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PubMed2026

Sugar rationing during the first 1000 days and early onset cancer: a natural experiment.

BACKGROUND: The "first 1000 days" of life is a critical window for metabolic programming, while the long-term oncological consequences of nutritional exposures during this period remain understudied. OBJECTIVES: We aimed to evaluate whether restricted sugar intake in utero and during early childhood reduces risk of early onset cancer diagnosis and mortality in adulthood, utilizing a natural experiment. METHODS: We analyzed 63,819 United Kingdom Biobank participants born between October 1951 and March 1956, spanning the end of United Kingdom sugar rationing (September 1953). Leveraging a quasi-experimental birth cohort design, we compared participants exposed to sugar rationing in utero and during infancy with those unexposed. Early onset cancer incidence (≤50 y) and mortality were ascertained via integrated national Cancer Registry and hospital inpatient records. Multivariable Cox proportional hazards models (including Gompertz distribution) were used to estimate hazard ratios (HRs), with exploratory site-specific analyses. RESULTS: Among 63,819 participants (56.3% female), 40,397 were exposed to rationing and 23,422 were unexposed. Early life sugar restriction significantly reduced early onset cancer risk (HR: 0.66; 95% confidence interval: 0.53, 0.81; P < 0.001). A dose-response relationship was observed, with peak protection in individuals exposed for ≤24 mo postnatally. This protection was observed systemically across solid tumors, independent of specific cancer sites. Specificity was corroborated by null associations with negative controls (herpes zoster and cataract). No significant difference was found for cancer-specific mortality. CONCLUSIONS: Restricting sugar intake during the first 1000 days is associated with a reduced risk of early onset cancer, extending the disease-free lifespan. The divergence between reduced incidence and unchanged mortality suggests early life metabolic environments primarily influence tumor latency rather than biological aggressiveness. These findings highlight the potential long-term public health implications of early life dietary guidelines against the rising burden of early onset cancer.

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PubMed2026

Effectiveness of a digi-physical tool and working method for paediatric obesity treatment in Abu Dhabi: a non-inferiority intervention study using an external historical comparator.

BACKGROUND: Effective paediatric obesity treatment requires high intensity, scalable interventions. A digi-physical tool for paediatric obesity treatment has shown positive results in Stockholm, Sweden. This study evaluates whether the same treatment method is effective in a different cultural setting. METHODS: This non-inferiority intervention study, using an external historical comparator, included 60 consecutively recruited children aged 6-15.9 years with obesity who initiated treatment at Sheikh Shakhbout Medical City in Abu Dhabi between June and December 2023. Patients were treated with Evira, a digi-physical tool and working method enabling high intensity individualized care, real-time monitoring, and interactive patient-clinician communication. The primary outcome was BMI z-score change at 26 weeks. Non-inferiority was assessed using a predefined margin of 0.10 BMI z-score, with outcomes compared to a prior published trial in Stockholm (n = 107). RESULTS: A total of 112 children were included in the analysis (Abu Dhabi cohort, n = 35; Stockholm cohort, n = 77). The adjusted mean change in BMI z-score was - 0.20 (95% CI: - 0.28, - 0.12) in the Abu Dhabi cohort and - 0.20 (- 0.26, - 0.14) in the Stockholm cohort (p = 0.88). Non-inferiority was confirmed, (predefined margin 0.10 was not exceeded). A clinically significant BMI z-score reduction (≥ 0.20 units) was achieved by 45.7% of participants in Abu Dhabi and 36.4% in Stockholm (p = 0.35). Non-retention rates at 26 weeks were 41.7% vs. 28.0%, respectively (p = 0.07). CONCLUSIONS: The findings provide promising evidence that treatment outcomes achieved with the digi-physical treatment tool were comparable in the Abu Dhabi and Stockholm cohorts, supporting its feasibility in a second cultural and healthcare setting.

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PubMed2026

Risk stratification in aortic stenosis: exercise haemodynamics to refine risk in early cardiac damage stages.

AIMS: To describe exercise haemodynamics across cardiac damage stages and evaluate the incremental prognostic impact of cardiac damage stage and exercise-induced pulmonary hypertension (exPHT) in patients with symptomatic moderate aortic stenosis (AS) and asymptomatic severe AS. METHODS AND RESULTS: A total of 436 consecutive patients with ≥ moderate AS (74 ± 10 years, 32% women, 56% severe AS) underwent cardiopulmonary exercise testing with echocardiography. The primary endpoint was heart failure (HF) death and HF hospitalizations. Cardiac damage stage was 0 in 93 patients, 1 (LV damage) in 135, 2 (LA/mitral damage) in 135, and 3-4 (pulmonary vasculature/tricuspid or RV damage) in 73. Higher stages were associated with worse exercise capacity and haemodynamics. Over a median follow-up of 37 months, 65 patients met the primary endpoint. After adjustment for age, AS severity, and aortic valve replacement, cardiac damage stage and exPHT were independently associated with HF outcomes [HR per stage increase 1.51 (1.26-1.82); P < 0.001; exPHT HR 2.36 (1.10-5.07); P = 0.03]. exPHT improved risk stratification in early-stage disease (stages 1-2), conferring an approximately five-fold higher risk of HF events in patients with exPHT [HR 4.45 (1.58-12.59); P < 0.01]. CONCLUSION: In patients with ≥ moderate AS and discordant symptoms, cardiac damage stage and exPHT independently refined HF risk stratification. ExPHT provides incremental prognostic value in early damage stages (1-2), representing over half of the cohort, supporting a stepwise approach of routine damage staging with selective with exPHT assessment with exercise echocardiography in this subgroup to guide more personalized management and potentially optimize AVR timing.

Humans↗

PubMed2026

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

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PubMed2026

Association of Early Knee Extension Range of Motion Deficits With Cartilage T2 Relaxation Following Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) injury significantly increases the risk for developing knee osteoarthritis (OA), yet the early contributors to cartilage degeneration remain poorly understood. While range of motion (ROM) deficits after ACL reconstruction (ACLR) are associated with long-term development of radiographic OA, the association between early ROM recovery and cartilage composition has not been established. HYPOTHESIS: Knee extension ROM deficits at 2 months after ACLR would be associated with worsening tibiofemoral and patellofemoral cartilage T2 relaxation times at 6 months. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 30 participants (15-35 years) were enrolled within 1 month of ACL injury and before ACLR. At 2 months post-ACLR, active knee extension ROM was measured in the supine position using a goniometer. An extension deficit was considered >3° less extension in the injured knee compared to the uninjured side. Quantitative magnetic resonance imaging-based T2 relaxometry of the injured knee was performed preoperatively and at 6 months post-ACLR to measure percent change in mean T2 relaxation times in predefined tibial and femoral cartilage regions. Independent t tests were used to compare changes in T2 values between participants with and without an extension deficit. RESULTS: The mean age of the participants was 18.8 ± 3.9 years, and 63.3% were female. Fifteen (50.0%) participants exhibited an extension deficit at 2 months. Those with an extension deficit demonstrated a greater increase in T2 relaxation time in the anterior (mean difference, 10.21% [95% CI, 3.67%-16.76%]; P = .003) and weightbearing (mean difference, 6.14% [95% CI, 2.19%-10.09%]; P = .004) cartilage of the medial femoral condyle. No significant group differences were observed in other cartilage regions (all P > .05). CONCLUSION: Knee extension ROM deficits at 2 months post-ACLR are associated with early compositional changes in the medial femoral cartilage, indicating a potential relationship between limited extension and OA risk.

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PubMed2026

The impact of supernormal lung function on mortality risk in adults with and without sleep-disordered breathing.

BACKGROUND: In the general population, supernormal lung function is associated with a lower risk of all-cause mortality. RESEARCH QUESTION: It remains unclear whether sleep-disordered breathing (SDB) affects this relationship. METHODS: This cohort analysis included 4,839 adults. Lung function was categorised as supernormal (FEV1 > ULN), normal (LLN ≤ FEV1 ≤ ULN), and below normal (FEV1 < LLN). SDB severity was classified using apnoea-hypopnoea index categories: no SDB (<5 events/hour), mild SDB (5-<15 events/hour), moderate SDB (15-<30 events/hour), and severe SDB (≥30 events/hour). The association between lung function and all-cause mortality was assessed using Cox proportional hazards models with subgroup analyses according to SDB severity and formal testing for interaction. Analyses were repeated using FVC-defined lung function groups as an alternative definition of supernormal lung function. RESULTS: Among the included participants, 4,068 (84.1%) had normal lung function, 369 (7.6%) had supernormal lung function, and 402 (8.3%) had below normal lung function. During 52 421.5 person-years of follow-up (median 11.72 years; IQR, 10.46-12.56), 1,188 deaths occurred. Compared with the normal lung function group, the supernormal lung function group had a lower prevalence of baseline hypertension and cardiovascular disease. The association between lung function and all-cause mortality varied across SDB severity strata (P for interaction = 0.034). A lower mortality risk associated with supernormal lung function was observed in participants without SDB (HR: 0.24, 95% CI: 0.06-0.97), whereas this association was not statistically significant in the mild, moderate, or severe SDB strata. Below normal lung function was generally associated with an increased all-cause mortality risk. Sensitivity analyses using FVC-defined lung function groups yielded broadly consistent findings. CONCLUSION: Supernormal lung function was associated with lower all-cause mortality primarily among individuals without SDB. These findings underscore the importance of considering SDB severity when assessing the health implications of lung function.

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PubMed2026

Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogenous disease with frequent late-stage diagnosis and high mortality rates, for which no reliable screening tests exist. In recent years, epigenetic biomarkers in the form of DNA methylation in CpG-rich regions have gained increased attention in the scientific community due to their robust nature and accessibility, allowing for diagnosis without the need for invasive surgery. In this study, we investigated the aberrant methylation of promoter regions in early stage EOC through non-parametric methods, with the purpose of characterizing candidate epigenetic biomarkers. The approach was used on a cohort of early stage EOC samples, and results were compared to existing programs for differential methylation. Significant regions were then used to construct a CpG panel for stratifying EOC histotypes through predictive classification in external data. Identified promoter regions were highly reproducible across cohorts, and the constructed CpG model stratified histotypes in external cohorts through predictive classification. Comparisons against other DMP and DMR callers showed a degree of homogeneity between results but also revealed promoter regions that were overlooked despite clear signs of aberrant methylation. Finally, EOC histotypes were found to differ in their methylation distribution types, and results indicate that methods sensitive to non-normally distributed data may be poorly suited to compare groups with different distribution types. The non-parametric approach identified aberrantly methylated promoter regions that were highly reproducible across cohorts. Results from predictive classification indicate that these regions may be useful for the purpose of EOC histotype stratification.

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PubMed2026

The knee-ankle link: impact of knee varus severity on distal joint malalignment and concomitant pathologies.

BACKGROUND: Knee varus deformity is traditionally managed as an isolated joint pathology; however, persistent distal symptoms following proximal realignment suggest a more extensive kinetic chain dysfunction. The degree to which knee varus severity dictates distal malalignment and secondary pathologies remains poorly quantified in the current literature. METHODS: This systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines (PROSPERO: CRD420261363327). A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was performed from inception to April 2026. Studies examining the relationship between knee varus (HKA angle) and radiographic distal alignment or pathologies were included. Data synthesis utilized random-effects models, with prevalence analyzed via generalized linear mixed models (GLMM). RESULTS: Fourteen studies were included in the final synthesis. While pooling of continuous radiographic parameters was limited by high statistical heterogeneity in Talar Tilt (I2 = 96.5%), individual large-cohort data (Huang et al.) indicated that severe knee varus (HKA > 10°) was associated with increased odds of concomitant ankle osteoarthritis (OR 2.29; 95% CI 1.28-4.11) and a specific cohort prevalence of 37.1%. Furthermore, single-arm prevalence data revealed divergent trends across different study populations, with compensatory hindfoot valgus reaching 69.9% in some cohorts and rigid varus up to 63.9% in others. CONCLUSIONS: Severe genu varum is associated with distal kinetic chain alterations and concomitant ankle pathologies. However, due to the extreme heterogeneity and divergent distal adaptations observed across different cohorts, standardized knee-centric protocols may be insufficient. Further longitudinal and interventional studies are required to establish phenotype-specific rehabilitation guidelines.

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PubMed2026

Gelified ethanol for percutaneous sclerotherapy of bone lesions: a systematic review of clinical applications and outcomes.

PURPOSE: To systematically review the available evidence on the feasibility, safety, and clinical effectiveness of percutaneous sclerotherapy using radiopaque gelified ethanol (RGE, Discogel®) for bone lesions. METHODS: A systematic search of MEDLINE, Embase, Web of Science, and Cochrane CENTRAL was performed. Primary studies reporting clinical, technical, and safety outcomes following RGE sclerotherapy for bone lesions were included. Data on patient characteristics, lesion type, procedural details, and outcomes were extracted and synthesized descriptively. RESULTS: Six retrospective studies involving 55 patients (mean age 22.2 ± 20.4 years; range 3-65; 26 females) with 56 lesions and 119 procedures were included (mean 2.16 procedures per patient). Aneurysmal bone cysts (80%) and aggressive vertebral hemangiomas (18%) were the main indications. Technical success was reported in 100% of procedures. Pain outcomes were available for 28 patients, with complete resolution in 64.3% (18/28), partial reduction in 32.1% (9/28), and persistence in 3.6% (1/28). Radiological follow-up (50 lesions) demonstrated complete response in 96% and partial response in 4%. No major adverse events were reported according to CIRSE (≥ 4) or CTCAE (≥ 4) criteria. One SIR grade 3 vertebral fracture occurred without confirmed causal association to RGE. Subsequent surgery was required in 3.6% of lesions. CONCLUSION: Although limited to small retrospective series, current evidence suggests that RGE sclerotherapy is a safe and effective minimally invasive option for selected benign bone lesions. Prospective comparative studies with longer follow-up are warranted.

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PubMed2026

Intersphincteric resection versus abdominoperineal resection for lower rectal cancer: A systematic review and meta-analysis.

BACKGROUND: The optimal surgical approach for lower rectal cancer (LRC) remains debated, particularly between intersphincteric resection (ISR) and abdominoperineal resection (APR). While ISR offers potential sphincter preservation, its oncological efficacy compared to APR is unclear. METHODS: A systematic review was conducted to compare clinical and oncological outcomes of ISR versus APR in LRC patients. On December 8, 2024, a comprehensive search of Medline, Embase, Cochrane Library, Scopus, and Web of Science identified 24 retrospective studies involving 4502 patients. Key outcomes analyzed included positive circumferential resection margin (CRM), number of harvested lymph nodes (LNs), local recurrence (LR), length of hospital stay (LOS), early postoperative complications, and survival. RESULTS: Twenty-four retrospective studies involving 4502 patients (ISR: 2266 (50.3%) and APR: 1558 (34.6%)) met the eligibility criteria. ISR was associated with significantly lower rates of positive CRM (risk ratio (RR): 0.41, p < 0.001), decreased early postoperative complications (RR: 0.76, p < 0.001), lower LR (RR: 0.63, p = 0.0038), and improvement in five-year overall survival (5YOS) (hazard ratio (HR) = 0.42, p < 0.001) and five-year disease-free survival (5YDFS) (HR = 0.59, p < 0.001). CONCLUSIONS: ISR demonstrates several advantages over APR in selected LRC patients, including lower rates of positive CRM, fewer early postoperative complications, reduced LR, greater LN harvest, shorter LOS, and improved long-term survival outcomes (5YOS and 5YDFS). Therefore, ISR can be considered a safe and effective alternative to APR in appropriately chosen patients, with careful patient selection and surgical expertise remaining essential.

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PubMed2026

Suicidality risk of cancer caregivers: a systematic review and meta-analysis of observational studies.

BACKGROUND: The increase in the number of global cancer cases is expected to lead to a greater caregiving burden. However, few studies have investigated the risk of suicidality among cancer caregivers. OBJECTIVE: The aim of this systematic review was to explore the risk of suicidality among cancer caregivers. METHODS: For this systematic review, a comprehensive search of the PubMed, Embase, Cochrane, Web of Science databases, PsycINFO and Scopus databases was conducted from inception to 16 July 2025. A meta-analysis was performed to determine the odds ratios (ORs) for case-control and cross-sectional studies and the adjusted hazard ratios (aHRs) for cohort studies. RESULTS: Seven studies were included (four cohort studies, one case-control study and two cross-sectional studies), and 638,188 study subjects and 4,203,957 nonexposed subjects. The meta-analyses revealed that the ORs was 1.91 (95% confidence interval [CI]: 1.46-2.49) in the case-control study, cross-sectional studies, and one cohort study which reported ORs, and the aHRs was 1.32 (95% CI: 1.16-1.50) in the three cohort studies. Caregivers of patients with highly aggressive cancers had a greater risk of suicidality (aHR = 1.66; 95% CI: 1.48-1.86). Within the first 7 years following a patient's cancer diagnosis, the risk of suicidality among caregivers remained elevated (aHR = 1.42; 95% CI: 1.04-1.94). CONCLUSION: The results indicate the need for both clinical and societal awareness to reduce the risk of suicidality among cancer caregivers, especially those with highly aggressive cancers. TRIAL REGISTRATION: Registered prospectively in PROSPERO (https://www.crd.york.ac.uk/prospero/) with the registration number (PROSPERO CRD420251011926) and date of registration(15/03/2025).

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PubMed2026

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

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PubMed2026

Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review.

Synaptic dysfunction is increasingly recognized as an early and biologically relevant component of α-synucleinopathies. However, conventional imaging biomarkers mainly assess dopaminergic dysfunction, glucose metabolism, or structural damage rather than presynaptic density itself. Synaptic vesicle glycoprotein 2A (SV2A) PET enables in vivo assessment of presynaptic terminal integrity and may provide complementary information in Parkinson's disease (PD), Parkinson's disease dementia/dementia with Lewy bodies (PDD/DLB), and multiple system atrophy (MSA). This systematic review synthesized the available evidence on SV2A-targeted PET in parkinsonian α-synucleinopathies, focusing on regional imaging patterns, clinical associations, longitudinal findings, and methodological determinants of interpretation. Seventeen reports were included. In PD, the most recurrent finding was reduced SV2A binding in the substantia nigra, although additional involvement of brainstem, caudate, striatal, thalamic, raphe, or cortical regions was reported in selected cohorts. In PDD/DLB, abnormalities appeared broader and more cortical, with evidence of association between cortical SV2A binding and cognitive performance. In MSA, one study suggested a distinct infratentorial and cerebellar pattern with potential relevance for phenotypic stratification. SV2A PET is a promising research biomarker for biological characterization of synucleinopathies. However, the field remains limited by small cohorts, methodological heterogeneity, variable quantification strategies, limited longitudinal evidence, and potential cohort overlap. Multicentre validation and harmonized protocols are required before clinical translation.

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PubMed2026

Artificial intelligence in genitourinary oncology: publication trends and systematic review.

OBJECTIVE: To conduct an analysis of publication trends and a systematic review of randomized controlled trials (RCTs) to characterize the current state of artificial intelligence (AI) use in genitourinary (GU) oncology, as AI has emerged as a transformative tool in healthcare with potential applications in diagnostics, treatment planning, and prognostication. METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE; Ovid), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ultimate for studies related to AI and GU oncology, excluding non-English papers, non-human studies, review articles, and articles using AI solely for manuscript writing. Publication trends were analysed from 2013 to 2023 and categorized by study design and cancer type. RCTs were evaluated through systematic review using Covidence (Veritas Health Innovation Ltd, Melbourne, Victoria, Australia) for screening and data extraction. Two reviewers independently assessed all studies, with risk of bias (RoB) evaluated using the Cochrane RoB 2.0 tool. RESULTS: Of 2409 articles identified, 1220 met inclusion criteria. These included 962 retrospective articles, 175 prospective studies, 79 studies with combined retrospective/prospective methods, and four RCTs. Studies most commonly addressed prostate (n = 923), renal (n = 274), and urothelial (n = 194) cancers. Publications grew from 14 in 2013 to 362 in 2023, with substantial acceleration in 2019. Four RCTs were identified - one in urothelial cancer and three in prostate cancer. Two RCTs evaluated AI-based diagnostics, demonstrating improved performance over conventional methods; the remaining two RCTs evaluated AI in prognostication and treatment planning, showing improved gains in imaging interpretation and operational efficiency. RoB varied across studies, primarily related to randomisation and deviations from intended interventions. CONCLUSIONS: Artificial intelligence research in GU oncology has grown, although high-level evidence from RCTs remains limited. Existing trials underscore AI's promise in diagnostics, prognostication, and treatment planning, and the rapidly evolving nature of this field warrants continued prospective investigation.

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PubMed2026

Endoscopic Ultrasound-Guided Versus Transjugular Portal Pressure Measurements: Systematic Review and Meta-Analysis.

PURPOSE: Published reviews of endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) have emphasized feasibility and safety. We performed a systematic review and meta-analysis specifically to evaluate how closely EUS-based portal pressure measurements track invasive comparator measurements in prospective paired studies and to summarize agreement, technical success, and adverse events. METHODS: We searched major databases through January 2026 for prospective cohorts reporting same-patient EUS-based portal pressure measurement and invasive hemodynamic measurements. Correlations were pooled with random-effects models and analyzed separately for studies comparing EUS-PPG with hepatic venous pressure gradient (HVPG) and studies comparing EUS-based portal measurements with direct portal venous pressure. Agreement and threshold discordance were summarized descriptively. RESULTS: Six prospective cohorts (127 attempted procedures) were included. In studies using HVPG as the comparator, the pooled correlation was 0.82 (95% CI, 0.72-0.89; I2 = 0%). In studies comparing EUS-based portal measurements with direct portal venous pressure, the pooled correlation was 0.86 (95% CI, 0.72-0.93; I2 = 16.9%). Technical success was 95.3%. EUS-PPG-attributed adverse events occurred in 2.4% of procedures, with no procedure-related deaths. Agreement data were limited. Reported limits of agreement were wide (approximately - 6 to + 7 mmHg), and discrepancies of 5 mmHg or greater occurred in 4 of 30 paired measurements. CONCLUSIONS: EUS-based portal pressure measurement is feasible and shows a strong association with invasive hemodynamic comparators, but the evidence base remains small (six cohorts, 127 attempted procedures). Further study will be necessary to establish patient-level agreement, procedural reproducibility, EUS-specific clinically significant portal hypertension thresholds, and whether HVPG-based decision thresholds can be transferred to EUS-derived measurements.

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PubMed2026

RR-interval-based atrial fibrillation detection and burden estimation: cross-dataset validation and calibration-aware probability analysis.

Objective.Atrial fibrillation (AF) burden has become an increasingly important endpoint in long-duration rhythm monitoring, but reliable burden estimation requires more than accurate AF detection alone. In particular, when burden is derived by aggregating predicted AF probabilities over time, probability calibration may directly affect burden validity under external dataset shift.Approach.This study developed an interpretable-interval feature model for AF detection and evaluated it using record-wise cross-validation on a development cohort and independent cross-dataset external validation on public Holter electrocardiographic databases. Window-level performance was assessed using the area under the receiver operating characteristic curve (ROC-AUC), area under the precision-recall curve (PR-AUC), Brier score, expected calibration error (ECE), and calibration intercept and calibration slope. Recording-level AF burden was estimated using both probability-based and hard-label aggregation and evaluated using mean absolute error (MAE) and agreement analyses.Main results.The model showed high discrimination in both development and external evaluation, with external ROC-AUC ofand PR-AUC of. However, external calibration deteriorated despite preserved ranking performance, with Brier score of, ECE(15) of, calibration intercept of, and calibration slope of. In the external cohort, probability-based burden estimation preserved strong association with reference burden but showed weaker raw agreement than hard-label aggregation, with MAE ofversus, consistent with systematic probability underprediction. Repeated external recalibration across record-level splits substantially improved probability quality and probability-based burden estimation. Median probability-burden MAE decreased fromwithout recalibration toafter Platt recalibration andafter isotonic recalibration, while median ECE(15) decreased fromtoand, respectively.Significance.These findings indicate that-interval-based AF detection maintained strong ranking performance in the tested external cohort, but probability calibration should be evaluated explicitly when predicted probabilities are aggregated into AF-burden estimates.

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PubMed2026

Factors Impacting Overall Survival Post-Relapse in High-Risk Neuroblastoma: Children's Oncology Group Outcomes From 2000 to 2019.

PURPOSE: Prior studies of features impacting post-relapse survival in high-risk neuroblastoma (HRNB) evaluated patient cohorts that did not receive contemporary high-risk or relapse therapies. We describe overall survival (OS) after first progression or first relapse of HRNB in a modern cohort. METHODS: Patients with HRNB enrolled on COG ANBL00B1(NCT00904241) between 2000 and 2019, who had relapsed or progressive disease were eligible. Clinical and molecular risk factors at diagnosis, therapy era, clinical trial enrollment, and clinical features at relapse, including site of and time to relapse, were evaluated. OS post-relapse was compared between groups using log-rank tests and Cox models. RESULTS: Among 4253 eligible HRNB patients, 1616 had relapse or progression as a first event. Five-year OS post-relapse was 19.1 ± 1.1%. The risk group with the lowest post-relapse survival was observed in patients with INSS Stage 4 or 4S disease < 18 months of age at diagnosis with MYCN amplified (MYCN-A) tumors. The other significant most unfavorable factors at diagnosis included diagnosis 2000-2004, tumor MYCN-A, 1p loss of heterozygosity (LOH), and elevated LDH or ferritin. Unfavorable factors at relapse included the time to relapse < 36 months from diagnosis, and combined local and metastatic disease at relapse. Multivariable analysis indicated that those with tumors harboring 1p LOH, age ≤ 5 years at diagnosis, or earlier treatment therapy era (2000-2004) had a higher risk of post-relapse death. CONCLUSIONS: While the 5-year OS rate was low in this cohort, there are subsets of patients with relapsed HRNB who demonstrate long-term survival. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00904241.

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PubMed2026

Opposing kinase signaling may underlie the inverse relationship between cancer and Alzheimer's disease.

Cancer and Alzheimer's disease (AD) are leading causes of mortality and exhibit an inverse relationship, where AD patients have reduced cancer risk and vice versa. However, the molecular basis of this relationship remains poorly understood. We reanalyzed published proteomic and phosphoproteomic datasets to investigate this relationship. Differentially abundant proteins were identified in lung adenocarcinoma and glioblastoma samples relative to controls and compared with proteins altered in AD brains, revealing 37 proteins with opposing abundance patterns. Protein-protein interaction and pathway analyses revealed enrichment in kinase signaling and phosphorylation pathways. Phosphoproteomic analysis identified 52 differentially phosphorylated sites with opposing patterns, while kinase-substrate enrichment analysis identified 44 kinases with opposing inferred activity profiles. Integration of kinase activity and phosphosite data identified 29 kinase-phosphosite pairs, including 4 prioritized pairs with opposing patterns relevant to both diseases. Across seven independent cancer cohorts, 17 of 20 statistically significant phosphosite-cohort comparisons (85%) were concordant with the discovery findings, supporting reproducibility of the prioritized phosphosites. Together, these findings highlight opposing kinase signaling as a prominent feature of the inverse relationship and suggest potential biomarkers and therapeutic targets. This study provides a novel systems-level framework for investigating inverse relationships, supported by an R Shiny application for data exploration (https://advscancer.shinyapps.io/advscancer/). SIGNIFICANCE: This study presents an integrated proteomic and phosphoproteomic framework for investigating the inverse relationship between cancer and Alzheimer's disease (AD). By integrating differential protein abundance, phosphosite phosphorylation, inferred kinase activity, and curated kinase-substrate relationships, we identified opposing signaling patterns and prioritized four kinase-phosphosite pairs. Independent evaluation across seven CPTAC cancer cohorts supported the reproducibility of the prioritized phosphosite patterns. These findings provide insight into molecular processes potentially associated with the inverse relationship between cancer and AD, identify candidate biomarkers and therapeutic targets, and demonstrate the value of systems-level, data-driven approaches for investigating shared and opposing disease processes.

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