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PubMed2026

Development of a core descriptor set for studies assessing interventions for diabetes-related foot ulceration.

AIMS/HYPOTHESIS: Foot ulceration is a common complication of diabetes and is associated with high mortality and costs. The quality of evidence to inform clinical practice is limited, partly because clinical studies do not consistently report baseline participant characteristics. This study aimed to develop a core descriptor set (CDS), a minimum set of descriptors to be measured in all studies evaluating interventions for people with diabetes-related foot ulceration. METHODS: A longlist of descriptors was generated through a systematic review of studies assessing interventions for diabetes-related foot ulcers, pre-registered with PROSPERO (CRD42019128250). The identified descriptors were then ranked based on perceived importance by healthcare professionals from different fields and geographical locations using a nine-point Likert scale in the first round of a Delphi survey. Using standardised criteria, descriptors without consensus were re-ranked in round two. Critical descriptors and those without consensus after the Delphi process were discussed in the consensus meeting to finalise the CDS. RESULTS: The systematic review yielded 95 candidate descriptors. The two Delphi rounds were completed by 102 and 69 healthcare professionals, respectively. The Delphi process identified 34 critically important descriptors and 13 descriptors without consensus, which were discussed in the consensus meeting. The ratified CDS included 28 descriptors across nine domains: demographic variables; individual factors; ulcer characteristics; limb characteristics; ongoing medical interventions; previous surgical interventions; medication history; biochemical measurements; and quality of life/function/symptoms. CONCLUSIONS/INTERPRETATION: This CDS reflects characteristics important to health professionals and researchers when reporting clinical studies on diabetes-related foot ulceration. Its use will aid the reporting of future studies.

Humans↗

PubMed2026

Transverse Tibial Transport for Limb Salvage in Ischemic Lower Extremity Disease: Technique, Mechanisms, and Clinical Outcomes-A Systematic Review.

Transverse tibial transport (TTT) is a surgical technique derived from Ilizarov's distraction osteogenesis principles that stimulates angiogenesis and microcirculatory regeneration in the ischemic lower limb without directly manipulating macrovascular anatomy. By creating a proximal tibial cortical bone window and distracting it transversely using an external fixator, TTT triggers converging cascades of growth factor release, endothelial progenitor cell mobilization, and immunomodulation that translate into improved distal limb perfusion and wound healing. Combined TTT plus endovascular therapy improves amputation-free survival versus endovascular therapy alone. Prospective randomized trials and standardized international protocols are needed to consolidate TTT's role in multidisciplinary limb salvage pathways.

Humans↗

PubMed2026

Efficacy and safety of pantoprazole for stress-ulcer prophylaxis in critically ill patients: A systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Stress-related mucosal damage (SRMD) is common in critically ill patients, and pharmacologic prophylaxis remains essential. This study evaluated the efficacy and safety of pantoprazole for stress-ulcer prophylaxis in ICU patients. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted per PRISMA-2020 guidelines. PubMed, Scopus, and CENTRAL were searched for studies comparing pantoprazole with placebo in adult and pediatric ICU patients. The primary outcome was clinically important gastrointestinal (GI) bleeding; secondary outcomes included mortality, ventilator-associated pneumonia (VAP), and Clostridioides difficile infection. RESULTS: Seven RCTs (n ≈ 9127; pantoprazole = 4575; placebo = 4552) were included. Pantoprazole significantly reduced clinically important GI bleeding (RR = 0.53; 95% CI 0.29-0.94; p = 0.03) without affecting overall mortality (RR ≈ 0.99 [95% CI 0.92-1.05]; p = 0.68). Infection rates were similar between groups (VAP: RR = 0.99; p = 0.78; C. difficile: RR = 1.11; p = 0.73). Sensitivity analyses confirmed robustness. CONCLUSIONS: Pantoprazole effectively reduces clinically important GI bleeding without increasing infection or overall mortality.

Pantoprazole↗

PubMed2026

Metformin Adherence and Risk of Polyneuropathy in Type 2 Diabetes Mellitus: An International Matched Cohort Study with Independent Validation.

BACKGROUND: Metformin is a popular first-line glucose-lowering medication for type 2 diabetes mellitus (T2DM). Although metformin reduces the risks of various complications of diabetes, its potential to cause polyneuropathy by depleting vitamin B12 levels is concerning. This study investigated whether the adherence or discontinuation of metformin after adding-on a second-line antiglycemic agent increases the risk of polyneuropathy in patients with T2DM. METHODS: Data from TriNetX were obtained, and patients with T2DM who were receiving second-line antiglycemic agents were divided into metformin-adherent and metformin-nonadherent groups based on prescription claims data. Neuropathy incidence was evaluated using diagnostic claims and nerve conduction examinations. For independent confirmation and external validation of the primary findings, we used data from the National Health Insurance Research Database (NHIRD) of Taiwan. RESULTS: After matching, 58,027 patients were included in each group. Compared with metformin adherent patients, metformin nonadherent patients had a higher risk of polyneuropathy (adjusted hazard ratios [aHR] 1.26; 95% confidence interval [CI] 1.23-1.29; P < 0.001). Risks of diabetic foot ulcer, amputation, neuropathy-related medication use, and bone fracture were also higher among nonadherent patients. Sensitivity analyses confirmed the robustness of findings. In the validation NHIRD cohort (31,384 matched pairs), metformin nonadherence remained associated with increased polyneuropathy risk (aHR 1.25; 95% CI 1.10-1.42; P < 0.001). CONCLUSIONS: Metformin adherence in patients with T2DM who require second-line treatment may reduce the risk of polyneuropathy; vitamin B supplementation may enhance this benefit.

Humans↗

PubMed2026

Barefoot ambulation following partial foot amputation: A systematic review of biomechanical outcomes.

BACKGROUND: Partial foot amputation (PFA) is increasingly performed due to rising prevalence of diabetes and peripheral vascular disease. While PFA may preserve gait and reduce energy expenditure compared with transtibial amputation, biomechanical deficits are common. This review aimed to evaluate biomechanical outcomes during baref following PFA. METHODS: A systematic review was conducted. MEDLINE, Embase, CINAHL, SCOPUS and Web of Science databases were searched for studies reporting biomechanical outcomes in adults with PFA without prosthesis. Eligible outcomes included spatiotemporal metrics, joint kinematics and kinetics, plantar pressures, and ground reaction forces. FINDINGS: Twelve studies including a total of 101 participants met inclusion criteria. Across studies, PFA was associated with impaired barefoot gait. This included spatiotemporal changes, such as reduced walking speed and shorter step length, and kinetic changes, such as reduced ankle power. Elevated plantar pressures were commonly reported, particularly in the forefoot and midfoot, highlighting loading abnormalities in the residuum. Several studies also described proximal compensatory strategies at the knee and hip, suggesting that biomechanical consequences extend beyond the foot and ankle. However, the evidence base was limited by small sample sizes, inconsistent protocols, and substantial heterogeneity. INTERPRETATION: Barefoot walking is impaired after partial foot amputation and the degree of dysfunction may vary by amputation level. Abnormal loading and compensatory changes may extend beyond the foot and ankle to the knee and hip. Given the limited and methodologically heterogeneous evidence, larger prospective studies with standardised biomechanical outcomes are needed to clarify the effects of amputation level and aetiology. This standardisation is important to inform surgical planning, rehabilitation, and prosthetic device design.

Humans↗

PubMed2026

Foot exercise plus education versus brief advice for the treatment of plantar heel pain (FEET Trial): a feasibility randomised controlled trial.

BACKGROUND: Despite foot muscle strengthening being a target of exercise interventions for plantar heel pain (PHP) no study has measured foot muscle outcomes, and existing research is limited by a lack of control (no treatment) comparisons. OBJECTIVES: To determine the feasibility of conducting a randomised controlled trial and investigate the acceptability and credibility of comprehensive progressive foot exercise and education compared to brief advice for PHP. DESIGN: Randomised parallel group feasibility trial. METHOD: People with PHP were randomised (1:1 concealed allocation) to receive either foot exercise plus education or brief advice for twelve weeks. Primary outcomes included willingness to enrol, recruitment rate, adherence, logbook completion, dropout rate, early withdrawal reasons, adverse events, additional treatments sought, and credibility/expectancy. RESULTS: Twenty people with PHP (16 women; age 50 ± 9 years; body mass index = 30.7 ± 4.6 kg/m2) were recruited over 15 weeks (1.3 participants per week). Primary outcomes were willingness to enrol (80%), adherence (physiotherapy sessions attended: foot exercise plus education 85%, brief advice 100%; home exercise program: 62% daily sessions completed, 72% thrice weekly sessions completed), logbook completion (foot exercise plus education 75%, brief advice 90%), dropout rate (15%), and additional treatments sought (69%). There were no intervention-related adverse events, and credibility scores were higher for foot exercise plus education. CONCLUSIONS: This study confirms feasibility and acceptability of a protocol comparing foot exercise plus education with brief advice in individuals with PHP, generating key insights to inform future trial design.

Humans↗

PubMed2026

Response to Letter to the editor to comment on "Is arthroscopically-assisted reduction and internal fixation (ARIF) superior to percutaneous fixation in talar neck fractures? A proportional meta-analysis".

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Letter↗

PubMed2026

K-wire versus screw fixation in Scarf-Akin osteotomy for hallux valgus: A retrospective cohort study.

BACKGROUND: Retention of metal implants after Scarf-Akin osteotomy (SAO) may cause irritation and psychological discomfort, often necessitating a hardware removal procedure. This study aimed to introduce K-wire fixation, allowing for outpatient removal, and to compare it with screw fixation. METHODS: This retrospective study included 64 patients with hallux valgus, comprising 32 in the K-wire fixation group and 32 in the screw fixation group. Clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS), and patient satisfaction. Radiographic parameters included hallux valgus angle(HVA), intermetatarsal angle(IMA), and distal metatarsal articular angle(DMAA). RESULTS: Both groups showed significant clinical and radiographic improvement (P < 0.01). No significant between-group differences were observed in the other clinical or radiographic outcomes (P > 0.05). Treatment costs were significantly lower in the K-wire group (P < 0.001). CONCLUSIONS: K-wire fixation provides clinical and radiographic outcomes comparable to screw fixation, while avoiding the need for an additional procedure to remove the implant. LEVEL OF EVIDENCE: Level III.

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PubMed2026

Early radiographic loss of intermetatarsal angle correction after single first TMT arthrodesis (Modified Lapidus) versus three-corner TMT arthrodesis.

INTRODUCTION: The Lapidus procedure treats hallux valgus with first-ray hypermobility. It can be performed as a single first tarsometatarsal (TMT) arthrodesis or a three-corner TMT construct with additional intermetatarsal fusion. Early loss of correction remains a concern. This study compared early radiographic stability between techniques. METHODS: Fifty patients (15 three-corner TMT arthrodesis, 35 single first TMT arthrodesis) treated between 2014 and 2023 were retrospectively reviewed. Hallux valgus angle (HVA), intermetatarsal angle (IMA), Méary's angle, and tibial sesamoid position were measured on weight-bearing radiographs at 6 weeks and 6 months postoperatively. RESULTS: Both techniques achieved significant correction. The three-corner TMT arthrodesis group showed greater initial IMA correction at 6 weeks (p = 0.020) and maintained a lower IMA at 6 months (p = 0.001). Early IMA loss was greater after single first TMT arthrodesis (1.5°±1.7° vs 0.6°±0.8°, p = 0.013). CONCLUSION: Three-corner TMT arthrodesis was associated with greater early intermetatarsal stability than single first TMT arthrodesis.

Humans↗

PubMed2026

Which radiographic plane should be used to quantify the distal tibia angle on weightbearing CT images?

BACKGROUND: Precise quantification of distal tibial alignment is essential for planning corrective osteotomies and ankle joint replacement surgery. The lateral distal tibial angle (LDTA) is the principal radiographic parameter used for this purpose. While LDTA is increasingly measured on weightbearing cone-beam CT (WBCT) using two-dimensional coronal slices, the optimal measurement plane remains unclear. METHODS: In this retrospective comparative study, full-leg WBCT scans of patients scheduled for supramalleolar osteotomy (n = 20; mean age 47 ± 12.8 years) were analyzed. LDTA was measured on three coronal planes of the distal tibial plafond (anterior edge, mid-dome, posterior edge) and compared with semi-automated three-dimensional (3D) tibial alignment measurements as the reference standard. RESULTS: Mid-dome LDTA showed no significant difference from the 3D reference (p > 0.05) and demonstrated excellent agreement. Anterior measurements significantly overestimated LDTA, while posterior measurements underestimated it (both p < 0.05), with only fair agreement. CONCLUSION: LDTA should be measured at the mid-dome of the distal tibial plafond on WBCT to ensure accurate and reproducible alignment assessment. LEVEL OF EVIDENCE: Level III - Retrospective Comparative Study.

Humans↗

PubMed2026

Impact of Contact Lens Use on Clinical Profile and Outcomes of Fungal Keratitis: An 8-Year Retrospective Study.

PURPOSE: To compare clinical characteristics, microbiological profiles, treatment strategies, and outcomes between contact lens-associated (CL) and noncontact lens-associated (non-CL) fungal keratitis. DESIGN: Retrospective, comparative clinical cohort study. METHODS: A review of culture-proven fungal keratitis treated at a tertiary referral center between 2018 and 2025 was conducted. Cases were categorized as CL or non-CL-associated. Demographic, clinical, microbiological, treatment, and outcome data were analyzed and compared between groups. RESULTS: Thirty-seven eyes were included, comprising 16 CL and 21 non-CL cases. CL users presented earlier than non-CL patients (median 7 vs 14 days, P = .007) and had fewer associated ocular risk factors (31% vs 81%, P = .001). Baseline visual acuity and infiltrate size did not differ significantly between groups. Candida species were isolated in 21% cases, Fusarium in 16% and Aspergillus in 8%. Fusarium (19% vs 13%) and Candida (24% vs 19%) infections were slightly more frequent in non-CL cases. Overall, filamentous fungi were the predominant organism group. Topical voriconazole was the most frequently used antifungal agent (78%). All CL-associated cases resolved with medical therapy alone, with a median time to resolution of 38 days (IQR 22-58). In contrast, 76% of non-CL cases resolved medically (median 42 days, IQR 32-76), while 23% required therapeutic keratoplasty (P = .04). Final visual acuity was comparable between groups (logMAR 0.2 vs 0.5, P = .56). CONCLUSION: Contact lens-associated fungal keratitis is characterized by earlier presentation and fewer underlying ocular comorbidities, with favorable outcomes achieved through medical therapy alone. Despite similar microbiological profiles and treatment approaches, noncontact lens-associated fungal keratitis more frequently follows a complicated course requiring surgical intervention.

Humans↗

PubMed2026

Effect of urinary catheter securement band on meatal pressure injury in male intensive care patients: A randomized controlled trial.

OBJECTIVES: To investigate the effectiveness of a urinary catheter securement band in preventing meatal pressure injury (meatal-PI) in male ICU patients, and to identify associated risk factors and the timing of injury development. METHODS: A total of 248 adult male ICU patients were randomly allocated to an intervention group (n = 124) or a control group (n = 124) between December 2024 and April 2025. The intervention group received a catheter securement band in addition to standard care, while the control group received standard care alone. Meatal-PI was evaluated daily using a structured monitoring form and a validated staging system. RESULTS: The incidence of meatal-PI was significantly lower in the intervention group (6.5%) compared with the control group (16.1%) (p = 0.016). Multivariate analysis identified catheter securement, use of silicone catheters, higher Braden Scale scores, and shorter ICU length of stay as independent protective factors, while advanced age was associated with increased risk. Additional factors significantly associated with meatal-PI included comorbidities, higher device burden, latex catheter use, dry skin, lower Glasgow Coma Scale and Braden scores, sedation, and perineal oedema (p < 0.001). CONCLUSIONS: The use of a catheter securement band significantly reduces the incidence of meatal-PI in male ICU patients. Incorporating catheter securement devices into routine nursing care, prioritising silicone catheter use, and performing regular meatal assessments may enhance patient safety by reducing the risk of device-related pressure injuries. Further research comparing different catheter securement methods across diverse patient populations is warranted. IMPLICATIONS FOR CLINICAL PRACTICE: The use of catheter securement bands may reduce the incidence of meatal-PI in male ICU patients. Incorporating standardized catheter stabilization strategies into routine intensive care nursing practice may enhance patient safety and support pressure injury prevention efforts.

Humans↗

PubMed2026

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p < 0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2 = 50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

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PubMed2026

Effects of a programmed reflexology therapy on sleep quality, insomnia, and fatigue among individuals with poor sleep quality: evidence for autonomic nervous system modulation.

Poor sleep quality is closely associated with autonomic dysregulation and increased risks of cardiovascular, metabolic, and mental disorders. Foot reflexology is a widely used complementary therapy; however, its physiological mechanisms and comparative efficacy remain insufficiently explored. This study aimed to compare the effects of manual reflexology treatment (MRT) and foot massage equipment (FEM) on autonomic nervous system function, sleep quality, insomnia severity, and fatigue in adults with poor sleep quality. Using a randomized crossover design, 32 participants with poor sleep quality received MRT and FEM interventions for 6 weeks each (once weekly, 30-40 min/session). Heart rate (HR), blood pressure, and heart rate variability (HRV; time- and frequency-domain indices) were assessed at weeks 1 and 6 before and after each intervention. Subjective outcomes included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Fatigue Assessment Scale (FAS). Following MRT, participants demonstrated significantly greater reductions in global PSQI scores and all PSQI components compared with FEM. MRT also resulted in larger improvements in insomnia severity and both mental and physical fatigue. In contrast, FEM primarily improved physical fatigue. Physiologically, MRT induced an immediate decrease in HR and significant increases in HRV time-domain indices (SDNN, RMSSD, pNN50), which were sustained after 6 weeks. Frequency-domain analysis further revealed reduced LF, increased HF, and a lower LF/HF ratio, indicating enhanced parasympathetic activity and cumulative autonomic modulation. In conclusion, programmed manual reflexology, delivered according to the TIDieR framework, is more effective than mechanical foot massage in improving autonomic balance, sleep quality, insomnia severity, and fatigue in individuals with poor sleep quality. These findings support MRT as a feasible and evidence-based non-pharmacological complementary intervention for sleep health promotion. TRIAL REGISTRATION: clinicaltrials.gov; NCT Number: NCT07402460; Registered 3 February 2026.

Adult↗

PubMed2026

Risk factors associated with urinary tract infection within 4 days of male rectal cancer surgery in the era of enhanced recovery after surgery (ERAS) programs.

BACKGROUND: Bladder drainage is systematically used in rectal cancer surgery in male patients, even in the era of enhanced recovery after surgery (ERAS). However, little data is available on risk factors for urinary tract infection (UTI). Identifying the risk factors associated with UTI within 4 days of male rectal cancer surgery in an ERAS program could support more individualized decision-making. METHODS: We used data from the GRECCAR 10 randomized clinical trial, a comparison of outcomes of transurethral catheterization (TUC) or suprapubic catheterization (SPC). 240 patients were randomized, 209 retained in the study (TUC n = 99; SPC n = 109). Univariate and multivariate logistic regression post-hoc study analyses were performed to assess association between potential predictive factors and UTI within 30 days after surgery. RESULTS: Out of 208 patients (median age 64.5 years), 19 (9.1%) had UTI, 26 (12.5%) had bacteriuria and 145 (69.7%) had pyuria. Univariate analysis identified age ≥ 65 years (OR = 3.08 [1.07-8.89]; p = 0.038), hypertension (OR = 3.65 [1.23-10.84]; p = 0.020) and ASA score ≥ 3 (OR = 4.15 [1.53-11.2]; p = 0.005) as risk factors for UTI until POD4. Multivariate analysis identified ASA score ≥ 3 with a risk of UTI. CONCLUSION: Regarding male rectal cancer surgery, our study shows that nearly 1 in 10 patients had UTI within 4 days. An ASA score ≥ 3 is an independent risk factor linked to UTI. Identifying this risk factor for UTI is necessary to advise patients, support a tailored decision-making process, and prevent these complications.

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PubMed2026

Xerophthalmia and ocular manifestations of vitamin A deficiency in children in high-income countries: A systematic review.

Xerophthalmia is a vision-threatening eye condition caused by vitamin A deficiency (VAD). Cases of xerophthalmia in high-income countries (HICs) are vulnerable to misdiagnosis, causing delays in treatment and adverse visual outcomes. We define the features, causes and complications of VAD and xerophthalmia in children of HICs. Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD42024492023). We performed a search for eligible articles on Scopus, Web of Science, Cochrane, PubMed and Medline. Cases reporting on children under 18 years of age residing in HICs with ocular features of VAD were eligible for inclusion. The search yielded 2474 results; 43 case reports and case series met the inclusion criteria consisting of a total of 61 cases (mean age 9.9 ± 4.2 years, range 3-17 years). Xerophthalmia was graded according to the most advanced finding for each case: 21.3% had night blindness only; 29.5% had conjunctival xerosis or Bitot spots; 29.5% had corneal xerosis, ulceration or scarring; 1.6% had xerophthalmia fundus only; and 18.0% had ocular manifestations associated with VAD that are not encompassed under the WHO classification. These features included swollen optic discs, optic neuropathy, or ocular dryness. Restrictive dietary practises were the most common mechanism of deficiency (75%), and autism was the most common underlying condition (49%). This shows that VAD remains a cause of severe visual impairment in HICs, especially when associated with delays in diagnosis and treatment. Further research is required to establish the prevalence of xerophthalmia in HICs.

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PubMed2026

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals↗

PubMed2026

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale ≥3.0, n = 12) and controls (n = 10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p = 0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p < 0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p < 0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

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