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The neuroendoscopic factors affecting outcome of endoscopic third ventriculostomy in pediatric patients with post infectious hydrocephalus.

BACKGROUND: The role of endoscopic third ventriculostomy(ETV) in infective hydrocephalus remains uncertain. Infection alters cerebrospinal-fluid composition, flow-dynamics, absorptive capacity, undermining the effectiveness of ETV. AIMS AND OBJECTIVES: This study aims to describe the intraventricular morphological findings and its correlation with ETV outcomes in a cohort of paediatric infective hydrocephalus. METHODOLOGY: Total 98 cases of infective HCP underwent ETV, were studied for intraventricular findings. Thin transparent third ventricular floor were considered as type-1, transluscent as type-2, floor with granuloma as type-3 and unidentifiable anatomy as type-4. Infective deposits were sent for histopathology. RESULT: Overall ETV was successful in 46 patients (46.93%). Success rate of ETV in type 1 (72.7%) was better than type-2 (50%) and type-3 (33.3%). The difference between type-1 and type-3 was statistically significant, p = 0.01. The success rate in presence of pre-pontine adhesions (46 cases) was 34.7%, significantly lower than the 66.6% observed in their absence (p = 0.005). ETV was not successful in all the 7 cases withy type-4 floor. Tissue biopsy confirmed microbiological diagnosis in 13 cases and helped in modifying pharmacological treatment as per culture (two with tuberculosis and three with fungal infection). CONCLUSION: ETV offers a meaningful therapeutic option in post-infectious HCP. Endoscopic appearance of the third ventricular floor and the pre-pontine space may predict its outcome. A thin, transparent floor in the absence of cisternal adhesions is associated with best outcomes, while progressive floor thickening, granuloma formation, and pre pontine fibrosis each correlate with declining success rates. The culture from exudates often helps in achieving organism oriented pharmaco-therapy that improves ETV success rate.

Humans

Effects of low-dose esketamine on early quality of recovery following minimally invasive esophagectomy: a multicenter, randomized controlled study.

BACKGROUND: Patients undergoing minimally invasive esophagectomy (MIE) frequently experience moderate-to-severe postoperative pain and anxiety-depressive symptoms, compromising postoperative quality of recovery (QoR). Esketamine is a promising adjunct for analgesia and anxiolysis; however, the effect of low-dose esketamine on patient-centered recovery outcomes in MIE remains unclear. METHODS: In this double-blinded, multicenter randomized controlled trial, patients scheduled for elective McKeown esophagectomy were allocated to esketamine (0.25&#x2009;mg/kg loading dose and 0.125&#x2009;mg/kg/h continuous infusion during surgery) or placebo (equivalent volume and rate of saline). The primary outcome was the QoR-15 score on postoperative day (POD) 2. Secondary outcomes included QoR-15 scores on POD 1, 3, 7 and 30. Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A) and Depression Subscale (HADS-D) scores, numeric rating scale (NRS) pain scores, and the Brief Pain Inventory (BPI) scores on POD 1 to 3, and safety evaluations. RESULTS: A total of 198 patients were analyzed (esketamine, n&#x2009;=&#x2009;98; placebo, n&#x2009;=&#x2009;100). Intraoperative esketamine significantly improved QoR-15 scores on POD 2 (116.9&#x2009;&#xb1;&#x2009;9.4 vs. 110.2&#x2009;&#xb1;&#x2009;9.8, p&#x2009;<&#x2009;0.001) and POD 3 (123.6&#x2009;&#xb1;&#x2009;7.2 vs. 116.8&#x2009;&#xb1;&#x2009;8.4, p&#x2009;<&#x2009;0.001) compared with placebo. HADS-A and HADS-D scores were lower in the esketamine group on POD 1 to 3 (all p&#x2009;<&#x2009;0.001). Additionally, esketamine recipients reported significantly lower NRS scores at rest and during movement and BPI scores for pain severity and pain interference items (all p&#x2009;<&#x2009;0.001). There were no significant between-group differences in safety outcomes. CONCLUSIONS: Intraoperative low-dose esketamine improved early, patient-reported recovery after MIE by enhancing analgesia and reducing postoperative anxiety and depression without increasing adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Register (identifier: ChiCTR2400088916).

Humans

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I&#xb2;=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I&#xb2;=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I&#xb2;=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I&#xb2;=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

MRI-Negative Posterior Reversible Encephalopathy Syndrome: Comparison of Hypertensive Encephalopathy With and Without Vasogenic Edema.

OBJECTIVE: To explore whether posterior reversible encephalopathy syndrome (PRES) can present with negative magnetic resonance imaging (MRI) by comparing clinical features between cases of PRES with vasogenic edema and cases of hypertensive encephalopathy without MRI changes. PATIENTS AND METHODS: Patients diagnosed with hypertensive encephalopathy from August 1, 2008, to December 31, 2017, were identified retrospectively and matched by age (&#xb1;5 years) and sex in a 1:2 ratio to patients retrospectively identified as having PRES from January 1, 2002, to November 30, 2017. A review of MRI images and clinical information was performed. RESULTS: We identified 16 cases of hypertensive encephalopathy and 32 age- and sex-matched controls with PRES showing vasogenic edema on MRI. There were no statistically significant differences in the odds of presentation with headache (odds ratio [OR], 1.372; 95% CI, 0.458 to 4.106), encephalopathy (OR, 2.303; 95% CI, 0.433 to 12.236), visual disturbance (OR, 0.826; 95% CI, 0.185 to 3.697), or focal neurologic deficit (OR, 4.000; 95% CI, 0.767 to 20.872). Seizures were more common in patients with vasogenic edema (OR, 0.082; 95% CI, 0.010 to 0.664). There were no significant differences in odds of acute kidney injury (OR, 2.90; 95% CI, 0.679 to 12.449) or odds of having a history of malignancy (OR, 0.295; 95% CI, 0.076 to 1.152), transplantation (OR, 3.347; 95% CI, 0.594 to 18.880), or autoimmune disease (OR, 0.400; 95% CI, 0.104 to 1.532). Systolic blood pressure at presentation was higher in patients with hypertensive encephalopathy and negative MRI as compared with patients with PRES and vasogenic edema (OR, 1.03; 95% CI, 1.01 to 1.05). CONCLUSION: Most presenting symptoms and risk factors were not significantly different between cases of hypertensive encephalopathy with and without vasogenic edema, arguing that the diagnosis of PRES in the setting of acute severe hypertension may not depend on MRI confirmation.

Humans

Endovascular treatment after stroke beyond 24&#xa0;h vs 6-24&#xa0;h: a propensity score-matched cohort study.

BACKGROUND: Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) within 6-24&#xa0;h. However, the safety and feasibility of EVT for anterior circulation strokes beyond 24&#xa0;h remain uncertain. METHODS: We conducted a retrospective cohort study of consecutive patients with anterior circulation LVO who underwent EVT at Changhai Hospital from 2018 to 2023. Patients were stratified into late (6-24&#xa0;h) and very late (>24&#xa0;h) windows. Propensity score matching (PSM) was performed to adjust for baseline imbalances, including age, sex, NIHSS, ASPECTS, occlusion location, perfusion parameters, and vascular risk factors. The primary outcome was functional independence (modified Rankin Scale [mRS]&#xa0;&#x2264;&#xa0;2) at 3&#xa0;months. Secondary outcomes included successful reperfusion (TICI 2b-3) and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 1043 screened patients, 429 patients with anterior circulation LVO were included after exclusions, comprising 373 in the late window and 56 in the very late window. PSM yielded 42 matched pairs. Compared with the late window group, the very late window group showed no statistically significant differences in functional independence (54.8% vs. 57.1%; OR&#xa0;=&#xa0;0.908, 95% CI 0.382-2.153, p&#xa0;=&#xa0;0.830), successful reperfusion (88.1% vs. 92.9%; OR&#xa0;=&#xa0;1.800, 95% CI 0.481-7.096, p&#xa0;=&#xa0;0.460), sICH (2.4% vs. 9.5%; OR&#xa0;=&#xa0;0.232, 95% CI 0.012-1.652, p&#xa0;=&#xa0;0.200), intraprocedural complications (26.2% vs. 19.0%; OR&#xa0;=&#xa0;1.508, 95% CI 0.540-4.362, p&#xa0;=&#xa0;0.440), or postoperative complications (33.3% vs. 35.7%; OR&#xa0;=&#xa0;0.900, 95% CI 0.363-2.219, p&#xa0;=&#xa0;0.820). CONCLUSIONS: In this selected, single-center cohort of anterior circulation LVO patients undergoing EVT, treatment initiated beyond 24&#xa0;h appeared to have comparable effectiveness and safety to treatment initiated within 6-24&#xa0;h. Definitive evidence requires confirmation from adequately powered randomized controlled trials.

Humans

Impacts of climate-driven yield changes on the affordability of healthy diets: a modelling study.

BACKGROUND: Food security is central to global nutrition improvement and public health goals, and healthy diets represent a higher-level aspiration beyond merely avoiding hunger. Climate change poses an increasing threat to food systems by affecting crop yields and food prices. Although climate change-driven risks to hunger have been widely studied, the extent to which climate change undermines the affordability of healthy diets while accounting for socioeconomic responses and regional inequalities remains insufficiently understood. This study aimed to quantify the effects of climate change on the future affordability of healthy diets under alternative socioeconomic and climate scenarios. METHODS: We developed an integrated modelling framework that explicitly couples multimodel crop-yield projections with an integrated assessment model (Global Change Analysis Model [GCAM]). Yield responses from six global gridded crop models driven by four climate models were integrated into GCAM, allowing endogenous socioeconomic adjustments such as land-use shifts, production reallocation, and price responses to emerge under shared socioeconomic pathways (SSPs). Diet affordability was then assessed using the Food and Agriculture Organization of the UN's Cost and Affordability of a Healthy Diet framework across three socioeconomic-climate scenarios (SSP1-2.6, SSP2-4.5, and SSP3-6.0). FINDINGS: Under a high-emissions pathway (ie, SSP3-6.0), climate change was projected to render healthy diets unaffordable for a model-mean of 119 million people globally by 2100, even when CO2 fertilisation effects are included, with the upper end of the model ensemble reaching about 1&#xb7;6 billion people. In contrast, climate-induced affordability losses were found to be negligible under both a low-emissions pathway (ie, SSP1-2.6; -0&#xb7;3 million) and a medium-emission pathway (SSP2-4.5; +0&#xb7;2 million). Under a high-emission pathway, model-mean projections indicated that diet costs could increase by up to 12% in the most affected regions by the end of the century. Under medium emissions, cost increases were projected to remain below 4%, whereas under low emissions, affordability changes were projected to be minimum across regions (within approximately 0&#xb7;5%). Substantial regional disparities emerged, with the largest and most consistent affordability losses concentrated in low-income regions that contributed least to historical greenhouse gas emissions. Under SSP3-6.0, these disparities persisted particularly in regions of Africa and Asia despite projected three-to-five-fold increases in income over the century, with climate-induced disruptions to food systems increasing the number of people unable to afford a healthy diet through mid-century. INTERPRETATION: Climate change is likely to exacerbate global nutritional inequalities by disproportionately increasing the affordability risks of healthy diets in regions that have contributed least to historical greenhouse gas emissions. Under high-warming scenarios, socioeconomic development alone is insufficient to fully offset these risks, highlighting the structural vulnerability of low-income food systems to climate-driven price shocks. These findings suggest that in the absence of targeted interventions, climate change could continue to undermine progress towards equitable and health-oriented nutrition outcomes. FUNDING: Ministry of Science and Technology of the People's Republic of China; National Natural Science Foundation of China; National Aeronautics and Space Administration Goddard Institute for Space Studies Climate Impacts Group; Future of Life Institute; and Global Alliance for Improved Nutrition.

Journal Article

Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.

Psychedelic agents induce a window of heightened neuroplasticity that extends beyond acute intoxication, during which neural circuits are more amenable to change. This period may facilitate changes in cognition relevant to the treatment of psychiatric disorders. This systematic review synthesised clinical and preclinical evidence of subacute and long-term (&#x2265;1&#x202f;day) effects of classic and non-classic psychedelics on cognition. MEDLINE, EMBASE, APA PsycInfo and Web of Science were searched to identify human and animal studies investigating psychedelics and cognition (executive function, attention, decision-making). Sixty-seven (47 clinical, 20 preclinical) articles met inclusion criteria. Psilocybin demonstrated the most consistent evidence of subacute and longer-term cognitive improvement, particularly in cognitive flexibility and attention. Ketamine showed enhancement across cognitive domains, although findings were heterogeneous. LSD and DMT showed no consistent subacute changes, while MDMA was associated with transient cognitive impairments that resolved within days. Risk of bias assessments revealed selective outcome reporting, poor reporting of missing data and inadequate methodological detail, limiting the confidence of findings. Current evidence provides preliminary support for subacute changes in cognition following administration of select psychedelic agents. Cognitive improvements were more frequently seen in psychiatric populations than healthy subjects, which may reflect a remediation of existing cognitive deficit rather than enhancement above normal functioning. Adequately powered, controlled studies with standardised reporting of cognitive outcomes are required to determine the magnitude, durability and clinical relevance of psychedelic-associated cognitive change.

Hallucinogens

Factors associated with periprosthetic joint infection following total knee arthroplasty: an updated systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically evaluate factors associated with periprosthetic joint infection (PJI) following total knee arthroplasty (TKA), and thereby to provide evidence-based references for clinical prevention and perioperative risk stratification. METHODS: Computerized searches were conducted in the following databases from their inception until May 26, 2025: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. Two researchers independently screened the literature, extracted data, and assessed study quality. The methodological quality was assessed using the Newcastle-Ottawa Scale. Quantitative synthesis was performed when at least two studies reported comparable exposure definitions and sufficient comparator information; otherwise, narrative synthesis was used. Review Manager 5.4 software was used for the primary analysis. This study is registered on PROSPERO (CRD420251079339). RESULTS: A total of 25 observational studies were included in the qualitative synthesis, of which 24 contributed to the primary quantitative synthesis. Quantitatively pooled factors associated with PJI included male sex (OR&#xa0;=&#xa0;1.39, 95% CI 1.27-1.51), BMI &#x2265;30&#xa0;kg/m2 (OR&#xa0;=&#xa0;5.72, 95% CI 2.65-12.36), prolonged operative time, type 2 diabetes mellitus (OR&#xa0;=&#xa0;2.09, 95% CI 1.45-3.01), rheumatoid arthritis (OR&#xa0;=&#xa0;2.64, 95% CI 1.38-5.02), smoking (OR&#xa0;=&#xa0;1.65, 95% CI 1.34-2.04), blood transfusion (OR&#xa0;=&#xa0;2.27, 95% CI 1.59-3.25), American Society of Anesthesiologists score &#x2265;3 (OR&#xa0;=&#xa0;2.73, 95% CI 1.02-7.32), history of hormone therapy (OR&#xa0;=&#xa0;4.88, 95% CI 2.90-8.22), postoperative urinary tract infection (OR&#xa0;=&#xa0;3.59, 95% CI 1.15-11.21), intraoperative blood loss >200&#xa0;ml (OR&#xa0;=&#xa0;1.51, 95% CI 1.03-2.22), postoperative drainage tube placement duration &#x2265;24&#xa0;h (OR&#xa0;=&#xa0;2.23, 95% CI 1.50-3.32), preoperative anemia (OR&#xa0;=&#xa0;1.82, 95% CI 1.67-1.99), and combined pulmonary disease (OR&#xa0;=&#xa0;5.54, 95% CI 1.93-15.96). Age was narratively summarized because its classification differed substantially across studies. CONCLUSION: Multiple demographic, comorbidity-related, and perioperative factors were associated with PJI after TKA. However, because the included studies were observational and clinically heterogeneous, these findings should be interpreted as associations rather than causal effects. Optimization of modifiable factors may help reduce the burden of PJI, but further prospective studies using standardized PJI definitions and adjusted effect estimates are required.

Humans

Assessment of temporomandibular joint space changes after orthognathic surgery in skeletal malocclusion patients: a systematic review.

PURPOSE: To interpret postoperative changes in temporomandibular joint (TMJ) joint space dimensions and condylar position following orthognathic surgery in patients with skeletal malocclusions, and to determine whether reported alterations represent clinically meaningful displacement or physiological adaptive remodeling. MATERIALS AND METHODS: A comprehensive search of PubMed, SCOPUS, Web of Science, EBSCOhost, and Cochrane Library was performed to assess pre- and postoperative TMJ changes using three-dimensional imaging. Joint spaces including anterior (AJS), superior (SJS), and posterior (PJS) and condylar morphology were evaluated. Methodological quality was appraised using the Joanna Briggs Institute (JBI) checklist. Due to methodological and clinical heterogeneity, findings were synthesized narratively with attention to malocclusion type and surgical movement. RESULTS: A total of 16 studies consisting 628 patients undergoing BSSO, Le Fort I osteotomy, vertical ramus osteotomy, or bimaxillary surgery were included. Most studies reported minor, adaptive postoperative changes in AJS, SJS, and PJS. Class II patients showed more consistent increases in AJS/SJS, whereas Class III patients demonstrated variable posterior or anterior remodelling depending on surgical movement. Volumetric analyses revealed region-specific adaptations without significant condylar displacement. Postoperative temporomandibular disorder symptoms were infrequent, and no consistent evidence supported detrimental TMJ effects attributable to surgery. CONCLUSION: Postoperative TMJ joint space changes after orthognathic surgery primarily represent physiological adaptive remodeling rather than pathological condylar displacement, with reported variability driven by malocclusion type, surgical movement, fixation method, and imaging protocol. Recognizing these predictable patterns is essential to prevent overinterpretation of postoperative imaging and to improve clinical assessment through standardized three-dimensional and long-term evaluation strategies.

Humans

Clinical predictors of severe and fatal respiratory syncytial virus infection in adults and the elderly: A retrospective cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as a cause of severe respiratory illness in adults, especially the elderly and those with comorbidities. However, data on outcomes and risk factors for severe disease in this population remain limited. METHODS: We retrospectively analyzed 123 adult patients diagnosed with RSV infection at a tertiary center in Taiwan from 2015 to 2023. Clinical characteristics, laboratory data, detection of other pathogens, clinical course and outcome were reviewed. Multivariable logistic regression identified risk factors for severe RSV infection, including ICU admission and 30-day mortality. RESULTS: The mean age was 55.7 years; 50% were aged &#x2265;60 years and 13% were &#x2265;75 years. ICU admission occurred in 17%, with significant associations to viral coinfection and elevated C-reactive protein (CRP). Thirty-day mortality was 13%, and overall in-hospital mortality was 18%, all among patients with comorbidities. Independent predictors of 30-day mortality included late elderly (aOR 24.2, p&#x202f;=&#x202f;0.03), high CRP > 11.5&#x202f;mg/dL (aOR 16.4, p&#x202f;=&#x202f;0.005) and thrombocytopenia < 34,103/&#x3bc;L (aOR 11.4, p&#x202f;=&#x202f;0.01). CONCLUSION: Advanced age (&#x2265;75 years), high CRP, and severe thrombocytopenia are key predictors of mortality in adults RSV patients. These findings highlight the need for targeted prevention strategies, including vaccination, in high-risk populations.

Co-infection

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a &#x2265;&#xa0;75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans

Antimicrobial photodynamic therapy mediated by phenothiazine photosensitizers against Candida albicans and Candida auris: a systematic review.

Fungal infections caused by Candida albicans and Candida auris represent an increasing clinical challenge, particularly due to biofilm formation and rising antifungal resistance. Antimicrobial photodynamic therapy (aPDT) has emerged as a potential alternative strategy, with phenothiazine-based photosensitizers being among the most extensively investigated compounds. This systematic review aimed to evaluate the application of phenothiazine-mediated aPDT in in vitro studies against C. albicans and C. auris. A comprehensive search was conducted in PubMed, Embase, and Scopus, including studies published within the last 10 years. Forty in vitro studies met the eligibility criteria and were synthesized descriptively due to substantial methodological heterogeneity. Overall, aPDT was associated with reductions in fungal viability, with generally greater effects reported in planktonic models compared with biofilms. Methylene blue was the most frequently investigated photosensitizer, applied across a broad range of concentrations and dosimetric parameters, resulting in variable antifungal responses. Other phenothiazine derivatives, including toluidine blue O, dimethyl methylene blue, new methylene blue, and S137, were also associated with antifungal activity under specific experimental conditions but remain comparatively underexplored. Studies involving C. auris were less frequent and suggested lower susceptibility compared with C. albicans, particularly in biofilm models. Given the substantial variability in experimental protocols, especially regarding photosensitizer concentration, light parameters, and biofilm maturation, the findings should be interpreted with caution and limit direct comparison across studies. These findings support the antifungal potential of phenothiazine-mediated aPDT while emphasizing the need for methodological standardization and expanded investigation of C. auris.

Photochemotherapy

Efficacy and Safety of GLP-1 Receptor Agonists for the Management of Antipsychotic-Induced Weight Gain.

OBJECTIVE: The objective of this systematic review and meta-analysis was to compare the efficacy and safety of glucagon-like peptide-1 (GLP-1) receptor agonists for the management of antipsychotic-induced weight gain. DATA SOURCES: A systematic review was conducted following PRISMA methodology through July 2025 that evaluated the efficacy and safety of GLP-1 agonists for the management of antipsychotic-induced weight gain. STUDY SELECTION AND DATA EXTRACTION: Efficacy endpoints were change in body weight (kg), change in body mass index (BMI) (kg/m2), and change in HbA1c (%). The safety endpoint was gastrointestinal (GI) adverse effects. A P-value of 0.05 was considered statistically significant, and heterogeneity was reported as I2. DATA SYNTHESIS: Six studies were included in this systematic review, of which 4 trials were included in the meta-analysis. The difference found between GLP-1 agonists and placebo was a change in weight of -5.85 kg (P = 0.0622, 95% CI = -9.72 to -1.97), a change in BMI of -2.11 kg/m2 (P = 0.7692, 95% CI = -5.51 to 1.29), and a change in HbA1c of -1.58 (P = 0.6659, 95% CI = -4.75 to 1.58). The overall risk ratio for a patient to experience a GI-related adverse effect when taking a GLP-1 agonist compared to placebo was 1.83 (95% CI = 1.42 to 2.37). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: While the efficacy endpoints did not reach significance, this meta-analysis shows that select GLP-1 receptor agonists may be used to promote weight loss in patients taking antipsychotics. Controlling antipsychotic-induced weight gain helps patients remain adherent to therapeutic doses of their antipsychotic medications. CONCLUSION: The use of certain GLP-1 agonists may be considered to help promote weight loss in patients experiencing antipsychotic-induced weight gain.

Humans

Effects of Exergame Balance Training with Variable Cognitive Motor Challenges on Serum BDNF, p-tau181, and Cognitive Functions in Adults with Mild Cognitive Impairment: A Randomized Trial.

INTRODUCTION: Cognitive-motor exergame balance training may increase attentional demands and neuronal processing, potentially affecting serum levels of brain-derived neurotrophic factor (BDNF), A&#x3b2;1-42, and p-tau181, as well as train cognitive abilities in adults with mild cognitive impairment (MCI). This study aimed to compare the effects of exergame balance training of mild, moderate, high-difficulty, and Wii Fit&#x2122; groups on blood serum levels of BDNF, A&#x3b2;1-42, p-tau181, and cognition function in adults with MCI. METHODS: In this four-arm, parallel group randomized clinical trial, 97 adults with MCI were randomly assigned to exergame balance training groups of mild, moderate, high-difficulty, and Wii Fit exergame as a control group. All participants received 40 min/session, 3 times/week for 8 weeks. Assessment of serum levels of p-tau181, A&#x3b2;1-42, BDNF, and cognitive functions was conducted at baseline, after weeks 4 and 8. A mixed-model analysis of covariance was used, with post-baseline measurements (weeks 4 and 8) specified as the within-subject factor and the corresponding baseline value entered as a covariate to adjust for initial between-group variability. RESULTS: A significant group &#xd7; time interaction was found for BDNF, F(3,92) = 6.413, P = 0.017, &#x3b7;p2 = 0.181; p-tau181, F(3,92) = 4.640, P = 0.040, &#x3b7;p2 = 0.138; attention, F(3,92) = 4.171, P = 0.045, &#x3b7;p2 = 0.057; abstraction, F(3,92) = 4.263, P = 0.043, &#x3b7;p2 = 0.058; and visuospatial skills, F(3,92) = 6.931, P < 0.001, &#x3b7;p2 = 0.234. CONCLUSION: Cognitive-motor challenge-based exergame balance training was associated with an increase in serum BDNF, a reduction in p-tau181. In contrast, the A&#x3b2;1-42 levels remained stable. These changes were accompanied by improvement in selective cognitive functions (attention, abstraction, and visuospatial skills) in individuals with MCI. Greater effects were observed in moderate and high-difficulty groups, suggesting the importance of intervention intensity in promoting cognitive and neurobiological outcomes in MCI.

Humans

Effectiveness of a blended care intervention in physiotherapy with exercise and education for patients with hip or knee osteoarthritis (SmArt-E): A multicentre pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a twelve-month smartphone-assisted physiotherapy (SmArt-E) intervention versus usual care in hip and/or knee osteoarthritis (OA), and to assess usability and patient satisfaction with the digital support. METHOD: We conducted a multicentre, pragmatic, parallel-group randomized controlled trial in 27 physiotherapy practices in Germany. Patients with physician-diagnosed hip and/or knee OA aged &#x2265;50 (hip) or &#x2265;38 years (knee) were randomly allocated to SmArt-E (IG; n=166) or usual care (CG; n=164). The twelve-month intervention combined supervised and smartphone-assisted training and education (blended care). Primary outcomes were pain (NRS, 0-10) and physical function (HOOS/KOOS-ADL, 0-100) at twelve months. Secondary outcomes followed OARSI domains; usability and patient satisfaction were also assessed. RESULTS: Among 330 participants (mean age 64&#xb1;8 years), baseline NRS was 3.2&#xb1;2.3 in the CG and 3.5&#xb1;2.4 in the IG; HOOS/KOOS-ADL was 71.6&#xb1;17.7 and 69.4&#xb1;17.5, respectively. No significant between-group differences were found for pain (-0.36; 95% CI: -0.84 to 0.12; p=0.14) or physical function (2.66; 95% CI: -0.46 to 5.77; p=0.09). Among 13 secondary outcomes, significant differences favouring the IG emerged at three and twelve months for several domains; however, effect sizes were small and unlikely to be clinically meaningful. CONCLUSION: SmArt-E did not demonstrate superior effectiveness over usual care in mild hip and/or knee OA. Both groups improved over time, with slightly more favourable but clinically inconclusive outcomes in the IG. Findings highlight the need to refine the intervention, better identify eligible patients, and optimize digital and in-person components.

Humans

Risk factors for bleeding after endoscopic retrograde cholangiopancreatography: a systematic review and meta-analysis.

BACKGROUND AND AIMS: ERCP is associated with adverse events, including bleeding, which occurs in up to 1.3% of cases. This meta-analysis aims to identify and quantify risk factors associated with post-ERCP bleeding. METHODS: A comprehensive literature search of electronic databases was conducted from inception to January 10, 2025. Studies were eligible if they used multivariate analysis to identify predictors of post-ERCP bleeding. Risk factors reported in at least 2 studies were pooled using a random-effects model to calculate odds ratios (ORs) with 95% CIs. A further subgroup analysis was performed, including risk factors for postsphincterotomy bleeding and postendoscopic papillectomy bleeding. RESULTS: Twenty-seven studies (4 prospective and 23 retrospective studies) comprising 149,870 patients were included, of whom 1865 experienced post-ERCP bleeding. Twenty potential risk factors were analyzed. The meta-analysis identified several factors significantly associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis, including male gender (OR, 1.24; 95% CI, 1.05-1.46), anticoagulation therapy (OR, 2.75; 95% CI, 1.66-4.56), cirrhosis (OR, 2.54; 95% CI, 1.76-3.65), hemodialysis (OR, 5.82; 95% CI, 3.32-10.18), coagulopathy (OR, 11.01; 95% CI, 2.50-48.40), endoscopic sphincterotomy (EST) (OR, 3.19; 95% CI, 1.69-6.01), precut sphincterotomy (OR, 2.24; 95% CI, 1.52-3.30), and intraoperative bleeding (OR, 2.57; 95% CI, 1.80-3.66). Several factors in the pooled adjusted analysis were not found to be significantly associated with higher odds of post-ERCP bleeding, including high body mass index (BMI), nonsteroidal anti-inflammatory drug (NSAID) use, antiplatelet therapy, thrombocytopenia, common bile duct stones, cholangitis, endoscopic papillary balloon dilatation, and covered self-expandable metal stent insertion. CONCLUSIONS: This meta-analysis identified that the anticoagulation therapy, cirrhosis, hemodialysis, coagulation disorder, EST, precut sphincterotomy, and male gender are associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis. Conversely, age, high BMI, cholangitis, choledocholithiasis, pancreatic duct stones, needle-knife sphincterotomy, NSAID use, and antiplatelet therapy were not significantly associated with higher odds of post-ERCP bleeding in the pooled adjusted analysis. Incorporating our results into a prediction model may assist in identifying patients at increased risk, optimizing informed consent, and guiding prevention and management strategies for post-ERCP bleeding.

Humans

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20&#x2009;min of active or sham 6&#x2009;Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time&#x2009;&#xd7;&#x2009;group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time&#x2009;&#xd7;&#x2009;Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected &#x3b1;&#x2009;=&#x2009;0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (&#x3b2;&#x2009;=&#x2009;2.63, p=&#x2009;0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (&#x3b2;&#x2009;=&#x2009;1.99, p=&#x2009;0.037) and left medial amygdala (&#x3b2;&#x2009;=&#x2009;1.97, p=&#x2009;0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r&#x2009;=&#x2009;0.43, p=&#x2009;0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans

Systematic review of machine learning approaches for predicting sickle cell crisis and mortality risk at the climate-health nexus.

BACKGROUND: Sickle cell anemia (SCA) is a severe genetic blood disorder characterized by recurrent vaso-occlusive crises and increased mortality, with the greatest burden occurring in low- and middle-income countries. Climatic and environmental conditions, including temperature variability, humidity, rainfall, air pollution, and seasonal changes, have been associated with disease exacerbation. However, the extent to which these factors have been incorporated into predictive models remains unclear. This study systematically reviews the application of machine learning (ML) models for predicting SCA crises and mortality in relation to climate and environmental factors. METHODOLOGY: The PRISMA guidelines were used, and 34 peer-reviewed studies published between 2005 and 2026 were analyzed to identify the climate variables, ML approaches employed, and predictive performance. The reviewed studies applied a range of ML techniques, including artificial neural networks, random forests, support vector machines, decision trees, logistic regression, and deep learning models. Temperature, humidity, rainfall, wind speed, air quality indicators, and seasonal patterns were the most frequently examined environmental variables. RESULTS: The findings indicate that most existing models rely predominantly on clinical and demographic data, with limited integration of climate information and inadequate representation of high-burden regions, especially Sub-Saharan Africa. Studies incorporating environmental variables reported improved predictive performance and highlighted the potential of climate-informed early warning systems for SCA management. CONCLUSION: The review recommends development of interdisciplinary, climate-aware ML frameworks, expansion of longitudinal environmental datasets, and increased research in underrepresented regions to support climate-resilient and patient-centered SCA care.

Humans