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Search Results (13,333)

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Keywords = randomized controlled trial

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10 pages, 2799 KB  
Opinion
Oncological Feasibility of Conservative Axillary Surgery (Opinion Article): Tailored Axillary Surgery vs. Axillary Reverse Mapping-Guided Axillary Lymph Node Dissection
by Masakuni Noguchi, Yusuke Haba, Emi Morioka and Masafumi Inokuchi
Cancers 2026, 18(5), 854; https://doi.org/10.3390/cancers18050854 (registering DOI) - 6 Mar 2026
Abstract
Background: Tailored axillary surgery (TAS) and axillary reverse mapping (ARM)-guided axillary lymph node dissection (ALND) have been developed to avoid arm lymphedema without increasing a risk of axillary recurrence. However, the oncological feasibility of TAS and ARM-guided ALND remains a crucial consideration. Methods: [...] Read more.
Background: Tailored axillary surgery (TAS) and axillary reverse mapping (ARM)-guided axillary lymph node dissection (ALND) have been developed to avoid arm lymphedema without increasing a risk of axillary recurrence. However, the oncological feasibility of TAS and ARM-guided ALND remains a crucial consideration. Methods: This article reviewed the oncological feasibility of TAS and ARM-guided ALND based on the current literature. Results: For ALND performed after TAS, additional involved nodes were found in 70% of upfront surgery patients and 60% of neoadjuvant chemotherapy (NAC) patients. ARM nodes were also involved in up to 64.7% of patients after ALND. However, it is not necessary to preserve all ARM nodes and lymphatics because multiple ARM lymphatic pathways exist. Selective preservation of ARM nodes closest to the axillary vein significantly reduced the incidence of involved ARM nodes (from 64.7% to 15.7%). Conclusions: TAS and ARM-guided ALND remain much less radical than ALND. However, residual nodal disease after TAS or ARM-guided ALND does not always develop axillary recurrence. Postoperative irradiation is effective in achieving local control in patients with low-volume (microscopic) residual nodal disease after TAS or ARM-guided ALND. We await the long-term results of prospective randomized clinical trials comparing TAS and ARM-guided ALND with conventional ALND. Full article
(This article belongs to the Special Issue Insights from the Editorial Board Member)
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23 pages, 2242 KB  
Article
A Randomized Controlled Trial to Determine the Effects of Curcumin and Epigallocatechin-3-Gallate Supplementation on Serum Brain-Derived Neurotrophic Factor and Mood Disturbance in Adults
by Aidan M. Cavanah, Laura A. Delvers, Madison M. Aguilar, Elaine F. Molaison, Michael W. Greene, Michael D. Roberts and Andrew D. Fruge
Nutrients 2026, 18(5), 855; https://doi.org/10.3390/nu18050855 (registering DOI) - 6 Mar 2026
Abstract
Background/Objectives: Mood disorders like depression, anxiety, and stress have increased steadily among adults, with growing interest in non-pharmaceutical treatments to improve symptomology. Epigallocatechin-3-gallate (EGCG) and curcumin are polyphenols with evidence to support their positive impacts on mood disorder symptomology and potential mood-associated [...] Read more.
Background/Objectives: Mood disorders like depression, anxiety, and stress have increased steadily among adults, with growing interest in non-pharmaceutical treatments to improve symptomology. Epigallocatechin-3-gallate (EGCG) and curcumin are polyphenols with evidence to support their positive impacts on mood disorder symptomology and potential mood-associated biomarkers like brain-derived neurotrophic factor (BDNF). This study examined the effects of combined EGCG and curcumin supplementation on mood disturbance symptomology and serum brain-derived neurotrophic factor in adults. Methods: An 8-week randomized double-blinded placebo-controlled trial was conducted in adults (n = 64, 18–50 years old). Participants were randomized to a supplement group (n = 32; 350 mg EGCG and 1330 mg curcumin daily) or a matched placebo group (n = 32). Mood disturbance (DASS-21, GAD-7), sleep disturbance (GSAQ), and physical activity (IPAQ) were assessed at baseline, Week 4, and Week 8. Anthropometric measures, 24 h diet recalls, and fasted blood samples for serum BDNF were collected at baseline and Week 8. A multivariate ANOVA evaluated primary outcomes (DASS-21 composite score and BDNF), followed by repeated measures ANOVA for secondary outcomes (p < 0.05). Results: Significant improvements were observed across all participants for mood (DASS-21 composite and subscales, GAD-7, p < 0.001 for all), sleep (p < 0.001), and physical activity (p < 0.01), with no significant difference between supplement and placebo groups. Mean serum BDNF increased in both groups, but neither were statistically significant with no group-by-time interactions. Sugar intake (g/kg body weight) was positively correlated with mood symptoms at Week 8 in the supplement group. Baseline fruit and vegetable intake was associated with mood symptom severity at select time points; however, dietary changes during the intervention were not significantly related to changes in mood outcomes. Conclusions: Combined EGCG and curcumin supplementation did not show additional benefits beyond placebo for mood disturbance or serum BDNF over eight weeks. Observed improvements across both groups suggest that behavioral or lifestyle factors may play a larger role in short-term mood improvements than supplementation alone. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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14 pages, 255 KB  
Article
Safety of Sabin-Strain Inactivated Poliovirus Vaccine Administered Alone or Concomitantly with Other Vaccines: A Population-Based Post-Marketing Surveillance Study
by Lin Chang, Yuxi Liu, Yuan Ren, Jing Li, Xing Fang and Yurong Li
Vaccines 2026, 14(3), 241; https://doi.org/10.3390/vaccines14030241 (registering DOI) - 6 Mar 2026
Abstract
Background/Objectives: Sabin-strain inactivated poliovirus vaccine has been increasingly incorporated into routine immunization programs as part of the global strategy to eradicate poliomyelitis. As childhood immunization schedules become more complex, concerns persist regarding the safety of concomitant vaccination. Although randomized controlled trials and [...] Read more.
Background/Objectives: Sabin-strain inactivated poliovirus vaccine has been increasingly incorporated into routine immunization programs as part of the global strategy to eradicate poliomyelitis. As childhood immunization schedules become more complex, concerns persist regarding the safety of concomitant vaccination. Although randomized controlled trials and regional surveillance studies have demonstrated acceptable safety profiles, additional population-based real-world evidence remains valuable for evaluating the safety of sIPV administered concomitantly with other vaccines under routine programmatic conditions. Methods: A retrospective observational study was conducted using vaccination records and adverse events following immunization surveillance data collected in Liaoning Province, China, between 1 January 2022 and 30 June 2025. All reported adverse events following immunization following Sabin-strain inactivated poliovirus vaccine administration were extracted from the Chinese National AEFI Surveillance System. The reporting rates were calculated per 100,000 administered doses. Multivariable Poisson regression models with robust variance estimation were used to estimate adjusted rate ratios and 95% confidence intervals comparing standalone and concomitant sIPV administration, adjusting for sex, age in months, dose number, and city. Interaction analyses between vaccination mode and dose number were additionally performed. Results: A total of 205,576 sIPV doses were administered, including 144,724 doses administered alone and 60,852 doses administered concomitantly with other vaccines. Fifty-six adverse events following immunization were reported, corresponding to an overall reporting rate of 27.24 per 100,000 doses. Most reported adverse events following immunization were general reactions (91.07%), and all occurred within seven days after vaccination. The reporting rates for sIPV administered alone and concomitantly were 26.26 and 29.58 per 100,000 doses, respectively, with no significant difference between groups (p = 0.7869). After adjustment, concomitant sIPV administration was not associated with an increased risk of adverse events following immunization compared with standalone administration (adjusted rate ratios = 1.13, 95% confidence intervals: 0.59–2.16). No significant interaction between vaccination mode and dose number was identified. Conclusions: Sabin-strain inactivated poliovirus vaccine demonstrated a favorable safety profile when administered either alone or concomitantly with other vaccines. These findings support the continued use of flexible and synchronized vaccination strategies involving Sabin-strain inactivated poliovirus vaccine in routine immunization programs. Full article
(This article belongs to the Special Issue Vaccine Efficacy and Disease Burden Evaluation)
12 pages, 596 KB  
Article
Effects of Trunk Extension-Based Inspiratory Muscle Strengthening on Respiratory Function, Balance, and Gait in Patients with Stroke: A Randomized Controlled Trial
by Kwang-Bin An, Hye-Joo Jeon, Yu-Sik Choi, Soo-Yong Lee and Woo-Nam Chang
J. Clin. Med. 2026, 15(5), 2017; https://doi.org/10.3390/jcm15052017 (registering DOI) - 6 Mar 2026
Abstract
Objectives: This study investigated the effects of trunk extension-based inspiratory muscle strengthening on respiratory function, balance, and gait in patients with stroke. Methods: Thirty stroke patients were randomly assigned to the study group (n = 15) or control group (n = [...] Read more.
Objectives: This study investigated the effects of trunk extension-based inspiratory muscle strengthening on respiratory function, balance, and gait in patients with stroke. Methods: Thirty stroke patients were randomly assigned to the study group (n = 15) or control group (n = 15). The study group performed inspiratory muscle strengthening exercises in a trunk extension posture, while the control group received conventional inspiratory muscle training. Both groups trained five times per week for six weeks. Outcome measures included maximal inspiratory pressure (MIP), maximal inspiratory flow rate (MIFR), maximal inspiratory volume (MIV), peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1), Berg Balance Scale (BBS), weight distribution ratio (WDR), limits of stability (LOSs), Timed Up and Go (TUG), gait velocity, cadence, and stride length. Results: The study group showed significantly greater improvements in respiratory parameters (MIP, MIFR, MIV, PEF, FEV1) and functional outcomes (WDR, LOS, BBS, TUG, gait velocity, cadence, stride length) compared to the control group. Conclusions: Trunk extension-based inspiratory muscle strengthening effectively improves respiratory function, balance, and gait in stroke patients, and may serve as a valuable addition to stroke rehabilitation programs. Full article
(This article belongs to the Section Clinical Rehabilitation)
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15 pages, 1284 KB  
Article
Green Tea Catechin Plus Inulin Improves Insulin Resistance Without Reducing Visceral Fat and Shows Exploratory Gut Microbiota Signals in Adults with Visceral Obesity: A Double-Blind Randomized Controlled Trial
by Chikara Iino, Keita Mikami, Keisuke Furusawa, Satoshi Sato, Kenta Yoshida, Tohru Yamaguchi, Hiroto Bushita, Keita Kinoshita, Yuji Matsui, Seiya Imoto, Takuro Iwane, Yoshinori Tamada, Koichi Murashita, Shigeyuki Nakaji, Tatsuya Mikami and Hirotake Sakuraba
Nutrients 2026, 18(5), 851; https://doi.org/10.3390/nu18050851 (registering DOI) - 6 Mar 2026
Abstract
Background: Green tea catechins and inulin may improve metabolic health and modulate the gut microbiota; however, double-blind trials evaluating visceral fat, insulin resistance, and microbiota concurrently are limited. Methods: We conducted a double-blind, parallel-group, randomized, placebo-controlled trial in Japanese adults aged 20–75 years [...] Read more.
Background: Green tea catechins and inulin may improve metabolic health and modulate the gut microbiota; however, double-blind trials evaluating visceral fat, insulin resistance, and microbiota concurrently are limited. Methods: We conducted a double-blind, parallel-group, randomized, placebo-controlled trial in Japanese adults aged 20–75 years with visceral fat area (VFA) ≥ 80 cm2 and BMI ≥ 23 kg/m2 (trial registration: Japan Registry of Clinical Trials (jRCT), jRCTs021230004 (registered 16 May 2023)). Participants were randomized to a catechin + inulin beverage (catechins 400 mg/day; inulin 2.3 g/day) or placebo for 12 weeks. The primary outcome was the change in VFA (bioelectrical impedance). Secondary outcomes included HOMA-IR, metabolic markers, liver fat assessed by the controlled attenuation parameter (CAP), and genus-level gut microbiota. Results: Ninety-six participants were randomized (catechin + inulin, n = 49; placebo, n = 47); 47 and 44, respectively, were included in the full analysis set for the primary outcome. The 12-week change in VFA did not differ between groups (mean change: +0.91 vs. +4.61 cm2; p = 0.243). HOMA-IR decreased in the catechin + inulin group and increased in the placebo group, yielding a significant between-group difference (mean change: −0.32 vs. +0.18; p = 0.020). No other secondary outcomes showed significant between-group differences. In exploratory microbiota analyses, no genus remained significant after false discovery rate correction; however, Coprococcus and Bifidobacterium showed nominal between-group differences (unadjusted p < 0.05). Changes in Coprococcus were inversely correlated with changes in HOMA-IR (r = −0.28; p = 0.010). Conclusions: Catechin plus inulin for 12 weeks did not reduce visceral fat but was associated with improved insulin resistance. Exploratory analyses suggest a potential association between increased Coprococcus and improved HOMA-IR, warranting further investigation. Full article
(This article belongs to the Special Issue Dietary Interventions for Obesity and Obesity-Related Complications)
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26 pages, 2229 KB  
Article
Enhanced Neocollagenesis and Clinical Efficacy of a Novel Regenerative Diluent for Calcium Hydroxyapatite for Facial Rejuvenation: A 90-Day Clinical Trial
by Valéria Dal Col, Cassiano Marchi, Fábio Fernandes Ribas, Bárbara Barquette Silva da Rosa, Delcio Eustaquio de Paula Júnior, Maria Auxiliadora Dinalli Marchi, Maria Claudia Ferreira Cavalcanti Santos, Tarita Moioli Martins Abdala, Danielle Campos Ito Palhari, Maracelle do Nascimento Arruda, Natalia Magalhães Ferreira, Isabella Comério Fiorio, Fernanda Ferreira Dias, Laiza Grecco, Frederico Thiago Pereira Ramos Neves, Alexandre Todorovic Fabro, Andrea Jazel Rodríguez Herrera, Beatriz Domenici de Oliveira and Renata Viana
Cosmetics 2026, 13(2), 60; https://doi.org/10.3390/cosmetics13020060 (registering DOI) - 6 Mar 2026
Abstract
Facial aging is primarily characterized by the loss and disorganization of the dermal extracellular matrix (ECM), particularly collagen. Injectable biostimulators, such as calcium hydroxyapatite (CaHA), represent a vital non-surgical strategy to counteract these changes by inducing neocollagenesis. This 90-day clinical trial was designed [...] Read more.
Facial aging is primarily characterized by the loss and disorganization of the dermal extracellular matrix (ECM), particularly collagen. Injectable biostimulators, such as calcium hydroxyapatite (CaHA), represent a vital non-surgical strategy to counteract these changes by inducing neocollagenesis. This 90-day clinical trial was designed to comparatively evaluate the efficacy of a novel regenerative solution (RS) diluent, formulated to potentially enhance the biostimulatory effects of standard CaHA (STIIM product), against a conventional diluent (control) for the treatment of facial laxity. Twenty-one subjects (N = 21) were randomized to receive CaHA diluted with either RS or control formulation. Efficacy was assessed using histological analysis (collagen I area percentage), ultrasound (US) for dermal density, and clinical laxity scoring. Histological analysis, although limited by a small subsample size (N = 3), showed qualitative and exploratory evidence of collagen remodeling in both groups. However, the RS group showed enhanced dermal thickening via US (15% increase vs. 5% control, p-value = 0.012), and improvement in clinical laxity. Furthermore, histological findings, including Picrosirius red staining, indicated that the RS group resulted in qualitatively greater ECM organization and more robust type I collagen fibers compared to the control. The novel regenerative solution is safe and demonstrates enhanced neocollagenesis and clinical efficacy over the conventional formulation, validating its potential as a diluent for CaHA for optimized facial rejuvenation. Full article
(This article belongs to the Section Cosmetic Dermatology)
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11 pages, 692 KB  
Article
Oxygen-Enriched Oil-Based Dressing: A New Option for Tunneling Post-Surgical Diabetic Foot Ulcers
by Alessia Scatena, Sara Sandroni, Matteo Apicella, Michele Mantuano, Anna Ranchelli, Emanuele Bartolini, Rosa Nigro, Sofia Butini, Teresa Scognamiglio, Tommaso Anichini and Marco Meloni
Diabetology 2026, 7(3), 55; https://doi.org/10.3390/diabetology7030055 (registering DOI) - 6 Mar 2026
Abstract
Background: Postoperative wounds may arise from several etiologies, including open partial pedal amputation, postoperative infection, and dehiscence of surgical sites from wound failure or patient compliance issues. If negative pressure wound therapy is the gold standard, its application in the toes area could [...] Read more.
Background: Postoperative wounds may arise from several etiologies, including open partial pedal amputation, postoperative infection, and dehiscence of surgical sites from wound failure or patient compliance issues. If negative pressure wound therapy is the gold standard, its application in the toes area could be challenging, and as a consequence, standard care is most likely used. The control of the wound microenvironment, both in terms of pH levels and presence of reactive oxygen species, is a key part of the normal wound-healing process. This study evaluated the effectiveness of an oxygen-enriched oil-based device (OEOd) in post-surgical diabetic foot ulcers (DFUs). Methods: This prospective controlled comparative pilot study enrolled 40 patients with diabetes mellitus and post-surgical foot wounds (narrow and deep lesions, including tunneling ulcers) treated at the Diabetic Foot Unit of San Donato Hospital, Arezzo (March 2024–April 2025). Patients were allocated into two groups: those treated by the standard wound care (n = 20) and those treated by OEOd (n = 20). The primary outcome was complete wound healing at 16 weeks; other exploratory endpoints were wound area reduction at 4 and 16 weeks, onset of infection, need for re-intervention, and adverse events. Results: Complete wound healing was achieved in 85.0% of OEOd patients versus 45.0% in the control group (p = 0.020). At 16 weeks, wound area reduction was significantly greater in the OEOd group compared with standard therapy (89.8% vs. 64.0%, p = 0.013). Although infection rates (10.0% vs. 35.0%, p = 0.130) and need for re-intervention (0% vs. 25.0%, p = 0.056) did not reach statistical significance, both favored the OEOd group. No adverse events were reported. Conclusions: OEOd significantly improved the chance of healing post-surgery and showed favorable trends in reducing complications, with an excellent safety profile. Larger randomized controlled trials are warranted to confirm these findings and assess long-term outcomes. Full article
(This article belongs to the Special Issue Prevention and Care of Diabetic Foot Ulcers)
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17 pages, 1438 KB  
Review
Mapping High-Level Evidence in Neuroanesthesia: A Scoping Review of Multicenter Randomized Controlled Trials in Anesthesia for Neurosurgery
by Mouad Elganga, Abramo Aziz Rizk and Tumul Chowdhury
J. Clin. Med. 2026, 15(5), 2012; https://doi.org/10.3390/jcm15052012 (registering DOI) - 6 Mar 2026
Abstract
Background/Objectives: Anesthesia for intracranial neurosurgery presents unique challenges because of the sensitivity of the brain to perioperative physiological disturbances, yet neuroanesthetic practice remains highly variable and supported by a limited high-level evidence base. We conducted a scoping review to map and characterize [...] Read more.
Background/Objectives: Anesthesia for intracranial neurosurgery presents unique challenges because of the sensitivity of the brain to perioperative physiological disturbances, yet neuroanesthetic practice remains highly variable and supported by a limited high-level evidence base. We conducted a scoping review to map and characterize multicenter randomized controlled trials (RCTs) evaluating perioperative management strategies in adults undergoing intracranial neurosurgery. Methods: This scoping review was reported in accordance with the PRISMA extension for Scoping Reviews. MEDLINE, PubMed, EMBASE, Cochrane Central, and Web of Science were searched from inception to 25 June 2025. Multicenter RCTs enrolling adults undergoing intracranial neurosurgery and evaluating anesthetic, hemodynamic, ventilatory, or perioperative interventions were included. We prioritized mapping multicenter designs for their greater external validity and implementation potential. Data were extracted in duplicate and summarized descriptively. Results: Of 417 records identified, 13 multicenter trials (≥2 recruiting sites) involving 2765 participants across nine countries from 1997–2025 were included. Most trials evaluated anesthetic maintenance or opioid regimens (7/13), followed by post-craniotomy pain control (3/13), ventilation/brain relaxation strategies (1/13), antiemetic prophylaxis (1/13), and temperature management (1/13). Outcomes were predominantly short-term and process-based (hemodynamics 7/13, opioid use 7/13, emergence metrics 5/13). Patient-centered outcomes were rarely measured (mortality 1/13, functional neurological outcome 1/13, cognitive outcome 1/13; quality of life 0/13). Only one trial assessed outcomes at ≥72 h postoperatively. Over half of the included trials were judged at high risk of bias. Conclusions: Multicenter RCT activity in neuroanesthesia remains sparse and narrowly focused, highlighting the need for larger, methodologically robust trials targeting patient-centered and long-term outcomes. Full article
(This article belongs to the Special Issue Anesthesia and Intensive Care: Clinical Practices and Prospects)
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17 pages, 2007 KB  
Article
A Nutraceutical Approach for Hypertension: Randomized Controlled Trial of Grape Pomace Extract and L-Arginine
by Federico Abate, Elisabetta Schiano, Mariano Stornaiuolo, Fabrizia Guerra, Anna Terracciano, Gaetano Piccinocchi, Eugenio Caradonna, Fulvio Ferrara, Gian Carlo Tenore and Ettore Novellino
Antioxidants 2026, 15(3), 329; https://doi.org/10.3390/antiox15030329 (registering DOI) - 5 Mar 2026
Abstract
Hypertension remains a major global health challenge, and pharmacological therapy is often constrained by tolerability issues. Adjunctive approaches targeting the nitric oxide synthase and soluble guanylate cyclase–cyclic guanosine monophosphate (sGC–cGMP) pathway may offer additional benefits. This study investigated the efficacy and safety of [...] Read more.
Hypertension remains a major global health challenge, and pharmacological therapy is often constrained by tolerability issues. Adjunctive approaches targeting the nitric oxide synthase and soluble guanylate cyclase–cyclic guanosine monophosphate (sGC–cGMP) pathway may offer additional benefits. This study investigated the efficacy and safety of a nutraceutical formulation combining grape pomace extract (Taurisolo®) and L-arginine in patients with grade 1 and grade 2 hypertension. The formulation was designed to enhance nitric oxide (NO) bioavailability and support sGC–cGMP signaling. Taurisolo®, a polyphenol-rich extract, is known for its antioxidant and endothelial-protective properties, while L-arginine serves as the physiological substrate for endothelial NO synthase. Clinical outcomes included blood pressure changes, renal function parameters, and health-related quality of life assessed through the SF-12 questionnaire. Supplementation with Taurisolo® plus L-arginine resulted in significant and sustained reductions in systolic and diastolic blood pressure, with renal function remaining stable throughout the study. Participants also reported meaningful improvements in perceived health, emotional well-being, vitality, and social functioning. The intervention was well tolerated, with no major adverse effects. These findings support the potential of Taurisolo® combined with L-arginine as a safe and effective adjunctive strategy to conventional antihypertensive therapy, warranting further mechanistic investigation. Full article
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21 pages, 2415 KB  
Systematic Review
Shockwave or Ultrasound Therapy for Tendinopathy? A Systematic Review and Meta-Analysis
by Artur Dudoń and Magdalena Stania
J. Clin. Med. 2026, 15(5), 2007; https://doi.org/10.3390/jcm15052007 - 5 Mar 2026
Abstract
Background/Objectives: This systematic review and meta-analysis was designed to examine the efficacy of extracorporeal shock wave therapy (ESWT) and ultrasound therapy in the treatment of upper and lower limb tendinopathies. Methods: The protocol was registered in PROSPERO (CRD420251113976) and conducted in accordance with [...] Read more.
Background/Objectives: This systematic review and meta-analysis was designed to examine the efficacy of extracorporeal shock wave therapy (ESWT) and ultrasound therapy in the treatment of upper and lower limb tendinopathies. Methods: The protocol was registered in PROSPERO (CRD420251113976) and conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Electronic searches were performed in the PubMed, Embase, EBSCOhost, and Ovid MEDLINE databases up to August 2025, to identify randomized controlled trials (RCTs). Mean differences (MDs) and standardized mean differences (SMDs) were calculated with 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic, and a random-effects model was applied. Risk of bias was evaluated using the Risk of Bias (RoB 2) tool, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen RCTs involving 639 patients with tendinopathies were included. All studies were characterized by a high risk of bias. Very low-certainty evidence suggested that ESWT as monotherapy may reduce pain at rest compared with ultrasound therapy in patients with lateral epicondylitis (MD = −1.51; 95% CI: −2.71 to −0.31; p = 0.01), although the effect was highly heterogeneous (I2 = 89.8%; p = 0.002). In patients with upper- and lower-limb tendinopathy, ESWT combined with pharmacotherapy resulted in significantly lower pain intensity compared with ultrasound therapy combined with pharmacotherapy (SMD = −0.6; 95% CI: −1.07 to −0.14; p = 0.01). No significant differences in PRTEE (Patient-Rated Tennis Elbow Evaluation) scores were observed between ESWT and ultrasound monotherapy in patients with lateral epicondylitis (MD = −1.06; 95% CI: −11.06 to 8.94; p = 0.83; I2 = 75.82%), or between ESWT combined with other conservative treatments and ultrasound combined with other conservative treatments (MD = 0.46; 95% CI: −10.22 to 11.15; p = 0.93; I2 = 0%). Conclusions: Very low-certainty evidence suggests that ESWT may be more effective than ultrasound therapy in reducing pain when used as monotherapy in lateral epicondylitis, despite substantial heterogeneity, and when combined with pharmacotherapy in upper- and lower-limb tendinopathies. In terms of function, ESWT appears to provide improvements comparable to those of ultrasound therapy, as assessed by PRTEE scores, in patients with lateral epicondylitis, both as monotherapy and when combined with other conservative treatments. However, significant methodological limitations substantially limit confidence in these findings. Full article
(This article belongs to the Section Clinical Rehabilitation)
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17 pages, 1119 KB  
Review
The Vicious Cycle of Diabetic Kidney Disease, Vitamin D Deficiency, and Arterial Hypertension
by Barbara Kurzyna, Patrycja Czebreszuk, Wiktoria Szczerbińska, Bartłomiej Michalak, Maciej Walędziak and Anna Różańska-Walędziak
Healthcare 2026, 14(5), 662; https://doi.org/10.3390/healthcare14050662 - 5 Mar 2026
Abstract
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus that contributes substantially to chronic kidney failure and increased cardiovascular risk. Beyond progressive deterioration of renal function, DKD is associated with disturbances in endocrine and vascular regulation. Among these, alterations in vitamin [...] Read more.
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus that contributes substantially to chronic kidney failure and increased cardiovascular risk. Beyond progressive deterioration of renal function, DKD is associated with disturbances in endocrine and vascular regulation. Among these, alterations in vitamin D homeostasis and blood pressure (BP) control represent clinically relevant, yet incompletely integrated aspects of DKD pathophysiology. This narrative review synthesizes current evidence on the multidirectional relationships between DKD, vitamin D deficiency, and arterial hypertension (AH). Attention is given to renal mechanisms responsible for reduced vitamin D availability in DKD, including proteinuria-related loss of vitamin D-binding proteins, impaired proximal tubular reabsorption, decreased renal activation of vitamin D, and hormonal regulators such as fibroblast growth factor-23. It further discusses how insufficient vitamin D signaling may influence renal and vascular pathways involved in BP regulation. Mechanistic links between vitamin D deficiency and AH in DKD are discussed, with emphasis on maladaptive activation of the renin–angiotensin–aldosterone system (RAAS), persistent inflammation, oxidative stress, endothelial dysfunction, and insulin resistance. These interdependent processes promote both renal injury progression and sustained elevations in BP, forming a self-reinforcing pathogenic loop. Finally, available data on vitamin D-based therapeutic strategies in DKD are reviewed, including native vitamin D supplementation, active vitamin D metabolites, and vitamin D receptor agonists. Although experimental and observational studies suggest potential nephroprotective and vasculoprotective effects, evidence from randomized clinical trials remains heterogeneous. Further well-designed prospective studies are required to clarify the clinical utility of vitamin D interventions in patients with DKD and coexisting AH. Full article
(This article belongs to the Section Chronic Care)
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25 pages, 1130 KB  
Systematic Review
Effects of Aquatic Exercise on Sleep Quality in Patients with Chronic Diseases: A Meta-Analysis
by Shuzhang Zhou, Ming Fang, Billy Chun-Lung So, Hei Wa So, Paul H. Lee and Siushing Man
Healthcare 2026, 14(5), 661; https://doi.org/10.3390/healthcare14050661 - 5 Mar 2026
Abstract
Background/Objectives: This study systematically synthesized the evidence on the effectiveness of aquatic exercise (AE)-based interventions for improving sleep quality in patients with chronic diseases and identified key moderating factors. Methods: A meta-analysis of 11 randomized controlled trials sourced from Google Scholar, PubMed, Web [...] Read more.
Background/Objectives: This study systematically synthesized the evidence on the effectiveness of aquatic exercise (AE)-based interventions for improving sleep quality in patients with chronic diseases and identified key moderating factors. Methods: A meta-analysis of 11 randomized controlled trials sourced from Google Scholar, PubMed, Web of Science, Embase, Cochrane Library, and Scopus (published between 2016 and 2025) was conducted. Sleep quality was assessed using subjective tools (e.g., PSQI). Results: While AE-based interventions showed potential for enhancing nighttime sleep quality (standard mean difference = 0.825, p < 0.001), high statistical heterogeneity (I2 = 93.41%) was observed. Given this variance, the analysis prioritized the clinical outcomes of specific patient populations over the pooled effect size. Preliminary evidence suggests significant improvements were confirmed in populations with post-COVID syndrome (p < 0.001), Parkinson’s disease (p = 0.002), and chronic back pain (p = 0.008). Conversely, no significant benefits were observed in fibromyalgia (p = 0.191), ankylosing spondylitis (p = 0.737), or type 2 diabetes (p = 0.836). Moderator analysis further indicated that the mode of AE might influence outcomes, with recreational aquatic therapy and deep-water running suggesting superior efficacy compared to resistance training. Conclusions: AE-based interventions were suggested as an effective intervention for improving sleep quality. The observed benefits likely stem from the synergistic effects of physical exercise and the unique physiological properties of the aquatic environment, such as buoyancy and hydrostatic pressure. However, the field relies heavily on subjective questionnaires and lacks physiological mechanism studies. These findings provide a preliminary evidence-based framework for clinicians to develop targeted AE-based interventions for chronic disease patients. Full article
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14 pages, 859 KB  
Systematic Review
Assessing Motivation in Cerebral Palsy During Rehabilitation: A Systematic Review
by Daniela De Bartolo, Marco Iosa, Sara Simigliani, Fulvia Di Iulio, Irene Ciancarelli and Giovanni Morone
Brain Sci. 2026, 16(3), 291; https://doi.org/10.3390/brainsci16030291 - 5 Mar 2026
Abstract
Background: Motivation is widely recognized as a key factor influencing learning and rehabilitation outcomes in children with cerebral palsy (CP). Despite its acknowledged relevance, motivation is rarely assessed systematically in pediatric neurorehabilitation, and there is limited consensus regarding appropriate outcome measures. Objectives: [...] Read more.
Background: Motivation is widely recognized as a key factor influencing learning and rehabilitation outcomes in children with cerebral palsy (CP). Despite its acknowledged relevance, motivation is rarely assessed systematically in pediatric neurorehabilitation, and there is limited consensus regarding appropriate outcome measures. Objectives: This systematic mapping review aimed to examine how motivation-related constructs are assessed in rehabilitation studies involving children with CP, identifying the instruments used and evaluating the extent to which motivation is explicitly measured across different rehabilitation contexts. Methods: The review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420250651843). PubMed and Scopus were searched for studies published between 2013 and 2025. Eligible studies included rehabilitation interventions for children with CP that incorporated a clearly defined motivation-related outcome. Study quality and risk of bias were assessed using Joanna Briggs Institute tools and the RoB 2 tool. Results: Nine studies met the inclusion criteria, including 109 subjects, comprising randomized controlled trials and case series. Most studies involved children with mild to moderate motor impairment (GMFCS or MACS levels I–II). Motivation was assessed through heterogeneous approaches, including self-efficacy, mastery motivation, participation, adherence, and intrinsic motivation, with data collected from children, parents, therapists, or dyads. Conclusions: Although motivation is frequently cited as a critical component of effective rehabilitation in children with CP, its assessment remains inconsistent and methodologically fragmented. This mapping review, based on a limited and heterogeneous evidence base, highlights the need for standardized, validated, and developmentally appropriate tools to measure motivation-related constructs in pediatric CP rehabilitation. Full article
(This article belongs to the Special Issue Advances in Pediatric Neurological Disease Research)
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21 pages, 5768 KB  
Systematic Review
Complex Effects of B-Vitamin Combinations on Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials over Three Decades
by Ruodi Ren, Andrew Yang, Allison Chow, Kunkun Wang, Shan Wang, Christopher Leo, Yun Lu and Mengyan Li
Nutrients 2026, 18(5), 842; https://doi.org/10.3390/nu18050842 - 5 Mar 2026
Abstract
Background and Purpose: The effects of B-vitamin combinations on the prevention of cardiovascular diseases, such as myocardial infarction (MI) and stroke, remain controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) over three decades to evaluate the association between [...] Read more.
Background and Purpose: The effects of B-vitamin combinations on the prevention of cardiovascular diseases, such as myocardial infarction (MI) and stroke, remain controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) over three decades to evaluate the association between B-vitamin combinations and mortality and arterial thrombotic outcomes. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for RCTs with minimal duration over 24 months published between January 1996 and November 2025. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. Random-effects models were used in this meta-analysis to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Results: Thirteen randomized trials enrolling 68,363 participants across both primary and secondary prevention populations were included. B-vitamin combinations were associated with a nonsignificant reduction in stroke and 3-point major adverse cardiovascular events (MACE) (stroke: RR 0.91, 95% CI 0.81–1.04; MACE: RR 0.93, 95% CI 0.86–1.01). No significant effects were observed for all-cause mortality (RR 1.01, 95% CI 0.96–1.06), cardiovascular mortality (RR 0.97, 95% CI 0.88–1.07), or MI (RR 0.97, 95% CI 0.91–1.03). In primary prevention populations, B-vitamin combinations were associated with significant reductions in stroke (RR 0.79, 95% CI 0.68–0.93) and MACE (RR 0.80, 95% CI 0.69–0.92). A modest reduction in MACE was also observed in secondary prevention populations (RR 0.91, 95% CI 0.83–0.99). Between-study heterogeneity was minimal to low for ischemic outcomes, supporting the robustness of these estimates, whereas substantial heterogeneity was observed for mortality outcomes in secondary prevention populations. Conclusions: The evidence is limited by heterogeneity in trial populations, vitamin formulations and doses, and outcome definitions, with substantial between-study inconsistency for mortality outcomes and imprecision in subgroup estimates derived from a small number of contributing trials. Overall, B-vitamin combinations do not confer consistent benefit for major cardiovascular outcomes but may reduce stroke and MACE in selected primary prevention populations, suggesting that baseline cardiovascular risk and regional folic acid fortification modify treatment effects and should guide future trial design and clinical use. Full article
(This article belongs to the Special Issue Vitamins and Human Health: 3rd Edition)
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20 pages, 1359 KB  
Article
Eccentric Isokinetic Rehabilitation for Chronic Lateral Epicondylitis in Female Swimmers: A Randomized Controlled Trial of Bilateral Neuromuscular Adaptations and Functional Performance
by Wissem Dhahbi, Hatem Ghouili, Halil İbrahim Ceylan, Nessrine Adhadhi, Souhail Bchini, Manel Bessifi, Nagihan Burçak Ceylan, Valentina Stefanica, Nejmeddine Ouerghi and Nadhir Hammami
Medicina 2026, 62(3), 494; https://doi.org/10.3390/medicina62030494 - 5 Mar 2026
Abstract
Background and Objectives: This study investigated the efficacy of eccentric isokinetic muscle strengthening versus passive motion protocols on neuromuscular function and performance capacity in female swimmers with chronic lateral epicondylitis. Materials and Methods: Twenty-five swimmers (age 46.1 ± 3.1 years) with [...] Read more.
Background and Objectives: This study investigated the efficacy of eccentric isokinetic muscle strengthening versus passive motion protocols on neuromuscular function and performance capacity in female swimmers with chronic lateral epicondylitis. Materials and Methods: Twenty-five swimmers (age 46.1 ± 3.1 years) with lateral epicondylitis exceeding three months’ duration completed a randomized controlled trial comparing eccentric training in Controlled Active Motion mode (experimental group (EG), n = 13) against passive motion in Continuous Passive Motion mode (control group (CG), n = 12). Both groups performed 18 supervised sessions over six weeks (60°/s angular velocity, progressive loading 1–12 sets × 5 repetitions). Bilateral concentric peak torque of elbow extensors and flexors constituted the primary outcomes. Secondary measures included push-up performance, explosive power assessed by the Seated Medicine Ball Chest Push Test, and goniometric range of motion. Linear mixed-effects models and analysis of covariance with baseline adjustment were employed. Results: Eccentric training produced side-specific strength adaptations in elbow flexors (confirmed interaction: F1,23 = 8.56, p = 0.008, ηp2 = 0.271), with the experimental group demonstrating balanced bilateral gains, whereas the control group exhibited asymmetric responses favoring the non-dominant limb. EG demonstrated superior functional gains: push-up repetitions increased 4.15 ± 1.77 versus 2.17 ± 1.27 in CG (adjusted difference = 3.21 repetitions, 95% CI [1.52, 4.90], p = 0.001, d = 1.31), while explosive power improved 0.32 ± 0.09 m versus 0.10 ± 0.06 m (adjusted difference = 0.35 m, 95% CI [0.25, 0.45], p < 0.001, d = 1.20). Range of motion remained unchanged across groups (all p > 0.65). Conclusions: Eccentric isokinetic strengthening confers substantial advantages over passive motion protocols for restoring upper-body muscular endurance and ballistic force production in swimmers with lateral epicondylitis, supporting its integration into rehabilitation frameworks for the management of tendinopathy. Full article
(This article belongs to the Section Sports Medicine and Sports Traumatology)
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