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PubMed2026

Restrictive vs Liberal Transfusion Strategy in Traumatic Brain Injury: A Secondary Analysis of the TRAIN Trial.

IMPORTANCE: Anemia is a prevalent condition among patients with traumatic brain injury (TBI); however, the optimal hemoglobin (Hb) threshold to initiate red blood cell transfusion (RBCT) is not well defined. OBJECTIVE: To assess which of 2 different Hb thresholds for guiding RBCT in patients with anemia and TBI is associated with a more favorable neurological outcome. DESIGN, SETTING, AND PARTICIPANTS: This was a preplanned secondary analysis of the Transfusion Strategies in Acute Brain Injured Patients multicentric randomized clinical trial, conducted in 72 intensive care units across 22 countries between September 1, 2017, and December 31, 2022. Follow-up was completed June 30, 2023. Only patients with TBI were included in the present analysis, conducted from February to May 2025. INTERVENTIONS: Liberal (transfusion at Hb <9 g/dL [to convert to g/L, multiply by 10.0]) vs restrictive (transfusion at Hb <7 g/dL) RBCT strategy over a maximum of 28 days. MAIN OUTCOME AND MEASURES: The primary outcome was the occurrence of unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5 (overall range, 1-8, with higher scores indicating more favorable outcome) at 180 days. In addition, 14 prespecified serious adverse events, including infection and cerebral ischemia, were assessed. Data were analyzed using both the intention-to-treat and per-protocol principles. RESULTS: Of 486 patients who presented with TBI (mean [SD] age, 46.8 [17.6] years; 347 [71.4%] male), 475 were included in the primary outcome analysis: 236 were randomized to the liberal transfusion strategy group and 239 to the restrictive transfusion strategy group. Both groups had similar baseline characteristics. In total, 534 RBCTs were administered in the liberal transfusion strategy group, compared with 246 RBCTs in the restrictive group. At 180 days after randomization, 138 patients (58.5%) in the liberal group had unfavorable neurological outcome compared with 161 patients (67.4%) in the restrictive group (relative risk [RR], 0.86 [95% CI, 0.75-1.00]; P = .047; fragility index = 1). There were no significant differences in the occurrence of secondary outcomes (eg, 28-day mortality: 42 of 240 [17.5%] vs 51 of 244 [20.9%]; RR, 0.84 [95% CI, 0.58-1.21]; P = .34) or serious adverse events (eg, RR, 1.13 [95% CI, 0.88-1.43]; P = .34 for infection and RR, 0.87 [95% CI, 0.40-1.90]; P = .72 for cerebral ischemia). After adjustment for several confounders, being randomized to the liberal group was associated with a lower observed probability of unfavorable neurological outcome (odds ratio, 0.60 [95% CI, 0.38-0.94]; P = .03). CONCLUSIONS AND RELEVANCE: In this secondary analysis of a multicenter randomized clinical trial, a liberal RBCT strategy was associated with a lower risk than a restrictive RBCT strategy of unfavorable neurological outcome at 180 days among patients with TBI. These findings should be interpreted with caution in light of the inherent uncertainty of the estimate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02968654.

Humans↗

PubMed2026

Pcgf5 controls the exit from totipotency in mouse embryonic stem cells.

Mouse embryonic stem cell (ESC) cultures contain a rare subpopulation of two-cell-like cells (2CLCs) that transiently reactivate a two-cell embryo-like transcriptional program characteristic of zygotic genome activation (ZGA), including the endogenous retrovirus MERVL and Zscan4, and thereby regain a totipotent-like state. Polycomb repressive complex 1 (PRC1)-mediated H2AK119ub1 has been implicated in restraining entry into the 2C-like state through Pcgf6, yet the factors governing exit from this state and loss of totipotency remain poorly defined. Here, we show that among the six Pcgf paralogs, Pcgf5, which is most prominently upregulated in 2CLCs and forms an MERVL-driven chimeric transcript (Pcgf5MT2C_Mm) during ZGA in 2-cell embryos, controls exit from the 2C-like state in mouse ESCs. Using a reporter ESC line carrying MERVL-tdTomato and Zscan4c-EGFP (MtZG), we manipulated Pcgf5 dosage bidirectionally. Doxycycline (Dox)-inducible overexpression (OE) of Pcgf5 reduced the double-positive (DP) 2C-like population. Conversely, CRISPR-mediated knockout (KO) of Pcgf5 by targeting a common exon shared by all Pcgf5 variants (hereafter, total Pcgf5) increased the DP population. Time-lapse imaging directly confirmed that these changes reflected genuine differences in duration of the 2C-like state: OE shortened, whereas KO prolonged, the time cells spent in this state. These findings reveal that a Polycomb group factor controls not only entry into but also exit from the 2C-like state.

Animals↗

PubMed2026

Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 ± 9 years, 41% were women, mean eGFR was 48.2 ± 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗

PubMed2026

Lower urinary tract evaluation in children with cerebral palsy: A crossectional study.

INTRODUCTION: Cerebral palsy (CP) is a chronic, non-progressive motor disorder affecting voluntary movement and posture. Lower urinary tract (LUT) dysfunction is highly prevalent in children with CP. This study aims to evaluate LUT function in children with CP. MATERIAL AND METHODS: This cross-sectional study was conducted at a tertiary care hospital. Patients aged 5-18 years with established CP diagnosis were included. Evaluation included clinical history, physical examination, urinary ultrasonography with post-void residual (PVR) measurement, and urodynamic studies when indicated. Patients were categorized into three groups; group-1 (LUT dysfunction), group-2 (symptomatic), and group-3 (asymptomatic) for analysis. RESULTS: The study included 97 children with CP (41 girls, 56 boys; median age 8 years). Of the patients, 61.8% were ambulatory (GMFCS I-III) and 38.2% were non-ambulatory (GMFCS IV-V). At least one LUT symptom was detected in 75.3% of patients. Incontinence was the most common symptom at 69.1%. Incontinence prevalence was significantly higher in non-ambulatory patients (81.1% vs 61.7%, p = 0.044). Invasive urodynamics was performed in 19 patients, and LUT dysfunction was diagnosed in 89.5% of them (19.3% of the entire population). Prematurity rate was significantly higher in patients with LUT dysfunction (94.1% vs 64.8%, p = 0.017). Binary logistic regression analysis identified elevated PVR as the strongest independent risk factor for LUT dysfunction (OR = 108, p < 0.001). Abnormal urinary frequency (OR = 14.9, p = 0.022) and quadriplegia (OR = 10.3, p = 0.016) were other independent risk factors. ROC analysis determined the optimal cut-off value for PVR as 19 mL (sensitivity 58.82%, specificity 94.92%). In the intergroup analysis, multinomial logistic regression identified elevated PVR as the strongest predictor (Group-1 vs Group-2: OR = 101; Group-1 vs Group-3: OR = 24, both p < 0.003). Lower gestational age was also an independent risk factor in both comparisons (OR = 1.25-1.26, p < 0.020). DISCUSSION: This study demonstrates LUT dysfunction affects 19.3% of children with CP, strongly correlating with motor impairment severity. Elevated PVR emerged as the strongest independent predictor (OR = 108), offering a practical non-invasive screening tool. Our proposed urodynamic criteria achieved 94.7% diagnostic yield, enabling selective evaluation. Limitations include single-center design and cross-sectional methodology without longitudinal follow-up. These findings support integrating systematic urological assessment into standard CP care for early intervention. CONCLUSION: LUT dysfunction prevalence is high in children with CP, and symptom frequency increases with higher GMFCS levels. Elevated PVR is the strongest predictor, with a clinically applicable cut-off value of 19 mL. Particularly in quadriplegic, non-ambulatory, and premature patients, close follow-up and urodynamic evaluation when necessary should be performed with a multidisciplinary approach.

Humans↗

PubMed2026

Impact of renal dysfunction on immediate versus staged revascularization of non-culprit lesions in patients with ST segment elevation myocardial infarction: a pre-specified subgroup analysis of the randomized MULTISTARS AMI trial.

BACKGROUND: Renal dysfunction might affect outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI). METHODS: In MULTISTARS AMI, patients with STEMI and MVD were randomized to immediate or staged PCI of non-culprit lesions. In this pre-specified analysis, patients were stratified according to the presence of renal dysfunction at baseline, defined at an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m2. Patients with an eGFR < 30 ml/min/1.73 m2 were excluded from the trial. The primary endpoint was a composite of death, non-fatal myocardial infarction, stroke, unplanned revascularization, or hospitalization for heart failure at 1 year. RESULTS: In MULTISTARS AMI, 108 (13%) of 832 patients had renal dysfunction. The primary endpoint occurred more frequently in patients with renal dysfunction (19.4% vs. 11.2%, unadjusted HR 1.82, 95% CI 1.13-2.94), primarily driven by higher rates of death. Among patients with renal dysfunction, the rates of the primary end point were 14.5% and 24.5% in the immediate and staged PCI groups (unadjusted HR 0.55, 95% CI 0.23-1.33). There was no interaction between renal dysfunction and the randomized treatment assignment with respect to the primary end point (adjusted HR 1.30, 95% CI 0.8-2.20, pint 0.82). The occurrence of acute renal insufficiency was statistically similar in patients with renal dysfunction who underwent immediate and staged PCI (10.9% vs. 18.9%, unadjusted HR 0.61, 95% CI 0.22-1.72, pint 0.09). Renal dysfunction at baseline emerged as a strong risk factor for the development of acute renal insufficiency (adjusted HR 5.0, 95% CI 2.30-10.70, p < 0.01). CONCLUSIONS: Outcomes with immediate compared to staged multivessel PCI did not appear significantly altered by the presence of renal dysfunction at baseline. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275).

Humans↗

PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗

PubMed2026

Effects of Esketamine on Postoperative Hospital Anxiety and Depression Scale Scores in Patients Undergoing Laparoscopic Radical Resection for Colorectal Cancer.

OBJECTIVE: To investigate the effects of intravenous esketamine on postoperative Hospital Anxiety and Depression Scale (HADS) scores in patients undergoing laparoscopic radical resection for colorectal cancer. METHODS: In this prospective, randomized, placebo-controlled study, adult patients for elective laparoscopic radical resection were randomly assigned (1:1) to a control group (group C) or an esketamine group (group PE). Group C received conventional general anesthesia and patient-controlled intravenous analgesia (PCIA). In group PE, esketamine 0.5 mg/kg was injected during induction of anesthesia, with esketamine 1 mg/kg added to PCIA. Primary outcome was HADS score on postoperative day 1. Secondary outcomes included HADS scores on postoperative days 3 and 7, sleep quality scores, postoperative level of consciousness, complication rate, length of hospital stay, 24 h inflammatory factors, and satisfaction scores. RESULTS: Group PE showed significantly lower HADS-A and HADS-D scores on postoperative days 1 and 3 , reduced 24 h interleukin-6 (IL-6) leveland higher patient satisfaction compared with group C (all p < 0.05). CONCLUSIONS: Esketamine given during induction and in PCIA reduced early-stage postoperative HADS scores and improved patient satisfaction in colorectal cancer patients.

Humans↗

PubMed2026

Vertical distribution of accessory canals in different tooth types: A systematic review and meta-analysis.

OBJECTIVE: To systematically analyze the vertical distribution of accessory canals and propose potential root-end resection levels in different tooth types. DATA: Proportional distribution of accessory canals (PD-AC) in 1 mm intervals, cumulative proportions within 2 mm and 3 mm (CP-AC0-2 and CP-AC0-3), mean distance from accessory foramen to root apex or main foramen (MD-AF), and prevalence of accessory canals in 2D cross-sections (PR-AC-2D). SOURCES: A systematic search of electronic databases was conducted through December 25, 2025. The review was registered in PROSPERO (CRD420251107855). STUDY SELECTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the AQUA tool. Nineteen studies were included for qualitative synthesis, of which eleven provided sufficient data for meta-analysis. A random-effects model was used, and subgroup analyses were stratified by tooth type, accessory canal type, and country. Within 0-1 mm, 1-2 mm, 2-3 mm, and 3-4 mm from the apex, 41.5%, 34.3%, 9.9%, and 4.4% of accessory canals were located, respectively. Molars had significantly higher proportions than anterior teeth both within 2 mm (90.0% vs. 72.4%) and 3 mm (96.9% vs. 87.5%). Of apical ramifications, 86.4% were within 2 mm. The pooled MD-AF was 1.472 mm. PR-AC-2D decreased from 29.3% at 1 mm to 1.3% at 5 mm. All studies presented moderate to high risk of bias. CONCLUSIONS: A 2 mm root-end resection level may be sufficient for molars, whereas anterior teeth may require a higher level. Further randomized controlled trials are needed. CLINICAL SIGNIFICANCE: A 2 mm resection may adequately expose or remove most accessory canals in molars, potentially preserving more root length while maintaining treatment efficacy. In anterior teeth, a traditional 3 mm resection remains advisable until further evidence becomes available.

Humans↗

PubMed2026

Robotic surgery for gastric gastrointestinal stromal tumors: a systematic review.

Robotic surgery is used for selected gastric gastrointestinal stromal tumours (GISTs), particularly when location makes conventional wedge resection difficult. We synthesised technical, perioperative, pathological, functional and oncological outcomes. PubMed/MEDLINE, Scopus and the Cochrane Library were searched from inception to 14 August 2026. Primary reports with at least three eligible robotic gastric-GIST patients were included. Two reviewers independently selected studies, extracted data and completed design-specific JBI appraisal. Because outcome definitions, denominators and reporting were heterogeneous, findings were synthesised narratively in accordance with SWiM guidance rather than pooled. Twenty-three studies, including six comparative cohorts, were included. Institutional robotic cohorts contained 3-45 eligible patients; one national registry included 1,567 robotic cases. Tumour size ranged from 2.68 ± 1.55 to 7.9 ± 1.8 cm among studies reporting means. Most institutional reports described R0 resection in all eligible patients; exceptions were 23/24 and 24/25, while the registry reported 1,425/1,567 R0 resections. Grade III morbidity occurred in 2/25 patients in one function-preserving series. Registry 30- and 90-day mortality after robotic resection were 0.5% and 0.8%, respectively. Comparative studies did not demonstrate superior postoperative or oncological outcomes with robotic surgery. Robotic gastric-GIST resection appears feasible in selected patients and may facilitate organ-preserving surgery at anatomically challenging sites. Current observational evidence does not establish comparative functional, oncological or economic superiority.

Humans↗

PubMed2026

HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials.

BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peripherally restricted kappa-opioid receptor (KOR) agonist that selectively targets visceral pain pathways enriched with KORs, may provide adequate analgesia without systemic adverse events. METHODS: We conducted a pooled post-hoc analysis of data from two phase III, multicenter, triple-blinded, randomized controlled trials (Study 301, HSK21542 vs placebo; Study 303, HSK21542 vs tramadol vs placebo). Eligible patients undergoing elective gynecological surgery were included. The primary outcome was the summed pain-intensity difference over 12 and 24 hours (SPID 12h and SPID 24h ). Secondary outcomes were pain-relief quality (proportion of patients relieved from severe pain with a pain numerical rating score ≤ 3 between 0 and 24 hours) and rescue-analgesic requirements (number of doses and time to first rescue analgesic). Adverse events were also assessed. RESULTS: A total of 370 patients were analyzed: 150 received HSK21542, 139 received a placebo, and 81 received tramadol. After inverse probability of treatment weighting (IPTW) adjustment, baseline characteristics were well-balanced across treatment groups (all standardized mean differences [SMD] <0.1; see Table 1 for 95% CIs). HSK21542 produced greater reductions in pain intensity over 12 and 24 hours than placebo (least-squares mean differences -8.1 and -16.3 for SPID 12h and SPID 24h , respectively. Both P < .001) and no statistically significant difference was observed between HSK21542 and tramadol ( P > .05). Significantly more patients in the HSK21542 group were relieved from severe pain at 0 to 12 hours (92.7% vs 82.7%, P < .001) and required fewer rescue doses at 0 to 12 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) and 0 to 24 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) than those in the placebo group, whereas no significant differences with tramadol both in 0 to 12 and 0 to 24 hours. HSK21542 was also associated with significantly lower incidences of nausea (24.7% vs 66.7%) and vomiting (21.3% vs 60.5%) than tramadol. Only one case of dizziness occurred in the tramadol group. CONCLUSIONS: HSK21542 could provide adequate postoperative analgesia with few adverse events in patients undergoing gynecological surgery.

Humans↗

PubMed2026

E-cigarette product characteristics and packaging features and interest in e-cigarette use: Results from a randomized within-person trial nested in three prospective cohorts.

BACKGROUND: Product characteristics and packaging may be key targets for regulation to reduce e-cigarette use among youth, but existing data are limited. METHODS: Data are from an experimental study (2018-2020) nested within three prospective cohorts (age 14-26) in southern California (N = 3565). Participants were shown five e-cigarette (e-liquid) packages in a random order that varied in flavor (sweet vs. tobacco), flavor name (descriptive ["blueberry cheesecake"] vs. concept ["smurf cake"] vs. none [number only]), and cartoon image on package (yes/no). For each stimuli, survey items assessed the following outcomes: product appeal (self-enjoyment, others' enjoyment; Likert scale [1-5]), susceptibility to use (use if friends offered, curiosity; 4 ordered responses [definitely not-definitely yes]), peer acceptability (definitely not-definitely yes), and perceived harm (definitely not-definitely yes). Mixed effects proportional odds models evaluated within-person effects of each factor (flavor, flavor name, cartoon) with each outcome. RESULTS: Participants reported greater appeal, susceptibility, and peer acceptability (OR range=3.7-16.9; ps<0.05), and lower perceived harm (OR=0.61; 95%CI=0.53, 0.70) for sweet (vs. tobacco-flavored) e-cigarettes; effects were progressively stronger for younger cohorts. The descriptive flavor name rated higher than the concept flavor (OR range=1.13-2.02; ps<0.05) or number only (OR range=1.18-1.69; ps<0.05) for appeal and susceptibility measures; no differences for concept vs. number were found. The cartoon image rated higher for appeal, curiosity, and peer acceptability (OR range=1.24-1.51; ps<0.05). CONCLUSIONS: Sweet flavors, descriptive flavor names, and cartoon images may increase the appeal of e-cigarettes among youth and young adults with no history of e-cigarette use, and are key targets for regulation.

Humans↗

PubMed2026

Genomic characterization and pathogenicity of ruminant Listeria monocytogenes isolates in a murine oral infection model.

Listeria monocytogenes is a major foodborne pathogen; its ruminant isolates display zoonotic characteristics, causing similar clinical signs in humans, including abortion and encephalitis. However, data on whole genome sequencing and pathogenicity of ruminant L. monocytogenes isolates remain sparse. This study aimed to analyze the genotypic characteristics of L. monocytogenes isolates from ruminants with listeriosis. Furthermore, we assessed the in vivo pathogenicity of four ruminant L. monocytogenes isolates, characterized via whole-genome sequencing-based genetic clustering, in orogastrically inoculated mice. The isolate LM18 (serotype 1/2b, ST224, SL6178) had the lowest lethal dose compared to the other three isolates including previous hypervirulence type (serotype 4b, ST1, SL1) and caused secondary bacteremia in lungs, with sustained bacterial loads in the spleen and liver. Genomic (listeria pathogenicity island -1 and -3) and virulence gene (actA and llsX) mutation analyses associated with virulence suggested from well-recognized studies could not elucidate the virulence of the isolates. SSI-1, which only exists in the isolate LM18 (serotype 1/2b, ST224, SL6178), may help L. monocytogenes survive in the gastrointestinal environment, thereby affecting its virulence. Further research should investigate the role of SSI-1 in the pathogenicity of L. monocytogenes. Moreover, additional studies utilizing larger datasets of ruminant isolates are required to validate our genotypic characterization and to obtain a comprehensive picture of further genotypic differences crucial for L. monocytogenes pathogenicity.

Animals↗

PubMed2026

PCa Detection in PI-RADS 4 and 5 Lesions: Comparison of [68Ga]Ga-PSMA-11 PET/CT-Guided Robot-Assisted Biopsy Versus mpMRI Cognitive-Fusion TRUS-Guided Prostate Biopsy.

Lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 4 or greater on multiparametric MRI (mpMRI) indicate a high likelihood of prostate cancer (PCa), and guidelines recommend a targeted biopsy. We aimed to compare the diagnostic performance of robotic arm-assisted [68Ga]Ga-PSMA-11 PET/CT-guided prostate biopsy (PGPB) with mpMRI-directed cognitive-fusion transrectal ultrasound-guided biopsy (MCFB) in biopsy-naïve men with clinical findings suggestive of PCa. Methods: This prospective, single-center, randomized clinical trial (NCT05137561) enrolled biopsy-naïve men age 50-90 y with elevated levels of prostate-specific antigen (≥4 ng/mL) and abnormal digital rectal examination findings. All participants underwent mpMRI, and those with a PI-RADS score of 4 or greater were randomized into 2 arms. In arm 1, participants underwent PGPB for a [68Ga]Ga-PSMA-avid lesion, and participants in arm 2 underwent MCFB. Participants in arm 1 with PET-negative findings subsequently underwent MCFB, and participants with negative biopsy results underwent PET and PGPB. The primary outcome was the detection of PCa. Secondary outcomes included complication rates and participant-reported pain. Result: Of the 267 participants enrolled, 81.3% (217) had lesions with a PI-RADS score of 4 or greater and were randomized to either PGPB (n = 112) or MCFB (n = 105). PCa was detected in 97.1% of participants (101/104) in arm 1 and 81.0% (85/105) in arm 2 (P < 0.05). PGPB showed higher diagnostic accuracy for PI-RADS 5 lesions (100% vs. 95.1%, P = 0.09). Major complications were observed in arm 2 only (n = 5). Arm 1 had significantly fewer complications (10.8% vs. 51.4%, P < 0.01), a lower median visual analog scale score for pain (3 vs. 5), and shorter procedure times. The core positivity rate was higher in arm 1 (60% ± 20%), despite obtaining fewer cores. Conclusion: [68Ga]Ga-PSMA-11 PGPB demonstrated higher diagnostic performance, fewer complications, and better tolerability compared with MCFB. This approach enables integrated diagnosis and staging, offering a promising alternative for efficient, safe, and accurate evaluation of prostate cancer.

Humans↗

PubMed2026

Carboxyl group number and acidity of organic acids regulate structural reorganization and low glycemic index in cassava pyrodextrins via molecular interactions.

Transforming high-glycemic cassava starch into functional dietary fiber via pyrodextrinization is a promising way to valorize tuber crops, yet the molecular mechanisms catalyzed by organic acids with different carboxyl numbers and acidity remain unclear. This study investigates how carboxyl number and acidity of acetic acid (AA), tartaric acid (TA), and citric acid (CA) affect structural reorganization and low glycemic properties of cassava pyrodextrins. Compared with AA, TA, and CA with stronger acidity and more carboxyl groups promoted more extensive hydrolysis, transglycosylation, repolymerization, and esterification. These changes increased indigestible glycosidic linkages and the branching degree, while reducing molecular weight. Molecular docking confirmed stronger hydrogen-bonding interactions between TA/CA and starch chains. Furthermore, TA- and CA-catalyzed pyrodextrins exhibited superior anti-digestive properties with resistant starch up to 54.26% and an estimated glycemic index as low as 42.46, highlighting the critical role of carboxyl numbers and acidities in modulating the functionality of pyrodextrins.

Manihot↗

PubMed2026

Higher versus Routine Intraoperative Blood Pressure Targets in Noncardiac Surgery: A Systematic Review and Meta-analysis with Trial Sequential Analysis of Randomized Trials.

BACKGROUND: Observational studies consistently link intraoperative hypotension to adverse postoperative outcomes, leading guidelines to recommend maintaining mean arterial pressure 60 to 65 mmHg or greater during noncardiac surgery. Whether targeting higher intraoperative blood pressure values improves clinical outcomes remains uncertain. METHODS: The authors conducted a Preferred Reporting Items for Systematic Reviews and Meta-analyses-guided search on PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Embase from inception to April 2026. Randomized trials comparing higher intraoperative blood pressure targets, either as fixed absolute thresholds or personalized to preoperative baseline, versus routine blood pressure management in adults undergoing elective noncardiac surgery with general anesthesia were included. Outcomes included in-hospital or 30-day mortality, postoperative delirium, acute kidney injury (AKI), 30-day major cardiovascular events, acute myocardial injury, stroke, length of stay, and intraoperative hypotension. RESULTS: Fifteen trials (15,603 patients) were included. Higher targets did not reduce AKI (risk ratio [RR], 0.95; 95% CI, 0.85 to 1.06; P = 0.36; I 2 = 16%) or acute myocardial injury (RR, 1.02; 95% CI, 0.94 to 1.12; P = 0.59; I 2 = 0%) compared with routine targets, with firm evidence from trial sequential analysis. Higher targets were associated with a significant reduction in postoperative delirium (RR, 0.73; 95% CI, 0.54 to 0.98; P = 0.04; I 2 = 26%), although trial sequential analysis indicated the cumulative evidence remained insufficient to draw firm conclusions. No significant effect was observed on in-hospital or 30-day mortality (RR, 1.00; 95% CI, 0.75 to 1.34; P = 1.00; I 2 = 0%); evidence on 30-day major cardiovascular events, stroke, and length of stay was similarly insufficient to draw firm conclusions. CONCLUSION: In adults undergoing elective noncardiac surgery, targeting higher intraoperative blood pressure values does not improve major postoperative outcomes compared with routine management. A potential reduction in postoperative delirium warrants confirmation in adequately powered trials.

Humans↗

PubMed2026

Impact of Diabetes on Outcomes of Contemporary PCI Guided by OCT vs Angiography: The ILUMIEN IV Trial.

BACKGROUND: Patients with diabetes are at higher risk for adverse events after percutaneous coronary intervention (PCI) compared with patients without diabetes. OBJECTIVES: This study sought to assess the influence of diabetes and complex lesions on the outcomes of patients undergoing PCI with and without optical coherence tomography (OCT) guidance during a follow-up period of 2 years. METHODS: Patients in ILUMIEN IV randomized to OCT-guided vs angiography-guided PCI were grouped into those with (n = 1,044) and without diabetes (n = 1,443). Study endpoints were target vessel failure (TVF) and serious major adverse cardiovascular events (MACE). RESULTS: After adjustment for differences in clinical and angiographic characteristics, the 2-year rates of both TVF (9.9% vs 6.3%; adjusted HR: 1.48; 95% CI: 1.09-2.02; P = 0.01) and serious MACE (5.3% vs 2.7%; adjusted HR: 1.77; 95% CI: 1.14-2.76; P = 0.01) were increased in diabetic compared with nondiabetic patients, consistently in patients with and without complex lesions (Pinteraction = 0.22 and 0.14, respectively), although the highest 2-year rates were in patients with diabetes and complex lesions. In all randomized patients, OCT guidance compared with angiography guidance did not reduce TVF or serious MACE. These effects were consistent in patients with and without diabetes (Pinteraction = 0.41 and 0.20, respectively), and were not modified by treatment of complex lesions. CONCLUSIONS: In the large-scale ILUMIEN IV trial, patients with diabetes remained at increased risk for adverse events after PCI compared with nondiabetic patients despite the use of OCT procedural guidance. Patients with diabetes and complex lesions were at particularly high risk for adverse outcomes after PCI.

Humans↗

PubMed2026

Genetic Screening of Colombian Patients With Early-Onset Parkinson Disease.

BACKGROUND AND OBJECTIVES: Early-onset Parkinson disease (EOPD), defined as symptom onset before 50 years of age, accounts for approximately 10% of patients and is suggested to have a greater genetic component than typical late-onset forms of the disease. Recessive variants in PRKN, PINK1, and DJ-1, are the most common genetic cause of EOPD, however, most studies are in patients of white ancestry. This study aims to analyze genetic variants in PRKN, PINK1, and DJ-1 in Colombian patients to help address the gap in EOPD genetic research of South American populations. METHODS: We analyzed 43 unrelated patients with EOPD using Sanger sequencing for the PRKN, PINK1, and DJ-1 genes and employed multiplex ligation-dependent probe amplification to detect copy number variants. Additionally, long-read whole-genome sequencing was conducted on 3 unresolved patients with age at onset before 30 years of age (long-read sequencing [LRS] patient A-C). RESULTS: We identified known pathogenic single-nucleotide variants and copy number variants in the PRKN gene accounting for 2 patients' disease (4.6% of patients). We observed 2 pathogenic variants in PRKN (c.155delA; p.N52Mfs*29 and c.1083+1G>A) in patient 1, who reported an age at onset of 16 years. We further detected a homozygous duplication of PRKN exons 5-6 in an additional patient, age at onset of 18 years. DISCUSSION: Our study helps characterize genetic contributors to EOPD in Colombian patients, demonstrating genetic forms (PRKN, PINK1, and DJ-1) are rare. Our results highlight a need to include diverse populations in research to improve genetic understanding of disease.

Journal Article↗

PubMed2026

The clinical value of adding immune checkpoint inhibitors to radiotherapy for cancer: a systematic review and meta-analysis.

BACKGROUND: While several randomized clinical trials (RCTs) have explored the addition of immune checkpoint inhibitor (ICI) treatment for patients undergoing radiotherapy, studies systematically assessing the clinical value of such interventions are lacking. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant RCTs of cancers that received ICIs plus radiotherapy or radiotherapy. Eligible studies were those published in English as of 14 April 2024. Two independent reviewers screened the included studies and extracted relevant data, then selected the random or fixed-effects model based on the I2 statistic. The main outcomes were hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS); Odds ratios (ORs) with 95% CIs for objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stratified analysis was performed based on cancer type, ICI type, and the timing of ICI addition. The study was registered on PROSPERO (CRD42024551008). RESULTS: 15 RCTs with 7947 patients were included. Pooled HRs were 0.865 (95% CI, 0.730-1.000; I2 = 72.1%) for OS and 0.799 (0.677-0.922; I2 = 82.0%) for PFS in cancer patients. In cancer types, adding immunotherapy to radiotherapy significantly improved patients with non-small-cell lung cancer (OS: 0.544 [0.371-0.717]; PFS: 0.527 [0.438-0.617]) and cervical cancer (OS: 0.722 [0.578-0.867] and PFS: 0.754 [95%CI, 0.621-0.887]). Regarding the ICIs schedule, adjuvant ICI therapy with pooled HRs was 0.742 (0.649-0.834) for OS and 0.638 (0.579-0.697) for PFS. In addition, the pooled ORs for the incidence of grade 3 or higher treatment-related and immune-related adverse events were 1.227 (1.059-1.421; I2 = 71.9%) and 2.217 (1.743-2.821; I2 = 74.0%), respectively. CONCLUSION: Adding immunotherapy to radiotherapy can provide significant clinical benefits for patients with NSCLC and cervical cancer, and the addition of these ICIs in the adjuvant stage is supported.

Humans↗