Journal of Clinical Medicine

14 pages, 1014 KB

Open AccessReview

Understanding Peritoneal Fluid Estrogen and Progesterone Concentrations Permits Individualization of Medical Treatment of Endometriosis-Associated Pain with Lower Doses, Especially in Adolescents Not Requiring Contraception

by Philippe R. Koninckx, Anastasia Ussia, Leila Adamyan, Arnaud Wattiez and Paola Vigano

J. Clin. Med. 2025, 14(20), 7196; https://doi.org/10.3390/jcm14207196 (registering DOI) - 12 Oct 2025

Abstract

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 [...] Read more.

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 adolescents. Results: Oral contraceptives (OCs) were designed to inhibit ovulation in all women, and doses are much higher than the mean ovulation-inhibiting dose. Therefore, in most women, half a dose and in some women, even less is sufficient to inhibit ovulation. The inhibition of ovarian function and ovulation decreases estrogen and progesterone concentrations in plasma and peritoneal fluid. Surprisingly, the effect on peritoneal fluid steroid hormone concentrations has not been considered to explain the impact on endometriosis-associated pain. The lowering of the high estrogen concentrations in peritoneal fluid is sufficient to explain the pain decrease in superficial and ovarian endometriosis. A direct progesterone effect is unlikely, given the high progesterone concentrations in the peritoneal fluid of ovulatory women. In 8 adolescents, half an OC dose resulted in an apparently similar pain relief as a full dose (personal observation). Conclusions: The decrease in ovarian and superficial pelvic endometriosis-associated pain with OCs can be explained by lowering the intra-ovarian and the high estrogen concentrations in peritoneal fluid after ovulation. A direct progesterone effect is unlikely. Since OCs are severely overdosed in most women, half a dose is sufficient in most with fewer side effects, permitting individualization of therapy in women not requiring contraception. Understanding peritoneal fluid also explains that hormone replacement therapy is not contraindicated in most women with a history of endometriosis. Since the mechanisms of medical therapy of endometriosis-associated pain and the prevention of progression might be different, the growth of lesions must be monitored during treatment. Full article

(This article belongs to the Special Issue Management of Endometriosis: Evidence-Based Updated by Collective Clinical Experience and New Perspectives from Research)

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10 pages, 1194 KB

Open AccessArticle

Lipedema and Hypermobility Spectrum Disorders Sharing Pathophysiology: A Cross-Sectional Observational Study

by Elettra Fiengo and Andrea Sbarbati

J. Clin. Med. 2025, 14(20), 7195; https://doi.org/10.3390/jcm14207195 (registering DOI) - 12 Oct 2025

Abstract

Background/Objectives: Lipedema is a chronic, progressive disorder of the adipo-fascial tissue characterized by abnormal subcutaneous fat accumulation, inflammation, fibrosis, pain, and edema. Despite its considerable impact on patients’ quality of life, it remains underdiagnosed. Recent studies have suggested a potential overlap between lipedema [...] Read more.

Background/Objectives: Lipedema is a chronic, progressive disorder of the adipo-fascial tissue characterized by abnormal subcutaneous fat accumulation, inflammation, fibrosis, pain, and edema. Despite its considerable impact on patients’ quality of life, it remains underdiagnosed. Recent studies have suggested a potential overlap between lipedema and hypermobility spectrum disorders (HSDs), both involving connective tissue dysfunction. This work explores the shared pathophysiological features of lipedema and HSD, highlighting clinical correlations, comorbidities, and the need for integrated diagnostic and therapeutic approaches. Methods: A cross-sectional observational study was conducted through an online survey targeting individuals with lipedema and a control group with lymphedema. The questionnaire assessed symptoms typically associated with HSD, including musculoskeletal, gastrointestinal, urogynecological, vascular, and neuropsychological manifestations. Descriptive statistics were used to evaluate clinical patterns in both groups. Results: Among the lipedema patients, 44% reported joint hypermobility and 60% recalled being hypermobile during childhood. High rates of pediatric overweight (50%), low muscle tone (55%), and exercise-induced fatigue (70%) were observed. Adult symptoms included joint pain (notably in the ankles, knees, cervical spine, sacrum, and feet), digestive issues (50%), and thyroid disorders (24.4%). Compared with the control group, patients with lipedema showed significantly more connective tissue-related motor deficits and systemic symptoms. Conclusions: Connective tissue laxity may play a critical role in the pathogenesis of lipedema, contributing to multisystemic manifestations through vascular, lymphatic, gastrointestinal, and musculoskeletal involvement. The high prevalence of HSD-like features calls for a paradigm shift in the understanding of lipedema as a systemic disorder. Early identification of connective tissue alterations, especially in children with familial predisposition, could enable timely interventions, potentially mitigating disease progression. A multidisciplinary, evidence-based approach is essential for accurate diagnosis and effective management. Full article

(This article belongs to the Section Clinical Rehabilitation)

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17 pages, 317 KB

Open AccessReview

Effects of Air Pollution on Dialysis and Kidney Transplantation: Clinical and Public Health Action

by Sławomir Jerzy Małyszko, Adam Gryko, Jolanta Małyszko, Dominika Musiałowska, Anna Fabiańska and Łukasz Kuźma

J. Clin. Med. 2025, 14(20), 7194; https://doi.org/10.3390/jcm14207194 (registering DOI) - 12 Oct 2025

Abstract

Air pollution is associated with many adverse health outcomes, including kidney diseases. Kidney diseases, especially chronic kidney disease, are a significant public health issue globally. The burden of kidney disease is expected to rise due to population aging and the growing prevalence of [...] Read more.

Air pollution is associated with many adverse health outcomes, including kidney diseases. Kidney diseases, especially chronic kidney disease, are a significant public health issue globally. The burden of kidney disease is expected to rise due to population aging and the growing prevalence of diabetes and hypertension. End-stage kidney disease is associated with significant healthcare costs, morbidity, and mortality. Long-term exposure to air pollution was associated with increased risk for chronic kidney disease progression to kidney replacement therapy. Evidence on the effect of short-term exposure to air pollution on renal function is rather limited. Kidney transplant patients are likely to be even more susceptible to detrimental effects of air pollutants. Exposure to air pollution results in a higher risk for delayed graft function, acute rejection, and mortality. In this review we would like to summarize the state of knowledge on the influence of air pollution on outcomes in end-stage kidney failure and kidney transplantation. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

13 pages, 8649 KB

Open AccessArticle

Negative Pressure Wound Therapy in the Treatment of Complicated Wounds of the Foot and Lower Limb in Diabetic Patients: A Retrospective Case Series

by Octavian Mihalache, Laurentiu Simion, Horia Doran, Andra Bontea Bîrligea, Dan Cristian Luca, Elena Chitoran, Florin Bobircă, Petronel Mustățea and Traian Pătrașcu

J. Clin. Med. 2025, 14(20), 7193; https://doi.org/10.3390/jcm14207193 (registering DOI) - 12 Oct 2025

Abstract

Background: Diabetes-related foot diseases represent a global health problem because of the associated complications, the risk of amputation, and the economic burden on health systems. Negative pressure wound therapy (NPWT) is a technique that uses sub-atmospheric pressure to help promote wound healing [...] Read more.

Background: Diabetes-related foot diseases represent a global health problem because of the associated complications, the risk of amputation, and the economic burden on health systems. Negative pressure wound therapy (NPWT) is a technique that uses sub-atmospheric pressure to help promote wound healing by reducing the inflammatory exudate while keeping the wound moist, inhibiting bacterial growth, and promoting the formation of granulation tissue. Objective: This study aimed to assess the effectiveness of NPWT in preventing major amputation in diabetic patients with complicated foot or lower limb infections and to contextualize the results through a review of the existing literature. Materials and methods: We conducted a retrospective study at the First Surgical Department of “Dr. I. Cantacuzino” Clinical Hospital in Bucharest, Romania, over a 15-year period, including 30 consecutive adult patients with diabetes and soft tissue foot or lower limb infections treated with NPWT. Patients with non-diabetic ulcers, incomplete medical data, or aged under 18 were excluded. All patients underwent initial surgical debridement, minor amputation, or drainage procedures, followed by the application of NPWT using a standard protocol. Dressings were changed every 2–4 days for a total of 7–10 days. Antibiotic therapy was adapted according to the culture results. The primary outcome was limb preservation, defined as avoidance of major amputation. Secondary outcomes included in-hospital mortality and wound status at discharge. Results: NPWT was associated with a favorable outcome in 24 patients (80%), defined by wound granulation or healing without the need for major amputation. Five patients (16.6%) underwent major amputation because of failure of the primary lesion treatment, and one patient died. No statistically significant association was observed between the outcomes and standard classification scores (WIFI, IWGDF, and TPI). A comprehensive literature review helped to integrate these findings into the existing pool of knowledge. Conclusions: NPWT may support limb preservation in selected diabetic foot cases. While the retrospective design and the small sample size of the study limit generalizability, these results reinforce the need for further controlled studies to evaluate NPWT in real-life clinical settings. The correct use of NPWT combined with etiological treatment may offer a maximum chance to avoid major amputation in patients with diabetes-related foot diseases. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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14 pages, 534 KB

Open AccessArticle

From Intracoronary Physiology to Endotype-Based Treatment: Quality of Life Improvement for INOCA Patients

by Barbara Vitola, Laima Caunite, Karlis Trusinskis, Iveta Mintale and Andrejs Erglis

J. Clin. Med. 2025, 14(20), 7192; https://doi.org/10.3390/jcm14207192 (registering DOI) - 12 Oct 2025

Abstract

Background/Objectives: Ischemia with non-obstructive coronary arteries (INOCA) remains an underdiagnosed and undertreated condition due to the extensive diagnostic testing required and heterogeneous pathophysiology of different endotypes, each of which require tailored treatment. This study aimed to explore the effect of intracoronary physiology [...] Read more.

Background/Objectives: Ischemia with non-obstructive coronary arteries (INOCA) remains an underdiagnosed and undertreated condition due to the extensive diagnostic testing required and heterogeneous pathophysiology of different endotypes, each of which require tailored treatment. This study aimed to explore the effect of intracoronary physiology testing-based endotype-specific medical therapy on quality of life in patients with INOCA. Methods: Intracoronary physiology testing was performed in patients presenting with cardiac symptoms, evidence of significant ischemia on non-invasive testing, and non-obstructive epicardial coronary arteries. Microvascular angina (MVA) was defined as coronary flow reserve ≤ 2.5 and an index of microvascular resistance ≥ 25. Vasospastic angina (VSA) was defined as a >90% vasoconstriction of an epicardial artery during acetylcholine provocation test in the presence of ischemic electrocardiogram changes and chest pain. Quality of life was evaluated using the Seattle Angina Questionnaire 7 (SAQ-7) before the start of new treatment and at the three months follow-up. Results: The total study population consisted of 35 patients (80% women), of whom MVA was observed in 19 (54.3%), VSA in 9 (25.7%), and the combination of MVA and VSA in 3 (8.6%) cases. Four patients (11.4%) had no pathology on intracoronary physiology testing detected. High rates of dyslipidemia (100%), arterial hypertension (85.7%), diabetes (17.1%), and depression and anxiety (34.3%) were documented. In the isolated MVA and VSA groups, adjustment of medical therapy resulted in an improvement in the SAQ-7 summary score at 3 months (p < 0.001 and p = 0.007, respectively). There was no change of SAQ-7 summary score in the mixed endotype group (p = 0.11). Conclusions: Adjustment of medical therapy according to intracoronary physiology testing-based phenotype resulted in improved quality of life as assessed by the SAQ-7. Our findings highlight the importance of invasive testing in patients with clinically suspected INOCA. Full article

(This article belongs to the Section Cardiovascular Medicine)

14 pages, 605 KB

Open AccessStudy Protocol

Monitoring and Follow-Up of Patients on Vitamin K Antagonist Oral Anticoagulant Therapy Using Artificial Intelligence: The AIto-Control Project

by Adolfo Romero-Arana, Nerea Romero-Sibajas, Elena Arroyo-Bello, Adolfo Romero-Ruiz and Juan Gómez-Salgado

J. Clin. Med. 2025, 14(20), 7191; https://doi.org/10.3390/jcm14207191 (registering DOI) - 12 Oct 2025

Abstract

Background: Vitamin K antagonist oral anticoagulant (VKA) therapy, using warfarin or acenocoumarol in our health system, is indicated, according to clinical guidelines, for the prophylaxis of thromboembolic events. In Málaga, the VKA patient management program currently includes a total of 856 patients. [...] Read more.

Background: Vitamin K antagonist oral anticoagulant (VKA) therapy, using warfarin or acenocoumarol in our health system, is indicated, according to clinical guidelines, for the prophylaxis of thromboembolic events. In Málaga, the VKA patient management program currently includes a total of 856 patients. Hypothesis: The use of an AI-based application can enhance treatment adherence among VKA patients participating in self-monitoring and self-management programs. Furthermore, it can support the comprehensive implementation of the system, leading to reduced costs and fewer interventions for anticoagulated patients. Methods: The study will be conducted in several phases. The first phase involves the development of the application and the integration of Artificial Intelligence (AI) and Machine Learning (ML) algorithms. The second phase includes preliminary testing and validation of the developed application. The third phase consists of full implementation, along with an assessment of user-identified needs and potential quality improvements. Expected Results: The implementation of the AIto-Control app is expected to reduce healthcare-related costs by decreasing primary care visits and hospital admissions due to thromboembolic or bleeding events. Additionally, it aims to ease the workload on both primary care and hospital services. These outcomes will be achieved through the involvement of advanced practice nurses who will supervise app-based monitoring and patient education. Full article

(This article belongs to the Special Issue Thrombosis and Haemostasis: Clinical Advances)

9 pages, 289 KB

Open AccessProtocol

Changes in Gut Microbiome According to Probiotic Intake in Rectal Cancer Patients Undergoing Diverting Stoma Repair: Study Protocol

by Hyeung-min Park, Jaram Lee, Soo Young Lee, Chang Hyun Kim and Hyeong Rok Kim

J. Clin. Med. 2025, 14(20), 7190; https://doi.org/10.3390/jcm14207190 (registering DOI) - 12 Oct 2025

Abstract

Background: The gut microbiome is crucial in sustaining intestinal balance and general health. Following rectal cancer surgery, the creation of a diverting stoma to protect the anastomosis results in a defunctioned colon, leading to dysbiosis. The effect of probiotic intake on gut [...] Read more.

Background: The gut microbiome is crucial in sustaining intestinal balance and general health. Following rectal cancer surgery, the creation of a diverting stoma to protect the anastomosis results in a defunctioned colon, leading to dysbiosis. The effect of probiotic intake on gut dysbiosis following ileostomy repair remains uncertain. Thus, this study aims to determine the changes in gut microbiota based on the intake of probiotics after diverting stoma repair. Methods: This single-center, parallel, prospective pilot study will include patients with primary rectal cancer planning to undergo a diverting stoma during rectal cancer surgery. The study will comprise 20 patients, with 10 patients receiving synbiotics after stoma repair and 10 patients not receiving probiotics. The primary endpoint is the change in the gut microbiota of the resting colon based on the intake of probiotics, assessed through fecal testing at the following time points: before bowel resection, immediately after diverting stoma repair, and 3 weeks after diverting stoma repair. Changes in gut microbiota will be evaluated using alpha- and beta-diversity analyses based on 16S rRNA sequencing of fecal samples. Discussion: This study is the first prospective cohort trial investigating changes in the gut microbiota of the resting colon based on oral probiotic administration in patients undergoing diverting stoma repair. This trial is anticipated to clarify the impact of probiotic intake in these patients. Trial registration: Clinical Research Information Service (CRIS) of the Republic of Korea, KCT0008392, Registered on 27 April 2023. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

18 pages, 321 KB

Open AccessReview

Renal Cell Carcinoma with Duodenal Metastasis: Is There a Place for Surgery? A Review

by Fayek Taha, Rami Rhaiem, Stephane Larre, Ali Reza Kianmanesh, Yohan Renard and Belkacem Acidi

J. Clin. Med. 2025, 14(20), 7189; https://doi.org/10.3390/jcm14207189 (registering DOI) - 12 Oct 2025

Abstract

Introduction: Renal cell carcinoma (RCC) develops metastatic disease in 30–50% of patients during their disease course, with approximately one quarter presenting with metastases at diagnosis. While the lungs, liver, bones, brain, and adrenal glands are the most frequent metastatic sites, duodenal involvement [...] Read more.

Introduction: Renal cell carcinoma (RCC) develops metastatic disease in 30–50% of patients during their disease course, with approximately one quarter presenting with metastases at diagnosis. While the lungs, liver, bones, brain, and adrenal glands are the most frequent metastatic sites, duodenal involvement is exceptionally rare. This uncommon presentation poses diagnostic and therapeutic challenges, particularly regarding the role of surgical resection in the metastatic setting. Objective: We aim to evaluate the clinical presentation, management strategies, and outcomes of patients with duodenal metastasis from RCC, with particular emphasis on the potential role of surgery, through a systematic review of the literature. Methods: A comprehensive electronic search of Medline, Embase, and Scopus was conducted according to PRISMA guidelines. The following MeSH terms were applied: Kidney Neoplasms [MeSH] AND Duodenal Neoplasms/metastasis [MeSH]. Eligible studies included original reports or case series describing RCC with duodenal metastasis. Demographic, clinical, surgical, and survival data were extracted and synthesized. Results: Of 89 records identified, 83 underwent full-text review and 51 met inclusion criteria, representing 55 patients. The median age at diagnosis was 64 years, and 80% of primary tumors arose from the right kidney. Nearly all patients (98%) were symptomatic, most commonly with upper gastrointestinal bleeding, anemia, or obstructive features. Pancreaticoduodenectomy was the predominant surgical approach, performed with curative intent in selected cases. Patients undergoing surgery achieved a 5-year overall survival of 70%, compared with 0% among non-operated patients. Conclusions: Duodenal metastasis from RCC remains an uncommon entity, limiting the strength of available evidence. Nevertheless, our findings suggest that surgical management—when feasible and decided within a multidisciplinary framework—can provide meaningful survival benefit and should be considered as a complement to contemporary systemic therapies for metastatic RCC Full article

(This article belongs to the Special Issue Renal Cell Carcinoma: From Diagnostic to Therapy)

11 pages, 733 KB

Open AccessArticle

Linking Intradialytic Blood Volume Dynamics to Extracellular Fluid Status: Toward Personalized Fluid Assessment in Hemodialysis

by Martin Russwurm, Marvin Braun, Julia Menne, Lara Ploeger, Marc Miran, Fabian Max, Lotte Dahmen, Joachim Hoyer and Johannes Wild

J. Clin. Med. 2025, 14(20), 7188; https://doi.org/10.3390/jcm14207188 (registering DOI) - 12 Oct 2025

Abstract

Background: Accurate assessment of volume status remains a central challenge in hemodialysis (HD). Although bioimpedance spectroscopy (BIS) can quantify fluid compartments, it is time-consuming and requires a lot of personnel. Modern HD machines provide continuous relative blood volume (RBV) monitoring. We examined [...] Read more.

Background: Accurate assessment of volume status remains a central challenge in hemodialysis (HD). Although bioimpedance spectroscopy (BIS) can quantify fluid compartments, it is time-consuming and requires a lot of personnel. Modern HD machines provide continuous relative blood volume (RBV) monitoring. We examined whether intradialytic RBV dynamics reflect pre-dialysis extracellular fluid (ECW) status to inform personalized fluid management. Methods: In an ancillary, monocentric, prospective study of the SkInDialysis trial (DRKS00036332), 11 maintenance-HD patients underwent three standardized dialysis sessions with simultaneous measurement of RBV and BIS. BIS was performed at five time points per session (pre-HD; 20, 80, and 160 min after the start of HD; and post-HD). Ultrafiltration (UF), RBV, total body water (TBW), ECW, and intracellular water (ICW) were recorded. Results: Mean total UF was 2809 ± 894 mL/session. RBV declined to 94.7 ± 3.1% at 20 min and to 87.6 ± 5.5% by the end of the session. TBW decreased by 2.9 ± 2.7%, driven by ECW reduction (−3.15 ± 2.9%) over ICW (−1.1 ± 1.65%). Cumulative UF correlated with declines in TBW (R² = 0.18; p = 0.02) and ECW (R² = 0.23; p = 0.01) and more modestly with ICW (R² = 0.16; p = 0.04). In contrast, ΔRBV (pre- vs. post-HD) did not correlate with UF, weight loss, or compartmental water changes. Early steady-state RBV at 80 min correlated with pre-HD ECW (R² = 0.19; p = 0.02) and more strongly with the pre-HD ECW/ICW ratio (R² = 0.34; p = 0.001). Conclusions: In this small, repeated-measures cohort, absolute early steady state RBV levels were associated with pre-dialysis ECW and the ECW/ICW ratio, whereas RBV change (ΔRBV) did not track absolute fluid removal. Our data support a time-anchored RBV level as a pragmatic, device-embedded indicator of the pre-dialysis extracellular reservoir. Full article

(This article belongs to the Special Issue Hemodialysis: Clinical Updates and Advances)

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13 pages, 240 KB

Open AccessArticle

Factors Associated with Radiological Examination of Patients with Non-Specific Low Back Pain

by Asma S. Alrushud, Muteb J. Alqarni, Salman Albeshan, Areej S. Aloufi, Mawaddah H. Aljohani, Mohammed A. Alqarni, Somyah A. Alhazmi, Yazeed I. Alashban and Dalia M. Alimam

J. Clin. Med. 2025, 14(20), 7187; https://doi.org/10.3390/jcm14207187 (registering DOI) - 12 Oct 2025

Abstract

Background/Objectives: Non-specific low back pain (LBP), a highly prevalent musculoskeletal condition, may be associated with overuse of radiological imaging, despite clinical guidelines restricting its use to cases with suspected serious pathology. This study investigated demographic, clinical, and physiotherapy-related factors influencing radiological imaging [...] Read more.

Background/Objectives: Non-specific low back pain (LBP), a highly prevalent musculoskeletal condition, may be associated with overuse of radiological imaging, despite clinical guidelines restricting its use to cases with suspected serious pathology. This study investigated demographic, clinical, and physiotherapy-related factors influencing radiological imaging use in patients with non-specific LBP. Methods: A retrospective cross-sectional study included 179 non-specific LBP patients from an outpatient physiotherapy clinic in Saudi Arabia. Patient data were anonymized and retrieved from electronic health records, including demographic, clinical, physiotherapy and imaging information. Independent variables included patient demographics, non-specific LBP characteristics, physiotherapy engagement, and pain-related outcomes. Descriptive, inferential, and multiple linear regression analyses were conducted to identify predictors of radiological imaging. Results: Among the total study sample (n = 179), 159 (88.8%) patients underwent radiological imaging, primarily X-ray (32.4%) and Magnetic Resonance Imaging (8.4%); 48.0% received multiple imaging modalities. Significant predictors of imaging use included gender (p < 0.001), higher body mass index (BMI) (p = 0.012), greater physiotherapist experience (p = 0.019), and presence of comorbidities (p = 0.023). Non-specific LBP medication use was negatively associated with imaging (p = 0.032). Physiotherapy engagement and pain-related outcomes showed no significant impact on imaging use. Conclusions: Gender, BMI, physiotherapist experience, and comorbidities could influence radiological imaging use in non-specific LBP patients. These findings highlight potential biases in imaging referral patterns and reinforce the need for adherence to evidence-based guidelines to prevent unnecessary imaging, reduce healthcare costs, and enhance patient care. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

8 pages, 629 KB

Open AccessCase Report

Persistent Liver Manifestations in Allopurinol-Induced Sweet’s Syndrome: An Uncommon Case Report

by Amalia Papanikolopoulou, Sofia M. Siasiakou, Kosmas Pantazopoulos, Ioannis P Trontzas, Eleni Fyta, Oraianthi Fiste, Ekaterini Syrigou and Nikolaos Syrigos

J. Clin. Med. 2025, 14(20), 7186; https://doi.org/10.3390/jcm14207186 (registering DOI) - 12 Oct 2025

Abstract

Background/Objectives: Sweet’s syndrome (SS), also known as acute febrile neutrophilic dermatosis, is a rare inflammatory skin disorder that may also present with extracutaneous manifestations. Liver involvement is thought to result from sterile neutrophilic infiltration, mirroring the skin pathology and highlighting the syndrome’s systemic [...] Read more.

Background/Objectives: Sweet’s syndrome (SS), also known as acute febrile neutrophilic dermatosis, is a rare inflammatory skin disorder that may also present with extracutaneous manifestations. Liver involvement is thought to result from sterile neutrophilic infiltration, mirroring the skin pathology and highlighting the syndrome’s systemic inflammatory nature. Timely recognition, exclusion of infectious or autoimmune etiologies, and prompt corticosteroid therapy are critical for favorable outcomes. Methods: Herein, we present the case of a 73-year-old man with hyperuricemia who developed both cutaneous and systemic manifestations of SS seven days after initiating allopurinol treatment. His symptoms included fever, conjunctivitis in the right eye, and painful, non-pruritic erythematous plaques, some with pustules, on the lower limbs, palms, and face. Results: Initial laboratory investigations revealed neutrophilic leukocytosis, elevated inflammatory markers, and renal and hepatic dysfunction. Empirical treatment with antibiotics and antivirals failed to improve his condition. The patient discontinued allopurinol and initiated a high-dose corticosteroid regimen, leading to rapid resolution of fever and improvement in skin lesions. Laboratory parameters gradually normalized, except for persistent high liver enzymes. A comprehensive diagnostic workup ruled out infectious, autoimmune, and malignant causes. Imaging studies, including CT, MRI, and MRCP, showed no structural liver abnormalities. Skin biopsy findings were consistent with SS, demonstrating dense neutrophilic infiltrates in the reticular dermis and papillary dermal edema. After his discharge, he was followed up by the Hepatology unit. The patients’ liver enzyme levels normalized within three months with no recurrence or late complications one year later. Conclusions: In the context of drug-induced SS, persistent hepatic abnormalities, although rare, may occur in patients without underlying liver disease. Full article

(This article belongs to the Special Issue Fresh Insights in Skin Disease)

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19 pages, 431 KB

Open AccessArticle

A New Model for Screening for Late-Onset Preeclampsia in the Third Trimester

by Clara Jiménez-García, Ana María Palacios-Marqués, José Antonio Quesada-Rico, Paloma Baviera-Royo, Encarnación Pérez-Pascual, Inmaculada Baldó-Estela and Víctor García-Sousa

J. Clin. Med. 2025, 14(20), 7185; https://doi.org/10.3390/jcm14207185 (registering DOI) - 12 Oct 2025

Abstract

Background/Objectives: Screening for late-onset and term preeclampsia (PE) is essential, as the early identification of women at high risk enables closer monitoring and reduces adverse outcomes. The existing algorithms combining maternal factors, biophysical and biochemical markers have not been validated outside the [...] Read more.

Background/Objectives: Screening for late-onset and term preeclampsia (PE) is essential, as the early identification of women at high risk enables closer monitoring and reduces adverse outcomes. The existing algorithms combining maternal factors, biophysical and biochemical markers have not been validated outside the populations in which they were originally developed. This study aimed to evaluate the predictive performance of the Fetal Medicine Foundation (FMF) third-trimester algorithm in our population and develop a novel model to improve the predictions. Methods: An observational, analytical, prospective cohort follow-up study was conducted at the Health Department of Alicante, Dr. Balmis General University Hospital, including 1580 singleton pregnancies recruited between February 2022 and November 2023 during routine third-trimester ultrasounds. Maternal clinical characteristics, blood pressure, the uterine artery pulsatility index (UtA-PI), and the sFlt-1/PlGF ratio were recorded. The FMF third-trimester algorithm was retrospectively applied at the end of pregnancy using clinical, biophysical, and biochemical data from 30 + 0 to 37 + 6 weeks via the freely accessible online calculator. The data analysis was performed using SPSS v.28 and R v.4.3.1. Results: A total of 1580 women were included, with a prevalence of late-onset PE of 2.9%. The FMF model achieved an area under the curve (AUC) of 0.87 (95% CI: 0.81–0.92), while our own model showed a superior performance, with an AUC of 0.94 (95% CI: 0.92–0.97). Conclusions: The FMF third-trimester algorithm demonstrated a good predictive performance for late-onset PE. Our newly developed model achieves an even higher predictive accuracy and offers a simplified approach to excluding the UtA-PI, which facilitates its use in routine clinical practice. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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10 pages, 1650 KB

Open AccessArticle

Radiographic Outcomes After Growing Rod Treatment in Early-Onset Scoliosis: With Versus Without Final Fusion Surgery

by Yunjin Nam, Udit Patel, Sangmin Lee, Jungwook Lim, Jae Hyuk Yang and Seung Woo Suh

J. Clin. Med. 2025, 14(20), 7184; https://doi.org/10.3390/jcm14207184 (registering DOI) - 12 Oct 2025

Abstract

Background/Objectives: Early-onset scoliosis (EOS) is often treated with growing rods, which use distraction-based correction to control deformity while allowing spinal growth. Although effective in the coronal plane, this technique may adversely affect sagittal alignment, particularly thoracic kyphosis and lumbar lordosis. Whether final [...] Read more.

Background/Objectives: Early-onset scoliosis (EOS) is often treated with growing rods, which use distraction-based correction to control deformity while allowing spinal growth. Although effective in the coronal plane, this technique may adversely affect sagittal alignment, particularly thoracic kyphosis and lumbar lordosis. Whether final fusion surgery is necessary after the growing rod treatment remains controversial. This study compared radiographic outcomes, including coronal and sagittal parameters, between patients with and without final fusion to clarify the value of final fusion. Methods: We retrospectively reviewed 19 EOS patients treated with growing rods between 2015 and 2019. Patients undergoing posterior spinal fusion after lengthening were classified as the final fusion group (n = 9), while those with more than 12 months of follow-up without fusion formed the graduated group (n = 10). Demographics, surgical variables, and radiographic parameters (Cobb angle, correction rate, coronal balance, clavicular angle, thoracic kyphosis, lumbar lordosis, sagittal vertical axis) were compared. Results: Baseline characteristics were similar. At final follow-up, the final fusion group had significantly better outcomes in Cobb angle (24.2° vs. 34.9°, p = 0.002), correction rate (66.6% vs. 40.1%, p = 0.001), and coronal balance (−1.5 mm vs. 19.7 mm, p = 0.004). Sagittal alignment did not differ significantly, but preservation of thoracic kyphosis tended to favor the fusion group. Conclusions: Final fusion surgery after growing rod treatment achieved superior coronal correction and balance compared with observation alone. Although sagittal alignment was not statistically different, a trend toward better thoracic kyphosis preservation was observed. Final fusion should be considered for larger residual curves or coronal imbalance, while observation may suffice in well-corrected cases. Full article

(This article belongs to the Special Issue Scoliosis: Advances in Diagnosis and Management)

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13 pages, 2044 KB

Open AccessHypothesis

Correlation Between Severity of Obstructive Sleep Apnea and Dental Arch Form in Adults

by Derek Mahony, Stewart Harding, Chitta Ranjan Chowdhury, Abdolreza Jamilian, Asal Fetrati, Niroj Bhattarai, Peter Borbély and Krisztina Kárpáti

J. Clin. Med. 2025, 14(20), 7183; https://doi.org/10.3390/jcm14207183 (registering DOI) - 11 Oct 2025

Abstract

Objectives: This study examines the relationship between maxillary morphology and the severity of obstructive sleep apnea (OSA) in adults, with a focus on intermolar distance (IMD) and palatal height (PH) as predictive factors. Methods: A retrospective observational study was conducted at private orthodontic [...] Read more.

Objectives: This study examines the relationship between maxillary morphology and the severity of obstructive sleep apnea (OSA) in adults, with a focus on intermolar distance (IMD) and palatal height (PH) as predictive factors. Methods: A retrospective observational study was conducted at private orthodontic practices in Sydney, Australia. A total of 100 adults (50 OSA patients and 50 controls) were included. OSA diagnosis and severity were confirmed via hospital-based polysomnography. Digital maxillary models were analyzed using the Medit Link software (version 3.2.0; Medit Corp., Seoul, Republic of Korea), and IMD and PH were measured. Statistical analyses included one-way ANOVA and linear regression modeling, with adjustments for age and sex. Results: The OSA group exhibited significantly narrower IMD (28.96–35.01 mm) and higher PH (21.68–29.56 mm) compared to the control group (IMD: 36.35–41.50 mm; PH: 18.57–23.51 mm). A negative correlation was observed between IMD and PH across all groups. Linear regression analysis demonstrated a strong association between these craniofacial parameters and OSA severity (R² = 0.76, p < 0.001). IMD was negatively correlated with the Apnea-Hypopnea Index (AHI) (p = 0.003), while PH was positively correlated (p < 0.001). The inclusion of demographic variables did not significantly enhance the predictive model. Conclusions: Maxillary morphology associates with OSA severity, with narrower IMD and greater PH linked to higher AHI. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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14 pages, 2491 KB

Open AccessArticle

Impact of Computed Tomography-Defined Osteopenia on Outcomes of Transcatheter Aortic Valve Implantation: A Single-Center Retrospective Study

by Hiroshi Kurazumi, Ryo Suzuki, Takato Nakashima, Ryosuke Nawata, Toshiki Yokoyama, Kazumasa Matsunaga, Yosuke Miyazaki, Atsuo Yamashita, Takayuki Okamura, Akihito Mikamo, Motoaki Sano and Kimikazu Hamano

J. Clin. Med. 2025, 14(20), 7182; https://doi.org/10.3390/jcm14207182 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: Transcatheter aortic valve implantation (TAVI) is a standard treatment for severe aortic stenosis, especially in older adults and high-risk patients. However, many TAVI candidates have osteopenia or osteoporosis, indicated by low bone mineral density (BMD), which is linked to frailty and [...] Read more.

Background/Objectives: Transcatheter aortic valve implantation (TAVI) is a standard treatment for severe aortic stenosis, especially in older adults and high-risk patients. However, many TAVI candidates have osteopenia or osteoporosis, indicated by low bone mineral density (BMD), which is linked to frailty and adverse outcomes. Although prior research suggests an association with poor clinical outcomes, data remain limited. We investigated the impact of osteopenia on TAVI outcomes, hypothesizing that a lower BMD is associated with poor perioperative outcomes and decreased long-term survival. Methods: In this single-center retrospective study, we analyzed data from 411 patients who underwent TAVI at Yamaguchi University Hospital from 2014 to 2024. Clinical and survival data were collected, and Cox regression analysis was used to identify independent predictors of mortality. Preoperative BMD was measured using computed tomography, defining osteopenia as <135 Hounsfield units at L1. Patients were categorized as having mild, moderate, or severe osteopenia. Results: Early clinical outcomes and procedural success were similar; however, patients with osteopenia had longer intensive care unit stays (p = 0.04) and higher late cardiac mortality (p < 0.001). Six-year survival was 36.2% and 88.1% in patients with and without osteopenia, respectively (p < 0.0001). Cox regression analysis revealed osteopenia as a mortality risk factor (hazard ratio: 6.75, 95% confidence interval: 2.96–15.38, p < 0.0001). Severe osteopenia was associated with the poorest outcomes. Conclusions: Osteopenia is an independent predictor of poor long-term survival after TAVI. These findings underscore the importance of comprehensive risk assessment, suggesting that targeted interventions may improve outcomes. Full article

(This article belongs to the Section Cardiology)

12 pages, 965 KB

Open AccessArticle

Short-Term Outcomes of Post-Mastectomy Immediate Pre-Pectoral Reconstruction with Implant and Acellular Dermal Matrix

by Beatriz Costeira, Beatriz Gonçalves, António Soares, Rodrigo Oom, Cristina Sousa Costa, João Vargas Moniz, Nuno Abecasis and Catarina Rodrigues dos Santos

J. Clin. Med. 2025, 14(20), 7181; https://doi.org/10.3390/jcm14207181 (registering DOI) - 11 Oct 2025

Abstract

Introduction: Pre-pectoral breast reconstruction using implant and acellular dermal matrix (ADM) has become one of the main techniques for immediate reconstruction after mastectomy, with variable approaches and complication rates reported in literature. This study aims to evaluate the early outcomes of this technique, [...] Read more.

Introduction: Pre-pectoral breast reconstruction using implant and acellular dermal matrix (ADM) has become one of the main techniques for immediate reconstruction after mastectomy, with variable approaches and complication rates reported in literature. This study aims to evaluate the early outcomes of this technique, at a single tertiary oncology center. Methods: We performed a retrospective analysis of a prospectively maintained database including women who underwent immediate pre-pectoral reconstruction with implant and ADM following mastectomy between January 2021 and August 2023. The primary outcome was reconstructive failure within 3 months, defined as the need for removal of the implant placed during the index surgery. Secondary outcomes included complications at 3 months and predictive factors for complications. Results: A total of 247 reconstructions were performed in 200 patients, 83.4% following oncological mastectomy and 16.6% after risk-reducing surgery. The median age was 49 (43–56) years; 15.5% of patients were obese and 26.5% were active smokers. Skin-sparing mastectomy was performed in 16.6% and nipple-sparing in 83.4%, with a Wise-pattern incision in 73.3%. Reconstructive failure occurred in 7.7%, with one case (0.4%) of total reconstruction loss. The overall complication rate was 14.6%—skin flap ischemia occurred in 12.6%, primary implant infection in 2.0% and bleeding in 0.8%. The reoperation rate was 8.4%. No predictive factors for complications were identified. Conclusions: In this series, including a high proportion of high-risk patients, immediate pre-pectoral reconstruction with implant and ADM appears safe, with a low rate of early complications. No predictive factors for complications were found, supporting widening its indications. Full article

(This article belongs to the Section Plastic, Reconstructive and Aesthetic Surgery/Aesthetic Medicine)

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40 pages, 829 KB

Open AccessSystematic Review

Evaluating Behavioural Interventions for Oropharyngeal Dysphagia in Adults: A Systematic Review and Meta-Analysis of Swallowing Manoeuvres, Exercises, and Postural Techniques

by Silvia Adzimová, Renée Speyer, Reinie Cordier, Catriona Windsor, Žofia Korim and Miroslav Tedla

J. Clin. Med. 2025, 14(20), 7180; https://doi.org/10.3390/jcm14207180 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: To assess the effectiveness of the most commonly used swallowing manoeuvres, exercises, and postural strategies as standalone interventions in the behavioural management of oropharyngeal dysphagia in adults. Methods: Systematic searches of two electronic databases, Embase and PubMed, were conducted in [...] Read more.

Background/Objectives: To assess the effectiveness of the most commonly used swallowing manoeuvres, exercises, and postural strategies as standalone interventions in the behavioural management of oropharyngeal dysphagia in adults. Methods: Systematic searches of two electronic databases, Embase and PubMed, were conducted in accordance with PRISMA guidelines to identify studies with comparison groups, including (pseudo) randomised controlled trials, comparative studies with concurrent controls, and within-subject or crossover study designs. The methodological quality of the included studies was assessed using the standard quality assessment tool (QualSyst). Results: Seventeen studies met the eligibility criteria, evaluating the effects of chin tuck, effortful swallow, the Mendelsohn manoeuvre, the modified jaw opening exercise, the volitional laryngeal vestibule closure manoeuvre, and the Shaker exercise. Most studies reported positive treatment outcomes, supporting the benefits of both compensatory and rehabilitative interventions across diverse populations, mainly derived from mixed groups and individuals post stroke. However, due to the limited number and significant heterogeneity of studies, a meta-analysis was only performed for the chin tuck, which showed a moderate positive effect. Overall, the evidence is preliminary and should be interpreted with caution. Conclusions: While current findings support the benefits of standalone behavioural interventions in oropharyngeal dysphagia, future research should focus on high-quality study designs with larger populations. Such studies need to consider variability in patient characteristics, intervention protocols, and outcome measures, with the use of advanced statistical methods enabling more definitive conclusions about the effectiveness of these interventions. Full article

(This article belongs to the Section Otolaryngology)

11 pages, 1244 KB

Open AccessArticle

Ultrasound Assessment of Breech Engagement: Breech Progression Angle and Prediction of External Cephalic Version Success

by Javier Sánchez-Romero, Rosa María Gallego-Pozuelo, Cristina Ortuño-Hernández, Ana Martínez-Zarco, Rocío Barroso-Linares, Fernando Araico-Rodríguez, José Eliseo Blanco-Carnero, Aníbal Nieto-Díaz and Catalina de Paco-Matallana

J. Clin. Med. 2025, 14(20), 7179; https://doi.org/10.3390/jcm14207179 (registering DOI) - 11 Oct 2025

Abstract

Objectives: To evaluate the role of breech progression angle (BPA), a novel transperineal ultrasound parameter, as a predictor of external cephalic version (ECV) success, and to compare BPA between breech and transverse lie presentations. Methods: This prospective exploratory study was nested [...] Read more.

Objectives: To evaluate the role of breech progression angle (BPA), a novel transperineal ultrasound parameter, as a predictor of external cephalic version (ECV) success, and to compare BPA between breech and transverse lie presentations. Methods: This prospective exploratory study was nested within a randomized clinical trial (NCT06449430) at Virgen de la Arrixaca University Hospital, Murcia, Spain. Eligible participants were pregnant women ≥18 years with a singleton fetus in non-cephalic presentation at term, without contraindications to vaginal birth. BPA was measured transperineally following standardized methodology prior to ECV, performed under either spinal analgesia or propofol sedation. Logistic regression models adjusted for maternal and obstetric variables assessed the association between BPA and ECV success. Receiver operating characteristic (ROC) curves were generated to evaluate predictive accuracy. Results: A total of 117 women were included: 100 with breech and 17 with transverse lie presentations. Median BPA was significantly higher in breech compared with transverse lie (87.2° vs. 70.2°, p < 0.001). In the overall cohort, BPA was not significantly associated with ECV success (OR 0.97, 95% CI 0.94–1.00; p = 0.068). However, in breech presentations, BPA was independently associated with ECV success (adjusted OR 0.95, 95% CI 0.91–0.99; p = 0.015). The area under the ROC curve for BPA predicting ECV success in breech cases was 0.64 (95% CI 0.53–0.73). Predictive accuracy was poor for transverse lie (AUC 0.27, 95% CI 0.08–0.56). Conclusions: BPA measured by transperineal ultrasound does not provide clinically useful information for predicting the success of external cephalic version, either in breech or transverse lie. Full article

(This article belongs to the Special Issue New Perspectives in Maternal–Fetal Medicine)

11 pages, 481 KB

Open AccessSystematic Review

Ultrasound-Guided Localization of the Refill Port for Intrathecal Infusion Pump Recharge: A Systematic Review

by Beatriz Lechuga Carrasco, Nicolás Cordero Tous, Andrés Reinoso-Cobo, Jonathan Cortés-Martín, Juan Carlos Sánchez-García, Raquel Rodríguez-Blanque and Rafael Gálvez Mateos

J. Clin. Med. 2025, 14(20), 7178; https://doi.org/10.3390/jcm14207178 (registering DOI) - 11 Oct 2025

Abstract

Background: Managing pain with intrathecal infusion pumps has significantly improved the treatment of individuals whose pain is uncontrollable by other methods. Using ultrasound to locate the refill port of these infusion pumps may offer an improvement over traditional methods. Objective: The objective of [...] Read more.

Background: Managing pain with intrathecal infusion pumps has significantly improved the treatment of individuals whose pain is uncontrollable by other methods. Using ultrasound to locate the refill port of these infusion pumps may offer an improvement over traditional methods. Objective: The objective of this systematic review is to update existing knowledge on the use of ultrasound for locating the refill port in intrathecal infusion pumps. Methods: The PRISMA review protocol was followed, and the review was registered in PROSPERO under registration number CRD 42024595671. Results: The main findings indicate that this technique is primarily used only in complex cases where access is difficult. Pain assessment, patient satisfaction, and recharge time compared to the traditional method are crucial factors for selecting the type of process to implement. Conclusions: No conclusive data are presented regarding the technique’s effect on pain reduction, patient satisfaction, reduction in time spent refilling the pump, or the prior experience level of the professional performing it, but notable improvements in these aspects are observed in certain situations. Full article

(This article belongs to the Special Issue Clinical Advances in Pain Management)

12 pages, 424 KB

Open AccessArticle

Peer Relationships and Psychosocial Difficulties in Adolescents: Evidence from a Clinical Pediatric Sample

by Leonardo Tadonio, Antonella Giudice, Claudia Infantino, Simone Pilloni, Matteo Verdesca, Viviana Patianna, Gilberto Gerra and Susanna Esposito

J. Clin. Med. 2025, 14(20), 7177; https://doi.org/10.3390/jcm14207177 (registering DOI) - 11 Oct 2025

Abstract

Background: Adolescence is a critical developmental stage marked by vulnerability to psychological difficulties. While family relationships, peer bonds, prosocial behaviors, and health-risk factors have been linked to adolescent mental health, few studies have examined their joint effects in clinical pediatric populations. This [...] Read more.

Background: Adolescence is a critical developmental stage marked by vulnerability to psychological difficulties. While family relationships, peer bonds, prosocial behaviors, and health-risk factors have been linked to adolescent mental health, few studies have examined their joint effects in clinical pediatric populations. This study assessed demographic, clinical, relational, and behavioral predictors of psychological difficulties in Italian adolescents. Methods: A cross-sectional sample of 177 adolescents (aged 11–14 years) from a pediatric clinic completed the Strengths and Difficulties Questionnaire (SDQ). The Total Difficulties (SDQ TD) score was the main outcome. Associations were tested with ordinary least squares (OLS) and confirmed using robust MM regression. Bootstrap confidence intervals and Benjamini–Hochberg corrections were applied. Sensitivity analyses excluded the Peer Problems subscale to address part–whole overlap. Results: Higher friendship satisfaction was consistently associated with fewer psychological difficulties, confirming its role as a strong protective factor. Prosocial behavior and male sex were also linked to fewer difficulties in initial analyses, though these associations were less stable after correction. Sensitivity analyses further supported the protective value of friendship satisfaction, even when accounting for overlap with peer problems. Despite relatively low overall levels of psychological difficulties, nearly one-quarter of adolescents met the clinical cut-off for eating disorder risk. Conclusions: Friendship satisfaction was the strongest protective factor, while prosocial behavior and sex showed weaker consistency. Findings suggest that distinct aspects of peer relationships jointly shape adolescents’ psychological outcomes. Interventions promoting social functioning may support mental health in clinical youth populations. Full article

(This article belongs to the Special Issue Targeted Diagnosis and Treatment of Maladaptive Developmental Trajectories and Psychopathological Manifestations in Children and Adolescents)

15 pages, 510 KB

Open AccessReview

Sleep Bruxism and Hypobaric Hypoxia Exposure: Exploring the Physiological Association

by Eduardo Pena, Maria Paz Yanez and Francisca Montini

J. Clin. Med. 2025, 14(20), 7176; https://doi.org/10.3390/jcm14207176 (registering DOI) - 11 Oct 2025

Abstract

Sleep bruxism (SB) is a masticatory muscle activity during sleep which can be categorized as primary, when it remains unclear whether the phenomenon is directly linked to a specific disorder, or if it only coexists, and secondary, when it is proven to be [...] Read more.

Sleep bruxism (SB) is a masticatory muscle activity during sleep which can be categorized as primary, when it remains unclear whether the phenomenon is directly linked to a specific disorder, or if it only coexists, and secondary, when it is proven to be associated with a particular disorder, treatment or lifestyle and bruxism that is part of the signs of a disorder. In this way, SB is associated with various factors, including obstructive sleep apnea and gastroesophageal reflux (GER), where evidence suggests SB has a protective role in airway patency, potentially triggered by microarousals and autonomic instability, especially under hypoxia conditions. Since hypobaric hypoxia exposition—generated by high-altitude exposure—produces a decrease in the partial pressure of oxygen, it triggers alterations in cardiac rhythm and gastric function, which could be associated with physiological alterations mentioned in SB. Therefore, the aim of this review is to determine the effect of hypobaric hypoxia exposure on the physiological and molecular alterations during sleep bruxism. Method: The SANRA-guided narrative review synthesized recent human and animal studies on hypoxia’s physiological and molecular effects in sleep bruxism. In conclusion, SB is associated with GER and autonomic dysregulation, which are present in hypobaric hypoxia conditions, where respiratory disturbances, microarousals, and increased muscle activity are associated with SB. High-altitude exposure triggers oxidative stress, genetics, and sleep alteration, which exacerbate its severity. Moreover, neurophysiological and molecular mechanisms, including TRPV1 and HIF-1α activation, are implicated. Finally, polysomnography remains the gold standard for diagnosis; however, studies at high altitude are needed to confirm this association. Full article

(This article belongs to the Special Issue Bruxism and Temporomandibular Disorders: Current Advances and Future Challenges)

22 pages, 3500 KB

Open AccessReview

Allergic Contact Dermatitis: Immunopathology and Potential Therapeutic Strategies

by Anders Boutrup Funch, Carsten Geisler and Charlotte Menné Bonefeld

J. Clin. Med. 2025, 14(20), 7175; https://doi.org/10.3390/jcm14207175 (registering DOI) - 11 Oct 2025

Abstract

Allergic contact dermatitis (ACD) is a common inflammatory skin disease induced by exposure of the skin to contact allergens. Classically, ACD is defined as a delayed-type (type IV) hypersensitivity reaction mediated by allergen-specific T cells, with symptoms peaking 48–72 h after exposure to [...] Read more.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease induced by exposure of the skin to contact allergens. Classically, ACD is defined as a delayed-type (type IV) hypersensitivity reaction mediated by allergen-specific T cells, with symptoms peaking 48–72 h after exposure to the contact allergen. This delayed response to the contact allergen is seen during patch testing, where allergen-naïve, unaffected skin of allergic individuals is exposed to the contact allergen. However, in daily life and in certain occupational settings, allergic individuals often experience rapid flare-ups/exacerbations with intensely itching erythema, oedema, and often vesicles within hours after re-exposure to the specific contact allergen. These rapid flare-ups only develop at skin sites previously exposed to the contact allergen. Thus, it is important to distinguish between the rapid-onset reaction typically experienced by the allergic individual and the delayed-type reaction typically seen after patch testing. This review summarizes current insights into the immunopathology of rapid- versus delayed-type ACD reactions and outlines potential therapeutic opportunities, as well as their current limitations, against rapid-onset ACD, including modulation of cytokine signaling, T cell survival, checkpoint pathways, and redox balance. Full article

(This article belongs to the Special Issue Novel Insights into the Prevention and Treatment of Contact Dermatitis)

27 pages, 761 KB

Open AccessReview

Diagnostic Utility of Red Flags for Detecting Spinal Malignancies in Patients with Low Back Pain: A Scoping Review

by Gianluca Notarangelo, Michele Margelli, Giuseppe Giovannico, Francesco Bruno, Claudia Milella, Daniel Feller, James Dunning, Lorenzo Storari, Firas Mourad and Filippo Maselli

J. Clin. Med. 2025, 14(20), 7174; https://doi.org/10.3390/jcm14207174 (registering DOI) - 11 Oct 2025

Abstract

Introduction: While low back pain (LBP) is most often associated with musculoskeletal issues, in a minority of cases, it can be caused by serious underlying conditions such as cancer. Recognizing malignancy early remains a major clinical challenge, as the warning signs, known [...] Read more.

Introduction: While low back pain (LBP) is most often associated with musculoskeletal issues, in a minority of cases, it can be caused by serious underlying conditions such as cancer. Recognizing malignancy early remains a major clinical challenge, as the warning signs, known as red flags (RFs), are often vague and inconsistent. Methods: A comprehensive search of six databases (PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, and SciELO) and grey literature was conducted for studies published from January 1999 to March 2025. Eligible sources included studies describing adult patients with cancer presenting with LBP. Study selection and data extraction were independently performed by two reviewers. Results: We included 70 studies, most of which were case-based, along with reviews and observational research. In these studies, cancer prevalence among patients with LBP ranged from 0.1% to 1.6%, with metastatic disease being the most common finding. A prior history of cancer emerged as the most reliable red flag (specificity up to 0.99), while other signs and symptoms were less consistent. Notably, combining multiple RFs, such as a history of cancer and unexplained weight loss, significantly improved the diagnostic accuracy (LR+ = 10.25 in one study). Conclusions: While current evidence is limited and largely based on case-based studies, some RFs, particularly a history of cancer, show greater diagnostic value. In patients with LBP associated with underlying malignancy, RFs seem to be more useful for ruling in rather than ruling out (i.e., screening) serious pathologies. Most RFs have poor standalone accuracy; however, considering combinations of RFs within the broader clinical context may improve early detection of spinal malignancy in patients with LBP. Full article

(This article belongs to the Special Issue Musculoskeletal Diagnosis and Treatment: Connecting Gaps to Enhance Patient Care)

18 pages, 1542 KB

Open AccessArticle

DiabCompSepsAI: Integrated AI Model for Early Detection and Prediction of Postoperative Complications in Diabetic Patients—Using a Random Forest Classifier

by Sri Harsha Boppana, Sachin Sravan Kumar Komati, Raja Hamsa Chitturi, Ritwik Raj and C. David Mintz

J. Clin. Med. 2025, 14(20), 7173; https://doi.org/10.3390/jcm14207173 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: Postoperative complications such as wound infections and sepsis are common in diabetic patients, often resulting in longer hospital stays and higher morbidity. This study hypothesizes that a Random Forest Classifier can accurately predict these complications, enabling early clinical interventions. The model utilizes [...] Read more.

Background/Objectives: Postoperative complications such as wound infections and sepsis are common in diabetic patients, often resulting in longer hospital stays and higher morbidity. This study hypothesizes that a Random Forest Classifier can accurately predict these complications, enabling early clinical interventions. The model utilizes ensemble learning to integrate diverse patient data and improve predictive accuracy beyond traditional risk assessments. Methods: A comprehensive retrospective analysis was performed using data extracted from the National Surgical Quality Improvement Program (NSQIP) database. The dataset encompassed a wide array of variables, including demographic factors, clinical markers, and detailed surgical data (specialty, type of anesthesia, duration of surgery). Each variable was meticulously encoded into numerical formats, with categorical variables transformed through one-hot encoding, and continuous variables were normalized. The dataset was partitioned into training (80%) and testing (20%) subsets, ensuring a balanced representation of the target outcomes. The Random Forest Classifier was selected due to its robustness in handling high-dimensional data and its ability to model complex interactions between variables. Results: The Random Forest model showed accuracy rates of 94.38% for wound infection and 94.94% for sepsis. Precision and recall metrics also exceeded 94%, highlighting the model’s accuracy in identifying true positives and reducing false positives. ROC curve analysis yielded AUC values of 0.92 for wound infection and 0.95 for sepsis, indicating strong discriminative capability. Feature importance analysis further identified key predictors, including surgical duration, specific laboratory markers, and patient comorbidities. Conclusions: This study demonstrates the Random Forest Classifier’s strong predictive ability for postoperative wound infections and sepsis in diabetic patients. The model’s high-performance metrics indicate its potential for real-time risk stratification in clinical workflows. Future research should validate these findings in diverse populations and surgical settings. Incorporating this predictive model into clinical practice has the potential to significantly improve patient outcomes and reduce healthcare costs. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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18 pages, 5627 KB

Open AccessFeature PaperArticle

Precision Assessment of Facial Asymmetry Using 3D Imaging and Artificial Intelligence

by Mohamed Adel, Katie Jo Hunt, Daniel Lau, James K. Hartsfield, Hugo Reyes-Centeno, Cynthia S. Beeman, Tarek Elshebiny and Lina Sharab

J. Clin. Med. 2025, 14(20), 7172; https://doi.org/10.3390/jcm14207172 (registering DOI) - 11 Oct 2025

Abstract

Objectives: There is a growing interest among practitioners in employing artificial intelligence (AI) to enhance the precision and efficiency of diagnostic methods. The objective of this study is to assess the precision of an AI-based method for facial asymmetry assessment using 3D [...] Read more.

Objectives: There is a growing interest among practitioners in employing artificial intelligence (AI) to enhance the precision and efficiency of diagnostic methods. The objective of this study is to assess the precision of an AI-based method for facial asymmetry assessment using 3D facial images. Methods: The study included 130 patients (84 female, 46 male), analyzing 3D facial images from the Vectra^® M3 imaging system using both manual and AI-based methods. Seven bilateral facial landmarks were identified for manual analysis, calculating the asymmetry index for facial symmetry assessment. An AI-based program was developed to automate the identification of the same landmarks and calculate the asymmetry index. The reliability of the manual measurements was assessed using intraclass correlation coefficients (ICC) with 95% confidence intervals (CI). Precision of automated landmark identification was compared to the manual method. Results: The ICCs for the manual measurements demonstrated moderate to excellent reliability, both within raters (ICC = 0.62–0.99) and between raters (ICC = 0.72–0.96) each calculated with 95% CI. Agreement was observed between the manual and automated methods in calculating the asymmetry index for five landmarks. There was a statistically significant difference between the two methods in determining the asymmetry index for alare (median: 2.05 mm manual vs. 1.54 mm automated, p = 0.0056) and cheilion (median: 2.77 mm manual vs. 2.30 mm automated, p = 0.0081). Conclusions: The AI-based method provides efficient and comparable precision of facial asymmetry analysis using 3D images. The disagreement observed between the two methods can be addressed through further improvement and training of the automated software. This innovative approach opens doors to significant advancements in both research and clinical orthodontics. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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18 pages, 929 KB

Open AccessArticle

Real-World and Clinical Implications of Patient Education, Lifestyle and Treatment Adherence in Romanian Diabetes Care: An Observational Study

by Ozana-Andreea Măriuț, Ana Flavia Burlec, Irina Macovei, Cornelia Mircea, Mădălina Elena Datcu, Monica Hăncianu and Andreia Corciovă

J. Clin. Med. 2025, 14(20), 7171; https://doi.org/10.3390/jcm14207171 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: Diabetes mellitus is a major global health concern requiring both preventive strategies and patient-centered clinical management. This study evaluated knowledge, lifestyle behaviors, treatment adherence and the use of digital tools among Romanian patients with diabetes in a real-world setting. Methods: A cross-sectional [...] Read more.

Background/Objectives: Diabetes mellitus is a major global health concern requiring both preventive strategies and patient-centered clinical management. This study evaluated knowledge, lifestyle behaviors, treatment adherence and the use of digital tools among Romanian patients with diabetes in a real-world setting. Methods: A cross-sectional observational study was conducted on 100 patients recruited from community pharmacies in Iași, Romania. Data were collected using a structured 27-item questionnaire addressing demographics, disease management, adherence, lifestyle factors, and complications. Results: Most participants had type 2 diabetes. Engagement in healthy behaviors was suboptimal, with low levels of daily physical activity and limited routine glucose monitoring. Complications and treatment-related side effects were frequent, reflecting a high disease burden. Treatment adherence was significantly higher among younger patients, those with type 1 diabetes and individuals who had set long-term health goals. The use of digital technologies was low overall but more common in younger participants. Conclusions: This study identifies critical gaps in lifestyle practices, adherence and technology uptake among Romanian patients with diabetes. These findings carry important clinical implications, as poor adherence and limited self-management are closely linked to complications and higher healthcare spending. The findings suggest that patient education, integrating validated digital tools and enhancing the role of community healthcare providers could support better adherence and reduce long-term complications. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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15 pages, 2338 KB

Open AccessArticle

Repeatability and Reproducibility of a Saccadic Eye Movement Time Test

by Antonio Ríder-Vázquez, Estanislao Gutiérrez-Sánchez, Daniel Velasco-Olea, Clara Martinez-Perez and María Carmen Sánchez-González

J. Clin. Med. 2025, 14(20), 7170; https://doi.org/10.3390/jcm14207170 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: Reliable and objective assessment of saccadic duration is crucial in sports vision, yet standardized clinical tools remain scarce; therefore, this study evaluated the intraobserver and interobserver repeatability of saccadic time measurements using COI-SV^® software, and analyzed the influence of age [...] Read more.

Background/Objectives: Reliable and objective assessment of saccadic duration is crucial in sports vision, yet standardized clinical tools remain scarce; therefore, this study evaluated the intraobserver and interobserver repeatability of saccadic time measurements using COI-SV^® software, and analyzed the influence of age and sex. Methods: Saccadic duration was assessed in 78 participants using a 20/40 Snellen letter stimulus appearing in four directions (up, down, left, right) at two distances. The shortest response time per direction was recorded. General mean values (total, vertical, horizontal, short, long, and ratios) were calculated. Repeatability was evaluated through a protocol of four test repetitions (two intrasession and two intersession with different examiners). ANCOVA and Pearson correlation assessed sex and age effects. Repeatability indices and Bland–Altman plots were used to determine agreement. Results: Regarding sex, there were no significant differences between men and women. Saccadic duration showed a direct relationship with age (p < 0.05), indicating that older participants had worse saccadic time values (longer times). Overall, intraexaminer repeatability was poor, whereas interexaminer reproducibility was between fair and good. Bland–Altman analysis showed limits of agreement ranging from −159.0 to 220.3 milliseconds (ms) for specific time values and from −87.0 to 122.52 ms for general values, which may be useful in clinical practice. Conclusions: The study shows that the COI-SV^® software provides moderate to good interexaminer reliability and poor to acceptable intraexaminer repeatability of saccadic duration measurements, indicating that further refinement and validation are needed before considering clinical implementation. Full article

(This article belongs to the Section Ophthalmology)

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17 pages, 6053 KB

Open AccessArticle

Tandem Detethering: A Novel One-Stage Approach Combining Cervicothoracic Cord Release Followed by Filum Terminale Sectioning

by Natalie Amaral-Nieves, Emilija Sagaityte, Belinda Shao, Shailen Sampath, Rahul Sastry, Prakash Sampath, Petra M. Klinge and Deus Cielo

J. Clin. Med. 2025, 14(20), 7169; https://doi.org/10.3390/jcm14207169 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: We report a prospective series of five patients with symptomatic cervicothoracic spinal cord tethering from prior surgical interventions for acquired and congenital spinal pathologies. Each patient demonstrated incidental radiographic evidence of a low-lying conus or a fatty/thickened filum terminale (FT), suggesting [...] Read more.

Background/Objectives: We report a prospective series of five patients with symptomatic cervicothoracic spinal cord tethering from prior surgical interventions for acquired and congenital spinal pathologies. Each patient demonstrated incidental radiographic evidence of a low-lying conus or a fatty/thickened filum terminale (FT), suggesting concomitant symptomatic conus tethering as a potential contributor. Therefore, all underwent single-stage “tandem detethering”, consisting of microsurgical release of the cervicothoracic pathology followed by FT resection. Methods: Patients’ charts were reviewed for preoperative presentation, imaging, intraoperative findings, surgical details, FT pathology, and six-month outcomes. Results: Preoperative tethering occurred at sites of prior interventions: (i) thoracic arachnoid cyst decompression after Chiari surgery, (ii) cervical lipomyelomeningocele repair, (iii) thoracic ependymoma resection, (iv) syringosubarachnoid shunt placement, and (v) laminectomies for recurrent syrinx. Lumbar MRI demonstrated a low-lying conus in two patients and a fatty/thickened FT in four patients. Intraoperatively, all patients exhibited an abnormal FT (tight, fat-infiltrated, thickened, or dysplastic). No intraoperative complications or neuromonitoring abnormalities were observed. At six months, all patients demonstrated improvement in motor, sensory, pain, and urinary/bowel symptoms. Complications included two pseudomeningoceles requiring repair and one case of recurrent cauda tethering following FT resection. Conclusions: In patients with symptomatic cervicothoracic tethering, a concomitant low-lying conus or pathological FT may contribute to symptomatology by perpetuating biomechanical stress and, if not surgically addressed, may limit neurological recovery. This concept provides a rationale for considering tandem detethering under such circumstances. Full article

(This article belongs to the Special Issue Advances and Trends in Pediatric Surgery)

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12 pages, 2610 KB

Open AccessArticle

Combined Use of Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in the Differential Diagnosis of Sellar Tumors: A Single-Centre Experience

by Adrian Korbecki, Marek Łukasiewicz, Arkadiusz Kacała, Michał Sobański, Agata Zdanowicz-Ratajczyk, Karolina Szałata, Mateusz Dorochowicz, Justyna Korbecka, Grzegorz Trybek, Anna Zimny and Joanna Bladowska

J. Clin. Med. 2025, 14(20), 7168; https://doi.org/10.3390/jcm14207168 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: To evaluate whether incorporating both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in pituitary MRI examinations improves differential diagnosis by providing additional diagnostic value. Methods: A retrospective analysis was performed on 88 patients with histologically confirmed sellar or parasellar tumors who underwent [...] Read more.

Background/Objectives: To evaluate whether incorporating both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in pituitary MRI examinations improves differential diagnosis by providing additional diagnostic value. Methods: A retrospective analysis was performed on 88 patients with histologically confirmed sellar or parasellar tumors who underwent 1.5T MRI with DWI and dynamic susceptibility contrast PWI (DSC-PWI) between October 2007 and April 2023. DWI parameters included minimum apparent diffusion coefficient (ADCmin) and relative ADCmin (rADCmin). PWI parameters included mean and maximum relative cerebral blood volume (rCBV, rCBVmax) and relative peak height (rPH, rPHmax), normalized to white matter. Tumor regions of interest were manually segmented, excluding calcified or hemorrhagic areas. Group comparisons and ROC analyses assessed diagnostic performance of individual and combined parameters. Results: Significant differences in diffusion and perfusion metrics were observed among the five tumor types. The combined analysis of DWI and PWI improved diagnostic accuracy in selected comparisons. The greatest benefit occurred in distinguishing meningiomas from solid non-functional pituitary adenomas (pituitary neuroendocrine tumors-PitNET), where the combination of ADCmin and rPHmax yielded an AUC of 0.818, sensitivity of 88%, and specificity of 76%, exceeding the performance of either parameter alone. In other comparisons, including meningiomas versus invasive PitNETs and adamantinomatous craniopharyngiomas, combined analysis did not substantially improve accuracy when single parameters, particularly rCBVmax (AUC = 0.995), already demonstrated excellent performance. Conclusions: Integration of DWI and PWI into pituitary MRI protocols enhances diagnostic performance in selected tumor groups. The additive value is context-dependent, supporting the tailored application of these sequences in the evaluation of sellar and parasellar tumors. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

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15 pages, 249 KB

Open AccessArticle

Cultural Adaptation and One-Year Follow-Up of the Mom-to-Mom Program Among Minority Arab Bedouin Women: Addressing Postpartum Depression

by Samira Alfayumi-Zeadna, Anna Schmitt, Rosa Abu Agina, Ilana Schmidt and Julie Cwikel

J. Clin. Med. 2025, 14(20), 7167; https://doi.org/10.3390/jcm14207167 (registering DOI) - 11 Oct 2025

Abstract

Background/Objectives: There is a growing need for programs addressing perinatal mental health, particularly for new mothers. Postpartum depression (PPD) may occur during pregnancy or within the first year postpartum, with both short- and long-term negative consequences for both mothers and their infants. [...] Read more.

Background/Objectives: There is a growing need for programs addressing perinatal mental health, particularly for new mothers. Postpartum depression (PPD) may occur during pregnancy or within the first year postpartum, with both short- and long-term negative consequences for both mothers and their infants. This study describes the cultural adaptation, implementation, and one-year follow-up of the Mom-to-Mom (M2M) program for minority Bedouin women in Southern Israel. Methods: We conducted a community-based intervention (M2M) emphasizing cultural adaptation. Outreach efforts were conducted in collaboration with healthcare professionals to encourage referral to the M2M program. A total of 111 mothers completed a self-administered questionnaire that included socio-demographic characteristics and PPD symptoms (PPDs) at two time points: prior to the intervention (Time-1) and one year after participating in the program (Time-2). PPD was measured using the Edinburgh Postnatal Depression Scale (EPDS), using a score cutoff of ≥10. Results: There was a significant decrease in PPDs (EPDS ≥ 13) between Time-1 and Time-2 after one year of follow-up in the M2M program (from 45% to 19.8%). Of the participants, 75% were referred to the program by healthcare professionals. Among those with EPDS ≥ 10, 30% were referred to mental health services. This program provided education, professional support, and led to the establishment of the first M2M center within a Bedouin community, located in the Negev (Naqab). Conclusions: The results emphasize the importance of culturally sensitive approaches to increase awareness, early diagnosis, and professional support in addressing PPD, tailored to a cultural context. Culturally adapted programs can be effective in minority populations and contribute to reducing disparities in maternal mental health care. Full article

(This article belongs to the Special Issue Perinatal Mental Health Management)

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J. Clin. Med., Volume 14, Issue 20 (October-2 2025) – 68 articles

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