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Comparative efficacy and safety of bi-flanged metal stents versus lumen-apposing metal stents for endoscopic drainage of pancreatic fluid collections: a systematic review and meta-analysis.

INTRODUCTION: Pancreatic fluid collections (PFCs), particularly walled-off necrosis, are common complications of acute pancreatitis that often require endoscopic drainage. Bi-flanged metal stents (BFMS; NAGI; Taewoong Medical, Gyenoggi-do, Korea) and electrocautery-enhanced lumen-apposing metal stents (LAMS; AXIOS, Boston Scientific Corporation, Marlborough, Massachusetts, USA) are frequently used, but comparative data remain limited. This study aims to compare the efficacy and safety of BFMS and LAMS in the endoscopic drainage of PFCs. METHODS: This meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive database searches were conducted through November 2024 to identify studies comparing BFMS and LAMS for endoscopic ultrasound-guided drainage of PFCs. Outcomes were pooled using a random-effects model with RevMan Web, and statistical significance was defined as a P value less than 0.05. RESULTS: Three studies ( n  = 627; 329 BFMS and 298 LAMS) met inclusion criteria. No significant differences were observed between BFMS and LAMS for technical success [odds ratio (OR): 1.16; 95% confidence interval (CI): 0.55-2.43] or clinical success (OR: 0.97; 95% CI: 0.51-1.87). Similarly, there were no differences in walled-off necrosis recurrence (OR: 2.01; 95% CI: 0.17-24.02), number of direct endoscopic necrosectomy sessions (OR: 0.52; 95% CI: 0.05-5.12), or mean number of endoscopic procedures (mean difference: 0.18, 95% CI: 2.08-2.45). Adverse events were also comparable between groups, including bleeding (OR: 0.64), infection (OR: 1.18), stent migration (OR: 1.83), and stent occlusion/dysfunction (OR: 1.71). CONCLUSION: BFMS and LAMS provide equivalent efficacy and safety in the endoscopic ultrasound-guided drainage of PFCs. Either stent type represents a viable therapeutic option. Further large-scale prospective studies are warranted to refine stent selection strategies.

Humans

Comparative evaluation of molecular technologies for the identification of prevalent non-tuberculous mycobacteria in pulmonary infections: a systematic review and meta-analysis.

BACKGROUND: The increasing prevalence of non-tuberculous mycobacteria pulmonary disease (NTM PD) is a burden to public health. Successful management of NTM PD critically depends on accurate species identification and reliable drug susceptibility testing to guide appropriate antibiotic therapy. Emerging molecular technologies offer rapid diagnostic solutions compared to conventional methods, but their performance varies. This study aims to provide a comprehensive evaluation of current molecular techniques for NTM identification and to present a global antibiotic resistance profile. METHODS: A systematic literature search was conducted in PubMed and Web of Science for studies published between 2005 and 2024. Studies applying molecular methods for NTM identification and resistance detection in humans were included. Data on study characteristics, diagnostic methods, sample types, sample sizes, identification sensitivity, and drug susceptibility results were extracted. Meta-analysis was performed using R with the meta4diag package. The quality of included studies was assessed using the QUADAS-2 tool. RESULTS: The analysis included 49 studies on NTM identification and 33 studies on antibiotic resistance. For species identification, all evaluated molecular technologies (MALDI-TOF MS, PCR-based methods, Sequencing, DNA chip, and DNA strip) demonstrated high pooled sensitivities (>0.92). Subgroup analysis revealed that sample type significantly affected performance for MALDI-TOF MS. Preliminary analysis of antibiotic resistance rates revealed varying patterns. For slowly growing mycobacteria, a significantly high Ethambutol resistance rate was observed in M. avium (69.20%). Among rapidly growing mycobacteria, resistance to Imipenem was notable (54.22%), and Clarithromycin resistance varied significantly within the Mycobacterium abscessus complex. CONCLUSION: Emerging molecular technologies have revolutionized the methodology for NTM identification with excellent performance. However, their performance can be influenced by sample type, particularly for MALDI-TOF MS. The alarming and heterogeneous antibiotic resistance patterns also highlight the critical need for rapid and accurate species identification and drug susceptibility testing to inform effective therapeutic strategies. Key messagesMolecular technologies demonstrate high accuracy for NTM identification.Antibiotic resistance is a serious concern with variations among NTM species and subspecies.Rapid and accurate species identification and drug susceptibility testing are crucial for guiding effective clinical management of NTM PD.

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

Sex- and age-specific associations of VEGFA polymorphisms with multiple sclerosis susceptibility.

AIM: To evaluate six VEGFA polymorphisms (rs1570360, rs699947, rs3025033, rs2146323, rs1413711 and rs833061) and serum VEGFA concentrations in 270 Lithuanian patients with multiple sclerosis (MS) and 270 matched healthy controls. METHODS: Genotyping was performed using real-time PCR, and serum VEGFA levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were conducted using IBM SPSS version 31.0. RESULTS: Nominal differences in VEGFA genotype and allele distributions were observed in sex- and age-stratified analyses. Among females, the rs1413711 C allele was more frequent (p = 0.005), whereas the rs833061 C allele was less frequent (p = 0.006), in MS patients than controls. In participants aged >38 years, the rs1413711 C allele was also more frequent in MS cases (57.5% vs. 46.0%, p = 0.008). Logistic regression identified nominal associations, particularly for rs1413711, rs699947 and rs833061, but none remained significant after correction for multiple testing. Serum VEGFA levels were higher in MS patients than controls (p = 0.004). Nominal genotype-related differences in serum VEGFA levels and haplotype associations with reduced MS odds were also observed, but did not remain significant after multiple-testing correction. No consistent associations were found between VEGFA variants and clinical parameters. CONCLUSION: VEGFA genetic variation and elevated serum VEGFA may be associated with MS, but the genetic findings require confirmation in larger independent cohorts.

Humans

Complication rates of 16- and 18-gauge needles for native kidney biopsies: a systematic review and proportional meta-analysis.

This systematic review and meta-analysis evaluated complication rates and diagnostic yield reported in studies of adult native kidney biopsy using 16-gauge (16 G) or 18-gauge (18 G) needles. We included randomized trials and cohort studies of real-time ultrasound-guided biopsies, including case series. MEDLINE, Embase, and CENTRAL were searched through October 2024. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using Joanna Briggs Institute tools. Random-effects meta-analyses estimated pooled proportions with 95% confidence intervals (CI), and univariable random-effects meta-regression explored study-level associations with major complications, transfusion, or gross hematuria. We screened 4,499 titles and abstracts and reviewed 319 full-text articles; 62 studies comprising 68 biopsy series were included. The pooled major complication rate in studies using 16 G needles was 1.83% (95% CI: 1.20-2.79) and 1.29% (95% CI: 0.78-2.13) in studies using 18 G needles, with no statistically significant difference. Mean glomerular yield was 18.8 with 16 G and 17.5 with 18 G needles. In study-level meta-regression, studies with higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, or lower mean hemoglobin reported higher pooled complication rates. Most studies were single-arm cohorts; between-needle differences therefore reflect indirect study-level contrasts. Interpretation is limited by retrospective design and heterogeneity across studies. Overall, studies using both needle sizes reported low complication rates and similar diagnostic yield, although definitions and reporting varied. Direct comparative studies are needed to determine whether meaningful differences exist.

Humans

Symptoms and treatment response to florensocatib and inhaled tobramycin in bronchiectasis: Post hoc analysis of two randomized trials.

Inhaled antibiotics and DPP-1 inhibitors improve clinical outcomes in bronchiectasis, but whether baseline symptom burden predicts differential treatment responses remains unclear. In this post hoc analysis of two multicenter randomized trials (SAVE-BE, n = 224; TORNASOL, n = 357), we evaluate the association between baseline Quality of Life-Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and treatment effects of florensocatib and inhaled tobramycin. In SAVE-BE, florensocatib reduces exacerbation rates versus placebo (relative risk [RR], 0.47; 95% confidence interval [CI], 0.33-0.67; p < 0.0001), with RRs of 0.53 and 0.40 observed in patients with high and low symptom burdens, respectively, but no significant symptomatic improvement. In TORNASOL, tobramycin produces clinically meaningful QoL-B-RSS improvements (exceeding the 8-point cutoff in high-symptom patients) and ameliorates bronchitic symptoms, with greater benefits in those with higher baseline symptom burden. These hypothesis-generating findings suggest that baseline symptom burden may identify differential responses to anti-inflammatory versus anti-infective therapies in bronchiectasis and support its potential as a simple, practical stratification tool to guide personalized treatment.

Humans

MIC-based tuberculosis drug susceptibility testing using Sensititre MYCOTB: a diagnostic accuracy meta-analysis.

Accurate drug susceptibility testing (DST) is crucial for designing effective regimens for multidrug-resistant (MDR) and pre-extensively drug-resistant tuberculosis (pre-XDR TB). Sensititre MYCOTB enables simultaneous determination of minimum inhibitory concentrations (MICs) for multiple drugs, but its diagnostic performance varies across studies. This meta-analysis evaluated the diagnostic performance of Sensititre MYCOTB for key MDR and pre-XDR TB drugs. The protocol was registered in PROSPERO (CRD420251230599). PubMed, Cochrane, Google Scholar, Scopus, ONOS, Web of Science, ScienceDirect, and registries were systematically searched for studies published between 2010 and 2025. Studies comparing the Sensititre MYCOTB with reference DST for Mycobacterium tuberculosis complex (MTBC) were included. Bias assessment and pooled diagnostic accuracy estimates were generated. Fourteen studies, including 1,728 isolates, were analyzed. Rifampicin and isoniazid demonstrated high sensitivity (0.976 [95% CI: 0.94-0.99] and 0.977 [95% CI: 0.95-0.99]) and specificity (0.958 [95% CI: 0.84-0.98] and 0.957 [95% CI: 0.83-0.99], respectively) with low heterogeneity. Amikacin, kanamycin, and ofloxacin demonstrate good diagnostic accuracy, with high specificity (>0.98 [95% CI]). Moderate diagnostic accuracy was observed for ethambutol, streptomycin, ethionamide, and rifabutin. Cycloserine, moxifloxacin, and para-aminosalicylic acid showed inconsistent performance despite excellent specificity (>0.97 [95% CI]). Sensitivity analysis partially improved pooled sensitivity for moxifloxacin 0.801 (95% CI: 0.585-0.924) and para-aminosalicylic acid 0.76 (95% CI: 0.518-0.894), whereas cycloserine remained at 0.436 (95% CI: 0.190-0.725), although heterogeneity persisted. Sensititre MYCOTB DST demonstrates high diagnostic accuracy for MDR-TB and pre-XDR-TB drugs, while caution is required with cycloserine, moxifloxacin, and para-aminosalicylic acid. These findings support the integration of MIC-based testing into clinical decision-making.

Microbial Sensitivity Tests

Repetitive transcranial magnetic stimulation in functional motor disorders: A systematic review of effects and targets.

OBJECTIVE: To evaluate the effectiveness, safety, and potential mechanistic implications of repetitive transcranial magnetic stimulation (rTMS) in adults with functional motor disorders (FMD), focusing on possible phenotype-specific responses and stimulation protocols. METHODS: Seven databases were searched from inception to July 2026. Randomised and non-randomised interventional studies were included. Risk of bias and evidence certainty were assessed using PEDro, RoB 2, JBI tools, and GRADE. Because of substantial clinical and methodological heterogeneity, findings were synthesised qualitatively. RESULTS: Fourteen studies were included. The primary motor cortex was targeted in 11 studies. Functional tremor showed the most consistent evidence with inhibitory stimulation: one small sham-controlled trial found a significant group-by-time effect on tremor severity (p&#xa0;=&#xa0;0.007), while an uncontrolled prospective series reported 40&#xa0;% reduction in postural tremor amplitude (p&#xa0;=&#xa0;0.05). Evidence for functional weakness was conflicting: excitatory M1 stimulation increased objective strength by 25&#xa0;% versus 10&#xa0;% with sham (p&#xa0;=&#xa0;0.004), whereas the largest inhibitory sham-controlled trial found no benefit (p&#xa0;=&#xa0;0.80). No severe adverse events were reported, but safety reporting was incomplete. GRADE certainty was moderate for tremor and very low for all other outcomes. CONCLUSIONS: Current evidence is insufficient to establish the efficacy of rTMS in FMD or to recommend phenotype-specific protocols. Preliminary findings support further investigation of inhibitory stimulation for functional tremor, whereas evidence for excitatory stimulation in functional weakness remains uncertain. SIGNIFICANCE: The possible interaction between phenotype and stimulation direction is hypothesis-generating. rTMS should currently be considered an experimental, context-sensitive adjunct within multidisciplinary care, pending adequately powered phenotype-stratified sham-controlled trials. Prospero Registration Number: CRD420251250969.

Humans

Identifying biomarkers of accelerated ageing in cancer patients from routine clinical data.

INTRODUCTION: Cancer and ageing have a bidirectional relationship: age is the strongest risk factor for cancer, and cancer and treatments can accelerate ageing. Therefore, biological age can differ from chronological age; biomarkers are needed to stratify interventions to minimise accelerated ageing. METHODS: PhenoAge was calculated from routine blood test results of patients attending a Geriatric Oncology clinic. PhenoAgeAccel was the residual from a regression of PhenoAge against age. RESULTS: Data were available for 173 patients (62% male). Mean PhenoAge was higher than age (84.3 (12.6) vs 76.2 (7.24), p&#x202f;<&#x202f;0.001), though the two were correlated (r&#x202f;=&#x202f;0.579, p&#x202f;<&#x202f;0.001). Unlike age, PhenoAge and PhenoAgeAccel were associated with one-year mortality (PhenoAge OR=1.083, 95% CI: 1.038-1.136; PhenoAgeAccel OR=1.096, 95% CI: 1.047-1.155). PhenoAge correlated with Clinical Frailty Score and Timed Up and Go (CFS: Rs=0.31, p&#x202f;<&#x202f;0.001; TUG: Rs=0.25, p&#x202f;<&#x202f;0.005); there were no correlations with age. PhenoAgeAccel correlated with the number of CGA interventions made (Rs=0.17, p&#x202f;<&#x202f;0.05), unlike age and PhenoAge. Patients with diabetes mellitus had a higher PhenoAgeAccel compared to those without (3.40 vs -1.71, p&#x202f;=&#x202f;0.002). In patients receiving systemic anti-cancer treatment, patients with PhenoAgeAccel calculated pre-treatment had less age acceleration than those with PhenoAgeAccel calculated post-treatment, both overall (2.18 vs -2.87; p&#x202f;=&#x202f;0.048) and in matched samples (n&#x202f;=&#x202f;21, 7.76 vs -2.87, p&#x202f;<&#x202f;0.001). CONCLUSIONS: PhenoAgeAccel is a greater predictor of risk than chronological age in older people with cancer. This makes it a promising biomarker to stratify patients for holistic geriatric assessment, dose reductions, or future geroprotective measures which could be integrated within electronic healthcare record systems.

Humans

Impaired adaptation to smoke-derived phenolic compounds in Listeria monocytogenes CC204 from smoked salmon and trout.

Listeria monocytogenes is a major foodborne pathogen in ready-to-eat smoked fish products. This study evaluated whether clonal complex affiliation contributes to variability in growth responses to stresses representative of smoked salmon and trout processing. Ten strains were studied, including strains from CC121, CC26 and CC204, the three major clonal complexes reported in the French smoked salmon and trout sectors, together with the EGDe reference strain. Strains were exposed to salt, cold, smoke-derived phenolic compounds and combined stress conditions. Growth responses were compared with whole-genome-based phylogeny, and the impaired phenotype observed under phenolic exposure was further investigated using viable counts, live/dead microscopy and comparative genomics. Growth profiles were partly structured by clonal complex, with strains from the same clonal complex showing similar behaviour across stress conditions. Salt and cold reduced growth globally, while smoke-derived phenolic compounds were the most discriminating conditions. CC204 strains showed markedly lower growth rates under phenolic exposure than CC121, CC26 and EGDe. This phenotype was not associated with loss of cultivability or significant loss of membrane integrity. Comparative genomics did not identify a clear gene-content determinant explaining the CC204 phenotype. These results suggest that CC204 has an impaired adaptive response to smoke-derived compounds, likely involving regulatory or physiological mechanisms.

Listeria monocytogenes

Pharmacogenomic and drug interactions risk in cardio-oncology: A precision medicine perspective for India.

Cardio-oncology patients may face complex treatment regimens due to the concurrent existence of cancer and cardiovascular disease, leading to a considerable polypharmacy burden. This significantly increases the prospect of drug-drug interactions (DDIs) and gene-drug interactions. The majority of these interactions arise from comparable pharmacokinetic and pharmacological pathways associated with drug transporters and cytochrome P450 enzymes. The significance of pharmacogenomics in tailored treatment strategies are emphasised by the fact that genetic variability enhances individual differences in drug response, safety, and efficacy. This narrative review focus on the effects of key genetic polymorphisms (e.g., DPYD, CYP2C19, and CYP2C9) on the metabolism and efficacy of commonly prescribed anticancer and cardiovascular medications such as fluoropyrimidines, clopidogrel, and warfarin. In addition it explore the role of pharmacogenomic variants on drug-drug interactions within the field of cardio-oncology. The study ultimately emphasizes the necessity of precision medicine in India to address the genetic diversity and underrepresentation in global genomic databases. The absence of pharmacogenomic testing, infrastructural deficiencies, financial constraints, and insufficient clinical integration hinder the widespread use of this technology in India. The Genome India Project and other national initiatives establish the foundation for pharmacogenomic-guided therapy. Utilizing genetic data, together with artificial intelligence-based predictive tools, for clinical decision-making may enhance medication safety and yield optimal outcomes in Indian cardio-oncology patients.

Humans

Genomic insights into end-use grain quality and nutritional traits of an ancient Indian dwarf wheat ( Triticum sphaerococcum Percival) population using a multi-locus genome-wide association study.

BACKGROUND: Triticum sphaerococcum, an ancient hexaploid wheat species, is renowned for its stress resilience and superior nutritional quality. A panel of 116&#x2009;T. sphaerococcum accessions (the largest known collection at a single site globally), with six bread wheat released varieties, was evaluated for its potential for genetic quality improvement. Field experiments were conducted under standard, heat and moisture-deficit conditions across two cropping seasons for ten grain end-use quality and nutritional traits. RESULTS: Genotypes showed highly significant differences (P&#x2009;&#x2264;&#x2009;0.001) for measured traits, with high broad-sense heritability resulting from substantial genotypic variance contributions. Triticum sphaerococcum consistently outperformed T. aestivum across environments, with moisture-deficit stress proving more detrimental to quality parameters than heat stress, while micronutrient content increased under stressed conditions. Trait correlations revealed that the gluten index (GI) correlated negatively with the grain hardness index (GHI), wet gluten (WG), and water-binding capacity (WB), while positively correlating with dry gluten (DG) and protein content (PRO), whereas grain iron (GFE), zinc (GZN), and protein showed consistent positive interrelationships. Two superior accessions, PAUTS10 (WG 35.13%, DG 13.71%, PRO 16.42%, GZN 50.89&#x2009;ppm) and Sonamoti (WG 33.33%, DG 12.92%, PRO 16.27%, GZN 56.03&#x2009;ppm), were identified, surpassing the best check variety HD3226 for quality and nutritional parameters. Multi-locus genome-wide association studies identified 30 stable quantitative trait nucleotides across environments, with candidate gene analysis revealing genes involved in transcription regulation, biosynthetic processes, metal ion homeostasis, and transport. CONCLUSIONS: Triticum sphaerococcum demonstrated superior grain quality and micronutrient potential compared with modern wheat, highlighting its value as a genetic resource for biofortification. The identification of elite accessions and stable quantitative trait nucleotides (QTNs) provides useful targets for breeding programs aimed at improving protein and micronutrient content. Integrating ancient germplasm with modern genomic tools can accelerate the development of nutritionally enhanced wheat varieties. &#xa9; 2026 Society of Chemical Industry.

Triticum

Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that accounts for about 15%-20% of childhood leukemias. Despite therapeutic advances, relapses remain common, and survival for high-risk patients is below 60%. Unlike adult AML, pediatric AML displays distinct genetic mutations, including FLT3-ITD, NPM1, KMT2A rearrangements, and core-binding factors (CBF) fusions, as well as extensive epigenetic dysregulation. Aberrant DNA methylation, histone modifications, and altered non-coding RNA expressions disrupt hematopoietic differentiation and activate oncogenic transcriptional networks. Recent advances in silico transcriptomic analysis have transformed the study of pediatric AML by integrating gene expression and epigenetic data to identify molecular drivers and regulatory networks. Computational RNA-seq pipelines and pathway analyses have highlighted key epigenetic regulators, including DNMT3A, TET2, and HDACs, as potential therapeutic targets. Multi-omics approaches combining transcriptomic, methylomic, and chromatin accessibility data are increasingly used to define biomarkers for diagnosis, prognosis, and therapeutic response. This review provides a comprehensive overview of the molecular and epigenetic landscape of pediatric AML, emphasizing the power of in silico transcriptome analysis to uncover disease mechanisms, refine patient stratification, and guide the development of precision-based epigenetic therapies aimed at improving long-term outcomes in children with AML.

Humans

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans

Wedge tarsectomy using patient specific instrumentation for complex multiplanar foot deformity Reconstruction: A prospective case series.

BACKGROUND: Bony correction in complex cavovarus deformities is often multiplanar. We examine our results following wedge tarsectomy (WT) using patient-specific instrumentation (PSI). METHODS: This single-centre, prospective case series evaluated noncorrectable cavovarus feet undergoing PSI-guided WT. Accuracy of PSI guides/plans, operative duration, and adjunctive procedures were recorded. Weightbearing CT (WBCT) measurements and PROM scores were recorded preoperatively and postoperatively, with 1 year follow-up. Data was then statistically analysed. RESULTS: Eleven patients were included. Planned correction was achieved (two required minor intraoperative adjustments to the initial osteotomy and nine required adjunctive procedures). Mean operative time was 135&#x202f;min. Postoperative improvements were significant radiologically and in MOxFW walking distance. All fused by 3 months, with no significant complications. CONCLUSION: PSI-guided wedge tarsectomy safely achieves predictable multiplanar corrections. Our unit's experience has been excellent, with improvement in patients' walking, particularly with larger deformity corrections. LEVEL OF EVIDENCE: Level IV, prospective case series.

Humans

A User-Friendly Protocol for Microinjection into Teleost Embryos to Study Gene Function.

Zebrafish (Danio rerio) and medaka (Oryzias latipes) are popular teleost models used in developmental biology and functional genomics. To achieve high-quality and reproducible microinjections, it is essential to have robust protocols for breeding, egg collection, and the precise delivery of genetic material. In this protocol, we present a comprehensive and optimized methodology for setting up breeding tanks under controlled photoperiod conditions to maximize egg yield while minimizing contamination. We provide detailed procedures for sex identification, pair selection, the use of grated breeding inserts, and methods to increase egg collection efficiency. We outline procedures for making injection gel beds, pulling needles, and calibration using one-microliter microcapillaries to achieve consistent nanoliter-scale injections. Our protocol outlines settings for the pico-liter injector that are optimized to deliver a precise amount per pulse with minimal variability. Finally, we demonstrate the application of these methods for gene knockdown using morpholino antisense oligonucleotides, gene knockout using CRISPR-Cas9, and gain-of-function mRNA overexpression experiments. Phenotypic assessments conducted at various developmental stages to evaluate gene-specific effects reveal consistent phenotypic outcomes between the morpholino and CRISPR-Cas9 approaches. This easy and comprehensive protocol enables efficient, precise, and scalable genetic manipulation of zebrafish and medaka embryos, thereby supporting advanced functional studies in developmental biology and disease modeling. To our knowledge, this is the first unified protocol for both zebrafish and medaka microinjection systems achieving 97.7% phenotype penetrance in CRISPR-Cas9 knockouts with precision together with a triple validation approach that confirms gene function across multiple techniques.

Animals

Melatonin Levels in 89 Individuals With Smith Magenis Syndrome.

In patients with Smith-Magenis syndrome (SMS), an inverted circadian rhythm of melatonin (MT) contributes to the sleep disturbance. Standard treatment of sleep disturbance with MT often leads to extremely high daytime MT levels, resulting in even more sleep disorders. We therefore retrospectively evaluated the MT data of 89 SMS patients. Mean MT levels in participants on exogenous MT were significantly higher than in participants that did not use MT (p&#x2009;=&#x2009;<&#x2009;0.0001). In 9 participants with very high MT levels, these dropped significantly after discontinuation of exogenous MT (p&#x2009;=&#x2009;0.0037). In 12 participants, MT levels were significantly higher after MT therapy start compared to MT levels before MT start (p&#x2009;=&#x2009;0.028). MT is catabolized principally by the CYP1A2 enzyme, with a half-life of about 40&#x2009;min. CYP1A2 genotyping was performed in five participants with high MT levels during MT use. Although clinically suspected to be a poor CYP1A2 metabolizer, all five turned out to have haplotype CYP1A2*1F, which is associated with increased enzyme activity. This shows that genotyping of CYP1A2 is not suitable to estimate the level of CYP1A2 enzyme activity. When prescribing MT, it is strongly recommended to measure a MT level prior to treatment in order to determine the dose to be given. Checks of the MT level during treatment are necessary due to the frequent occurrence of poor CYP1A2 metabolism. Since CYP1A2 genotyping does not provide adequate information about the level of CYP1A2 enzyme activity, we propose a simple way to determine CYP1A2 phenotype.

Humans

A systematic literature review of cultural concepts taught by pharmacist preceptors during pharmacy student experiential placements.

BACKGROUND: Cultural concepts such as cultural intelligence, awareness, competency and safety are essential in guiding culturally responsive care in health professional practice. Pharmacist preceptors play a pivotal role in sharing both clinical and cultural safe practice with pharmacy students. Culturally responsive care can contribute to achieving health equity, which is especially important for Indigenous communities. AIM: To review literature on cultural concepts in pharmacist preceptorship practices, and how these concepts are taught and communicated to pharmacy students during experiential learning. METHOD: The systematic review followed the PRISMA 2020 guideline. Scopus, PubMed, and Google Scholar were used to identify articles specific to pharmacist preceptors and pharmacy students published between 2015 and 2025, and available in English. RESULTS: Three full-text articles met the inclusion criteria. Major themes and subthemes were identified; pharmacist preceptors lacked preparedness to teach cultural concepts, resulting in variability in preceptors' understanding of cultural concepts and confidence in fulfilling preceptor responsibilities, underutilised structured frameworks to guide students' learning, challenges with preceptorship due to limited resources and support, and the influence of preceptorship on student learning, which impacted students' learning and competency. CONCLUSION: Pharmacy students had minimal exposure to culturally informed pharmacist preceptorship. It is likely that pharmacist preceptors require country-specific educational resources to support culturally safe preceptorship. Future research is required to substantiate these findings, and to guide culturally responsive practice and promote equitable health outcomes in diverse populations.

Humans