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Search Results (6,057)

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28 pages, 1053 KB  
Systematic Review
Intelligent Orthotics Technology in the Management of Diabetic Foot Ulcers and Knee Osteoarthritis: A Comprehensive Systematic Review
by Wissam Osman Soubra, Dennis John Cordato, Kaneez Fatima Shad and Sara Lal
Appl. Sci. 2026, 16(13), 6301; https://doi.org/10.3390/app16136301 (registering DOI) - 23 Jun 2026
Abstract
Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables [...] Read more.
Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables early detection of abnormal force distribution and gait biomechanics, allowing for the redirection of forces away from affected ulcers or arthritic joints. This is the first systematic review to synthesise clinical evidence for smart orthotics technology with real-time plantar pressure sensor biofeedback across both diabetic foot ulcer prevention and knee osteoarthritis management simultaneously. A search of the PROSPERO register confirmed no existing registration covers this specific combination. Objectives: To examine the clinical evidence for the use of standard and smart orthotics in the prevention and management of diabetic foot ulcers (DFUs) and knee OA, and to evaluate their impact on plantar pressure redistribution, ulcer recurrence, pain, biomechanics, and economic burden. Eligibility criteria: Studies published in English involving human adult participants (≥18 years) with a clinical diagnosis of diabetes mellitus (at risk of DFU or with peripheral neuropathy) or knee OA, where the intervention involved any orthotic device or smart/intelligent insole with clinical outcomes reported, were included. Studies on healthy individuals only, those not reporting participant age, and non-weight-bearing protocols not differentiated from weight-bearing were excluded. Information sources: Five databases were searched: CINAHL (EBSCO Information Services, Ipswich, MA, USA), PubMed Advanced (National Library of Medicine, Bethesda, MD, USA), Wiley Online Library (John Wiley & Sons, Hoboken, NJ, USA), Cochrane Library (Cochrane Collaboration, London, UK), and Google Scholar (Google LLC, Mountain View, CA, USA). Searches were completed in May 2026. Methods: We conducted a comprehensive literature review. This review was structured and reported with reference to the PRISMA 2020 statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis; University of Ottawa, Ottawa, ON, Canada) to guide transparency of reporting. It does not constitute a full Cochrane-style systematic review; risk of bias assessment was applied to key included studies and GRADE (Grading of Recommendations Assessment, Development and Evaluation; McMaster University, Hamilton, ON, Canada) certainty ratings were applied informally and narratively rather than as formal per-outcome evidence profiles. Five databases were searched yielding 92,637 records. After removal of 398 duplicates by Rayyan, 92,239 records remained. A subsequent automated keyword-based relevance filter applied within Rayyan (Rayyan AI, Doha, Qatar), prior to human screening, excluded 84,572 records that did not contain any terms related to orthotics, diabetic foot, or knee osteoarthritis, yielding 7667 records for human title/abstract screening. A narrative synthesis approach was adopted owing to the heterogeneity of study designs and outcome measures across included studies, which precluded meta-analysis. This review was not prospectively registered. A complete list of all 78 included studies, including those not individually discussed in the results and discussion. Results: The available clinical studies report promising findings for orthotics and smart orthotics in pain reduction, ulcer prevention, and potential reduction in economic burden, though conclusions are limited by small sample sizes, heterogeneity, and predominantly open-label designs. Recent research found that orthotics can be used to alter the gait pattern that influences knee OA by reducing excessive force on the affected joint. A randomised controlled trial demonstrated an 80% relative risk reduction in DFU recurrence (RR = 0.20; 95% CI: 0.06–0.79; p = 0.022), with absolute event rates of 6.3% in the intervention group versus 30.8% in controls (ARR = 24.5%); a second trial reported a 71% reduction in ulcer incidence over 18 months; and a third randomised controlled trial demonstrated statistically significant plantar pressure reduction (p < 0.01) in patients with diabetic neuropathy. Conclusions: The available evidence suggests that orthotics may be associated with improved pressure redistribution, reduced ulcer incidence, and benefit in the management of knee OA. Although the number of studies directly comparing smart orthotics with standard orthotics remains limited, the limited comparative studies suggested that smart orthotics showed promising results in reducing ulcer incidence, providing the patient with real-time feedback to offload via their electronic devices. These findings, while preliminary, highlight the potential of smart orthotic technology as an adjunct to standard orthotic care in reducing the overall burden of diabetic foot disease and knee osteoarthritis. Limitations: The primary methodological limitation of this review is the open-label design of all included smart orthotic trials, which precludes participant blinding and introduces performance bias. However, this limitation is structural and inherent to the wearable technology field—analogous to surgical trials—and is substantially mitigated by the use of objective primary outcome measures (plantar pressure and ulcer recurrence) across the three included RCTs, the consistency of effect direction across independent RCTs conducted in different countries, and a narrative sensitivity analysis confirming robustness of findings (Risk of Bias Across Studies Section). Formal per-outcome GRADE evidence profiles were not produced; overall certainty of evidence was assessed narratively with reference to GRADE domains and is judged to be low to moderate for smart orthotics in DFU prevention and low for knee OA management, consistent with the Level 2–3 evidence base and open-label study designs. Future adequately powered, multi-site RCTs with standardised outcome reporting, minimum 24-month follow-up, and integrated health economic modelling are the highest priority to extend these preliminary findings. Registration: This review was not prospectively registered. Full article
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7 pages, 213 KB  
Proceeding Paper
The Correlation Between Soil and Water-Derived Cadmium and Lead Exposure and Peripheral Artery Disease: A Ten-Year Scoping Review
by Kanellos Skourtsidis, Georgios Kiosis, Despoina Ioannou, Maria-Nefeli Georgaki, Konstantinos Stergiou, Theodora Papamitsou and Sofia Karachrysafi
Environ. Earth Sci. Proc. 2026, 44(1), 20; https://doi.org/10.3390/eesp2026044020 (registering DOI) - 23 Jun 2026
Abstract
Peripheral Artery Disease (PAD) is increasingly recognized as a complex environmental pathology driven by “contaminant metals,” rather than solely lifestyle factors. This scoping review (2016–2025) analyses the correlation between anthropogenic soil/water-derived Cadmium (Cd) and Lead (Pb) and progressive vascular hardening. The analysis confirms [...] Read more.
Peripheral Artery Disease (PAD) is increasingly recognized as a complex environmental pathology driven by “contaminant metals,” rather than solely lifestyle factors. This scoping review (2016–2025) analyses the correlation between anthropogenic soil/water-derived Cadmium (Cd) and Lead (Pb) and progressive vascular hardening. The analysis confirms a robust, non-linear dose–response relationship. Chronic Cd exposure functions as a potent independent toxicant (Risk Ratio = 2.58 at 1 µg/L), significantly lowering Ankle–Brachial Index scores by inducing oxidative stress, inhibiting nitric oxide bioavailability, and displacing calcium in endothelial walls. Synergistically, Pb exposure, even at levels <5 µg/dL, compounds toxicity, amplifying arterial stiffness and hypertension. Consequently, “Heavy Metal Hardening” constitutes a critical link between water quality management and public health. Current regulatory thresholds appear insufficient to prevent chronic vascular remodeling, mandating urgent remediation of metal-laden aquifers and agricultural soils to mitigate this silent cardiovascular epidemic. Full article
26 pages, 5204 KB  
Review
Modern Era in Personalized Medicine of Dual Antiplatelet Therapy After Myocardial Revascularization
by Amin Dehghan, Niloufar Javadi, Suhail Q. Allaqaband and M. Fuad Jan
J. Clin. Med. 2026, 15(13), 4870; https://doi.org/10.3390/jcm15134870 (registering DOI) - 23 Jun 2026
Abstract
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor remains the cornerstone of antithrombotic management after myocardial revascularization. However, the traditional “one-size-fits-all” approach to DAPT duration and intensity fails to account for marked interindividual variability in drug response—driven by genetic polymorphisms, notably [...] Read more.
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor remains the cornerstone of antithrombotic management after myocardial revascularization. However, the traditional “one-size-fits-all” approach to DAPT duration and intensity fails to account for marked interindividual variability in drug response—driven by genetic polymorphisms, notably CYP2C19 variants like CYP2C19*2, which reach a frequency of up to 75% in specific groups like the Melanesian population—comorbidities such as diabetes and chronic kidney disease, and dynamic clinical factors including age and concomitant medications. We examine the current landscape of precision medicine tools for individualizing DAPT, including platelet function testing, point-of-care genotyping, validated clinical risk scores, and emerging artificial intelligence (AI)–based predictive models. Evidence from landmark trials is synthesized to evaluate escalation, de-escalation, and duration-tailoring strategies within the ischemic–bleeding trade-off framework. Special populations requiring individualized approaches are reviewed, including patients with atrial fibrillation, the elderly, and those requiring urgent noncardiac surgery with perioperative bridging. Future directions, including multi-omics integration, novel antiplatelet agents, and AI-driven clinical decision support systems, are also explored. As a narrative review, conclusions should be interpreted as reflective of current evidence synthesis rather than systematic-review-grade evidence, given the absence of formal risk-of-bias scoring or meta-analytic pooling. Personalized DAPT guided by complementary genetic and phenotypic testing, integrated with dynamic risk stratification, offers a paradigm shift from empiric therapy toward precision-guided antithrombotic management with the potential to simultaneously reduce ischemic and bleeding complications. Full article
(This article belongs to the Special Issue Advances in Antiplatelet Therapy After Cardiovascular Surgery)
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30 pages, 511 KB  
Review
Beyond the Intestinal Mucosa in Long-Standing Inflammatory Bowel Disease: Consequences of Chronic Inflammation and Endoscopic Approaches to Diagnosis and Management
by Sabina Gabriela Luca, Oana Cristina Petrea, Cristina Muzica, Ana Maria Singeap, Ana Maria Buzuleac, Adriana Dunca, Alexandru Sebastian Cotleț, Simona Stefania Juncu and Anca Trifan
Medicina 2026, 62(6), 1208; https://doi.org/10.3390/medicina62061208 (registering DOI) - 22 Jun 2026
Abstract
Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC), chronic immune-mediated conditions of the gastrointestinal tract characterized by alternating periods of disease activity and remission with a complex multifactorial pathogenesis. Persistent intestinal inflammation in IBD is a key driver of [...] Read more.
Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC), chronic immune-mediated conditions of the gastrointestinal tract characterized by alternating periods of disease activity and remission with a complex multifactorial pathogenesis. Persistent intestinal inflammation in IBD is a key driver of disease progression and is strongly associated with the development of complications such as dysplasia, colorectal cancer (CRC), intestinal strictures, and fistulas. It may also result in changes in anorectal function, identifiable and classifiable using high-resolution anorectal manometry. Histologic and endoscopic assessments are essential for the evaluation of intestinal inflammation. Cumulative inflammatory burden (CIB) is an important concept that quantifies inflammatory exposure in IBD over time by integrating the severity and duration of histologic inflammation across the disease course, highlighting the importance of long-term inflammatory activity in the development of CRC. Histologic healing may be an important therapeutic target in IBD to reduce the risk of long-term complications. In parallel, emerging precision medicine approaches aim to improve risk stratification and enable early, individualized interventions to reduce disease-related outcomes. Endoscopy also plays a fundamental role in monitoring high-risk patients and guiding treatment decisions. This review aims to characterize the main intestinal complications extending beyond the mucosa that are associated with cumulative chronic inflammation in patients with IBD, including dysplasia, CRC, strictures, fistulas, and anorectal dysfunction in an era increasingly focused on achieving complete mucosal healing. Particular attention is drawn to the significant role of persistent histologic and endoscopic inflammation in disease progression and development of complications, highlighting the specific features and associated risk factors of these disease-related outcomes. Throughout, this review emphasizes the fundamental role of endoscopy in the timely detection, monitoring, and therapeutic management of IBD-related complications, thereby reinforcing its role in comprehensive patient care. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Inflammatory Bowel Disease (IBD))
12 pages, 985 KB  
Article
10-Year Change in the Laboratory-Based Prevalence of Chronic Kidney Disease in Patients from a Brazilian Cardiologic Center
by Farid Samaan, Rubens Carvalho Silveira, Kleber Gomes Franchini, Fausto Feres, Gianna Mastroianni-Kirsztajn and Ricardo Sesso
Epidemiologia 2026, 7(3), 87; https://doi.org/10.3390/epidemiologia7030087 (registering DOI) - 22 Jun 2026
Abstract
Background: We aim to estimate the variation in the prevalence of chronic kidney disease (CKD) in patients from a Brazilian cardiologic center. Methods: The outpatient serum creatinine level and urine albumin–creatinine ratio (UACR) in samples from patients ≥18 years old between 2014 and [...] Read more.
Background: We aim to estimate the variation in the prevalence of chronic kidney disease (CKD) in patients from a Brazilian cardiologic center. Methods: The outpatient serum creatinine level and urine albumin–creatinine ratio (UACR) in samples from patients ≥18 years old between 2014 and 2023 were evaluated. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Participants were categorized into low-, moderate-, high- or very high-risk groups according to the CKD heatmap, which combines eGFR with UACR results. Results: The mean number of adults with serum creatinine results per year was 36,477 ± 7239, and the mean number of those with UACR results was 16,870 ± 4310. The age- and sex-adjusted prevalence of participants with CKD increased significantly (from 20% to 31%; R2 = 0.853; p < 0.001), as was the prevalence of individuals in the high or very high CKD risk groups (14% to 21%; R2 = 0.945; p < 0.001). The cumulative incidence of CKD during the study period was 21.7% and was higher in females and in older age groups. Conclusions: The roughly 50% increase in the laboratory-based CKD prevalence over 10 years underscores the need for healthcare services to adapt to managing a population with growing complexity and a heightened risk of requiring kidney replacement therapy. Full article
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20 pages, 546 KB  
Review
Radiation-Induced Rhinosinusitis After Treatment of Nasopharyngeal and Selected Sinonasal Cancers: A Narrative Review
by Olawunmi O. Oyedeji and Emmanuel O. Oisakede
Sinusitis 2026, 10(1), 15; https://doi.org/10.3390/sinusitis10010015 (registering DOI) - 22 Jun 2026
Abstract
Radiotherapy is central to the treatment of nasopharyngeal carcinoma and selected sinonasal malignancies, but sinonasal toxicity remains incompletely characterized. Radiation-induced rhinosinusitis (RIR) is increasingly recognized after head-and-neck radiotherapy, particularly in nasopharyngeal carcinoma, where the paranasal sinuses and drainage pathways may receive substantial incidental [...] Read more.
Radiotherapy is central to the treatment of nasopharyngeal carcinoma and selected sinonasal malignancies, but sinonasal toxicity remains incompletely characterized. Radiation-induced rhinosinusitis (RIR) is increasingly recognized after head-and-neck radiotherapy, particularly in nasopharyngeal carcinoma, where the paranasal sinuses and drainage pathways may receive substantial incidental dose. Reported prevalence varies widely because studies use different endpoints, including radiologic mucosal thickening, endoscopic inflammation, and patient-reported symptoms. Across available nasopharyngeal carcinoma cohorts, imaging-defined sinonasal inflammatory changes are common, with reported rates generally ranging from approximately 30% to more than 70% depending on timing, radiation technique, and diagnostic criteria. This narrative review summarizes current evidence on the epidemiology, pathophysiology, dosimetric predictors, imaging findings, prevention, and management of RIR. Radiation-induced sinonasal injury appears to arise from epithelial damage, impaired mucociliary clearance, altered local defense, and chronic mucosal remodeling. Available data suggest that higher doses to the paranasal sinuses and drainage pathways, baseline sinus disease, and tumor extension into sinonasal structures increase risk, although validated dose constraints are not yet established. We propose a harmonized reporting framework that integrates symptoms, endoscopy, imaging, dosimetry, baseline sinonasal status, and oncologic context. Greater recognition of RIR as a clinically meaningful survivorship toxicity may support more consistent outcome reporting, prospective studies, and future radiation-planning strategies aimed at reducing sinonasal morbidity. Full article
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30 pages, 2427 KB  
Review
Multimorbidity in Chronic Overlapping Pain Conditions: From Burden to Integrated Care
by Emmanuel d’Incau, Chelsea Marie Kaplan, Jean-Arthur Micoulaud-Franchi, Christin Veasley and Richard Ohrbach
J. Clin. Med. 2026, 15(12), 4835; https://doi.org/10.3390/jcm15124835 (registering DOI) - 22 Jun 2026
Abstract
Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, [...] Read more.
Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, chronic tension-type headache, irritable bowel syndrome, endometriosis, interstitial cystitis/bladder pain syndrome, vulvodynia, and myalgic encephalomyelitis/chronic fatigue syndrome. When multiple COPCs coexist, they are associated with a disproportionate multimorbidity burden, including greater pain, poorer psychological well-being, functional limitations, disability, fatigue, sleep disturbances, diminished quality of life, and increased healthcare utilization. Despite their impact, COPCs remain under-recognized, underdiagnosed, and undertreated. Combining structured literature searches and citation tracking with narrative syntheses, this review examines comorbid relationships, the burden of multimorbidity, and potentially overlapping nociplastic mechanisms. By adopting a multimorbidity-based perspective rather than a one-disease, one-treatment approach, it highlights barriers to care—including limited clinical awareness, under-recognition of additional COPCs, limited mechanistic understanding, and fragmented care—and proposes integrated strategies emphasizing prevention, systematic screening, mechanism-informed assessment, and coordinated, patient-centered multimodal management. Full article
(This article belongs to the Section Clinical Neurology)
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12 pages, 878 KB  
Article
Pure Nodal Small Lymphocytic Lymphoma: Clinical, Pathologic, and Outcome Features in a Single-Center Cohort
by Andreea Georgiana Stoica, Mariana Așchie, Miruna Gherase-Cristian, Anca Florentina Mitroi, Georgeta Camelia Cozaru, Mădălina Boșoteanu, Cristina Cioti, Sorin Deacu and Irina Tica
Medicina 2026, 62(6), 1200; https://doi.org/10.3390/medicina62061200 (registering DOI) - 22 Jun 2026
Abstract
Background and Objectives: Small lymphocytic lymphoma (SLL) represents the tissue-based manifestation of chronic lymphocytic leukemia (CLL). Despite their shared biological background, patients with SLL have been underrepresented in CLL-focused clinical trials, and data addressing the clinical behavior of pure nodal SLL remain [...] Read more.
Background and Objectives: Small lymphocytic lymphoma (SLL) represents the tissue-based manifestation of chronic lymphocytic leukemia (CLL). Despite their shared biological background, patients with SLL have been underrepresented in CLL-focused clinical trials, and data addressing the clinical behavior of pure nodal SLL remain scarce. The present study aimed to identify factors associated with time to first treatment (TTFT) and progression-only survival in patients with pure nodal SLL. Materials and Methods: In this prospective observational study, 46 patients with pure nodal SLL were included and followed for a median duration of approximately 5 years. Clinical, laboratory, histopathological, and TP53-related parameters were evaluated for their prognostic impact on TTFT and progression-only survival. Results: On univariable analysis, advanced-stage disease, hemoglobin < 10 g/dL, elevated serum β2M, elevated lactate dehydrogenase, del(17p), and aberrant p53 immunohistochemical expression were significantly associated with shorter TTFT and progression-only survival. Conclusions: Pure nodal SLL is a heterogeneous entity with a variable clinical course. Easily assessable clinical and biological parameters, including TP53 abnormalities, may help predict treatment requirement and disease progression, thereby contributing to better risk stratification and more individualized management. Kaplan–Meier analysis demonstrated significantly shorter time-to-first-treatment (TTFT) among patients with elevated β2M levels (≥3.5 mg/L), bulky lymphadenopathy (≥5 cm), and advanced-stage disease. Full article
(This article belongs to the Section Hematology and Immunology)
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28 pages, 10095 KB  
Review
Gymnema sylvestre as a Multi-Target Antidiabetic Agent: Mechanistic Insights and Metabolic Regulation
by Sedef Ziyanok-Demirtas and Irem Serin
Int. J. Mol. Sci. 2026, 27(12), 5609; https://doi.org/10.3390/ijms27125609 (registering DOI) - 22 Jun 2026
Abstract
Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high [...] Read more.
Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. Gymnema sylvestre (Retz.) R.Br. ex Sm (GS), traditionally known as “gurmar” (“sugar destroyer”), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of G. sylvestre, focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that G. sylvestre modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure–molecular target–metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, G. sylvestre represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research. Full article
(This article belongs to the Special Issue Molecular Mechanism of Diabetes and Its Complications)
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15 pages, 904 KB  
Article
Discharge Practices After Hospitalization for COPD Exacerbations: A Physician Survey and SWOT Analysis
by Sanja Dimic-Janjic, Mihailo Stjepanovic, Ivan Cekerevac, Sanja Hromis, Ivana Buha, Vojislav Cupurdija, Ivan Kopitovic, Rade Milic, Biljana Zvezdin, Ivana Stankovic, Jelena Jankovic, Nikola Trboljevac, Maja Omcikus, Lidija Isovic, Nikola Kostadinovic, Nikola Subotic and Marija Vukoja
Healthcare 2026, 14(12), 1786; https://doi.org/10.3390/healthcare14121786 (registering DOI) - 20 Jun 2026
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Abstract
Background/Objectives: Discharging patients after hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (COPD) is a critical transition in care associated with a high risk of early readmission. This survey aimed to describe physician-reported discharge practices following COPD exacerbations, identify perceived gaps [...] Read more.
Background/Objectives: Discharging patients after hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (COPD) is a critical transition in care associated with a high risk of early readmission. This survey aimed to describe physician-reported discharge practices following COPD exacerbations, identify perceived gaps and organizational barriers, explore attitudes toward structured COPD discharge summaries, and use a SWOT analysis as an interpretative framework. Methods: In this cross-sectional observational survey, 100 physicians involved in COPD care were recruited from the official mailing list of the Respiratory Society of Serbia, which represents approximately 71% of the Society’s members. The survey assessed discharge procedures, multidisciplinary practices, patient education, comorbidity management, perceived causes of readmission, and barriers to structured discharge summaries. Data were analyzed descriptively and complemented with a structured SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis. Results: Most respondents worked in tertiary care settings and were involved in managing patients hospitalized for COPD exacerbations. Although 24% of physicians routinely used structured discharge summaries, 45% reported never using them. The most frequently perceived contributors to 30-day readmissions were active smoking (90%), poor treatment adherence (81%), comorbidities (77%), and incorrect inhaler technique (72%). Major barriers to implementing structured discharge summaries included the lack of standardized templates, time constraints, poor coordination across healthcare levels, and technical limitations. Willingness to implement structured discharge tools was high (mean score 8.86/10). SWOT analysis identified strong professional support for discharge standardization alongside organizational and system-level barriers to implementation. Conclusions: This exploratory survey identified important gaps between recommended and routine COPD discharge practices and highlighted organizational barriers to implementation. The findings may inform future evaluation and development of structured discharge tools in this healthcare setting. Full article
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17 pages, 1064 KB  
Review
Olfactory Dysfunction in Chronic Rhinosinusitis: Mechanisms, Diagnosis, and the Role of Endoscopic Sinus Surgery
by Nikolaos Tsetsos
J. Clin. Med. 2026, 15(12), 4797; https://doi.org/10.3390/jcm15124797 (registering DOI) - 20 Jun 2026
Viewed by 68
Abstract
Chronic rhinosinusitis (CRS) constitutes a multicausal inflammatory disease of the nose and paranasal sinuses, often associated with olfactory dysfunction (OD), a symptom that significantly impacts patients’ quality of life. OD in CRS was traditionally thought to be related to mechanical obstruction of the [...] Read more.
Chronic rhinosinusitis (CRS) constitutes a multicausal inflammatory disease of the nose and paranasal sinuses, often associated with olfactory dysfunction (OD), a symptom that significantly impacts patients’ quality of life. OD in CRS was traditionally thought to be related to mechanical obstruction of the olfactory cleft, but is now considered to be multifactorial, involving conductive, inflammatory, and sensorineural mechanisms as well. Type-2 inflammatory response (high interleukins IL-4, IL-5, IL-13), eosinophilia, and increased IgE are involved in epithelial damage, impaired neurogenesis, and persistent olfactory loss, especially in chronic rhinosinusitis with nasal polyps (CRSwNP). In addition, peripheral chronic inflammation may also play a role in central neural remodeling, which may potentially affect olfactory function. Objective psychophysical testing is necessary to accurately assess olfactory function because self-reports may lack reliability. Management strategies aim at reducing inflammation and restoring sinonasal ventilation. First-line therapy with intranasal corticosteroids and short courses of systemic corticosteroids may be useful for symptomatic relief. Biologic agents directed against type-2 inflammation have demonstrated significant benefits in selected cases. Functional Endoscopic Sinus Surgery (FESS) plays an important role in the treatment of refractory CRS to restore the airflow and to improve the delivery of topical drugs. Olfactory outcomes following surgery, however, are variable and often incomplete, reflecting underlying inflammation and neuroepithelial damage. Disease recurrence, especially in type-2–driven CRS, affects long-term outcomes, underscoring the necessity to incorporate surgery in an individualized, endotype-informed treatment strategy. Full article
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13 pages, 5839 KB  
Article
Systemic AAV-hGCDH Gene Therapy Alleviates Glutaric Acid Accumulation and Attenuates Chronic Brain Vacuolation in a Novel Mouse Model of Glutaric Aciduria Type I
by Su Jin Kim, Yu Hwa Nam, Eun Young Joo, Jisun Park, Saeyoung Park, Sung-Chul Jung and Dong-Kyu Jin
Int. J. Mol. Sci. 2026, 27(12), 5569; https://doi.org/10.3390/ijms27125569 (registering DOI) - 20 Jun 2026
Viewed by 43
Abstract
Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase (GCDH) deficiency, leading to the accumulation of neurotoxic metabolites that can cause both acute encephalopathic crises and progressive, insidious brain injury. Current management primarily relies on a protein-restricted diet, [...] Read more.
Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase (GCDH) deficiency, leading to the accumulation of neurotoxic metabolites that can cause both acute encephalopathic crises and progressive, insidious brain injury. Current management primarily relies on a protein-restricted diet, which remains therapeutically insufficient and burdensome for patients, highlighting the need for disease-modifying therapies. In this study, we established a novel GA1 mouse model using CRISPR/Cas9 technology and evaluated the preclinical efficacy of systemic recombinant adeno-associated virus (rAAV)-mediated gene therapy. Under standard dietary conditions without high-lysine challenge, our GA1 model exhibited sustained cerebral and hepatic glutaric acid (GA) accumulation and distinct chronic vacuolation in the hippocampus and cerebellum, mirroring the insidious-onset GA1 phenotype. Five-week-old mice received a single intravenous injection of rAAV-hGCDH using either rAAV2/8 or rAAV2/9 serotypes. Systemic rAAV-mediated gene therapy significantly reduced GA accumulation and attenuated chronic neuropathological changes in this GA1 mouse model for both serotypes. Our findings support the hypothesis that peripheral metabolic correction may play an important role in preventing the chronic neuropathological changes associated with GCDH deficiency. However, further investigation using tissue-specific expression systems is required to definitively delineate the relative contributions of hepatic versus central GCDH restoration to the observed neuroprotection. Full article
(This article belongs to the Topic Advances in Gene Therapy of Human Diseases)
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23 pages, 1569 KB  
Review
Specificity vs. Synergy Between Single-Strain and Multi-Strain Probiotics for Ulcerative Colitis Treatment: A Review of the Literature
by Muhammad Ikhmal Rosali, Dinesh Prasad V. Thanga Velu, Mohd Helmy Mokhtar, Raja Affendi Raja Ali, Norfilza Mohd Mokhtar and Adila A. Hamid
Biomedicines 2026, 14(6), 1386; https://doi.org/10.3390/biomedicines14061386 - 19 Jun 2026
Viewed by 326
Abstract
Ulcerative colitis (UC) is a chronic disease marked by mucosal inflammation of the colon, and its prevalence has progressively increased worldwide. Gut dysbiosis is recognized as a key contributor to its pathogenesis. Although conventional treatments are effective in managing symptoms, they often fail [...] Read more.
Ulcerative colitis (UC) is a chronic disease marked by mucosal inflammation of the colon, and its prevalence has progressively increased worldwide. Gut dysbiosis is recognized as a key contributor to its pathogenesis. Although conventional treatments are effective in managing symptoms, they often fail to address the underlying gut microbial imbalance, prompting growing interest in microbiota-based therapies. Probiotic supplementation has demonstrated potential to modulate the disease. However, its clinical application is limited by variability in formulations and strain composition. Debate persists regarding the relative benefits of single-strain probiotics (SSPs), which depend on strain specificity, versus multi-strain probiotics (MSPs), which may provide synergistic effects. The literature remains inconclusive, with some studies indicating that MSPs outperform SSPs, while others emphasize the importance of strain specificity. This review describes the mechanistic basis of both approaches and descriptively synthesizes their clinical efficacy in UC management based on the clinical studies published between 2018 and 2025. Several studies report that both SSPs and MSPs are associated with clinical improvements, including reduced disease activity, symptom alleviation, and enhanced endoscopic outcomes. Given the methodological heterogeneity across included studies, comparative findings should be interpreted with appropriate caution. A direct head-to-head trial could provide a better understanding to determine the optimal approach. Advancing toward personalized probiotic therapy may further enhance the clinical application of probiotics for disease management. Full article
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17 pages, 2661 KB  
Systematic Review
Health Effects of Plant-Based Diets in People with Overweight or Obesity: A Systematic Review and Meta-Analysis
by Ildikó Csölle, Viktória Cseh, Gábor Veres, László Czina, Daniela Kuellenberg de Gaudry, Dávid U. Nagy, Almut Georgi and Szimonetta Lohner
Nutrients 2026, 18(12), 1987; https://doi.org/10.3390/nu18121987 - 19 Jun 2026
Viewed by 258
Abstract
Background/Objectives: Nutrition plays a core role in chronic disease management, and there is growing interest in the health impact of plant-based diets (PBDs) in people with overweight or obesity. We conducted this systematic review and meta-analysis to summarize the evidence on the health [...] Read more.
Background/Objectives: Nutrition plays a core role in chronic disease management, and there is growing interest in the health impact of plant-based diets (PBDs) in people with overweight or obesity. We conducted this systematic review and meta-analysis to summarize the evidence on the health effect of PBDs compared to omnivorous diets in overweight or obese individuals. Methods: We searched the databases Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to 3 January 2024. Two review authors independently screened studies for eligibility, extracted data, evaluated the risk of bias, and rated the certainty of the evidence using GRADE. This study is registered with PROSPERO, CRD42021225525. We used random-effects meta-analysis to analyze data. Results: Of 2664 records identified, 10 randomized controlled trials (RCTs) and six ongoing studies met the inclusion criteria. The available evidence suggests little to no difference between plant-based and omnivorous diets for body weight, systolic blood pressure, diastolic blood pressure, serum glucose, serum insulin, insulin sensitivity, total cholesterol, triglyceride, HDL cholesterol and body fat mass. Plant-based diets may slightly reduce LDL cholesterol. They may also reduce BMI and HbA1c, although the certainty of the evidence is very low. Longer-duration dietary interventions (14 weeks or more) showed greater improvements in BMI, LDL cholesterol and HbA1c. Conclusions: Plant-based diets may represent a dietary option for people with overweight or obesity and may support modest improvements in selected cardiometabolic outcomes, although the available evidence is limited and uncertain. Most outcomes showed little or no difference between PBDs and comparison diets, while the observed effects on BMI and HbA1c were supported by very low certainty evidence. Full article
(This article belongs to the Section Nutrition and Obesity)
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24 pages, 785 KB  
Review
Peripheral Nerve Stimulation for Perioperative Care in Oncologic Surgical Cases: A Narrative Review
by Taylor Johnson, Jeremy Ashton Hunter Boyd, Sreyansh Rishabh and Sanjib Adhikary
Healthcare 2026, 14(12), 1767; https://doi.org/10.3390/healthcare14121767 - 19 Jun 2026
Viewed by 307
Abstract
Background: Cancer pain affects approximately 44.5% of all patients with malignancy and up to 55–65% of those with advanced or metastatic disease; a substantial proportion remain inadequately controlled with conventional pharmacological approaches alone. Peripheral nerve stimulation (PNS), a minimally invasive neuromodulatory strategy, has [...] Read more.
Background: Cancer pain affects approximately 44.5% of all patients with malignancy and up to 55–65% of those with advanced or metastatic disease; a substantial proportion remain inadequately controlled with conventional pharmacological approaches alone. Peripheral nerve stimulation (PNS), a minimally invasive neuromodulatory strategy, has emerged as a potential opioid-sparing analgesic option for the perioperative management of oncologic surgical patients. Objectives: This narrative review synthesizes current evidence on the application, mechanisms, clinical efficacy, safety, and integration of temporary and permanent PNS systems in cancer patients, with specific focus on cancer-specific pain syndromes, key clinical studies, opioid-sparing immunological implications, evidence quality, and directions for future research. Methods: As a narrative review, this work was structured in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) to ensure methodological transparency. A focused, non-systematic literature search of PubMed/MEDLINE, Embase, and the Cochrane Library was performed from database inception through March 2026, supplemented by hand-searching of reference lists and targeted retrieval of clinical practice guidelines. Sources were selected on the basis of relevance to PNS or closely analogous peripheral neurostimulation modalities in oncologic, perioperative, or chronic pain contexts. Evidence was synthesized narratively, with each cited study graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 Levels of Evidence framework to enable transparent calibration of confidence. Results: Available preliminary and largely extrapolated evidence supports PNS as a promising but not yet established useful adjunct in oncologic perioperative care; because cancer-specific data rest substantially on a single pilot study (n = 12), one retrospective review (n = 15), and extrapolation from non-cancer populations, these conclusions should be regarded as hypothesis-generating. Randomized controlled trial data from non-cancer cohorts demonstrate opioid consumption reductions of approximately 80–90% in the PAINfRE trial, while the post-amputation trial demonstrated ≥50% pain-relief responder rates and reductions in pain interference, with clinically meaningful improvements in pain and function. Oncologic-specific pilot and retrospective evidence confirms feasibility and a 58–67% success rate across diverse cancer pain subtypes. Conclusions: The opioid-sparing properties of PNS carry additional biological plausibility for preserving perioperative antitumor immune function. High-quality prospective trials specifically designed for oncologic surgical populations remain needed to establish evidence-based recommendations. Full article
(This article belongs to the Special Issue Anesthesia, Pain Management, and Intensive Care in Oncologic Surgery)
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