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PubMed2026

Simultaneously PYCR-1 and ALH-6 inhibition exacerbates 6-PPD quinone toxicity via disrupting proline and glutamate metabolisms and activating insulin signals in Caenorhabditis elegans.

Glutamate synthesized from the proline can serve as a precursor for key intermediate metabolites of citric acid cycle. Recently, we observed reduced glutamate content and expression of alh-6 controlling glutamate synthesis by 6-PPD quinone (6-PPDQ) in Caenorhabditis elegans. However, possible effect of 6-PPDQ on proline synthesis and the association with 6-PPDQ toxicity induction remain unclear. After 0.1-10 μg/L 6-PPDQ exposure, proline content was further reduced, and expression of pycr-1 governing proline biosynthesis was decreased. In 6-PPDQ exposed nematodes, RNA interference (RNAi) of pycr-1 decreased α-ketoglutarate content, enhanced mitochondrial dysfunction, reduced nicotinamide adenine dinucleotide (NADH) and reduced flavine adenine dinucleotide (FADH₂) contents, inhibited mitochondrial complex I/II activities, and decreased expressions of gas-1 and mev-1. Moreover, compared to single RNAi, double RNAi of pycr-1 and alh-6 exacerbated the 6-PPDQ toxicity in reducing α-ketoglutarate, NADH, and FADH₂ contents, and suppressing mitochondrial complex I/II activities and gas-1 and mev-1 expressions. Additionally, double RNAi of pycr-1 and alh-6 intensified toxicity of 6-PPDQ on longevity and caused upregulation of insulin ligand and receptor genes and downregulation of daf-16 and its targeted genes in 6-PPDQ exposed nematodes. Furthermore, after 6-PPDQ exposure, daf-16 RNAi suppressed pycr-1 and alh-6 expressions, suggesting formation of a regulatory feedback loop between pycr-1/alh-6 and daf-16. Our findings highlight involvement of disrupted proline and glutamate metabolisms in 6-PPDQ-induced mitochondrial dysfunction and reduced longevity.

Animals↗

PubMed2026

Should we consider excessive weights in pediatric kidney transplant recepient candidates?: A systematic review and meta-analysis of kidney transplantation outcomes.

INTRODUCTION: In adult populations, excess body weight has been associated with an increased risk of adverse clinical outcomes and mortality following kidney transplantation. In contrast, the influence of obesity on transplantation outcomes among pediatric populations is not yet fully understood. This study aimed to evaluate the association between pre-transplant excess weight and post-transplant outcomes in pediatric kidney transplant recipients. MATERIAL & METHODS: A systematic literature search was performed across PubMed, ScienceDirect, and the Cochrane Library, covering publications up to December 31, 2025. The quality of the included studies was evaluated using the ROBINS-E tool. Statistical analysis was conducted using Review Manager version 5.4. RESULTS: From a total of 1465 records screened, six studies that included 65,483 participants were selected in the meta-analysis. The results indicated that pre-transplant excess weight was significantly associated with an increased risk of acute rejection (OR = 1.09; P = 0.009), delayed graft function (OR = 1.17; P < 0.00001), 1-year graft failure (OR = 1.16; P = 0.0002), and 5-year graft failure (OR = 1.13; P = 0.009). Although 5-year mortality was also higher among recipients with excess weight, this association was not statistically significant (OR = 1.08; P = 0.11). CONCLUSION: Pediatric patients with pre-transplant excess weight had higher post-transplant odds of acute rejection, delayed graft function, and both 1-year and 5-year graft failure compared to those without excess weight. These findings highlight the importance of assessing and managing excess weight prior to kidney transplantation to help prevent adverse outcomes in the future.

Humans↗

PubMed2026

Evaluating the need for late angiography for complete obliteration of AVMs after endovascular treatment: collaborative AVM center experience and a systematic review.

Brain arteriovenous malformations (bAVMs) can be treated curatively by endovascular embolization. However, limited data exist on late recanalization rates. We investigated the rate of late bAVM recanalization following complete endovascular obliteration, confirmed by primary control angiography.We performed a single-center retrospective cohort study on late recurrences in adult patients with bAVMs after complete endovascular obliteration at a Radboud - Isala - MUMC+ (RIM) collaborative AVM center in the Netherlands between 2014 and 2022.Additionally, we conducted a systematic review to evaluate the rate of late recanalization following complete endovascular obliteration, confirmed on primary control angiography, in adults with bAVMs. The protocol for this review was registered in PROSPERO (CRD42024546875).Our retrospective study revealed 42 adult patients treated by endovascular means only; 90.5% (38 patients with mean age of 48.1 years) had confirmed complete obliteration. Both primary (6 months post-treatment) and secondary (more than 1 year post-treatment) angiographic control confirmed complete obliteration in 21 of 23 patients with complete follow-up. Mean follow-up was 47.8 months. Two late recurrences (9.5%) were detected at 5- and 6-years' follow-up imaging.Our systematic review included two studies encompassing a total of 19 patients with mean angiographical follow-up of 20.8 months. There were no late recurrences.Late bAVM recurrence after endovascular treatment with proven complete obliteration may be underestimated owing to limited long-term follow-up. Our findings suggest that after a 6-month angiographic confirmed obliteration, a 5-year angiographic imaging control is justified.

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

Evaluating the persistence of semen under controlled environmental conditions.

When semen is deposited at a crime scene, it may be exposed to harmful environmental conditions. It is important to understand to what extent the different components of semen, specifically acid phosphatase (AP), prostate specific antigens (PSA), sperm and DNA, may become less detectable after exposure to high temperatures and varying levels of humidity. In this study, semen (50 μL) was deposited onto squares of black cotton and exposed to 45 °C and a relative humidity (RH) of 10 or 80% for 0, 7, 14, 21 or 28 days (n = 5 per day, per climate condition). Source testing included AP test reagent, ABAcard® p30 immunoassay kits, and hematoxylin and eosin staining. DNA was extracted using the DNA IQ™ System (Promega, Australia) and quantified using Quantfiler Trio™ (Thermo Fisher Scientific, Australia). Over the 28-day period under both RH conditions, the time taken for a positive AP test to develop increased significantly (p < 0.01) and the number of sperm observed decreased significantly (p < 0.01). All ABAcard® p30 tests were positive regardless of exposure time or conditions. No impact on the quantity of DNA recovered was observed when semen was exposed to 45 °C and 10% RH, with a higher median quantity of DNA recovered at day 28 compared to day 0. In contrast, when the RH was raised to 80%, the median quantity of DNA recovered was substantially less at day 28 (81.5 ng, IQR: 87.5 ng) compared to day 0 (181.5 ng, IQR: 1172.4 ng). This study highlights the impact that temperature and RH may have on the persistence of AP, PSA, sperm and DNA over time.

Humans↗

PubMed2026

Genetic Ancestry and Carrier Variant Frequency Enrichment in a Colombian Andean Population: Insights From the Eje Cafetero.

Colombia is one of the most genetically diverse populations in Latin America, and its demographic process has promoted the persistence and local enrichment of deleterious alleles, increasing the frequency of autosomal recessive disorders, particularly in semi-isolated Andean populations such as the Eje Cafetero. However, exome-based reference data from this region remain scarce, limiting ancestry-aware variant interpretation and carrier screening strategies. We aimed to characterize the ancestry proportions of this population using exome data, and to estimate the carrier frequency and distribution of pathogenic and likely pathogenic (P/LP) variants in clinically relevant recessive genes. We conducted a cross-sectional study with whole-exome sequencing (WES) in 316 unrelated individuals from the Colombian Eje Cafetero. P/LP variants were evaluated in 454 genes associated with autosomal recessive disorders. The global ancestry proportions were estimated using a validated panel of 250 exome-compatible ancestry-informative markers. Carrier frequencies were compared against Non-Finnish Europeans (NFE) and Admixed Americans (AMX) from gnomAD v4. The cohort showed predominant European ancestry (mean 51%), followed by Native American (36%) and African (13%) components. We identified 151 carriers of 89 distinct pathogenic variants across autosomal recessive genes. The most frequent variants were SERPINA1 c.863A>T (5.5%), CFTR c.1210-11T>G (3.5%), and PYGM c.1094C>T (1.5%). Also, recurrent variants were significantly enriched compared with both NFE and AMX populations, supporting regional founder effects. This study represents one of the most comprehensive exome-based genetic characterizations of the Colombian Eje Cafetero, revealing ancestry-specific enrichment of clinically relevant autosomal recessive variants driven by founder effects.

Female↗

PubMed2026

Genetic determinants of gestational diabetes mellitus in thai pregnant women: role of GCKR, CDKAL1, TCF7L2, NEDD1, and CMIP variants.

BACKGROUND: Gestational diabetes mellitus (GDM) has a high global prevalence and arises from complex interactions between genetic predisposition and environmental factors. GDM is associated with metabolic disturbances and chronic low-grade inflammation, both of which contribute to its pathogenesis. This study aimed to investigate the association between GDM and 135 single-nucleotide polymorphisms (SNPs) across 20 genes related to metabolic traits. METHODS: In this case-control study, 152 pregnant women with GDM and 684 pregnant women with normal glucose tolerance (NGT) who underwent antenatal examination at Siriraj Hospital, Bangkok, were enrolled. Clinical data and blood samples were collected from all participants. Genomic DNA was isolated and subjected to whole-genome sequencing using the DNBSEQ-T7RS high-throughput sequencing platform. Genotype analyses were performed using R software, and haplotype analyses were conducted using the online SNPStats software. RESULTS: After adjusting for maternal age and pre-pregnancy body mass index, polymorphisms in TCF7L2 (rs34872471, rs7901695, rs4506565, rs7903146, rs12243326, and rs12255372), NEDD1 (rs10431408, rs11830756, rs249579, rs249585, and rs4762339), CMIP (rs2306115 and rs201681534), CDKAL1 (rs4710942), GCKR (rs2293572 and rs2293571), and GCK (rs5883890) were significantly associated with the risk of GDM. Haplotype analysis demonstrated that the TCF7L2 rs12243326-rs12255372 CA haplotype was associated with a decreased risk of GDM (OR = 0.44, 95% CI: 0.23-0.81), while the NEDD1 rs249579-rs249585-rs4762339 GGT haplotype was associated with an increased risk of GDM (OR = 1.40, 95% CI: 1.08-1.82). CONCLUSIONS: These findings suggest that genetic variations in TCF7L2, NEDD1, CMIP, CDKAL1, GCK, and GCKR contribute to GDM susceptibility in the Thai population.

Humans↗

PubMed2026

Robot-assisted bladder diverticulectomy in adults: a systematic review and pooled analysis of perioperative and functional outcomes.

Robot-assisted bladder diverticulectomy (RABD) is used for symptomatic acquired bladder diverticula, but evidence is dispersed across small single-centre series and the only dedicated systematic review dates from 2010. We reviewed contemporary perioperative and functional outcomes of RABD. Following a protocol registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/54CFT ), PubMed, Embase, the Cochrane Library, Scopus and Web of Science were searched from inception to 30 August 2026 (initial search June 2026, re-run and broadened for this version), following PRISMA 2020. Eligible studies were original series of five or more adults undergoing robot-assisted bladder diverticulectomy reporting extractable outcomes. Two reviewers independently screened, extracted data and appraised risk of bias with the Joanna Briggs Institute checklist for case series, with third-reviewer adjudication. Binary outcomes were pooled as proportions with Wilson 95% confidence intervals (CI); continuous outcomes were summarised as patient-number-weighted descriptive values, because mixed median/mean reporting and clinical heterogeneity precluded a formal pooled-effect meta-analysis. Twelve studies (146 patients) were included and all outcomes were extracted from the full-text reports. A transperitoneal route was used throughout. There were no conversions to open surgery (0/129; 95% CI 0-2.9%). Major complications (Clavien-Dindo ≥ III) occurred in 3.0% (4/135; 95% CI 1.2-7.4%). Patient-number-weighted descriptive values (combining study-level medians and means, and therefore not a pooled mean) were: operative time 163 min, blood loss 99 mL, length of stay 3.6 days and catheter duration 7.7 days. Symptom scores and post-void residual improved in every reporting series, significantly in five. The single non-randomised comparison with open surgery reported fewer major complications after RABD (5% [1/20] vs. 50% [3/6], p = 0.007), but the open arm comprised only six patients and this finding should not be regarded as comparative evidence. Across these series, RABD was feasible with low reported short-term morbidity in selected patients: no conversions to open surgery were recorded in the studies reporting conversion status, the major-complication rate was low, and symptom scores and post-void residual improved in every series that measured them. A minority of patients had an incidentally detected intradiverticular tumour; oncological outcomes were not an endpoint of this review. Evidence remains limited by small, heterogeneous, mostly retrospective series, so these findings should be read as descriptive; prospective comparative data are warranted.

Humans↗

PubMed2026

Aortoesophageal Fistula: Mending the Lethal Connection-A Systematic Review and Meta-Analysis.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare, life-threatening condition with limited high-quality evidence to guide management. METHODS: We conducted a systematic review and meta-analysis of PubMed and Scopus through December 2025, evaluating survival and complication outcomes according to treatment strategy and morphological severity. Patients were categorized into 5 groups: TEVAR alone, staged TEVAR followed by surgery, primary open or hybrid surgery, TEVAR with esophageal stenting, and supportive/palliative care. Outcomes were pooled as proportions with 95% confidence intervals (CIs). RESULTS: A total of 167 reports representing 528 patients were included. Overall 30-day mortality was 31.2% (95% CI 27.0% to 35.7%) and 1-year mortality 41.2% (95% CI 36.2% to 46.4%). Infection occurred in 32.6%, reintervention in 20.2%, and recurrence in 13.2%. Staged TEVAR followed by surgery showed favorable survival (30-day 12.7%, 1-year 26.1%) but high infection (66.7%) and reintervention (43.2%) rates. TEVAR with esophageal stenting had the lowest early mortality (5.0%) but frequent reintervention (54.5%) and 1-year mortality of 33.3%. TEVAR alone demonstrated the lowest 1-year mortality among definitive strategies (25.5%) but notable recurrence (26.9%). Primary open or hybrid surgery carried higher early and late mortality, while supportive/palliative care had the worst outcomes. Morphological severity correlated strongly with mortality, infection, reintervention, and recurrence, with type IV lesions showing particularly poor prognosis. CONCLUSION: Despite contemporary management, AEF carries high early and late mortality. Definitive strategies, particularly staged TEVAR followed by surgery, offer improved survival but increased complications. Morphology-guided, individualized management is recommended.

Adult↗

PubMed2026

Response-adapted surgical de-escalation following neoadjuvant immunotherapy in resectable mucosal HNSCC A systematic review and meta-analysis.

INTRODUCTION: Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020-2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I2 statistic. RESULTS: The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9-88.2) for the former and 82% (75.2-87.2) for the latter (P=.751), and the respective pooled OS was 92.3% (87.5-95.3) and 91.4% (80.3-96.5) (P=.839). The pooled pCR rate was 41.7% (95% CI 5.4-48.4; I2=.0) for RAS and 19.8% (95%CI 13.3-29.6; I2=.62) for BPS (P=.001), while the MPR was not significantly different (59.6%, versus 48.5%, P=.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. CONCLUSIONS: RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.

Humans↗

PubMed2026

Artificial Intelligence Cannot Replace Peer Reviewers but May Help Editors Triage: A Comparative Analysis of a Large Language Model and Human Reviewer Recommendations at the American Journal of Sports Medicine.

BACKGROUND: The peer review system faces increasing strain from rising manuscript volumes, reviewer fatigue, and well-documented interreviewer disagreement. Large language models (LLMs) have shown potential to support the peer review process, but their ability to replicate editorial decisions at high-impact medical journals and their utility as manuscript screening tools remain unknown. PURPOSE: To compare the agreement between an LLM and the final editorial decision on manuscripts submitted to the American Journal of Sports Medicine and to evaluate the potential of LLMs as a manuscript screening tool. STUDY DESIGN: Cross-sectional agreement study. METHODS: Fifty-four manuscripts randomly selected from submissions to the American Journal of Sports Medicine (September 2024-October 2024) were reviewed by a locally deployed LLM (Ministral 3 14B; Mistral AI) using a standardized prompt. The artificial intelligence (AI) produced a categorical recommendation (reject, cascade, revision, or accept) and a numerical score (0-100) for each manuscript. Agreement with the final editorial decision was assessed by Cohen kappa (4-category model) for pooled human reviewers (n = 139 reviews) and the AI (n = 54). Screening performance was evaluated by positive predictive value (PPV), sensitivity, and specificity. RESULTS: Pooled human reviewers demonstrated fair agreement with the final decision (κ = 0.181 [P < .001]; 42.4% agreement), while the AI demonstrated slight, nonsignificant agreement (κ = 0.126 [P = .099]; 37.0% agreement). The AI recommended revision for 61.1% of manuscripts, of which 72.7% were ultimately rejected or cascaded, demonstrating systematic "revision bias." When the AI recommended rejection, 54.5% of those manuscripts were ultimately rejected and 27.3% were cascaded; when the AI recommended cascade, 50% were rejected and 50% were cascaded. However, when the AI recommended rejection or cascade (n = 21), 90.5% received a final decision of rejection or cascade (PPV, 90.5%; specificity, 81.8%). Manuscripts with an AI score <70 were rejected or cascaded 88.0% of the time (PPV, 88.0%). CONCLUSION: AI cannot replicate the nuanced judgment of human peer reviewers at a high-impact sports medicine journal. When AI recommended rejection or cascade, 90.5% of manuscripts received that final decision (descriptive PPV, 90.5%; 95% CI, 71.1%-97.3%), suggesting potential utility as an exploratory first-pass screening tool warranting further validation in larger cohorts. However, AI could not reliably distinguish manuscripts destined for outright rejection from those that would be cascaded to a sister journal-an important limitation for editorial triage applications.

Sports Medicine↗

PubMed2026

Postoperative complications and outcomes after surgical treatment for tophaceous gout: A systematic review and meta-analysis.

BACKGROUND: Surgical treatment remains necessary for selected patients with tophaceous gout, particularly when mechanical limitation, nerve compression, ulceration, infection, deformity, or failure of conservative treatment is present. However, postoperative outcomes after surgery for tophaceous gout have not been comprehensively quantified. This systematic review and meta-analysis evaluated postoperative complication profiles and recurrence burden after surgical treatment for tophaceous gout. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted from database inception to March 25, 2026. Original studies reporting postoperative outcomes after surgical treatment for tophaceous gout were included. Pooled event rates with 95% confidence intervals (CIs) were calculated using a random-effects single-arm meta-analytic approach. Primary outcomes were postoperative infection, delayed wound healing, and recurrence. Secondary outcomes were reoperation, amputation, and overall complications. Functional outcomes were summarized descriptively. RESULTS: 18 retrospective studies were included. The pooled postoperative infection rate was 11.3% (95% CI 8.0%-15.7%), delayed wound healing 9.9% (95% CI 5.1%-18.2%), and recurrence 8.5% (95% CI 4.7%-14.9%). Secondary pooled rates were 9.7% (95% CI 5.5%-16.7%) for reoperation, 3.7% (95% CI 2.0%-6.8%) for amputation, and 24.0% (95% CI 14.0%-38.1%) for overall complications. Significant subgroup differences were identified only for infection according to anatomic site and intervention type. Sensitivity analyses showed that pooled estimates were robust. The certainty of evidence was very low for all outcomes. CONCLUSIONS: Surgical treatment for tophaceous gout is associated with measurable postoperative risks, particularly infection and overall complications. These findings support careful perioperative counseling, structured postoperative surveillance, integrated long-term urate-lowering management, and more standardized reporting of perioperative risk factors and postoperative outcomes in future surgical studies of tophaceous gout.

Humans↗

PubMed2026

Efficacy and safety of microwave ablation for the treatment of pulmonary osteosarcoma oligometastases.

PURPOSE: Evaluate efficacy and safety of microwave ablation (MWA) for pulmonary osteosarcoma oligometastases. METHODS: Twenty-two patients (median age, 16 years [range, 9-41 years]; 15 male) with pulmonary osteosarcoma oligometastases who underwent MWA from January 2018 to December 2023 were included, with 27 MWA sessions for 36 lung metastases. Technical success and complications were evaluated in all 22 patients, while efficacy and survival were evaluated in 19 patients with 24 MWA sessions in treatment of 32 tumors. Technical success was assessed for each tumor. Local tumor control, progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Complications were classified using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Technical success was achieved in all 36 tumors (100.0%). Local tumor progression occurred in five of 32 tumors (15.6%). The estimated local tumor control rates at 12, 24 and 36 months were 96.9%, 86.1% and 81.5%, respectively. No significant difference in local control was found between tumors ≤ 10 mm and > 10 mm (p = .470). Twelve of 19 patients (63.2%) developed new lung metastases outside the ablation area, including one with concurrent newly developed bone metastases and one with recurrence of primary osteosarcoma. The median PFS was 21.5 months. The estimated OS rates at 12, 24 and 60 months were 100.0%, 94.4% and 94.4%, respectively. Major complications occurred in five of 27 sessions (18.5%). CONCLUSIONS: MWA preliminarily demonstrates a high technical success rate, notable local tumor control, promising overall survival and acceptable safety for pulmonary osteosarcoma oligometastases.

Adolescent↗

PubMed2026

Accelerated Diagnostic Pathways for Suspected Acute Coronary Syndrome in Practice: A Randomized Trial of 0/1-Hour vs 0/3-Hour Troponin Testing.

BACKGROUND: For suspected acute coronary syndrome (ACS), guidelines recommend using high-sensitivity troponins (hs-cTn) in accelerated diagnostic pathways (ADPs) with 0/1-hour recommended over 0/3-hour ADP. However, implementation of these ADPs, with universal use of hs-cTns, has not been directly compared in randomized trials OBJECTIVES: This study sought to compare the efficiency and safety of the European Society of Cardiology (ESC) 0/1-hour and a 0/3-hour ADP when implemented in real-world clinical practice. METHODS: This pragmatic, randomized, noninferiority implementation trial compared the safety and efficiency of clinician decision making using these 2 pathways. To prevent incorporation bias, an independent hs-cTnI was used for formal adjudication using the fourth universal definition of myocardial infarction (MI). Efficiency was judged by the proportion of patients discharged within 4 hours. The safety endpoint was major adverse cardiac events (MACE) within 30 days (adjudicated index or representation type 1 MI, cardiovascular death, and urgent coronary revascularization) for those who were considered not to have ACS and discharged. The noninferiority margin, for absolute difference in sensitivity, between the ESC 0/1-hour and the 0/3-hour ADP was set at 3%, assessed with a 1-sided 97.5% CI. RESULTS: From December 2021 to July 2024, of 13,983 screened 3,543 individual patients with suspected ACS were recruited and consented from 2 major emergency departments in North-West England, with 100% follow-up achieved for all representations to any national hospital. The median age was 60 years (IQR: 49.5-70.5 years), 53% were men, 6.7%, and 7.6% had adjudicated index type 1 MI and MACE within 30 days, respectively. The turnaround time from sample to result for central laboratory hs-cTnT was 81 minutes (IQR: 69-101 minutes). The proportion of patients discharged within 4 hours was relatively low and did not differ substantially (21.8% vs 19.2%, P = 0.07). In addition, the 0/1-hour pathway was noninferior for safety, in patients discharged, compared with the 0/3-hour pathway, absolute difference in sensitivity was +4.2% (1-sided 97.5% CI: -2.5) in favor of the 0/1-hour pathway. The calculated sensitivities were 93.7% (95% CI: 88.4%-97.1%) vs 89.5% (95% CI: 82.7%-94.3%), respectively. CONCLUSIONS: Implementation of the ESC 0/1-hour pathway failed to discharge significantly more patients within 4 hours of presentation compared with the 0/3-hour ADP. In addition, The ESC 0/1-hour was noninferior to the 0/3-hour hs-cTn pathway for safety of discharge, although safety for both pathways was less than that imputed by observational studies. This trial demonstrates that perceived benefits to emergency department efficiency of a reduced sampling interval are mitigated by central laboratory turnaround times as well as system constraints. (Pragmatic Randomised Trial of the ESC 0/1 Versus 0/3 Hour Troponin Pathway [MACROS2]; NCT05322395).

Acute Coronary Syndrome↗

PubMed2026

Cryostick pre-cooling reduces pain during intra-articular knee injections: a randomized, contralateral-controlled trial.

BACKGROUND: Intra-articular knee injections are essential for osteoarthritis management but often limited by "needle phobia" and procedural pain. The cryostick, a high-thermal-conductivity device, is a potential analgesic; however, evidence regarding its efficacy in reducing pain and bleeding is limited. The purpose of the study was to evaluate whether cryostick application reduces procedural pain, reduces bleeding, and improves patient satisfaction during intra-articular knee injections. METHODS: This randomized, contralateral-controlled trial included 50 patients (100 knees) with bilateral knee osteoarthritis. One knee received a 20-s cryostick protocol (-20°C) immediately before injection; the contralateral knee received a standard injection. Primary outcome was pain intensity (100-mm VAS) during needle penetration and at 5-min post-injection. Secondary outcomes included bleeding area (mm2) and satisfaction (1-5 Likert scale). RESULTS: Cryostick application significantly reduced pain during needle penetration (Mean Difference [MD] -24.8 mm; 95% CI -29.9 to -19.7; P < 0.001) and at 5-min post-injection (MD -20.8 mm; 95% CI -26.8 to -14.8; P < 0.001). The Number Needed to Treat (NNT) to achieve the Minimal Clinically Important Difference (13 mm) was 1.28 (95% CI 1.15-1.54) during penetration and 1.79 (95% CI 1.45-2.36) at 5-min post-injection. The bleeding area was significantly smaller with cryostick (MD -4.82 mm2; P = 0.014). Patients reported significantly higher satisfaction scores with the cryostick (4.10 vs 2.96; P < 0.001). CONCLUSIONS: A 20-s cryostick application is a safe, well-tolerated, and effective adjunct for attenuating pain and bleeding during knee injections. This technically simple approach requires minimal complexity, offering an efficient, non-pharmacological tool to enhance patient comfort.

Humans↗

PubMed2026

Unravelling bioanalytical innovations, degradation processes, and impurity landscapes of VEGFR inhibitors.

From pre-formulation studies to clinical trials, VEGFR-targeted small-molecule tyrosine kinase inhibitors (TKIs) require rigorous analytical standards. Bioanalysis, stability-indicating studies, and impurity profiling are used to examine chromatographic advances for VEGFR-targeted TKIs like sunitinib, pazopanib, axitinib, sorafenib, cabozantinib, vandetanib, apatinib, lenvatinib, nintedanib, and regorafenib. An LC-MS/MS and UPLC-MS/MS routinely show sub ng/mL performance, as shown by LLOQs (0.2 ng/mL) for sunitinib and axitinib, 1 ng/mL for pazopanib, 5-7 ng/mL for sorafenib, 0.5-1.5 ng/mL for regorafenib metabolic products, and 0.1-0.5 ng/mL for lenvatinib. These approaches are used for pharmacokinetics and therapeutic drug monitoring due to their good correlation coefficient of 0.1-10,000 ng/mL, accuracy of 95%-108%, and precision of 15% RSD. UPLC-QTOF-MS/MS distinguishes degradants and metabolites during forced degradation studies, enabling structural elucidation following ICH M7 risk evaluation protocol. HPTLC/MLC offers fast, sensitive screenings, while RP-HPLC/DAD or HPLC-UV offer reliable, cost-effective routine quality-control solutions with LOD/LOQ in the μg/mL range and linearity of 10-240 μg/mL. This review lists the structures and CAS numbers of ten VEGFR-2 TKI degradants and metabolites, as well as pharmacopeial impurities in SMILES forms. It will be useful for future method development and regulatory applications. To ensure VEGFR-targeted TKI quality, safety, and therapeutic efficacy, LC-MS/MS for trace quantification and HRMS for structure elucidation provide a robust, future-oriented framework. To improve VEGFR-targeted TKI quality, safety, and regulatory compliance, analytical development should focus on HRMS-based impurity characterization, AI-assisted degradation prediction, green chromatography, and harmonized bioanalytical validation.

Humans↗

PubMed2026

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

PubMed2026

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (χ2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans↗