Journal of Clinical Medicine

9 pages, 219 KB

Open AccessArticle

Marginal Eyeliner Use and Meibomian Gland Function

by Mariam Alkawally, Rachelle J. Lin, Corina van de Pol, Alan Sasai, Andrew Loc Nguyen and Jerry R. Paugh

J. Clin. Med. 2026, 15(7), 2616; https://doi.org/10.3390/jcm15072616 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: To investigate whether chronic cosmetics use near or directly on the eyelid margin contributes to tear film instability and meibomian gland dysfunction. Methods: Subjects were enrolled in one of three groups: those who rarely wear makeup (No-M), those who wear it frequently [...] Read more.

Background/Objectives: To investigate whether chronic cosmetics use near or directly on the eyelid margin contributes to tear film instability and meibomian gland dysfunction. Methods: Subjects were enrolled in one of three groups: those who rarely wear makeup (No-M), those who wear it frequently but only outside the eyelid margin (Min-M), and those who wear it frequently and directly on the eyelid margin (W-M). Subjects were assessed for dry eye signs and symptoms by a masked examiner. Lipid layer thickness (LLT), tear meniscus height, meibomian gland excreta grade, number of glands secreting, corneal and conjunctival staining and tear breakup time were assessed. Results: 10 No-M, 18 Min-M, and 21 W-M subjects completed the study. Average fluorescein breakup time was 4.6 s in each group (p = 0.839, 1-way ANOVA). There were higher scores (worse findings) in the marginal eyeliner sample for symptoms (modified Schein, OSDI, SPEED), Oxford and total NEI staining and lower lid meibomian secretions. The W-M group demonstrated a statistically significant increase in the meibomian gland excreta grade (a worsening) compared to the No-M group (mean grades 1.2 and 0.55 respectively; Tukey test, adjusted p < 0.05, 95% CI 0.055–1.187). LLT, tear breakup time, eyelid marginal signs, and meibomian gland dropout had no differences among groups. Conclusions: Eyeliner wear both outside and on the eyelid margin demonstrated increased ocular staining and decreased gland excretion quality, compared to non-makeup users. The meibomian gland excreta decrement may lead to worsening meibomian gland function and potentially glandular atrophy over time. Full article

(This article belongs to the Special Issue Meibomian Gland Dysfunction and Dry Eye Diseases)

27 pages, 1103 KB

Open AccessReview

Autoantibody Profiling in Cardiomyopathies: Toward Immune-Guided Risk Stratification and Therapy

by Alberto Marmai, Giovanni Civieri, Laura Iop, Marika Martini, Marta Vadori, Emanuele Cozzi and Francesco Tona

J. Clin. Med. 2026, 15(7), 2615; https://doi.org/10.3390/jcm15072615 (registering DOI) - 29 Mar 2026

Abstract

Cardiomyopathies comprise a heterogeneous group of myocardial disorders characterized by structural and/or functional abnormalities in the absence of secondary causes of myocardial dysfunction. Although genetic determinants play a central role in many forms of the disease, incomplete penetrance and the frequent absence of [...] Read more.

Cardiomyopathies comprise a heterogeneous group of myocardial disorders characterized by structural and/or functional abnormalities in the absence of secondary causes of myocardial dysfunction. Although genetic determinants play a central role in many forms of the disease, incomplete penetrance and the frequent absence of identifiable pathogenic variants suggest that additional mechanisms contribute to disease onset and progression. Growing evidence supports the pathogenic role of autoimmune processes in several cardiomyopathy phenotypes. A spectrum of autoantibodies targeting cardiac self-antigens, including structural proteins, intercalated disc components, intracellular proteins such as calreticulin, and G protein-coupled receptors, has been identified in affected patients. Experimental and clinical data suggest that these autoantibodies may exert functional effects on cardiomyocyte signaling pathways and intercellular coupling, thereby promoting maladaptive remodeling, progressive ventricular dysfunction, and an increased risk of arrhythmias. Accordingly, autoantibody profiling may facilitate the identification of biologically distinct cardiomyopathy subsets with potential diagnostic and prognostic implications. From a therapeutic perspective, pathogenic autoantibodies can be removed from patient serum through plasmapheresis or immunoadsorption strategies, and these approaches have been associated with improvements in hemodynamic parameters and clinical outcomes in selected patients. Full article

(This article belongs to the Special Issue From Clinical Diagnosis to Effective Treatment of Cardiomyopathy)

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10 pages, 463 KB

Open AccessArticle

Evaluation of the Effects of COVID-19 Infection and COVID-19 mRNA Vaccine on Ovarian Reserve

by Zafer Basibuyuk, Ceren Cebi Basibuyuk, Seyma Okumus, Mahmut Oncul and Kutsiye Pelin Ocal

J. Clin. Med. 2026, 15(7), 2614; https://doi.org/10.3390/jcm15072614 (registering DOI) - 29 Mar 2026

Abstract

Objectives: This study aimed to investigate whether COVID-19 infection or COVID-19 mRNA vaccination affects ovarian reserve and reproductive hormone profiles in reproductive-aged women. Methods: This retrospective longitudinal (before–after observational) single-center study included women aged 16–44 years who presented to a tertiary [...] Read more.

Objectives: This study aimed to investigate whether COVID-19 infection or COVID-19 mRNA vaccination affects ovarian reserve and reproductive hormone profiles in reproductive-aged women. Methods: This retrospective longitudinal (before–after observational) single-center study included women aged 16–44 years who presented to a tertiary center between January 2021 and September 2023. Participants either had a confirmed COVID-19 infection by a positive polymerase chain reaction (PCR) test or had received two doses of a COVID-19 mRNA vaccine without prior infection. Women with available ovarian reserve parameters within six months of infection or vaccination were included. Anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), prolactin (PRL), thyroid-stimulating hormone (TSH), total testosterone, and free testosterone levels were evaluated at baseline and reassessed six months later. Menstrual cycle characteristics were recorded. Parametric and non-parametric statistical tests were applied as appropriate. Results: No statistically significant differences were observed in AMH, FSH, LH, E2, PRL, TSH, total testosterone, or free testosterone levels before and after COVID-19 infection or vaccination (all p > 0.05). Comparisons between infection and vaccination groups across age subgroups (<25, 25–35, ≥35 years) revealed no significant differences in ovarian reserve parameters. Menstrual irregularities were reported in 38.0% of women following infection and 18.6% following vaccination. All reported menstrual changes were transient and resolved within six months. Conclusions: COVID-19 infection and mRNA vaccination were not associated with detrimental effects on ovarian reserve or reproductive hormone profiles. Although transient menstrual irregularities were observed, no long-term adverse reproductive impact was detected. Larger prospective studies are warranted to confirm these findings. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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9 pages, 251 KB

Open AccessArticle

Role of Lifestyle and Nutrition in Menstrual Cycle Regularity: Associations with Body Composition and Dietary Habits

by Angela Andreoli, Eugenia Costantini, Qeta Megan, Artida Pashaj, Ersilia Buonomo, Emilio Piccione, Maria De Bonis and Francesco Giuseppe Martire

J. Clin. Med. 2026, 15(7), 2613; https://doi.org/10.3390/jcm15072613 (registering DOI) - 29 Mar 2026

Abstract

Background: Nutritional status and lifestyle factors are increasingly recognized as relevant modulators of women’s reproductive health. However, data remain limited on the relationship between body composition, dietary habits, and menstrual cycle characteristics in apparently healthy young women. This study aimed to assess [...] Read more.

Background: Nutritional status and lifestyle factors are increasingly recognized as relevant modulators of women’s reproductive health. However, data remain limited on the relationship between body composition, dietary habits, and menstrual cycle characteristics in apparently healthy young women. This study aimed to assess nutritional status, body composition, and lifestyle behaviors in young women and to explore their associations with menstrual cycle regularity. Methods: This cross-sectional study included 49 apparently healthy women aged 19–30 years. Anthropometric measurements and body composition were assessed using bioelectrical impedance analysis. Dietary habits were evaluated through a simplified food frequency questionnaire, and adherence to the Mediterranean diet was assessed using the PREDIMED score. Physical activity was estimated using MET values based on the Compendium of Physical Activities. Menstrual cycle characteristics were collected via questionnaire. Group comparisons were performed between women with regular and irregular menstrual cycles. Results: The sample was predominantly normal-weight (mean BMI 22.36 ± 4.26 kg/m²). Anthropometric and bioelectrical impedance parameters did not differ significantly between women with regular and irregular cycles. Women with irregular cycles showed higher resistance and extracellular water and lower phase angle and body cell mass, although differences were not statistically significant. A significant association was found for meat consumption, which was lower in women with irregular cycles (p = 0.007). No associations were observed for other dietary variables, physical activity, or meal frequency. Conclusions: Menstrual regularity in young women was not associated with major anthropometric differences but may be linked to subtle aspects of nutritional status and dietary habits. Lower meat consumption emerged as a potential dietary factor associated with menstrual irregularity. Although associations were modest, these findings support the relevance of nutritional and lifestyle factors in menstrual health. Larger longitudinal studies are needed to clarify these relationships. Full article

(This article belongs to the Section Obstetrics & Gynecology)

10 pages, 1071 KB

Open AccessArticle

Growth Differentiation Factor 15 and Physical Function Impairment in the SardiNIA Study

by Nicia I. Profili, Edoardo Fiorillo, Valeria Orrù, Maria Benelli, Francesco Cucca and Alessandro P. Delitala

J. Clin. Med. 2026, 15(7), 2612; https://doi.org/10.3390/jcm15072612 (registering DOI) - 29 Mar 2026

Abstract

Background: Sarcopenia is the age-related, progressive loss of strength, function, and skeletal muscle mass, which can be assessed with specific tests. The Growth differentiation factor 15 (GDF-15) has been proposed as a key biomarker of aging, and it has been associated with mitochondrial [...] Read more.

Background: Sarcopenia is the age-related, progressive loss of strength, function, and skeletal muscle mass, which can be assessed with specific tests. The Growth differentiation factor 15 (GDF-15) has been proposed as a key biomarker of aging, and it has been associated with mitochondrial dysfunction, cachexia, and physical impairment. Methods: The cohort of this study comes from the SardiNIA study, an ongoing longitudinal survey focused on the identification of genetic and phenotypic variants associated with aging. We assessed hand grip strength, gait speed, and GDF-15 in all samples. Linear multivariate analysis was used to assess the correlation after adjusting for a range of potential confounders. Results: The sample consisted of 4842 subjects (57.5% female) with a median age of 48.6 years. Levels of GDF-15 were comparable between males and females and showed a strong positive association with aging (rho 0.617, p < 0.001). Linear multivariate regression analyses showed that GDF-15 was negatively associated with gait speed and grip strength in both hands (respectively, Beta −0.09, Beta −0.07, and Beta −0.08, p < 0.001 for all). Conclusions: GDF-15 was negatively associated with physical function. GDF-15 may be considered a proxy for reduced physical performance. Future research is needed to understand the pathogenetic role of GDF-15 in the reduction in skeletal muscle in aging people. Full article

(This article belongs to the Section Geriatric Medicine)

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14 pages, 2719 KB

Open AccessReview

Extrinsic Left Atrial Compression: An Echocardiography-Guided Diagnosis Illustrated by Two Clinical Cases and a Structured Review of Published Cases

by Angelina Borizanova, Elena Kinova, Semra Beyti, Todor Angelov, Plamen Getsov and Assen Goudev

J. Clin. Med. 2026, 15(7), 2611; https://doi.org/10.3390/jcm15072611 (registering DOI) - 29 Mar 2026

Abstract

Background: Extrinsic compression of the left atrium (LA) is a rare and underrecognized condition that may result in significant hemodynamic compromise and atrial arrhythmias. The available evidence has been largely limited to isolated case reports and small case series, and clinical awareness [...] Read more.

Background: Extrinsic compression of the left atrium (LA) is a rare and underrecognized condition that may result in significant hemodynamic compromise and atrial arrhythmias. The available evidence has been largely limited to isolated case reports and small case series, and clinical awareness has remained low. Methods: We performed a structured review of published case reports and case series indexed in PubMed between 2016 and 2026 describing extracardiac LA compression. A predefined and reproducible literature search strategy with explicit eligibility criteria was applied. The structured review included 22 publications reporting 23 individual cases of LA compression; in addition, two institutional cases with distinct etiologies were presented separately. Demographic characteristics, presenting symptoms, diagnostic modalities, complications, management strategies, and outcomes were synthesized descriptively. Results: The structured review identified gastroesophageal disorders, particularly hiatal hernia, as the most frequent etiology, followed by vascular, mediastinal, malignant, and musculoskeletal causes. Dyspnea was the most common presenting symptom, while hemodynamic compromise, pulmonary edema, and atrial arrhythmia represented the most frequent complications. Transthoracic echocardiography was the initial diagnostic modality in all reported cases, with computed tomography required for definitive etiological diagnosis. The two institutional cases illustrated both a common cause, hiatal hernia mimicking intracardiac mass, and a rare, aggressive malignant cause with extensive mediastinal involvement. Conclusions: Extrinsic LA compression arises from diverse extracardiac pathologies and may be clinically severe. Transthoracic echocardiography can serve as a pivotal first-line tool for early recognition and differentiation from intracardiac masses, while cross-sectional imaging is essential for etiological clarification. By integrating institutional experience with a structured synthesis of published cases, this review can provide practical insights to support timely diagnosis and management of this potentially life-threatening condition. Full article

(This article belongs to the Section Cardiology)

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13 pages, 3777 KB

Open AccessArticle

Multiple Renal Arteries as a Potential Contributor to Hypertension in Children and Young Adults

by Ugo Giordano, Benedetta Leonardi, Giulia Cafiero, Marcello Chinali, Alessandro Arena, Flavia Cobianchi Bellisari, Eliana Tranchita, Federica Gentili, Maria Chiara Matteucci and Aurelio Secinaro

J. Clin. Med. 2026, 15(7), 2610; https://doi.org/10.3390/jcm15072610 (registering DOI) - 29 Mar 2026

Abstract

Background: Arterial hypertension in childhood is an increasing health concern, often associated with structural and functional cardiovascular or renal alterations. This study aimed to investigate the prevalence and type of non-stenotic renal artery anatomical variants in children with systemic hypertension and to assess [...] Read more.

Background: Arterial hypertension in childhood is an increasing health concern, often associated with structural and functional cardiovascular or renal alterations. This study aimed to investigate the prevalence and type of non-stenotic renal artery anatomical variants in children with systemic hypertension and to assess their possible association with cardiac involvement. Methods: A total of 107 children and adolescents with hypertension (mean age 15.4 ± 2.7 years) were evaluated. Hypertension was defined as blood pressure persistently above the 95th percentile for over one year, confirmed by 24 h ambulatory blood pressure monitoring. Patients with known secondary causes were excluded. All underwent renal vascular imaging by CT or MRI and echocardiographic assessment of left ventricular morphology and function. Results: Renal artery anatomical variants were found in 69 of 107 patients (65%), mainly unilateral or bilateral accessory polar arteries. Other anomalies found (left renal vein narrowing or duplication, severe left renal artery stenosis) were excluded from the statistical analysis. Normal renal vasculature was observed in only 32%. Left ventricular hypertrophy was detected in 41%, highlighting a significant prevalence of target-organ involvement. No statistically significant differences were found in terms of hypertension or hypertrophy between patients with renal artery anatomical variants and those without. However, patients with renal anomalies more frequently required dual antihypertensive therapy (p = 0.025). Conclusions: Renal artery anatomical variants, even in the absence of overt stenosis, may contribute to the pathogenesis of pediatric hypertension and complicate its management. Systematic evaluation of renal vasculature should be considered in the diagnostic workup to improve risk stratification and guide management strategies. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Disease: Clinical Updates and Perspectives: 2nd Edition)

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13 pages, 1796 KB

Open AccessArticle

Real-World Evaluation of an AI-Assisted Diagnostic Support System for Early Gastric Cancer: Diagnostic Performance, Confidence Stratification, and Determinants of False-Positive Diagnosis

by Satoshi Osawa, Takanori Yamada, Wataru Inui, Tomoyuki Niwa, Kenichi Takahashi, Takatoshi Egami, Keisuke Inagaki, Tomohiro Takebe, Tatsuhiro Ito, Satoru Takahashi, Shunya Onoue, Yusuke Asai, Kiichi Sugiura, Tomoharu Matsuura, Natsuki Ishida, Mihoko Yamade, Moriya Iwaizumi, Yasushi Hamaya and Ken Sugimoto

J. Clin. Med. 2026, 15(7), 2609; https://doi.org/10.3390/jcm15072609 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Artificial intelligence (AI)-assisted endoscopy has shown high sensitivity for early gastric cancer detection; however, false-positive diagnoses remain a clinical challenge. This study aimed to evaluate the real-world diagnostic performance of a commercially available AI system and to identify factors associated with [...] Read more.

Background/Objectives: Artificial intelligence (AI)-assisted endoscopy has shown high sensitivity for early gastric cancer detection; however, false-positive diagnoses remain a clinical challenge. This study aimed to evaluate the real-world diagnostic performance of a commercially available AI system and to identify factors associated with false-positive diagnoses, focusing on repeated AI evaluations and confidence stratification. Methods: This single-center retrospective study included 47 patients with 89 localized gastric lesions evaluated between March 2024 and March 2025. Endoscopic examinations were performed under white-light, non-magnified observation with repeated AI assessments of each lesion. The rates of “Consider biopsy” (B) judgments were calculated. Lesions with a B judgment rate of ≥50% were defined as AI-positive and classified into four AI confidence categories. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Factors associated with false-positive diagnoses were analyzed using penalized logistic regression. Results: The AI system demonstrated a sensitivity of 97.6% and an NPV of 95.7%, with a specificity of 45.8%. Pathology-positive rates decreased stepwise across the four AI confidence categories (p < 0.001). Among AI-positive lesions, low regional reproducibility, lesion size ≥ 30 mm, scar, and erosion were independently associated with false-positive diagnoses. In analyses restricted to non-neoplastic lesions, lesion size ≥ 30 mm remained significantly associated with false-positive diagnosis. Conclusions: In real-world clinical practice, a commercially available AI system provides high sensitivity for early gastric cancer detection. Incorporating confidence stratification and regional reproducibility into clinical decision-making may enhance the effective use of AI-assisted endoscopic diagnosis beyond binary interpretations. Full article

(This article belongs to the Special Issue Endoscopic Innovations in Gastrointestinal Diseases: From Diagnosis to Therapy)

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15 pages, 1004 KB

Open AccessArticle

“Echoes from the Dyad”: Relational Context of Postpartum Depression Risk

by Wioletta Tuszyńska-Bogucka and Katarzyna Bosowska

J. Clin. Med. 2026, 15(7), 2608; https://doi.org/10.3390/jcm15072608 (registering DOI) - 29 Mar 2026

Abstract

Background: Postpartum depression (PPD) is a clinically significant condition shaped by emotional regulation processes and close relational contexts. Anxiety is often theorized as a mediating mechanism linking relational vulnerabilities to depressive symptoms, yet empirical findings remain mixed. Objectives: This study examined whether state [...] Read more.

Background: Postpartum depression (PPD) is a clinically significant condition shaped by emotional regulation processes and close relational contexts. Anxiety is often theorized as a mediating mechanism linking relational vulnerabilities to depressive symptoms, yet empirical findings remain mixed. Objectives: This study examined whether state anxiety mediates the association between insecure attachment styles and PPD symptoms or whether its effects depend on relational context, specifically perceived partner support. Methods: In this cross-sectional study, a sample of 249 women assessed within 12 months postpartum completed self-report measures of attachment styles in the intimate relationship, state and trait anxiety, perceived partner support, and PPD symptoms. Hypotheses were tested using multiple regression analyses with heteroskedasticity-consistent standard errors, including mediation and moderation models. Results: Both anxious–ambivalent and avoidant attachment styles were associated with greater PPD symptom severity. State anxiety was neither an independent predictor nor a mediator of the attachment–PPD relationship. Instead, its association with PPD symptoms was conditional: anxiety was positively related to depressive symptoms only when perceived partner support was insufficient. Conclusions: Anxiety may function as a context-sensitive amplifier rather than a universal mechanism of postpartum depressive risk. These findings highlight the potential importance of relational context in understanding emotional vulnerability and depressive symptoms during the postpartum period. Full article

(This article belongs to the Special Issue Postpartum Depression: What Happened to My Wife?)

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15 pages, 1514 KB

Open AccessArticle

Palliative Healthy Donor Stool Transplantation (pFMT) in Patients with End-Stage Alcohol-Related Cirrhosis and Severe Unstable Decompensations—A Cohort Study

by Tharun Tom Oommen, Cyriac Abby Philips, Rizwan Ahamed, Arif Hussain Theruvath, Ajit Tharakan, Sasidharan Rajesh and Philip Augustine

J. Clin. Med. 2026, 15(7), 2607; https://doi.org/10.3390/jcm15072607 (registering DOI) - 29 Mar 2026

Abstract

Background and Aims: Severe alcohol-associated hepatitis (SAH) can trigger unstable decompensations in cirrhosis patients. They experience high rates of emergency department visits and hospitalization. We evaluated real-world clinical outcomes following palliative-faecal microbiota transplantation (pFMT) compared to best supportive care (BSC) in this critically [...] Read more.

Background and Aims: Severe alcohol-associated hepatitis (SAH) can trigger unstable decompensations in cirrhosis patients. They experience high rates of emergency department visits and hospitalization. We evaluated real-world clinical outcomes following palliative-faecal microbiota transplantation (pFMT) compared to best supportive care (BSC) in this critically ill population. Patients and Methods: From July 2021 to April 2024, 28 patients on pFMT were compared with 37 on BSC. Patients on pFMT received nasoduodenal healthy donor stool infusion daily for 5-days. Patients were followed up for portal hypertension-related events, infections, hospitalizations, extrahepatic organ failure and 6- and 12-months survival. 16S rRNA sequencing on stool samples collected at baseline and on follow up were analysed for changes in relative abundance (RA) of bacterial communities. Results: Patients were matched for age, type of decompensation and liver disease severity at enrolment. Twelve-month survival was 64.3% in pFMT versus 51.4% in BSC groups. pFMT dramatically reduced hospital readmissions (mean 0.76 ± 0.76 vs. 2.29 ± 1.27, p < 0.001). Unstable decompensations beyond 3 months occurred in 14.3% of pFMT versus 64.9% of BSC (p < 0.001). Organ failures were lesser with pFMT: acute kidney injury 7.7% versus 93.8% (p < 0.001), hepatic encephalopathy 7.1% versus 68.2% (p < 0.001). Infection burden was significantly lower (53.6% vs. 83.8%, p = 0.008), particularly infections requiring admission (17.4% vs. 66.7%, p < 0.001) with pFMT. Microbiome analysis revealed progressive expansion of Gram-negative genera in BSC, and beneficial Actinobacteria in pFMT-treated patients at 3, 6, and 12 months. Conclusions: Palliative FMT represents a unique disease-modifying intervention in end-stage alcohol-related cirrhosis, preventing organ failure progression, reducing healthcare utilization, and improving survival trajectories. Full article

(This article belongs to the Special Issue Advances in Gastroenterology and Hepatology: Bridging Basic Science, Clinical Insights, and Translational Medicine)

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13 pages, 556 KB

Open AccessReview

Medication Therapy Problems in Hospitalized Patients with Decreased Kidney Function Across the Spectrum of Kidney Disease: A Scoping Review

by Tomona Iso, Danielle Antwan, Melanie Galima, Monarc Manlongat, Safer Marogy, Redi Ndrekaj and Lisa Hong

J. Clin. Med. 2026, 15(7), 2606; https://doi.org/10.3390/jcm15072606 (registering DOI) - 29 Mar 2026

Abstract

Background: This scoping review aimed to identify gaps in the literature regarding medication therapy problems (MTPs) among hospitalized adults with decreased kidney function. Specifically, it aimed to answer the following questions: (1) What types of MTPs have been reported? (2) What is [...] Read more.

Background: This scoping review aimed to identify gaps in the literature regarding medication therapy problems (MTPs) among hospitalized adults with decreased kidney function. Specifically, it aimed to answer the following questions: (1) What types of MTPs have been reported? (2) What is the reported prevalence of MTPs? (3) Do MTPs differ by type of kidney disease? (4) What gaps exist regarding MTPs and pharmacists’ involvement? Methods: Studies involving adult patients with decreased kidney function that investigated MTPs were included. Studies focused exclusively on post-transplant care, chemotherapy, or a single MTP type were excluded. Literature searches were conducted in PubMed, EMBASE, Cochrane Library, Web of Science, and International Pharmaceutical Abstracts. Two independent reviewers screened and extracted data, with a third reviewer resolving discrepancies. All identified MTPs were re-categorized using the Pharmacy Quality Alliance (PQA) framework and the Pharmaceutical Care Network Europe (PCNE) classification. Results: A total of 23 studies met the inclusion criteria, including two conference proceedings, encompassing 7151 patients. The most common MTP framework was the PCNE classification (13 studies, 57%). Reclassification using the PQA yielded 10,596 MTPs, most frequently “Safety—dosage too high” (n = 2464) and “Effectiveness—dosage too low” (n = 2262). Reclassification using the PCNE yielded 11,574 MTPs, most frequently “Drug selection” (n = 6974) and “Dose selection” (n = 2636). All studies involved patients with chronic kidney disease (CKD), and two also included acute kidney injury (AKI). Conclusions: Dosage-related MTPs were most prevalent among hospitalized patients with decreased kidney function. Variability in MTP definitions, limited representation of patients with AKI and AKD, and minimal reporting on pharmacists’ roles reveal important gaps. Addressing these gaps through standardized MTP classification and further research in understudied kidney disease populations may enhance patient safety and support clinical pharmacists’ contributions to optimizing medication safety across the kidney disease continuum. Full article

(This article belongs to the Special Issue Drug-Related Problems: Clinical Pharmacy and Safety of Pharmacotherapy)

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19 pages, 5344 KB

Open AccessArticle

CBCT Volumetric Changes in Combined Nasal Cavity and Paranasal Sinuses Following RAMPA-ROA Therapy: A Retrospective Cohort Study with Reference to Longitudinal Growth Data

by Yasushi Mitani, Yuko Okai-Kojima, Mohammad Moshfeghi, Tonogi Morio, Shouhei Ogisawa and Bumkyoo Choi

J. Clin. Med. 2026, 15(7), 2605; https://doi.org/10.3390/jcm15072605 (registering DOI) - 29 Mar 2026

Abstract

Background: The interrelationship between craniofacial morphology and respiratory function is a central focus of orthodontic and dentofacial orthopedic research. This study aimed to evaluate the volumetric changes in the sinonasal complex (combined nasal cavity and paranasal sinuses) following Right Angle Maxillary Protraction Appliance [...] Read more.

Background: The interrelationship between craniofacial morphology and respiratory function is a central focus of orthodontic and dentofacial orthopedic research. This study aimed to evaluate the volumetric changes in the sinonasal complex (combined nasal cavity and paranasal sinuses) following Right Angle Maxillary Protraction Appliance (RAMPA) therapy using cone-beam computed tomography (CBCT) and to compare these outcomes with established longitudinal growth benchmarks. Methods: A retrospective cohort analysis was conducted on 60 pediatric patients (24 males, 36 females; mean age: 86.60 ± 24.22 months) with radiologically clear paranasal sinuses at baseline (T1). Participants underwent RAMPA therapy for an average of 8.38 months. Volumetric quantification of the entire sinonasal complex—including the nasal cavity and all four paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal)—was performed to ensure methodological alignment with existing normative growth data. Results: Total sinonasal volume increased significantly from 27,741.63 ± 10,675.85 mm³ at T1 to 32,248.00 ± 10,084.07 mm³ at T2 (p < 0.001), representing a mean gain of 4506.37 mm³ (16.24%). Notably, the annualized growth velocity under RAMPA therapy (6453 mm³/year) exceeded the physiological increment of age-matched normative data (~5418 mm³/year) by approximately 1.2 times. Despite a constricted baseline at T1 compared to normative values, the treatment group demonstrated a rapid “catch-up” growth trajectory. Conclusions: RAMPA therapy induces rapid and significant volumetric expansion of the sinonasal complex in pediatric patients, demonstrating a potent “acceleration effect” that surpasses natural physiological maturation. These findings suggest that orthopedic midfacial remodeling can effectively restructure the upper respiratory environment, bridging the gap between pathological constriction and normative developmental benchmarks in patients with maxillary hypoplasia. Full article

(This article belongs to the Special Issue Maxillomandibular Growth, Reconstruction and Rehabilitation: Orthodontic, Prosthodontic and Surgical Interventions from Childhood to Adulthood)

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20 pages, 836 KB

Open AccessReview

Intestinal Microbiota in Diabetes—Does the Pathomechanism and Diversity Depend on the Type of Diabetes and Coexisting Metabolic Disorders?

by Clara Leśniak, Zuzanna Poczta, Maja A. Różycka, Olga M. Włoch, Agnieszka Podeszwa, Aleksandra Siejek, Agnieszka Dobrowolska and Agnieszka Zawada

J. Clin. Med. 2026, 15(7), 2604; https://doi.org/10.3390/jcm15072604 (registering DOI) - 29 Mar 2026

Abstract

Emerging evidence strongly suggests that gut microbiota dysbiosis plays a significant role in the development and progression of both type 1 and type 2 diabetes mellitus. Quantitative and qualitative changes in the intestinal microbiota’s composition are linked to these distinct pathomechanisms. In type [...] Read more.

Emerging evidence strongly suggests that gut microbiota dysbiosis plays a significant role in the development and progression of both type 1 and type 2 diabetes mellitus. Quantitative and qualitative changes in the intestinal microbiota’s composition are linked to these distinct pathomechanisms. In type 1 diabetes mellitus, dysbiosis is thought to initiate or accelerate the autoimmune destruction of pancreatic beta cells. This may occur through increased intestinal permeability, which allows microbial components and endotoxins to enter the systemic circulation. This exposure triggers inflammatory and autoimmune responses in individuals who are genetically predisposed. Conversely, in type 2 diabetes mellitus, gut dysbiosis contributes significantly to the characteristic metabolic derangements. Specific microbial shifts can lead to impaired energy metabolism, contributing to insulin resistance in peripheral tissues. Furthermore, dysbiosis is associated with the altered production of microbial metabolites, such as short-chain fatty acids, and the induction of low-grade chronic inflammation, which contribute to the pathogenesis of type 2 diabetes mellitus. Hyperglycemia, dyslipidemia and other metabolic changes also influence the gut microbiota. Understanding these type-specific microbial roles offers potential for novel diagnostic and therapeutic strategies. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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14 pages, 694 KB

Open AccessReview

Myocardial Infarction as the First Clinical Manifestation of Coronary Artery Disease: A Scoping Review

by Maya D’Angelo, Angeliki Psycharis, Nicolo Piazza, Giuseppe De Luca and Elvin Kedhi

J. Clin. Med. 2026, 15(7), 2603; https://doi.org/10.3390/jcm15072603 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Acute myocardial infarction (AMI) remains a leading cause of death worldwide and sometimes occurs as the inaugural presentation of CAD. Studies have been heterogeneous in reporting what proportion this population represents; therefore, we sought to review the evidence of myocardial infarction [...] Read more.

Background/Objectives: Acute myocardial infarction (AMI) remains a leading cause of death worldwide and sometimes occurs as the inaugural presentation of CAD. Studies have been heterogeneous in reporting what proportion this population represents; therefore, we sought to review the evidence of myocardial infarction as the initial manifestation of CAD. Methods: We conducted a scoping review of 25 studies (1979–2021) assessing the prevalence, risk factors, and outcomes of patients who experience AMI as the first clinical manifestation of CAD. Results: Across studies, most found that half of AMI patients present with no prior angina or CAD diagnosis. These patients tend to be younger and have fewer traditional risk factors. Sex differences were inconsistently reported, though some studies suggest that women may be more likely to present with unheralded AMI. Diabetes and hypertension were interestingly more common in patients with known CAD. Patients with unheralded AMI demonstrate a larger infarct size and may have a higher likelihood of adverse cardiovascular events compared to those with known CAD. Conclusions: Our findings highlight a critical gap in the current risk models of CAD evaluation, which are often symptom-based and focused on detecting ischemia, thus failing to detect a significant proportion that present with AMI as their initial manifestation of CAD. Full article

(This article belongs to the Special Issue Acute Ischemic Heart Disease: Risk Factors, Diagnosis, Management and Prognosis)

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9 pages, 1745 KB

Open AccessArticle

Reliability of Preoperative MRI Findings for Differentiating Spontaneous Spinal Subdural and Epidural Hematomas: A Multi-Institutional Retrospective Study of 27 Surgically Treated Cases

by Shun Okuwaki, Hiroshi Takahashi, Katsuya Nagashima, Tomoyuki Asada, Takane Nakagawa, Takahiro Sunami, Yosuke Ogata, Kotaro Sakashita, Hisanori Gamada, Kousei Miura, Hiroshi Noguchi, Yosuke Takeuchi, Toru Funayama, Masao Koda and Masaki Tatsumura

J. Clin. Med. 2026, 15(7), 2602; https://doi.org/10.3390/jcm15072602 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Spontaneous spinal subdural hematoma (SSSDH) is a rare and severe condition that causes rapid neurological decline. Spontaneous spinal epidural hematoma (SSEH) presents similarly but is more common, and surgical management differs because SSSDH requires an intradural approach. Few studies have assessed the [...] Read more.

Background/Objectives: Spontaneous spinal subdural hematoma (SSSDH) is a rare and severe condition that causes rapid neurological decline. Spontaneous spinal epidural hematoma (SSEH) presents similarly but is more common, and surgical management differs because SSSDH requires an intradural approach. Few studies have assessed the reliability of magnetic resonance imaging (MRI) features used to distinguish SSSDH from SSEH in patients requiring surgery. Methods: We retrospectively reviewed 27 patients who underwent surgical evacuation of spinal hematomas at two institutions (2015–2025). Definitive hematoma location was determined intraoperatively. Four MRI features—shape (crescentic vs. biconvex), location (ventral vs. dorsal), craniocaudal length (<5 vs. ≥5 segments), and spinal region—were independently evaluated by two reviewers. Inter- and intra-rater reliability was assessed using agreement rate and Cohen’s kappa (κ) with 95% confidence intervals (95% CIs). Results: Among 27 cases, three (11.1%) were SSSDH and 24 were SSEH. Hematoma location, length, and spinal region demonstrated perfect inter- and intra-rater agreement (κ = 1.00). For hematoma shape, intra-rater agreement was good (96.2%, κ = 0.84; 95% CI 0.52–1.00), whereas inter-rater agreement was poor to fair (84.6%, κ = 0.26; 95% CI −0.25–0.77). Notably, two of the three SSSDHs demonstrated a biconvex configuration, and 83.3% of SSEHs also exhibited a biconvex morphology. Conclusions: MRI features such as hematoma location, extent, and spinal level were highly reproducible, whereas hematoma shape showed limited reliability. Although ventral hematomas most strongly suggest SSSDH, atypical SSEH presentations occur. When dorsal exposure reveals no epidural hematoma, intradural exploration should be promptly considered. Full article

(This article belongs to the Special Issue Clinical Advances in Spinal Neurosurgery)

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13 pages, 431 KB

Open AccessArticle

Clinical and Subclinical Congestion in Acute Heart Failure: A Multimodal Prognostic Assessment

by Sara Lozano-Jiménez, Paula Vela-Martín, Alba Martín-Centellas, Daniel de Castro, Cristina Mitroi, Francisco José Hernández-Pérez, Marta Cobo-Marcos, Sergio Martínez-Álvarez, Manuel Gómez-Bueno, Javier Segovia-Cubero, Jesús Álvarez-García and Mercedes Rivas-Lasarte

J. Clin. Med. 2026, 15(7), 2601; https://doi.org/10.3390/jcm15072601 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Congestion is a hallmark of heart failure (HF) and a major determinant of outcomes. Non-invasive tools enable detection of subclinical congestion, but their correlation and prognostic relevance remain incompletely defined. The present study aimed to assess the prevalence, evolution, interrelationships, and prognostic [...] Read more.

Background/Objectives: Congestion is a hallmark of heart failure (HF) and a major determinant of outcomes. Non-invasive tools enable detection of subclinical congestion, but their correlation and prognostic relevance remain incompletely defined. The present study aimed to assess the prevalence, evolution, interrelationships, and prognostic impact of clinical and subclinical congestion markers in patients hospitalized for HF. Methods: This single-centre, prospective cohort study included adults admitted with HF who underwent serial evaluations at admission, 72 h, pre-discharge, early outpatient follow-up and at 6 months. Clinical congestion was assessed using a standardized physical examination score. Subclinical congestion was evaluated using lung ultrasound (LUS), Venous Excess Ultrasound Score (VExUS), and Remote Dielectric Sensing (ReDS). Patients were classified according to the presence of clinical and/or subclinical congestion at discharge. The primary endpoint was a composite of all-cause mortality, HF readmission, or unscheduled visits requiring intravenous diuretics within six months. Results: Ninety-four patients (mean age 74 ± 11 years, 68% male) were included. While clinical congestion improved significantly during hospitalization, approximately 30% of patients remained clinically congested at discharge. Among clinically euvolemic patients, only 47% showed no evidence of subclinical congestion. Correlations between congestion markers were weak to moderate, suggesting complementary pathophysiological information. At discharge, pulmonary B-lines were the strongest predictor of the composite endpoint (hazard ratio [HR] 3.50, 95% CI 1.41–8.72), followed by clinical congestion (HR 2.67, 95% CI 1.13–6.30). Patients with clinical and subclinical congestion exhibited lower event-free survival. Conclusions: Subclinical congestion is common despite apparent clinical euvolemia and is associated with worse outcomes. Integrating clinical assessment with non-invasive congestion markers may improve post-discharge risk stratification in HF. Full article

(This article belongs to the Section Cardiology)

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18 pages, 1317 KB

Open AccessArticle

Safety and Efficacy of Ultrasound-Accelerated Endovascular Lysis in Postoperative Patients with Intermediate–High-Risk Pulmonary Embolism: A Retrospective Two-Center Study

by Abdelrahman Elhakim, Martin Knauth, Mohamed Elhakim, Osama Bisht, Jan-Erik Guelker and Hani Al-Terki

J. Clin. Med. 2026, 15(7), 2600; https://doi.org/10.3390/jcm15072600 (registering DOI) - 29 Mar 2026

Abstract

Background: Postoperative patients are at risk of pulmonary embolism. They typically exhibit multiple contributing factors such as comorbidities, immobility, blood loss, increased hematocrit, dehydration, long hospital stays, and a higher bleeding risk. PE management in this vulnerable group is challenging. Although current guidelines [...] Read more.

Background: Postoperative patients are at risk of pulmonary embolism. They typically exhibit multiple contributing factors such as comorbidities, immobility, blood loss, increased hematocrit, dehydration, long hospital stays, and a higher bleeding risk. PE management in this vulnerable group is challenging. Although current guidelines provide differing recommendations, many clinical questions remain unanswered. Decisions regarding periprocedural anticoagulation management must balance the thromboembolic and procedural higher bleeding risks. In addition, a recent major surgery is an absolute contraindication to systemic thrombolysis. Small doses of local lytics or a mechanical percutaneous embolectomy in the era of catheter-based therapy may be a safer option. However, the safety and efficacy of CDT have not been evaluated in this particular PE-vulnerable population. Methods: We performed a retrospective study of 35 postoperative patients with intermediate–high-risk PE treated with the EkoSonic Endovascular System. Operative bleeding risk, different management modalities, and post-PE-therapy presumptive complications were assessed before PE treatment. Results: Procedural success was achieved in 100% of cases. We observed a marked improvement in clinical and PE hemodynamics. One major bleeding, defined as life-threatening, required surgical intervention; four moderate bleedings, defined as bleeding without hemodynamic compromise, required intervention such as drainage. Minor bleeding was managed conservatively. Conclusions: Catheter-directed therapies may be an alternative to systemic reperfusion therapies for selected postoperative intermediate–high-risk PE-vulnerable populations. Full article

(This article belongs to the Section Respiratory Medicine)

15 pages, 961 KB

Open AccessArticle

CEA and CA-19-9 Dynamics Associate with Survival in Regorafenib-Treated Metastatic Colorectal Cancer: A Real-World Analysis

by Merih Yalçıner, Mehmet Berk Örüncü, Mehmet Kayaalp, Efe Cem Erdat, Engin Eren Kavak and Güngör Utkan

J. Clin. Med. 2026, 15(7), 2599; https://doi.org/10.3390/jcm15072599 (registering DOI) - 29 Mar 2026

Abstract

Background: Regorafenib is a standard late-line treatment for refractory metastatic colorectal cancer (mCRC), yet clinical outcomes remain heterogeneous. Identifying accessible biomarkers to predict therapeutic benefit is crucial for balancing efficacy and toxicity. This study evaluated the prognostic value of early dynamic changes in [...] Read more.

Background: Regorafenib is a standard late-line treatment for refractory metastatic colorectal cancer (mCRC), yet clinical outcomes remain heterogeneous. Identifying accessible biomarkers to predict therapeutic benefit is crucial for balancing efficacy and toxicity. This study evaluated the prognostic value of early dynamic changes in carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA-19-9). Methods: We conducted a retrospective real-world analysis of 61 heavily pretreated mCRC patients receiving regorafenib. Tumor markers were assessed at baseline and after the third cycle (approximately 12 weeks). Systematic threshold optimization using Cox proportional hazards regression and Akaike Information Criterion (AIC) was performed to identify optimal percentage change cutpoints for predicting survival. Results: The optimal thresholds for defining unfavorable marker increases were +14.6% for CEA and +23.5% for CA-19-9. Patients with CEA changes below the cutoff demonstrated significantly superior progression-free survival (PFS) (median 6.1 vs. 4.0 months, p = 0.012) and overall survival (OS) (11.05 vs. 6.0 months, p = 0.035). CA-19-9 changes below the cutoff were associated with improved PFS (p = 0.022) but did not reach statistical significance for OS (p = 0.23). In multivariable analysis, neither marker retained independent significance, likely due to collinearity. Conclusions: Early dynamics of routine tumor markers are prognostic in regorafenib-treated mCRC. specifically, a CEA increase of <14.6% significantly predicts improved survival outcomes. These findings support the utility of serial marker monitoring in real-world practice, though prospective validation is warranted. Full article

(This article belongs to the Section Oncology)

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11 pages, 1038 KB

Open AccessArticle

The Potential Role of Microsurgical Training in Robotic Surgery Education: A Prospective Simulation-Based Study

by Alberto Bolletta, Mirco Pozzi, Davide Di Seclì, Alfredo Dente, Luigi Bonat Guarini, Stefano Bacchini, Luigi Losco and Emanuele Cigna

J. Clin. Med. 2026, 15(7), 2598; https://doi.org/10.3390/jcm15072598 (registering DOI) - 29 Mar 2026

Abstract

Background/Objectives: Simulation has become an integral part of contemporary surgical training, allowing safe acquisition of technical skills with objective performance assessment. Microsurgery and robotic surgery share several technical features, including fine bimanual coordination, precise instrument control, and stereoscopic vision. This study aimed [...] Read more.

Background/Objectives: Simulation has become an integral part of contemporary surgical training, allowing safe acquisition of technical skills with objective performance assessment. Microsurgery and robotic surgery share several technical features, including fine bimanual coordination, precise instrument control, and stereoscopic vision. This study aimed to evaluate whether a structured microsurgical course is associated with improved performance on a robotic surgical simulator and to explore its potential role within robotic training pathways. Methods: A prospective study was conducted between October 2022 and November 2025 at a single academic center, including 56 participants divided into three groups. Group A consisted of surgical residents attending a 3-day Basic Microsurgery Course; Group B included residents who did not undergo training during the same period; and Group C comprised experienced microsurgeons. Groups A and B performed two robotic simulation tasks at baseline (T0) and after three days (T1). Group C was assessed at T1 only as a reference benchmark. Performance was evaluated using simulator-derived metrics. Statistical analysis was performed using paired and unpaired t-tests. Results: Group A showed significant improvement across several performance parameters following training, whereas no comparable changes were observed in Group B. At T1, Group A demonstrated better performance than Group B in multiple metrics. Group C achieved the highest scores and was considered a reference group. Conclusions: Structured microsurgical training was associated with improved performance in a robotic simulation setting. These findings suggest that microsurgical skills may be transferable to robotic tasks and may contribute to the early phases of robotic skill acquisition. Further studies are required to assess their impact in clinical practice. Full article

(This article belongs to the Special Issue Plastic and Reconstructive Surgery: Clinical Advances and Future Opportunities)

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