SEARCH · Search PubMed

Results for “Dual Anti-Platelet Therapy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

753 records · Page 2Linked to original sources

PubMed2026

Efficacy and Safety of a Single-Pill Triple Combination of Valsartan, Amlodipine, and Chlorthalidone in Patients With Essential Hypertension Inadequately Controlled on Dual Therapy With Valsartan and Amlodipine: A Randomized, Double-Blind, Multicenter, Phase 3 Trial.

Many hypertensive patients require three or more antihypertensive agents to achieve target blood pressure. This randomized, double-blind, multicenter phase 3 trial conducted in South Korea evaluated the efficacy and safety of a single-pill triple combination therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients whose blood pressure remained inadequately controlled on Val/Aml dual therapy. Patients uncontrolled after 4 weeks of Val/Aml 80/5 mg were randomized 1:1 to either Val/Aml/CTD 80/5/12.5 mg or Val/Aml 80/5 mg using a double-dummy design. After 2 weeks, doses were escalated to Val/Aml/CTD 160/5/25 mg or Val/Aml 160/5 mg, respectively, for a total treatment duration of 6 weeks. The primary endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Of 193 randomized patients, 178 completed the study. The least squares mean ± SE change in MSSBP was -19.70 ± 1.31 mmHg in the Val/Aml/CTD group versus -8.71 ± 1.26 mmHg in the control group, yielding a statistically significant between-group difference of -10.99 ± 1.81 mmHg (95% CI, -14.56 to -7.41; p < 0.0001). No serious adverse events occurred in the Val/Aml/CTD group, compared with an incidence of 1.98% in the control group (p = 0.4985). Triple combination therapy with Val/Aml/CTD demonstrated superior blood pressure reduction and a favorable safety profile in patients with essential hypertension inadequately controlled on Val/Aml dual therapy, supporting its use as an effective treatment option in this population. Trial Registration: This trial was prospectively registered at ClinicalTrials.gov (identifier: NCT06416865).

Humans↗

PubMed2026

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count < 50 × 109/L) received rhTPO (n = 80) or placebo (n = 40) once daily for up to 5 or 7 days. The primary endpoint was the proportion of patients with sustained platelet counts ≥ 50 × 109/L from 24 h before invasive procedure to 7 days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p < 0.0001). Preoperatively, platelet counts ≥ 50 × 109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p < 0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p < 0.0001). The median duration of platelet counts ≥ 50 × 109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0 days, p = 0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans↗

PubMed2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans↗

PubMed2026

Flap Versus Tunneling for Horizontal Ridge Augmentation With FDBA and i-PRF: A Randomized Controlled Clinical Trial.

AIM: This study evaluated the efficacy of conventional flap and tunneling techniques for horizontal alveolar ridge augmentation using freeze-dried bone allograft (FDBA) particles combined with injectable platelet-rich fibrin (i-PRF). MATERIALS AND METHODS: Forty-five patients were randomly allocated to one of three groups (n = 15 each): conventional flap (CF), tunneling with membrane (TM), or tunneling without membrane (TnM). Preoperative ridge width was measured via cone beam computed tomography (CBCT). All augmentation procedures incorporated FDBA and i-PRF; an absorbable collagen membrane was applied in the CF and TM groups. Follow-up assessments, including CBCT imaging and histomorphometric analysis, were conducted 6 months postoperatively. For normally distributed data, ANOVA with Tukey's post hoc test and paired samples t-test were applied. Non-normally distributed data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. RESULTS: Statistical analysis was performed on 43 patients. All groups demonstrated an increase in ridge width after 6 months. At the 2 mm level, the mean width gain was 1.28 mm (95% CI: 0.17 to 2.40) in the TM group, 2.85 mm (95% CI: 1.80 to 3.89) in the TnM group, and 1.95 mm (95% CI: 1.07 to 2.83) in the CF group. However, statistical analysis revealed no significant intergroup variation (p > 0.05). Histomorphometric assessments similarly demonstrated comparable outcomes across all groups, with no statistically significant differences observed (p > 0.05). CONCLUSION: Within the limitations of this study, the tunneling technique, regardless of membrane use, appears to be a clinically viable alternative to the conventional flap method for horizontal alveolar ridge augmentation. However, further studies with longer follow-up periods are required to substantiate these findings. TRIAL REGISTRATION: irct.behdasht.gov.ir identifier: IRCT 20101204005305N21.

Humans↗

PubMed2026

The effect of zalunfiban on high sensitivity cardiac troponin and the association with clinical outcomes in patients with STEMI.

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on Myocardial Infarction (MI) size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with 2 doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P = .006) and more frequent Q wave development (P < .001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P < .05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P = .03), cardiovascular death (OR 1.83 per log unit increase; P = .03), heart failure (OR 2.74 per log unit increase; P < .001) or the composite of death and heart failure (P < .001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P = .04) and across multiples ≥ 10 to ≥ 1,000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSIONS: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher-risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. TRIAL REGISTRATION: A phase 3 study of zalunfiban in subjects with ST-elevation MI (CELEBRATE); NCT04825743.

Humans↗

PubMed2026

Preparation and study of non-thrombotic and biostable sulfobetaine-modified small-diameter polyurethane vascular grafts.

A novel sulfobetaine-modified polysiloxane-polycarbonate polyurethane (ZSiPCU) was synthesized. In vitro characterizations revealed that polysiloxane surface enrichment endowed the material with excellent biostability. Importantly, sulfobetaine zwitterions formed a robust hydration layer, effectively suppressing protein adsorption and platelet adhesion to ensure outstanding hemocompatibility. Furthermore, the material supported the adhesion and proliferation of vascular endothelial cells, confirming its cytocompatibility, while its elastomeric matrix provided rapid mechanical self-sealing capabilities. Electrospun ZSiPCU grafts were evaluated in a 3-month rat abdominal aorta model, maintaining high patency rates and facilitating in situ luminal endothelialization and smooth muscle cell remodeling. Additionally, superior puncture resistance of the grafts was demonstrated by puncture tests, with complete hemostasis achieved within 2 mins through mechanical self-sealing.

Polyurethanes↗

PubMed2026

Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses.

Emerging evidence has demonstrated the additional therapeutic benefits of ticagrelor in acute coronary syndrome (ACS) patients with diabetes. However, the underlying mechanisms of this association remain elusive. Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on ticagrelor, plasma proteomics and type 2 diabetes was employed to identify causal mediator proteins. RNA sequencing (RNA-seq) of ticagrelor-treated HepG2 cells revealed the molecular pathways regulating glucose metabolism. Genetically proxied ticagrelor was significantly associated with a reduced risk of diabetes (OR = 0.859, 95% CI: 0.783-0.934, P = 7.98E-05), and 24.41% of this effect was mediated by upregulation of BDH2 protein. In vitro experiments confirmed the enhanced effect of ticagrelor on glucose consumption. Transcriptome analysis revealed that mitochondrial respiratory chain transfer and oxidative phosphorylation (OXPHOS) were significantly enriched, and genes related to ATP biosynthesis were significantly upregulated. These findings highlight the non-platelet function of ticagrelor in maintaining glucose homeostasis, providing insights into potential drug repurposing in the future.

Humans↗

PubMed2026

Low-Dose Perineural Dexamethasone Enhances Analgesia After Pediatric Hand Surgery Without Elevating Systemic Stress Markers: A Randomized Controlled Trial.

BACKGROUND: Supraclavicular brachial plexus block is a widely used technique for upper limb surgery in children. Although perineural dexamethasone has demonstrated efficacy in prolonging analgesia in adults, data on its optimal dosing and systemic safety in pediatric patients are limited. This study aimed to evaluate whether low-dose perineural dexamethasone can prolong postoperative analgesia without increasing systemic stress markers in young children undergoing hand or wrist surgery. METHODS: In this triple-blinded, randomized controlled trial (ClinicalTrials.gov Identifier: NCT06086392), 90 children aged 3 months to 6 years undergoing elective upper extremity surgery were assigned to receive supraclavicular brachial plexus block with 0.2% ropivacaine combined with either normal saline (control), dexamethasone 0.05 mg/kg, or dexamethasone 0.1 mg/kg. The primary outcome was time from arrival in the postanesthesia care unit to first administration of rescue opioid analgesia. Secondary outcomes included total opioid consumption, postoperative pain intensity using the FLACC scale, blood glucose levels, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and time to motor recovery. RESULTS: Both dexamethasone groups demonstrated significantly prolonged time to first opioid use compared with the control group (mean±SD: 19.4±2.2 h in the 0.1 mg/kg group, 16.0±1.9 h in the 0.05 mg/kg group, and 8.5±1.3 h in controls; P <0.0001). Total opioid consumption was significantly reduced in the dexamethasone groups. Postoperative pain scores were lower in both intervention groups, especially during the first 12 hours. No significant differences were found among groups in blood glucose, inflammatory markers, or incidence of nerve deficits. Motor recovery was delayed in the dexamethasone groups but did not interfere with early mobilization. CONCLUSIONS: Low-dose perineural dexamethasone (0.05 to 0.1 mg/kg) safely and effectively prolongs postoperative analgesia and reduces opioid needs in children undergoing upper limb surgery, without causing systemic metabolic or inflammatory disturbances. The 0.05 mg/kg dose may offer a more favorable balance between analgesic efficacy and motor recovery time. LEVEL OF EVIDENCE: Level I-randomized controlled trial.

Humans↗

PubMed2026

Maternal disease control and pregnancy outcomes with anti-CD20 therapy versus natalizumab in multiple sclerosis: a systematic review.

BACKGROUND: Management of multiple sclerosis (MS) during pregnancy requires balancing maternal disease control with fetal safety. Among high-efficacy disease-modifying therapies, anti-CD20 monoclonal antibodies and natalizumab are commonly used in women with active disease, yet their comparative effectiveness and safety during pregnancy remain incompletely defined. This systematic review evaluated maternal disease activity and pregnancy-related outcomes associated with anti-CD20 exposure compared with natalizumab in pregnant women with MS. METHODS: PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library were searched from inception through February 2026. Eligible studies included pregnant women with MS exposed to anti-CD20 before or during pregnancy and reporting maternal disease activity compared to natalizumab. RESULTS: Seven studies were included, comprising six observational cohort studies and one pharmacovigilance disproportionality analysis. Across studies, anti-CD20 exposure was consistently associated with lower relapse activity than natalizumab, particularly in the postpartum period. Anti-CD20 strategies were also associated with markedly lower postpartum MRI activity and more favorable disability-related outcomes where reported. Meta-analysis of three studies demonstrated a significant reduction in postpartum MRI activity with anti-CD20 therapy compared with natalizumab (RR 0.06, 95% CI 0.02-0.24; I² = 0%). No clear increase in major congenital anomalies was identified, although some data suggested higher odds of small for gestational age and maternal antibiotic use with anti-CD20 exposure. CONCLUSIONS: Anti-CD20 therapy was associated with lower maternal disease activity than natalizumab during pregnancy, especially for relapse prevention and postpartum MRI suppression. However, evidence regarding fetal and neonatal safety remains limited, warranting cautious individualized treatment decisions and further comparative research.

Humans↗

PubMed2026

The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.

Our goal is to determine whether adjunctive aqueous suppressants (topical β-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (±timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.

Humans↗

PubMed2026

Frontline therapies for adult patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia: a systematic literature review.

OBJECTIVES: Philadelphia (Ph) chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) is the most common ALL in adults. Overall survival (OS) with frontline chemotherapy remains poor. Blinatumomab is currently the only targeted agent approved for frontline treatment. METHODS: We systematically reviewed 96 studies (43 interventional, 53 observational) between 2012-2026 evaluating frontline pharmacologic therapy in adults with Ph- B-ALL. RESULTS: Across chemotherapy studies, nearly half of patients relapsed within 3 years, and only 49%-69% survived beyond 3 years. Blinatumomab demonstrated robust and consistent efficacy in first complete response (CR1), supported by 2 randomized controlled trials (RCT) and 16 single-arm trials (SAT). In one RCT, blinatumomab reduced the risk of death by 59% versus chemotherapy alone (HR 0.41) when added to frontline consolidation in minimal residual disease (MRD) negative patients. Median OS reached 41.2 months in a SAT where blinatumomab monotherapy was administered to patients in MRD-positive CR1. SATs showed consistent efficacy outcomes regardless of age, MRD status, or chemotherapy backbone. DISCUSSION: Additional targeted therapies still under investigation have shown mixed results. CONCLUSION: Frontline inotuzumab (±blinatumomab) plus chemotherapy showed promise in older populations, while the efficacy benefit of rituximab was inconclusive. No new safety signals were identified in the frontline setting for targeted therapies.

Humans↗

PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗

PubMed2026

Direct Oral Anticoagulants as Primary or Secondary Treatment for Heparin-Induced Thrombocytopenia (HIT) and Associated Thromboembolism (HITT)-A Meta-Analysis.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is associated with a high risk for thrombosis. The role of direct oral anticoagulants (DOACs) is still emerging and data are limited considering efficacy and safety among patients with HIT. The aim of this review is to evaluate current data on DOACs as primary or secondary treatment among patients with HIT. METHODS: This is a systematic review utilising Pubmed, Scopus and Embase online databases. Eligible studies were published up to December 2024 evaluating DOACs as primary or secondary treatment among patients with HIT and/or associated thrombosis (HITT). Primary outcomes included thrombosis rate (TR) and bleeding rate (BR) during follow-up. RESULTS: A total of 44 publications were included (29 case reports, 5 case studies and 10 cohort studies [n > 10 patients]). Regarding treatment, 19 articles evaluated only rivaroxaban, 7 articles only apixaban, 11 articles only dabigatran and 7 articles more than one regimen. A total of 352 patients were included. Overall, 190 patients (53.8%) were given DOAC as primary treatment whereas 162 patients were given a parenteral treatment first and continued with a DOAC. Mean nadir platelet count at diagnosis was 63 000/μL. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6 months. TR was 20/352 (Pooled proportion = 0.064 [95% CI = 0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion = 0.039 [95% CI = 0.022-0.062]). Finally, there was no difference found regarding TR and BR between primary or secondary treatment, and among different regimens. CONCLUSIONS: DOACs are associated with low rates of thrombosis and major bleeding among patients treated for HIT or HITT, either as primary or secondary treatment. However, the certainty of evidence is very low because of the quality and limitations of the available studies.

Humans↗

PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans↗

PubMed2025

New insights into soil amendment: Impact of humic acid on typical antibiotic resistance in agricultural soil.

Humic acid (HA) addition can improve agricultural soil, but little is known about how it affects the soil resistome. In this study, we used selective agar plate combined with quantitative PCR (qPCR) and 16S rRNA gene sequencing to investigate how HA influences antibiotic resistant bacteria (ARB) and antibiotic resistant genes (ARGs) in soil contaminated with erythromycin and kanamycin. 0.1 % HA reduced the abundance of culturable erythromycin-resistant bacteria (ERB), while promoting the growth of kanamycin-resistant bacteria (KRB). Lysinibacillus and Paenibacillus were the dominant genera in ERB and KRB, respectively, governing the changes in their abundances. At this concentration, the Lysinibacillus abundance in ERB decreased from 96.74 % to 70.57 %. Meanwhile, that of Paenibacillus in KRB increased from 33.40 % to 77.44 %. The copy number of ermF decreased after HA addition, while that of ermB increased. Furthermore, 0.1 % HA significantly reduced the copy number and relative abundance of aadA1 and aac(6')-Ib (aka aacA4)-03 in the soil. Changes in these two types of ARB and ARGs were primarily driven by shifts in the microbial community structure. Soil physicochemical properties, particularly increased organic matter (OM), altered the absolute abundance of ermB. Meanwhile, changes in intI1 abundance determined the risk associated with aadA1 and aac(6')-Ib (aka aacA4)-03. These findings emphasize the dual role of HA in the dissemination of antibiotic resistance in agricultural soils and highlight the necessity of considering dose-dependent effects when applying HA as a soil amendment.

Soil Microbiology↗

PubMed2026

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans↗

PubMed2026

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans↗

PubMed2026

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1α axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans↗