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PubMed2025

Effect of transcutaneous vagus nerve stimulation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (tVNS) has shown potential in neurological, autoimmune, and cardiovascular disorders, but its effects on HD patients remain unclear. This study aimed to evaluate the efficacy and safety of tVNS in HD patients. METHODS: We conducted a randomized controlled clinical trial on patients receiving HD ≥6 months. The tVNS group received stimulation for 1 h during the first 2 h of HD sessions, three times weekly for 8 weeks, while the control group received standard care. The primary outcomes were dialysis efficiency (Single-pool Kt/V, Sp Kt/V) and dialysis-related symptoms (Dialysis Symptom Index, DSI), assessed every 4 weeks. Secondary outcomes included pain and fatigue scores, physical performance, Hemodialysis Comfort Scale, hemoglobin levels, Mini-Mental State Examination, and anxiety and depression scores, measured at baseline and 8 weeks after intervention. RESULTS: A total of 63 patients were enrolled in the study, with 32 patients assigned to the tVNS group and 31 patients to the control group. At 8 weeks, the tVNS group showed significant improvements in Sp Kt/V (1.31 ± 0.11 vs. 1.25 ± 0.10, p = 0.02), and DSI (12.09 ± 5.84 vs. 16.26 ± 5.27, p = 0.004), as well as reductions in pain and fatigue, and increases in physical function, comfort, and hemoglobin. However, there were no statistically significant changes observed in cognitive function, anxiety, or depression. CONCLUSIONS: tVNS could improve dialysis efficiency, symptoms, and physical function in HD patients, indicating it may have a role as a complementary therapy.

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PubMed2026

Endovascular intervention for acute stroke in the very late window: A meta-analysis of 90-day mRS and procedural outcomes.

OBJECTIVE: This study investigates the effectiveness of Endovascular Therapy (EVT) in very late windows (beyond 24 h) for patients with ischemic stroke, focusing on 90-day mortality, functional outcomes, and procedural success. METHODS: This systematic review and meta-analysis followed Cochrane and PRISMA guidelines to evaluate the effectiveness of endovascular therapy (EVT) in acute ischemic stroke patients. Literature from PubMed, Embase, Web of Science, and Scopus was reviewed using specific keywords. Studies included those after 2000 with outcomes such as functional independence (mRS 0-2), mortality, TICI scores, and neurological improvements. RESULTS: The data findings reveal mixed outcomes across studies on EVT beyond 24 h. Sarraj et al. (2023) found a significant improvement in functional independence with EVT (38% vs. 10%, p < 0.05), despite an increased risk of sICH. The forest plots for mRS and procedural outcomes show some significant results, such as Sarraj (2023) for mortality (p < 0.05), but most other studies indicated no statistically significant differences (p > 0.05). CONCLUSION: The study has concluded that Endovascular Therapy (EVT) beyond 24 h can improve functional outcomes and reduce mortality in selected ischemic stroke patients, though patient selection remains crucial.

Humans↗

PubMed2026

Eltrombopag Added to Standard Immunosuppressive Treatment as Front-Line Therapy for Severe Aplastic Anemia: Long-Term Outcomes of the Phase-3 Randomized Superiority EBMT-SAAWP RACE Study.

The RACE study (NCT02009747) compared horse antithymocyte globulin (hATG) plus cyclosporine A (CsA) ± eltrombopag as initial immunosuppressive treatment (IST) for severe aplastic anemia. Here we report the final 2-year analysis of this prospective randomized phase III study. One hundred ninety-seven treatment-naive patients were randomized to standard IST (hATG 40 mg/kg × 4 days and CsA 5 mg/kg/day; arm A; n = 101) or standard IST + eltrombopag at the dose of 150 mg/day (arm B; n = 96) from day +14 until 6 months (or 3 months, in case of complete response). The median follow-up was 23.2 months. The 2-year cumulative incidence of complete response was significantly superior in arm B (62.4% vs. 35.3%; p < 0.001). The 2-year overall survival (OS) was 86% in arm A and 91% in arm B (p = 0.081), with hazard ratio (HR), adjusted for age and disease severity, of 0.54 (p = 0.064). The 2-year disease-free survival (DFS) was 56% vs. 37% (adjusted HR = 0.49; p < 0.001), while event-free survival (EFS) was 48% vs. 32% (p < 0.001), with adjusted HR = 0.54 (p < 0.001), both significantly superior for arm B. The cumulative incidence of relapse was comparable in the two arms, while evolution to clinical paroxysmal nocturnal hemoglobinuria was 8% in arm A and 1% in arm B (p = 0.041). The risk of clonal evolution remained negligible, with one patient in arm A and two in arm B developing karyotypic abnormalities. The initial hematological response benefit of eltrombopag added to IST as front-line treatment of AA is associated with better 2-year OS, DFS, and EFS without increased risk of secondary myeloid malignancies.

Humans↗

PubMed2026

Timing of OMERACT core domain measurement in gout clinical trials: a systematic review of randomised trials.

AIMS: The Outcome Measures in Rheumatology (OMERACT) initiative has endorsed core domain sets for gout trials. The aims of this study were to evaluate the time points and frequencies at which the gout core domains are measured in existing gout urate-lowering therapy and gout flare trials, and whether all collected measurements were reported. METHODS: Urate-lowering therapy (n = 29) and gout flare randomised clinical trials (n = 14) from 2005 were identified from a prior systematic review of core domain reporting. Data were extracted for the time points and frequencies at which each core domain was measured, as well as whether all collected measurements were reported. RESULTS: In urate-lowering therapy trials, the core domains were measured at seven different frequencies. Serum urate and gout flares were most commonly measured monthly, and tophus burden was most commonly measured three monthly. Reporting of all collected measurements varied, from 24/29 (83%) trials for serum urate to 0/2 (0%) trials for activity limitation. In gout flare trials, core domains were measured at nine different frequencies. Pain, joint tenderness and joint swelling were most commonly measured monthly. Reporting of all collected measurements varied, from 13/14 (93%) trials for pain to 3/8 (37.5%) trials for joint tenderness. CONCLUSION: In both urate-lowering therapy and gout flare trials, there is substantial variability in when the core domains are measured, and reporting of collected measurements is inconsistent. This work provides the foundation for a consensus process to establish standardised time points and frequencies for measuring the OMERACT-endorsed gout core domains.

Gout↗

PubMed2026

From host response to genomic targets: electrochemical biosensing of tuberculosis biomarkers.

Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, with timely diagnosis continuing to be a major challenge, particularly in resource-limited settings. Conventional TB diagnostic methods are limited by low sensitivity, long turnaround times, and an inability to reliably differentiate latent from active disease. Biomarker-based diagnostic strategies have therefore gained increasing attention as they offer the potential to improve early detection, disease differentiation, and treatment monitoring. Herein, we examine electrochemical biosensing strategies for TB diagnostics using a biomarker-class-driven framework, covering host-response biomarkers (IFN-γ and TNF-α), pathogen-derived antigens (ESAT6, CFP10, CFP10-ESAT6, MPT64, Ag85, HspX and LpqH), cell-wall signatures and whole-cell markers (LAM and whole cell Mtb), and genomic markers (Mtb DNA and IS6110). Through structured comparison of recognition elements, biointerface designs, signal amplification strategies, electrochemical techniques, matrices, and validation levels, this review identifies the most promising technical approaches for different TB biomarker classes. It further highlights key translational bottlenecks, including limited clinical validation, buffer-based testing, complex multistep amplification, redox-probe dependence, matrix fouling, and insufficient evidence of manufacturability. This review therefore provides practical guidance for developing electrochemical TB biosensors that are analytically sensitive, clinically relevant, and suitable for decentralized diagnostic applications.

Biosensing Techniques↗

PubMed2026

EZH1/2 inhibition selectively targets SMARCA4/2 co-deficient lung cancer cells by suppressing stemness and proliferation.

SMARCA4-deficient thoracic malignancies comprise biologically heterogeneous tumors, ranging from conventional non-small cell lung cancer with SMARCA4 alterations to thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT), an aggressive entity frequently associated with concomitant SMARCA2 loss. However, the extent to which SMARCA4-deficient lung cancer cell lines recapitulate SMARCA4-UT-like biology remains incompletely defined. Here, we characterized lung cancer cell lines across distinct SMARCA4 and SMARCA2 states and identified a subgroup with SMARCA4/2 co-deficiency that exhibited reduced expression of epithelial lineage markers and transcriptional similarity to SMARCA4-UT and other SWI/SNF-deficient malignancies. The EZH1/2 inhibitor HM97662 selectively suppressed growth in SMARCA4/2-deficient cells, with limited effects in SMARCA2-proficient cells. EZH1/2 inhibition broadly reduced H3K27me3 and induced derepression of PRC2 targets regardless of drug sensitivity. However, its biological effects were most pronounced in SMARCA4/2-deficient cells, where it promoted apoptosis, reduced stemness marker expression, attenuated the SMARCA4-UT-associated transcriptional signature, and suppressed proliferative and mTORC1-related programs. Chromatin accessibility analysis further revealed cell-line-specific patterns of accessibility loss, with reduced accessibility at stemness-associated transcription factor motif-enriched regions coupled with transcriptional repression of nearby genes in SMARCA4/2-deficient cells. These findings support dual EZH1/2 inhibition as a potential therapeutic vulnerability in SMARCA4/2-deficient, SMARCA4-UT-like lung cancer cells.

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PubMed2026

Novel Proactive Speech-Language Intervention Is More Effective Than Usual Care: Randomized Controlled Trial of Babble Boot Camp for Infants With Classic Galactosemia.

PURPOSE: Speech and language disorders cannot be diagnosed and treated until children are approximately 2-4 years old. To investigate whether these disorders can be prevented, we developed and trialed Babble Boot Camp (BBC), the first proactive sustained intervention starting with precursor skills including cooing and babbling. METHOD: Participants were two randomly assigned groups of 22 infants with classic galactosemia, a metabolic disease with known risks for severe speech and language disorders. One group started BBC at under 6 months of age, and the other started at 15 months of age, both completing BBC at 24 months of age. Coached by a speech-language pathologist in weekly telehealth sessions, caregivers implemented BBC activities and routines daily at home. A typical control group and a group of children with classic galactosemia who received usual care participated as well. All children completed standardized assessments of speech and language at postintervention. RESULTS: Assessment scores showed that BBC was more effective than usual care for both intervention groups. Greatest benefits were seen in the group that started at or before 6 months of age, with a proportion of clinically concerning scores equal to that in the typically developing peers. No effects of sex, genotype, or milk consumption were evident in the outcomes. CONCLUSIONS: Findings motivate a paradigm shift from deficit-based to proactive approaches for infants with classic galactosemia. BBC is extensible to many other disorders, with trials currently underway for infants with Down syndrome and infants born preterm.

Humans↗

PubMed2026

From pathobiology to prescribing in obesity-driven HFpEF: A systematic review and practical therapeutic framework.

Heart failure with preserved ejection fraction (HFpEF) is increasingly driven by obesity and cardiometabolic dysfunction. In this phenotype, the dominant biology extends beyond congestion alone and includes visceral and epicardial adiposity, systemic inflammation, impaired myocardial energetics, endothelial dysfunction, and exertional elevation in filling pressures. We performed a PRISMA-compliant systematic review with structured narrative evidence synthesis to evaluate pharmacological therapy in obesity-driven HFpEF, searching PubMed/MEDLINE, Scopus, Web of Science Core Collection, ClinicalTrials.gov, and WHO ICTRP through December 2025. Eighteen reports were included in the final qualitative synthesis. The available evidence supports sodium-glucose cotransporter 2 inhibitors as the pharmacological foundation because they provide the most mature outcome data across the preserved ejection fraction spectrum. Semaglutide improves symptoms, physical limitations, exercise capacity, and body weight in dedicated obesity-related HFpEF trials, whereas tirzepatide extends this signal by improving clinical status and reducing worsening heart failure events. Finerenone broadens the therapeutic platform in HF with mildly reduced or preserved ejection fraction, although obesity-specific data remain indirect. Conventional neurohormonal therapies retain a selective role, but they are not the principal biological match for this phenotype. Obesity-driven HFpEF should therefore be managed as a cardiometabolic syndrome with heart failure expression, using a phenotype-based sequence that links diagnosis, decongestion, SGLT2 inhibition, obesity-directed therapy, and selective adjunctive intensification.

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PubMed2026

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n = 6; 16.2%), nicotine replacement therapy (n = 7; 18.9%), behavioral counseling (n = 12; 32.4%), or combined/multicomponent interventions (n = 12; 32.4%). Most studies were conducted in India (n = 26; 70.3%), followed by Pakistan (n = 6; 16.2%), Nepal (n = 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p = 0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

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PubMed2026

Cisplatin-Induced Hearing Loss Prevention With Intratympanic Therapy Systematic Review and Meta-Analysis.

INTRODUCTION: Cisplatin-induced hearing loss (CIHL) is a well-described, long-term consequence of cisplatin treatment for malignancy. Intratympanic (IT) injections have been trialed to prevent CIHL in humans. To provide clarity on which agents have been studied through IT injection and to review their efficacy for hearing loss prevention, we performed a systematic review and meta-analysis. DATA SOURCES: OVID Medline, Embase, Web of Science, and Cochrane Library were queried. METHODS: Databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective randomized trials were included, and a systematic review was performed for all studies. Demographic, audiometric, and therapeutic data were collected. Random-effects models were used to compare across studies, and subgroup analyses were performed for each IT agent. RESULTS: The initial database search yielded 1017 articles, which were screened according to inclusion and exclusion criteria. Ten studies were identified, involving a total of 284 patients. Studies included data on IT dexamethasone, IT N-acetylcysteine (NAC), and IT sodium thiosulfate (STS). Pooled analysis across all agents and frequencies did not reveal a significant difference in hearing thresholds between treatment and control ears [prediction interval [-3.77, 3.20], negative favors treatment). Subgroup analysis of IT dexamethasone [-1.74, 3.80] and IT NAC [-1.02, 4.64] also did not demonstrate significant differences. STS data were not amenable to pooled analysis; however, one study demonstrated a significant decrease in ASHA-defined ototoxicity (40% vs. 85%, P =0.0027). CONCLUSIONS: To date, no IT agent has consistently prevented CIHL, although limited data suggest that IT STS may decrease ototoxicity. More trials are necessary to fully elucidate these effects.

Humans↗

PubMed2026

Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

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PubMed2026

Implementation of Mobile Health Intervention Targeting Belongingness and Burdensomeness: An Ecological Momentary Assessment Study of Self-Injurious Thoughts and Behaviors in LGBTQ+ Individuals.

OBJECTIVE: The goal of this paper was to test a mobile health intervention designed to reduce self-injurious thoughts and behaviors in LGBTQ+ individuals. The intervention consisted of brief messages aimed at increasing feelings of belongingness and meaning. METHOD: We recruited LGBTQ+ individuals (N = 55) with past-month self-injurious thoughts and/or behaviors. Participants completed 14 days of ecological momentary assessment (EMA) of minority stress, thwarted belongingness, perceived burdensomeness, and self-injurious thoughts and behaviors. Then, participants were randomly assigned to receive brief messages designed to instill belongingness and meaning/purpose, or no intervention for 14 days. Then, participants completed an additional 14 days of EMA. RESULTS: Our results showed that participants in the control condition had significant increases in self-injurious thoughts and planning over time, whereas those in the intervention condition showed no significant change. For self-injurious behavior, thwarted belongingness, and perceived burdensomeness, there were significant decreases in the intervention condition, but no changes in the control condition. CONCLUSIONS: These results provide support for the interpersonal theory of suicide and indicate a potentially scalable mobile health intervention. PUBLIC HEALTH SIGNIFICANCE: This paper found evidence that a brief mobile health intervention reduced suicidal and non-suicidal self-injurious thoughts and behaviors among LGBTQ+ individuals.

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PubMed2026

Does future-oriented imagery rescripting increase willingness to carry out a social anxiety-related behavioral experiment? An extended replication.

BACKGROUND AND OBJECTIVES: Mental images of threat are common in social anxiety disorder and could impede exposure to fear-relevant situations. Landkroon et al. (2022) found that imagery rescripting of anticipated future threat, compared to no-task, increases willingness of non-clinical individuals to conduct a social anxiety-related behavioral experiment. The aim of this two-day preregistered extended replication study was to examine whether the effects persist beyond the intervention session by scheduling the behavioral experiment 1-7 days after the intervention. METHODS: On Day 1, 60 pre-screened participants were asked to design a behavioral experiment to test an idiosyncratic negative belief about a feared social situation. They were then randomly assigned to imagery rescripting (focused on their worst feared outcome of the behavioral experiment) or no-task. Participants' willingness to do the behavioral experiment and their threat beliefs was measured. On Day 2, they were asked to carry out the behavioral experiment. RESULTS: The imagery rescripting group, compared to the control group, did not show increased willingness or compliance to do the behavioral experiment on Day 1 or 2. Furthermore, the imagery rescripting did not lead to greater reductions in threat beliefs on either day. LIMITATIONS: The quality of the imagery rescripting intervention was not assessed, and given the brief nature of the intervention, any effects may have dissipated before participants decided whether to carry out the behavioral experiment. CONCLUSIONS: There was no evidence that imagery rescripting leads to changes in willingness or compliance to do a fear-relevant behavioral experiment. More research is needed to examine interventions that can enhance exposure in socially anxious people.

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PubMed2026

Patient expectations assessed before randomisation and after the first treatment session, and their associations with pain outcome at 3 months in patients with tennis elbow: a secondary analysis of a randomised controlled feasibility trial in Norwegian secondary care.

OBJECTIVE: To evaluate patients' expectations of pain improvement before randomisation (T1) and after the first treatment (T2), and to examine how expectations at these two time points were associated with pain outcome measured at 3 months (T3). DESIGN: Exploratory secondary analyses of a three-arm, randomised controlled feasibility trial in patients with tennis elbow comparing heavy slow resistance training, shock wave therapy and advice (1:1:1). SETTING: Outpatient clinic at Oslo University Hospital. PARTICIPANTS: Adults with lateral epicondylalgia, commonly known as tennis elbow. MAIN OUTCOME MEASURES: Expected pain was rated on a Numeric Rating Scale (NRS, 0-10) at T1 and T2. Present pain (NRS, 0-10) was reported at 3 months (T3). Changes in expectations from T1 to T2 were summarised descriptively. Univariable linear regressions assessed associations between T3 pain and expectations at T1 and T2, treatment group and baseline factors. Explained variance was quantified by R2. Multivariable models including demographics and baseline pain were evaluated via adjusted R2. RESULTS: Fifty-four participants were included. In the shock wave group, nine (47%) came to expect greater improvement from T1 to T2; by contrast, in the advice group, seven (41%) expected less improvement. Expectations at T1 were not associated with T3 pain, whereas expectations at T2 were positively associated with T3 pain (b=0.61, 95% CI 0.33 to 0.89, p<0.01, R2=0.27), suggesting that higher expected pain at T2 was associated with higher reported pain at T3. Adding education and baseline pain increased explained variance modestly (R2 from 0.27 to 0.32). CONCLUSION: In this study, expectations measured after randomisation and one treatment session were associated with pain at 3 months for patients with tennis elbow. Larger, prospectively designed studies should investigate how postrandomisation expectations relate to clinical outcomes in non-blinded musculoskeletal trials. TRIAL REGISTRATION NUMBER: NCT04803825.

Humans↗

PubMed2026

Outcomes of Stage IVA Cervical Cancer Treated with Radiation Therapy: A Systematic Review and Meta-Analysis.

FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We performed a systematic review and meta-analysis to evaluate survival outcomes, treatment-related morbidity, and prognostic factors in patients with stage IVA cervical cancer treated with definitive radiotherapy. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42024602426), PubMed, Embase, and Web of Science were searched through February 2025. Eleven studies comprising 492 patients met eligibility criteria. Pooled random-effects analyses demonstrated 2-, 3-, and 5-year disease-free survival rates of 41.5% (95% CI, 28.1-55.0), 34.2% (95% CI, 21.1-47.3), and 30.9% (95% CI, 16.0-45.8), respectively. Corresponding overall survival rates were 56.0% (95% CI, 46.2-65.9), 45.9% (95% CI, 35.9-55.9), and 34.8% (95% CI, 26.4-43.3). Weighted median disease-free survival and overall survival were 15.6 and 33.6 months, respectively. The pooled incidence of vesicovaginal or rectovaginal fistula was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 below 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy were consistently associated with improved outcomes. Despite curative-intent treatment, long-term survival remains poor and treatment-related morbidity substantial. Durable pelvic control remains the principal therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy appears essential for optimal outcomes, while future stage IVA-specific studies incorporating image-guided adaptive brachytherapy, advanced radiotherapy techniques, and systemic treatment intensification are needed to improve survival and reduce treatment-related morbidity.

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PubMed2026

The Impact of Upper Extremity Rehabilitation on Fatigue in Individuals With Multiple Sclerosis: A Systematic Review.

BACKGROUND: Although numerous interventions have been investigated to alleviate fatigue in people with multiple sclerosis (PwMS), evidence regarding the effects of upper extremity rehabilitation on fatigue remains limited. OBJECTIVE: The objective of this review was to evaluate and synthesize the available evidence on the effects of upper extremity rehabilitation interventions on fatigue in PwMS. METHODS: This review was conducted in accordance with the PRISMA guidelines and was prospectively registered in the PROSPERO database. A systematic search of PubMed, Web of Science, and Scopus was performed up to August 2026. Studies were eligible if they investigated the effects of upper extremity rehabilitation interventions on fatigue in PwMS. The risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 (RoB 2), and the certainty of the evidence was appraised using the GRADE methodology. RESULTS: Nine studies including 250 participants (136 intervention, 114 control) met the inclusion criteria. The included studies evaluated a range of technology-assisted, exercise-based, home-based, and task-oriented upper extremity rehabilitation approaches, with some interventions incorporating more than one therapeutic or technological component. Fatigue outcomes were measured using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Risk of bias was low in three randomized controlled trials, with some concerns in two and high in two; among the two crossover studies, one was rated as low risk and one as high risk. GRADE assessment showed low certainty of evidence for studies using the FSS and very low certainty for those using the MFIS, indicating an overall low certainty of the available evidence. CONCLUSIONS: The available evidence is insufficient to draw definitive conclusions regarding the effects of upper extremity rehabilitation on fatigue in PwMS. Further high-quality randomized controlled trials are required.

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PubMed2026

Whole genome sequencing of unusual Hepatitis C virus subtypes and drug resistance analysis during direct-acting antiviral therapy in India.

INTRODUCTION AND OBJECTIVES: Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment. PATIENTS AND METHODS: In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis. RESULTS: Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors. CONCLUSION: This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.

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PubMed2026

Bacterial Lysates Add-On Therapy to Reduce Postoperative Recurrence in Nasal Polyps.

OBJECTIVE: This study aimed to investigate the potential role of OM-85 in reducing polyp recurrence (PR). METHODS: A single-center randomized, prospective study was performed to compare the inter-group PR rate, patient-reported outcome measures (PROMs), CT and endoscopic scores. Hundred patients were randomized to receive either add-on OM-85 (34/50) or control group (43/50); 77 participants completed the 12-month follow-up. The OM-85 group received oral treatment for 10 days, followed by a 20-day washout (Months 1-3 and 7-9). Primary outcome was the PR rate. Secondary outcomes included PROMs, Lund-Kennedy (L-K) scores, Lund-Mackay (L-M) scores, and complete blood count (CBC) parameters. RESULTS: The PR rate was significantly lower in the OM-85 group (8.82%) than in the control group (27.91%, χ 2 = 4.408, p = 0.036). Univariable analysis identified pre-operative Lund-Mackay (L-M) score (p = 0.008) and hyposmia VAS score (p = 0.031) as significant predictors of PR. In multivariable analysis, the L-M score remained an independent predictor (OR = 1.15, p = 0.012), with an optimal cutoff of 10. The OM-85 group showed significant improvements in nasal obstruction, olfactory dysfunction, and mucopurulent discharge at 6 and 12 months (p < 0.05). Lund-Kennedy (L-K) score and 22-item Sinonasal Outcome Test (SNOT-22) score were also significantly improved (p < 0.05). Furthermore, the OM-85 group exhibited elevated white blood cell counts and lymphocyte percentages from 6 months onward (p < 0.05). CONCLUSION: Adjuvant OM-85 may reduce postoperative PR, with improved endoscopic and symptom scores, potentially mediated by enhanced systemic immune function.

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