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PubMed2026

Real-world clinical utility of exome sequencing in pediatric drug-resistant epilepsy: Experience from a tertiary center in Thailand.

BACKGROUND: Genomic testing has increasingly contributed to the diagnosis and management of pediatric drug-resistant epilepsy (DRE), particularly in patients with suspected genetic etiologies. This study evaluated the diagnostic yield and real- world clinical utility of whole-exome sequencing (WES) in children with DRE. METHODS: Children with DRE and seizure onset before 15 years of age were enrolled between January 2020 and December 2023. Clinical data, including demographics, seizure characteristics, developmental history, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and prior investigations, were reviewed. WES was performed in all probands and, when available, their parents. Variants were interpreted according to standard guidelines. Clinical utility and 1-year seizure and developmental outcomes were assessed from follow-up records. RESULTS: Fifty-six patients (23 males, 33 females) were included. The median age at seizure onset was 1 year (interquartile range [IQR] 0.3-4 years), and 96.4% had developmental comorbidities. Pathogenic or likely pathogenic variants were identified in 39% (22/56), with the highest diagnostic yield in children with seizure onset before 3 years of age. Channelopathies accounted for most genetically solved cases (68%), predominantly involving sodium channel genes. Genetic diagnoses provided clinical utility in 73% (16/22) of solved cases by guiding treatment and precision management. At 1-year follow-up, genetically solved patients showed more favorable seizure and developmental outcomes than those with genetically unsolved patients. CONCLUSION: WES achieved a 39% diagnostic yield and substantial clinical utility in pediatric DRE, particularly in early-onset and channelopathy-related disorders. These findings support early molecular diagnosis to facilitate genotype-informed management in appropriately selected children. However, the more favorable developmental and seizure outcomes observed in genetically solved patients should be interpreted with caution, as they may have been influenced by multiple factors beyond genetic diagnosis. In resource-limited settings, careful clinical phenotyping remains essential for treatment decisions and for prioritizing children for genomic testing.

Clinical utility↗

PubMed2026

Searching for New Genes That Cause Usher Syndrome.

PURPOSE: The purpose of this project was to identify novel Usher syndrome (USH) candidate genes from phenotyping data of 9139 knockout (KO) mouse lines. METHODS: We evaluated phenotype data for concurrent retinopathy and hearing abnormalities in single-gene KO mice generated by the International Mouse Phenotyping Consortium (IMPC). A search was performed to determine whether each gene had been previously associated with retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and the expression of human orthologues of candidate genes in the retina and inner ear. RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examinations, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of the 18 candidate genes partially overlapped with those of USH genes. Particularly, FER and DYRK1B proteins were predicted to interact with proteins encoded by known ciliopathy genes. ADIPOR1, ATP8B1, and MPDZ were associated with retinal degeneration in humans. CHSY1 and IDUA may be pathogenic causes of hearing impairment in people. Furthermore, CHSY1, CSTB, and SPRED1 were located adjacent to unsolved genetic loci related to USH. CONCLUSIONS: A screen of 9139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormalities consistent with the principal clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine the causation of retinal degeneration and hearing loss in patients.

Animals↗

PubMed2026

[A case of bilateral open-lip schizencephaly with West syndrome due to variant of PAFAH1B1 gene and literature review].

OBJECTIVE: To report the clinical manifestations, genetic features, diagnosis, treatment, and prognosis of a child with bilateral open-lip schizencephaly complicated by West syndrome due to a variant of PAFAH1B1 gene, and review the relevant literature. METHODS: Clinical data of a 4-month-old boy were retrospectively analyzed, and 35 previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of Gansu Provincial People's Hospital (Ethics No.: 2025-871). RESULTS: The 4-month-old boy presented with clustered flexor spasms, hypsarrhythmia on electroencephalography, and developmental regression. Brain magnetic resonance imaging revealed bilateral pachygyria, schizencephaly, and dysgenesis of the corpus callosum. Trio whole-exome sequencing identified a de novo heterozygous NM_000430.4: c.703_704delAG (p.Glu235Metfs*20) frameshift variant in the PAFAH1B1 gene. Sanger sequencing confirmed that neither parent carried this variant. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant has met the criteria for PVS1+PS2_Moderate+PM2_Supporting, and was classified as pathogenic. After treatment with adrenocorticotropic hormone combined with vigabatrin and other antiseizure medications, the epileptic spasms were controlled and the electroencephalographic abnormalities had improved. However, global developmental delay persisted at the 12-month follow-up. Analysis of the present case and 35 previously reported cases showed that PAFAH1B1-related phenotypes were highly consistent, mainly including infantile spasms (28/36), developmental delay/intellectual disability (29/36), and abnormal brain MRI findings (30/36), predominantly cortical malformations. The reported variant types included deletions, frameshift variants, nonsense variants, missense variants, and splice-site variants. CONCLUSION: PAFAH1B1 gene variants are an important cause for cortical malformations, including schizencephaly, and may lead to secondary West syndrome. This study has systematically summarized the genotypic and phenotypic features of bilateral open-lip schizencephaly complicated by West syndrome associated with a frameshift variant of the PAFAH1B1 gene. For infants with epileptic spasms or early-onset epilepsy accompanied by structural brain abnormalities, early genetic evaluation should be performed, and antiseizure treatment should be integrated with neurodevelopmental rehabilitation to facilitate long-term management.

Humans↗

PubMed2026

Hip Arthroscopy During Female Menstruation: A Retrospective Analysis of Safety and Clinical Outcomes With 24-Month Follow-Up.

OBJECTIVES: To investigate the safety and clinical outcomes of hip arthroscopy performed during menstruation in reproductive-age female patients, and to determine whether surgery during menstruation increases intraoperative risks or adversely affects postoperative recovery. Currently, clear clinical guidelines regarding the timing of elective orthopedic surgeries relative to the menstrual cycle are lacking, often leading to unnecessary surgical rescheduling. Therefore, this study aimed to provide evidence-based guidance for perioperative management and optimal surgical scheduling, thereby addressing a critical clinical need. METHODS: This retrospective cohort study included reproductive-age female patients who underwent hip arthroscopy at the First Medical Center of Chinese PLA General Hospital, the Fourth Medical Center of Chinese PLA General Hospital, and the Department of Sports Medicine at the Second Hospital of Shandong University from December 2018 to September 2023. Patients were categorized into the menstruation group (MP) and the non-menstruation group (NMP) based on whether they were menstruating on the day of surgery. The NMP group consisted of equally sized ovulatory (OP) and luteal (LP) phases. Perioperative outcomes included: intraoperative blood loss, anesthetic dosage, operative time, hemoglobin (Hb) change (within 24 h postoperatively), prothrombin time (PT), and activated partial thromboplastin time (APTT). Postoperative outcomes included analgesic consumption, duration of analgesic use, time to first unassisted weight-bearing ambulation, complications, and urinary tract infections. Functional outcomes were assessed at 24-month follow-up using the Visual Analog Scale (VAS), Modified Harris Hip Score (mHHS), International Hip Outcome Tool-12 (iHOT-12), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sports Specific Subscale (HOS-SSS). RESULTS: Of 884 eligible patients, 28 were included in the MP group and 56 matched patients in the NMP group. Operative time, anesthetic use, Hb change, PT, and APTT were comparable between the two groups (all p > 0.05). No serious complications or urinary tract infections occurred in either group. At the 24-month follow-up, both groups demonstrated significant improvements in VAS, mHHS, iHOT-12, HOS-ADL, and HOS-SSS (all p < 0.001), with no statistically significant differences observed between the groups. CONCLUSIONS: Hip arthroscopy during menstruation does not increase intraoperative bleeding, impair coagulation, or delay functional recovery for female patients. Menstruation should not be considered a contraindication when appropriate perioperative management is applied.

Humans↗

PubMed2026

Functional constipation in pregnancy and its association with dietary intake and physical activity: a cross-sectional study.

BACKGROUND: Functional constipation (FC) is a common complaint during pregnancy and has been reported to be associated with physical activity and dietary intake. However, previous studies have reported inconsistent findings. Therefore, this study aimed to determine the prevalence of FC and examine its association with physical activity and dietary intake among pregnant women. METHOD: In this cross-sectional study, 381 healthy pregnant women attending urban health centres in Tabriz, Iran, between January 2024 and February 2025, were selected using a multistage cluster sampling method. FC was diagnosed according to the Rome IV criteria. Data were collected through face-to-face interviews using the International Physical Activity Questionnaire (IPAQ) and the Food Frequency Questionnaire (FFQ). Multivariable Generalised Estimating Equations (GEE) analysis was performed to identify factors associated with FC. RESULTS: The overall prevalence of FC throughout pregnancy was 37%. In the first trimester, 41 out of 73 women (56%) had FC, while in the second trimester 53 out of 146 women (36%), and in the third trimester 47 out of 162 women (29%) were affected. Multivariate GEE indicated that both higher dietary fibre intake (aOR= 0.88, 95%CI 0.86-0.91, p < 0.001) and higher fluid intake (aOR= 0.59, 95%CI 0.52-0.67, p < 0.001) were associated with a reduced risk of FC. A normal BMI was associated with a lower risk of FC (aOR= 0.35, 95% CI 0.16-0.77, p = 0.009), whereas, secondary education was associated with a higher risk (aOR= 2.81, 95%CI 1.33-5.95, p = 0.007). Physical activity (aOR= 1.00; 95%CI 1.00 to 1.01; p = 0.168), and other demographic characteristics (p > 0.05) were not independently associated with FC after adjustment. CONCLUSION: FC is highly prevalent during pregnancy and may adversely affect women's quality of life. Higher dietary fibre and fluid intake were associated with lower odds of FC, highlighting the importance of healthy lifestyle behaviours during pregnancy. Prospective longitudinal studies are warranted to confirm these findings.

Humans↗

PubMed2026

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Cefiderocol susceptibility rates in carbapenem-resistant Gram-negative bacteria in a comparative, multicenter surveillance study in China.

BACKGROUND: Cefiderocol is a siderophore cephalosporin with potent, broad spectrum of activity against carbapenem-resistant (CR) Gram-negative bacteria. The objective of this surveillance study was to assess cefiderocol susceptibility in molecularly characterized CR Gram-negative pathogens collected from hospitalized patients across China. METHODS: Susceptibility testing was performed by the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines, using pre-prepared frozen 96-well microtiter Thermo Fisher plates. Susceptibilities to cefiderocol and most comparators were determined by Clinical and Laboratory Standards Institute breakpoints, to tigecycline by US Food and Drug Administration breakpoints, and to colistin by European Committee on Antimicrobial Susceptibility Testing criteria. Carbapenemases were identified by whole-genome sequencing and polymerase chain reaction. RESULTS: Of 149 CR Klebsiella pneumoniae, 95.3% were susceptible to cefiderocol (OXA-48-positive 100% [n = 15]; IMP-positive 100% [n = 9]; KPC-positive 95.4% [n = 108]; NDM-positive 88.2% [n = 17]) and against 103 NDM-positive CR Escherichia coli, cefiderocol susceptibility was 45.6%. Among comparator antibiotics, ceftazidime-avibactam was only active against K. pneumoniae carbapenemase-positive and OXA-48-positive K. pneumoniae isolates. Susceptibilities to tigecycline and colistin were between 22.2% and 97.1% and between 88.2% and 100% across CR Enterobacterales with different carbapenemases, respectively. High cefiderocol susceptibility rates were found for CR Pseudomonas aeruginosa (98.4%), CR Acinetobacter baumannii (99.6%), and Stenotrophomonas maltophilia (99.6%). Among comparator antibiotics, only colistin showed high activity against CR P. aeruginosa (99.2%) and CR A. baumannii (99.2%). CONCLUSIONS: Cefiderocol susceptibility rates were ≥88% against a collection of carbapenemase-positive CR Gram-negative isolates, except for lower susceptibility in NDM-positive CR E. coli isolates. Continuous monitoring of cefiderocol susceptibility is warranted.

Cefiderocol↗

PubMed2026

Long-term outcomes after a randomized phase II trial of nerve growth factor eye drops for optic pathway gliomas: four-year follow-up findings in children.

PURPOSE: A previous double-blind, randomized, placebo-controlled, phase II clinical trial reported beneficial effects of a short-term treatment (10 days) with murine nerve growth factor (mNGF) eye drops on visual function in children with optic pathway gliomas (OPG). The present study aimed to evaluate long-term changes in clinical and neuroradiological parameters in the cohort of OPG patients who had previously participated in the phase II mNGF trial. METHODS: Fifteen of the 18 patients originally enrolled in the phase II mNGF trial agreed to undergo clinical and neuroradiological monitoring over a 48-month follow-up period. Of these, 9 had originally been randomized to mNGF and 6 to placebo; no additional treatment (mNGF, chemotherapy, or radiotherapy) was administered during the extended follow-up. Every 6 months, patients underwent general clinical and neuro-ophthalmological examination, visual evoked potentials (VEP), and photopic negative response of the electroretinogram (PhNR). Brain MRI was performed every 12 months. RESULTS: Comparison of initial and final follow-up median values revealed no statistically significant changes in visual acuity, VEP amplitude, PhNR amplitude, or visual field radius. No significant differences were observed in any parameter relative to baseline values of the mNGF trial. Brain MRI demonstrated stable disease in all patients throughout the observation period. CONCLUSION: These findings, obtained in an observational extension of the original randomized cohort, indicate favorable long-term safety and tolerability of a short-term course of topical mNGF in children with OPG, with sustained visual and neuroradiological stability over four years, rather than evidence of persistent treatment efficacy. Further prospective, adequately powered and randomized clinical studies are needed to confirm both the short- and long-term clinical efficacy of NGF treatment in preventing OPG-induced visual loss.

Humans↗

PubMed2026

Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.

BACKGROUND: The Mizoram state of Northeast India has one of the highest HIV prevalence rates in Asia, yet the host genetic factors influencing HIV susceptibility in this Tibeto-Burman population remain uncharacterised. METHODS: We performed whole-exome sequencing using Illumina NovaSeq 6000, mean coverage 100X on 76 HIV-negative Mizo individuals. Variants were called using GATK HaplotypeCaller v4.3 against GRCh38p14, annotated with ANNOVAR, and filtered using hard-quality thresholds (QD ≥ 2, SOR ≤ 3, MQ ≥ 40, DP ≥ 10, GQ ≥ 20). The allele frequencies were compared against gnomAD v2.1.1 population databases. Hardy-Weinberg equilibrium was assessed using the Wigginton exact test with Bonferroni correction. RESULTS: Post-quality filtering resulted in 12,011 sample-variants across 2,821 unique positions from 36 HIV-associated loci (33 protein-coding genes, 2 chemokine ligands, and 3 lncRNA targets). Of these, 784 observations (51 unique positions) were high-impact nonsynonymous or loss-of-function variants. ADAR rs2229857 (p.K384R, NM_015840) was the most frequently observed variant (Mizo carrier frequency = 0.895; 95% CI: 0.806-0.946). CXCR1 rs16858808 (p.R335C) showed the greatest population enrichment (Mizo carrier frequency = 0.197; 95% CI: 0.123-0.300; 7.65-fold carrier-frequency enrichment versus gnomAD South Asian; CADD = 15.60). Sixteen of 20 tested variants deviated from Hardy-Weinberg equilibrium after Bonferroni correction (p < 0.0025), predominantly showing excess homozygosity consistent with the endogamous Mizo population. The protective variant CCR5-Δ32 was absent in all the 76 individuals tested. CONCLUSION: This first whole-exome characterization of HIV host genes in the Mizo population identifies CXCR1 rs16858808 as the most population-enriched functional variant and reveals a pervasive endogamy signature. These findings provide a population-specific genetic framework for future HIV susceptibility studies and ART pharmacogenomics research.

Humans↗

PubMed2026

Ten-Year Update of Nurse Practitioner Service Impact on Patient and Health Service Outcomes in Emergency Care Settings-A Systematic Review.

AIMS: To provide a 10-year update on the best available evidence evaluating the impact of nurse practitioner services on cost, waiting times, patient satisfaction, representation rates, and length of stay in emergency and urgent care settings. DESIGN: Systematic review. DATA SOURCES: The search was completed on January 28, 2025, in Embase (Elsevier), Medline (EBSCOhost), CINAHL (EBSCOhost), Cochrane Library (Wiley), Emcare (Ovid), Web of Science Core Collection (Clarivate) and Scopus (Elsevier). The data range (2014-2024) was used to limit the search. METHODS: The search was conducted with results imported into Covidence. In Covidence, two reviewers conducted screening, data extraction, and quality appraisal of articles, and findings were analysed using a narrative synthesis approach. Eligible studies examined nurse practitioner services in emergency or urgent care settings, reporting outcomes of cost, waiting times, patient satisfaction, representation rates, and length of stay. RESULTS: Title and abstract screening were performed on 2329 records. Of these, 236 full-text articles were reviewed, and 17 underwent critical appraisal and data extraction. Narrative analysis of outcome measures yielded mixed results, with both favourable and unfavourable findings reported regarding nurse practitioner services. CONCLUSIONS: Global evaluation of nurse practitioner services in emergency care remains inconsistent. Nevertheless, emerging evidence supports their positive impact, particularly in improving patient outcomes. To effectively inform policy, workforce planning and clinical integration, there is a need for professional benchmarks that provide clear frameworks for the evaluation of patient-centred outcomes and operational impacts in emergency departments. IMPLICATIONS: Evidence related to nurse practitioner services in emergency and urgent care clinics highlights the positive impact of nurse practitioner services on patient wait times and satisfaction; however, there is limited and variable evidence of impact on health care costs and outcomes. IMPACT: This paper recommends that evaluating emergency nurse practitioner services requires homogeneous research using consistent professional benchmarks and evaluation frameworks. REPORTING METHOD: This systematic review follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. PATIENT OR PUBLIC CONTRIBUTION: This study did not include patient or public involvement in its design, conduct, or reporting. TRAIL REGISTRATION: PROSPERO 2025 CRD420250645148.

Humans↗

PubMed2026

Clinical accuracy and short-term outcomes of intraoral photogrammetry for complete-arch implant rehabilitation: A retrospective multicentre study on 35 patients.

OBJECTIVES: To evaluate the clinical accuracy and short-term outcomes of complete-arch implant-supported fixed dental prostheses (ISFDPs) fabricated using an intraoral photogrammetry (IPG) based digital workflow in completely edentulous patients. METHODS: This multicenter retrospective clinical study included 35 patients rehabilitated with 52 complete-arch ISFDPs (10 FP1, 18 FP2 and 24 FP3 restorations) supported by 221 implants. All definitive prostheses were designed and fabricated using a fully digital workflow initiated by IPG acquisition with the Aoralscan Elite IPG® (SHINING 3D). The primary outcome was clinical accuracy, assessed at definitive prosthesis delivery through evaluation of passive fit using the Sheffield test and radiographic verification. Secondary outcomes included biologic and prosthetic complications, as well as implant and prosthesis survival rates during the follow-up. RESULTS: Passive fit was achieved in all definitive restorations (100%). Radiographic evaluation confirmed accurate marginal adaptation at the implant-prosthesis interface in all cases. No statistically significant differences in clinical accuracy were observed according to treated arch, number of supporting implants, or prosthetic design (P > .05). During a mean follow-up period of 12.1 ± 3.5 months, biologic and prosthetic complications were limited and generally minor. Implant survival was 99.5%, and prosthesis survival was 100%. CONCLUSIONS: Within the limitations of this retrospective clinical study, the IPG based workflow demonstrated high clinical accuracy and predictable short-term outcomes for complete-arch implant rehabilitation, consistently enabling passive fit and favorable prosthetic performance. CLINICAL RELEVANCE: IPG may represent a clinically reliable and predictable approach for complete-arch digital implant impression acquisition. The high rates of passive fit, together with the low incidence of biologic and prosthetic complications observed in this multicenter clinical study, support the use of IPG based workflows for the fabrication of complete-arch ISFDPs.

Humans↗

PubMed2026

Choice of Anesthesia in Microelectrode Recording-guided Deep Brain Stimulation Surgery for Parkinson's Disease (CHAMPION): A Noninferiority Randomized Controlled Trial.

BACKGROUND: Deep brain stimulation for Parkinson's disease is often performed under conscious sedation or general anesthesia. However, anesthetic agents may influence intraoperative microelectrode recording, and the optimal anesthesia method for microelectrode recording remains unclear. This study compared general anesthesia and conscious sedation in preserving microelectrode recording signal intensity during deep brain stimulation. METHODS: In this prospective, noninferiority randomized controlled trial, patients with Parkinson's disease (United Kingdom Brain Bank criteria) undergoing elective bilateral surgery were randomized 1:1 to the conscious sedation or the general anesthesia group. During surgery, a desflurane anesthetic titrated against the quality of the electrophysiologic signal was applied in the general anesthesia group, whereas patients in the conscious sedation group received dexmedetomidine anesthesia. The primary outcome was the proportion of patients with high-quality microelectrode recording (normalized root mean square greater than 2.0), assessed postoperatively off-line. Secondary outcomes included operation and recording duration, 6-month clinical efficacy, and complication rates. RESULTS: Of 188 randomized patients (94 general anesthesia, 93 conscious sedation), desflurane anesthesia was noninferior for high normalized root mean square proportion (89.4% vs . 90.3%; difference, -0.96%; 95% CI, -9.62 to 7.70). The general anesthesia group had shorter operative time (difference, -9.07 min; 95% CI, -13.99 to -4.14; P < 0.001). At 6 months, changes in Unified Parkinson's Disease Rating Scale score (difference, -2.50; 95% CI, -7.20 to 2.20; P = 0.297), levodopa equivalent daily dose (difference, -58.4 mg; 95% CI, -133.56 to 16.75; P = 0.128), and complication rates (general anesthesia: 10.9% vs . conscious sedation: 8.9%; P = 0.655) were comparable between the groups. CONCLUSIONS: General anesthesia is noninferior to conscious sedation for microelectrode-guided subthalamic nucleus deep brain stimulation, providing equivalent signal intensity and clinical outcomes while improving procedural efficiency, supporting its use as a valid clinical option.

Humans↗

PubMed2026

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans↗

PubMed2026

Stage-specific ROMO1 in rheumatoid arthritis: predictive immune insights into the MIF pathway and HLA-DR/IL2RA axis via integrated GWAS, transcriptomic, single-cell, and spatial profiling.

Emerging evidence links reactive oxygen species modulator 1 (ROMO1), a key mitochondrial ROS regulator, to rheumatoid arthritis (RA) pathogenesis. However, its exact mechanism remains elusive given the conflicting evidence about its specific function. We used a four-level integrative framework combining multi-omics data and literature‑supported mechanistic inference. At the genetic level, Mendelian randomization (MR) was performed to explore potential causal relationships between ROMO1, IL2RA, HLA-DR, MIF, and RA risk, followed by differential expression analysis and machine learning-based feature selection to identify key mROS genes. The temporal expression dynamics of ROMO1 were assessed in RA progression. At the cellular and tissue levels, we integrated single-cell RNA sequencing and spatial transcriptomics to map cell-type-specific expression and synovial localization of ROMO1-related immune cells and pathways. Finally, our multi-omics findings were contextualized with literature-supported mechanistic inference. (1) MR results were consistent with a potential protective effect of ROMO1 on RA (OR = 0.52) and its potential regulation of risk factors IL2RA (OR = 0.46) and HLA-DR (OR = 0.40). Conversely, IL2RA (OR = 1.42), HLA-DR (OR = 1.88), and MIF (OR = 1.17) were positively associated with RA risk. Additionally, ROMO1 was identified as a top candidate diagnostic predictor with stage-specific dynamics: downregulated in the early but upregulated in the late/remission stages. (2) Single-cell RNA sequencing showed ROMO1's cell-specific expression in CD14+ HLA-DR+ CD74+ monocytes and CD4+ IL2RA+ T cells. Cell communication analysis further suggested that these cells may participate in MIF pathway regulation. Spatial transcriptomics subsequently identified that ROMO1-related cells localized to synovial pathological regions, with MIF pathway changes correlated with RA progression. (3) Finally, literature-supported mechanistic inference suggests that ROMO1 may modulate mROS levels to promote anti-inflammatory M2 macrophage polarization, which could theoretically contribute to reduced systemic inflammation and the alleviation of multi-organ decline in RA. This integrated multi-omics investigation, supported by literature-based mechanistic inference, suggests ROMO1 as a stage-dependent biomarker candidate and potential immune regulator in RA.

Humans↗

PubMed2026

Are Adverse Childhood Experiences Associated with Metabolic Syndrome in Patients with Severe Mental Illness?

BACKGROUND: Patients with severe mental disorders (SMD) are at substantially elevated risk for metabolic syndrome (MetS), contributing to excess cardiovascular morbidity and premature mortality. Adverse childhood experiences (ACEs) have been associated with dysregulation of metabolic pathways, yet their contribution to MetS risk in SMD remains poorly understood. OBJECTIVE: This study aimed to investigate the association between ACEs and MetS in outpatients with bipolar disorder (BD) and schizophrenia (SZ) in clinical remission and to identify independent and incremental predictors of MetS using a hierarchical analytical framework. METHODS: This cross-sectional study included 140 outpatients with SMD (96 with BD and 44 with SZ) in clinical remission, recruited from a university hospital in Eastern Turkey. MetS was defined according to NCEP-ATP III criteria, and ACEs were assessed using the Turkish version of the Adverse Childhood Experiences Scale (ACE-TR). Hierarchical and multivariable logistic regression analyses were performed to examine factors associated with MetS. RESULTS: MetS was highly prevalent in this sample (46.4%). ACE-TR total score was independently and consistently associated with MetS across all hierarchical models (odds ratio [OR] range: 1.68-1.77), with each one-unit increase conferring approximately 71% higher odds in the fully adjusted model (OR = 1.71; 95% confidence interval [CI] 1.26-2.32; P = 0.001). The number of hospitalizations was the only other independently associated variable (OR = 1.19; 95% CI 1.02-1.39). Sexual abuse (16.9% vs. 2.7%; P = 0.004), emotional neglect (63.1% vs. 30.7%; P < 0.001), and physical neglect (30.8% vs. 14.7%; P = 0.022) were significantly more prevalent in the MetS group. ACE-TR total score was positively correlated with waist circumference and triglyceride levels. CONCLUSION: The strong and consistent association between ACEs and MetS underscores the importance of trauma-informed care models in psychiatric practice, where metabolic comorbidity remains a leading cause of premature mortality.

Humans↗

PubMed2026

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2 × 3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time × group interaction was detected for any ES biomarker, including 2-AG (F(2,88) = 0.17, p = 0.844) and AEA (F(2,88) = 1.20, p = 0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference + 81.6 m at 12 weeks (F(2,78) = 7.88, p = 0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78) = 2.83, p = 0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans↗

PubMed2026

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↗