, including IL-17, IL-21, IL-6, and TNF-α, which may play a role in disease progression. This study aimed to evaluate the serum levels of IL-17A, IL-21, IL-6, and TNF-α in patients with patchy AA compared with healthy controls and to assess their association with disease severity. Methods: A cross-sectional analytical study was conducted on 50 patients with patchy AA and 50 age- and gender-matched healthy controls. Blood samples were collected, and serum cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Results: Of the patients, 70% were female (35 patients) and 30% were male (15 patients). Disease severity distribution showed that 66% had mild AA, 22% had moderate AA, and 12% had severe AA. Compared with controls, AA patients exhibited significantly elevated serum levels of IL-6, TNF-α, IL-17A, and IL-21 (p < 0.001). Additionally, cytokine levels showed a positive correlation with both age and disease duration, suggesting their potential role in disease progression. Conclusions: These findings highlight the involvement of pro-inflammatory cytokines in the pathogenesis of patchy AA and their correlation with disease severity. Understanding these cytokine interactions may provide insights into targeted therapeutic strategies in managing AA. Full article

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