Cohort Analysis Research Articles

Endocan: A biomarker for endothelial dysfunction and inflammation, linking maternal obesity and pediatric obesity in a cohort of preterm neonates

ObjectivesNumerous animal and epidemiologic studies have demonstrated a positive association between maternal obesity in pregnancy and obesity in offspring. The biologic mechanisms of this association remain under investigation. One proposed mechanism includes fetoplacental endothelial dysfunction secondary to inflammation. Endocan is a relatively new biomarker for endothelial dysfunction and inflammation. Our objectives were to examine (1) the association between maternal obesity and neonatal serum endocan at birth, and (2) the association between neonatal serum endocan at birth and pediatric obesity at 24–36 months of age.Study Design: This was a secondary analysis of a prospective cohort of neonates born < 33 weeks gestation. Serum endocan was collected within 48 h of birth. Serum endocan levels were compared in neonates born to obese mothers vs. those born to non-obese mothers. BMI data were retrospectively collected from cohort neonates between 24 and 36 months of age. ResultsThe analysis included 120 mother/neonate dyads. Neonates born to obese mothers had higher median serum endocan at birth compared to neonates born to non-obese mothers (299 ng/L [205–586] vs. 251 ng/L [164–339], p = 0.045). In a linear regression modeled on neonatal serum endocan level, maternal obesity had a statistically significant positive association (p = 0.021). Higher mean serum endocan level at birth was associated with pediatric obesity between 24 and 36 months (obese vs. non-obese offspring; 574 ng/L (222) vs. 321 ng/L (166), p = 0.005). ConclusionsIn our cohort of preterm neonates, elevated serum endocan at birth was associated with both maternal obesity and downstream pediatric obesity. More research is needed to understand intergenerational transmission of obesity. A large focus has been on epigenetic modification. Endothelial dysfunction and inflammation may play important roles in these pathways. Effective biomarkers, including endocan, may also serve as intermediate outcomes in future pregnancy research.

Individualized radiology screening for newly diagnosed nasopharyngeal carcinoma

ObjectivesCurrent guidelines recommend universal PET/CT screening for metastases staging in newly diagnosed nasopharyngeal carcinoma (NPC) despite the low rate of synchronous distant metastasis (SDM). The study aims to achieve individualized screening recommendations of NPC based on the risk of SDM. Methods and materials18 pre-treatment peripheral blood indicators was retrospectively collected from 2271 primary NPC patients. A peripheral blood risk score (PBRS) was constructed by indicators associated with SDM on least absolute shrinkage and selection operator (LASSO) regression. The PBRS-based distant metastases (PBDM) model was developed from features selected by logistic regression analyses in the training cohort and then validated in the validation cohort. Receiver operator characteristic curve analysis, calibration curves, and decision curve analysis were applied to evaluate PBDM model performance. ResultsPre-treatment Epstein–Barr viral DNA copy number, percentage of total lymphocytes, serum lactate dehydrogenase level, and monocyte-to-lymphocyte ratio were most strongly associated with SDM in NPC and used to construct the PBRS. Sex (male), T stage (T3-4), N stage (N2-3), and PBRS (≥1.076) were identified as independent risk factors for SDM and applied in the PBDM model, which showed good performance. Through the model, patients in the training cohort were stratified into low-, medium-, and high-risk groups. Individualized screening recommendations were then developed for patients with differing risk levels. ConclusionThe PBDM model offers individualized recommendations for applying PET/CT for metastases staging in NPC, allowing more targeted screening of patients with greater risk of SDM compared with current recommendations.

Annual incidence and prevalence of injuries in elite male academy cricketers: A 4-year prospective cohort study

ObjectivesThe aim of this study was to describe the epidemiology of injuries; time-loss and non-time loss, in elite male academy cricket. DesignProspective cohort analysis. MethodsAnnual injury incidence and prevalence from all cricket related injuries were calculated for 348 male academy players (under-13 to under-18) from the 18 First-Class County Cricket clubs in England and Wales across four years (2017/18, 2018/19, 2020/21 and 2021/22), in accordance with the updated consensus statement for injury surveillance methods in cricket. ResultsThe average annual injury incidence was 115.0 injuries/100 players/year, with similar rates between time-loss (59.7 injuries/100 players/year) and non-time loss injury incidence (55.3 injuries/100 players/year). On average, 8.5 ​% of players were unavailable on any given day of the year due to injury. Match injury incidence (48.8 injuries/100 players/year) was higher than cricket-based training (25.2 injuries/100 players/year), gym-based training, illness, and ‘other’ injury incidences. Match bowling was the activity associated with the highest total (17.7 injuries/100 players/year), time-loss (10.3 injuries/100 players/year) and non-time loss (7.4 injuries/100 players/year) injury incidence. The lumbar spine was the body location most frequently injured (15.3 injuries/100 players/year) and was the most prevalent body location injured (2.9 ​% of players). ConclusionsThe findings from this study provide, robust evidence of the extent of the injury problem in elite male academy cricketers. Bowling poses the greatest risk to players and the lumbar spine is the most common and prevalent injury location.

Emergency presentation of colorectal cancer in older adults: A retrospective cohort analysis

IntroductionAdults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (<70 years) adults in our population. Materials and methodsThe electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (<70 years and ≥ 70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses. ResultsIn total, 1245 patients were diagnosed with CRC (median age 71 years, range 20–98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p < 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p < 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p < 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p < 0.001). Whilst older adults had poorer median OS than those aged <70 years (12.0 vs 34.4 months, p < 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6–4.7, stage IV HR 16.7, 95% CI 9.7–28.8, incomplete HR 8.2, 95% CI 4.6–14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7–4.0) were associated with poorer survival, whereas age and sex were not. DiscussionEmergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome.

Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans: From a Hospital Cohort Analysis to a Population-Wide Study.

GGC repeat expansions in the NOTCH2NLC gene are associated with a broad spectrum of progressive neurologic disorders, notably, neuronal intranuclear inclusion disease (NIID). We aimed to investigate the population-wide prevalence and clinical manifestations of NOTCH2NLC-related disorders in Koreans. We conducted a study using 2 different cohorts from the Korean population. Patients with available brain MRI scans from Seoul National University Hospital (SNUH) were thoroughly reviewed, and NIID-suspected patients presenting the zigzag edging signs underwent genetic evaluation for NOTCH2NLC repeats by Cas9-mediated nanopore sequencing. In addition, we analyzed whole-genome sequencing data from 3,887 individuals in the Korea Biobank cohort to estimate the distribution of the repeat counts in Koreans and to identify putative patients with expanded alleles and neurologic phenotypes. In the SNUH cohort, among 90 adult-onset leukoencephalopathy patients with unknown etiologies, we found 20 patients with zigzag edging signs. Except for 2 diagnosed with fragile X-associated tremor/ataxia syndrome and 2 with unavailable samples, all 16 patients (17.8%) were diagnosed with NIID (repeat range: 87-217). By analyzing the Korea Biobank cohort, we estimated the distribution of repeat counts and threshold (>64) for Koreans, identifying 6 potential patients with NIID. Furthermore, long-read sequencing enabled the elucidation of transmission and epigenetic patterns of NOTCH2NLC repeats within a family affected by pediatric-onset NIID. This study presents the population-wide distribution of NOTCH2NLC repeats and the estimated prevalence of NIID in Koreans, providing valuable insights into the association between repeat counts and disease manifestations in diverse neurologic disorders.

Identification of the CD8+ T-cell Related Signature for Predicting the Prognosis of Gastric Cancer Based on Integrated Analysis of Bulk and Single-cell RNA Sequencing Data.

The infiltration of CD8+ T cells in the tumor microenvironment is associated with better survival and immunotherapy response. However, their roles in gastric cancer have not been explored so far. In here, the profiles of GC gene expression were collected from The Cancer Genome Atlas database. Single-cell transcriptomic data originated from GSE134520. Cell clustering, annotation, and CD8+ T-cell differential genes were from the TISCH database. We determined 896 CD8+ T-cell differential genes by scRNA-seq analysis. After integrating immune-related genes, 174 overlapping genes were obtained and a novel risk model was subsequently built. The performance of CD8+ T-cell-associated gene signature was assessed in the training and external validation sets. The gene signature showed independent risk factors of overall survival for GC. A quantitative nomogram was built to enhance the clinical efficacy of this signature. Furthermore, low-risk individuals showed higher mutation status, higher immune checkpoint expression, low Tumour Immune Dysfunction and Exclusion (TIDE) scores, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immunotherapy. In addition, analysis of IMvigor210 immunotherapy cohort demonstrated that low-risk individuals had a favorable response to prognosis and immunotherapy. In conclusion, we generated a CD8+ T-cell-related signature that can serve as a promising tool for personalized prognosis prediction and guiding decisions regarding immunotherapy in GC patients.

Race has no impact on prostate cancer-specific mortality, when comparing patients with similar risk of other-cause mortality: An analysis of a population-based cohort.

Other-cause mortality (OCM) can serve as a surrogate for access-to-care. The authors sought to compare prostate cancer-specific mortality (PCSM) in Black versus White men matched based on their calculated OCM risk. The Surveillance, Epidemiology, and End Results (SEER) database was queried for Black and White men diagnosed with prostate cancer between 2004 to 2009, to collect long-term follow-up. A Cox regression was used to calculate the OCM risk using all available covariates. This calculated OCM risk was used to construct a 1:1 propensity score matched (PSM) cohort. Then, a competing-risks multivariable tested the impact of race on PCSM. A total of 94,363 patients were identified, with 19,398 Black men and 74,965 White men. The median (IQR) follow-up was 11.3 years (9.8-12.8). In the unmatched-cohort at 10-years, PCSM and OCM were 5.5% versus 3.5% and 13.8% versus 8.4% in non-Hispanic Black (NHB) versus non-Hispanic White (NHW) patients (all p<.0001). The standardized mean difference was <0.15 for all covariates, indicating a good match. In the matched cohort at 10-years, OCM was 13.6% and 10.0% in NHB versus NHW (p<.0001), whereas the PCSM was 5.3% versus 4.7% (p<.01). On competing-risks multivariable analysis on PCSM, Black men had a hazard ratio of 1.08 (95% confidence interval, 0.98-1.20) compared to White men with a p=.13. The results of this study showed similar PCSM in Black and White patients, when matched with their calculated OCM risk. This report is the first to indicate at a population-based level that race has no impact on PCSM. Prostate cancer is a very common cancer among men and it is associated with health disparities that disproportionately impact Black men compared to White men. There is an on-going discussion of whether disparities between these two groups stem from genetic or environmental factors. This study sought to examine if matching based on overall health status, a proxy for the impact of social determinants of health, mitigated significant differences in outcomes. When matched using risk of death from any cause other than prostate cancer, Black and White men had no significant differences in prostate cancer death.

Characterizing the distinct imaging phenotypes, clinical behavior, and genetic vulnerability of brain maturational subtypes in mood disorders.

Mood disorders are characterized by great heterogeneity in clinical manifestation. Uncovering such heterogeneity using neuroimaging-based individual biomarkers, clinical behaviors, and genetic risks, might contribute to elucidating the etiology of these diseases and support precision medicine. We recruited 174 drug-naïve and drug-free patients with major depressive disorder and bipolar disorder, as well as 404 healthy controls. T1 MRI imaging data, clinical symptoms, and neurocognitive assessments, and genetics were obtained and analyzed. We applied regional gray matter volumes (GMV) and quantile normative modeling to create maturation curves, and then calculated individual deviations to identify subtypes within the patients using hierarchical clustering. We compared the between-subtype differences in GMV deviations, clinical behaviors, cell-specific transcriptomic associations, and polygenic risk scores. We also validated the GMV deviations based subtyping analysis in a replication cohort. Two subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for Alzheimer's disease, and transcriptionally associated with Alzheimer's disease pathways, oligodendrocytes, and endothelial cells; and subtype 2, displaying globally decreased GMV deviations, more severe depressive symptoms, increased genetic vulnerability to major depressive disorder and transcriptionally related to microglia and inhibitory neurons. The distinct patterns of GMV deviations in the frontal, cingulate, and primary motor cortices between subtypes were shown to be replicable. Our current results provide vital links between MRI-derived phenotypes, spatial transcriptome, genetic vulnerability, and clinical manifestation, and uncover the heterogeneity of mood disorders in biological and behavioral terms.

Body Mass Index Greater Than 46 Associated With Increased Risk of 30 Day Complications Following Adult Tonsillectomy: A Retrospective Cohort Study.

Background: The study aimed to identify data-driven body mass index (BMI) thresholds that are associated with varying risk of 30 day complications following adult tonsillectomy. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was utilized to conduct a retrospective cohort analysis of patients undergoing adult tonsillectomy from 2005 to 2019. Stratum-specific likelihood ratio (SSLR) analysis was conducted to determine data-driven BMI strata that maximized the likelihood of 30 day complications following adult tonsillectomy. Patient demographics and clinical comorbidities were compared using chi-squared analysis and student t tests, where appropriate, for each stratum. Multivariable regression analysis was conducted to confirm association between identified data-driven strata with 30 day complication rates. Results: In total, 44,161 patients undergoing adult tonsillectomy were included in this study. SSLR analysis identified 2 BMI categories: 18 to 45 and 46+. Relative to the 18 to 45 BMI cohort, the 46+ BMI cohort was more likely to have 30 day all-cause complications after surgery [odds ratio (OR): 1.62, P = .007]. Specifically, the 46+ BMI cohort had significantly higher odds for 30 day major medical complications (OR: 2.86, P = .001), pulmonary domain complications (OR: 1.86, P = .041), unplanned reintubation (OR: 2.65, P = .033), and deep vein thrombosis (OR: 6.54, P = .026). Conclusions: We identified a BMI threshold of 46+ that was associated with a significantly increased risk of 30 day all-cause complications following adult tonsillectomy. These BMI strata can guide preoperative planning and risk-stratifying models for predicting 30 day complications in tonsillectomy surgery.

Postoperative Delirium Screening Characteristics in Pediatric Intestinal, Liver, and Renal Transplant Recipients: Single-Center Retrospective Cohort Study.

To describe and compare the results of delirium screening in the immediate post-transplant PICU admission for pediatric intestinal, liver, and renal transplant recipients. We also examined associations with known and suspected risk factors for pediatric delirium (PD). Retrospective analysis of a single-center cohort, 2016-2022. Twenty-four-bed PICU in a high-volume transplant center. All intestinal, liver, and renal transplant recipients under 23 years old admitted between July 2016 and August 2022. We identified 211 pediatric transplant recipients: intestinal (n = 36), liver (n = 78), and renal (n = 97). Results of the Cornell Assessment for PD during the immediate post-transplant PICU admission were reviewed and patients were categorized into screen positive, screen negative, and unscreened. Corresponding data on known and suspected risk factors for PD were also collected. Data on delirium subtypes were not collected. Screens were available for 156 of 211 patients (74%) who were included in the final analysis. The prevalence of a positive screen by transplant category was: intestine 80% (24/30), liver 75% (47/63), and renal 14% (9/63). A positive screen was associated with younger age, greater duration of mechanical ventilation, and greater PICU length of stay (LOS) in bivariate analysis. In multivariable analysis, age and PICU LOS remained strongly correlated with a positive screen (p < 0.05). Deep sedation and agitation as categorized by the State Behavioral Scale was associated with a positive screen, as was significant iatrogenic withdrawal symptoms (p < 0.05). Most patients screened positive by post-transplant days 2 and 3 (58/80 [72%] and 64/80 [80%], respectively). In our 2016 to 2022 experience, we found a high prevalence of positive PD screens in pediatric intestinal and liver transplant recipients in the immediate post-transplant PICU admission. A positive screen was associated with younger age and greater PICU LOS.

DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 therapy.

More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells. However, it inhibited recycling of endosomal PD-L1 and reduced surface PD-L1 levels, which led to defects in interaction with PD-1. Anti-PD-1 did not expand effector-like T cells within DRG2-depleted tumors and failed to improve the survival of DRG2-depleted tumor-bearing mice. Cohort analysis revealed that patients bearing melanoma with low DRG2 protein levels were resistant to anti-PD-1 therapy. These findings identify DRG2 as a key regulator of recycling of endosomal PD-L1 and response to anti-PD-1 therapy and provide insights into how to increase the correlation between PD-L1 expression and response to anti-PD-1 therapy.

Temporary immobilization methods for closed low-energy ankle fracture-dislocations: comparative analysis of a retrospective cohort.

Ankle fracture-dislocations (AFD) often necessitate staged management involving temporary external fixation (EF) due to mechanical instability or blistering. However, limited literature exists on the optimal temporary immobilization method for low-energy closed AFD. This study compared baseline patient and fracture characteristics, along with clinical and radiological outcomes between AFD initially immobilized with EF versus splinting. A retrospective cohort study was conducted involving patients with AFD temporarily immobilized using EF or splinting, followed by definitive open reduction and internal fixation. Quality of reduction (QOR) was assessed for each patient post-initial immobilization and after the definitive surgery. The study encompassed 194 patients: 138 treated with a splint (71.1%) and 56 (28.9%) with EF. Secondary loss of reduction had occurred in three patients who were splinted (2.2%). The mean ages in the EF and splint groups were 63.2 and 56.1years, respectively (p = 0.01). Posterior malleolus fracture (PMF) and blisters were more prevalent in EF patients (69.6% vs. 43.5% for PMF and 76.8% vs. 20.3% for blisters, respectively; p = 0.05 and p < 0.01). Postoperative complication rates were 8.9% for EF versus 10.9% for splinting (p = 0.69). Satisfactory final QOR was attained in 79.8% of patients treated with a splint versus 64.3% with EF (p = 0.02). Patients immobilized by EF presented with poorer baseline characteristics and had more unstable injuries. Nevertheless, postoperative complication rates were comparable. Thus, EF appears to be a valuable tool for standardizing outcomes in AFD patients with a less favorable prognosis.

Increased CSF DOPA Decarboxylase Correlates with Lower DaT-SPECT Binding: Analyses in Biopark and PPMI Cohorts.

Recent studies identified increased cerebrospinal fluid (CSF) DOPA decarboxylase (DDC) as a promising biomarker for parkinsonian disorders, suggesting a compensation to dying dopaminergic neurons. A correlation with 123I-FP-CIT-SPECT (DaT-SPECT) imaging could shed light on this link. The objective is to assess the relationship between CSF DDC levels and DaT-SPECT binding values. A total of 51 and 72 Parkinson's disease (PD) subjects with available DaT-SPECT and CSF DDC levels were selected from the PPMI and Biopark cohorts, respectively. DDC levels were analyzed using proximity extension assay and correlated with DaT-SPECT striatal binding ratios (SBR). All analyses were corrected for age and sex. CSF DDC levels in PD patients correlated negatively with DaT-SPECT SBR in both putamen and caudate nucleus. Additionally, SBR decreased with increased DDC levels over time in PD patients. CSF DDC levels negatively correlate with DaT-SPECT SBR in levodopa-treated PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Decade-Long Cohort Analysis of Human Cytomegalovirus (HCMV)-Induced Early and Late Renal Rejection in Post-Transplant Patients in the Eastern Indian Population

A Decade-Long Cohort Analysis of Human Cytomegalovirus (HCMV)-Induced Early and Late Renal Rejection in Post-Transplant Patients in the Eastern Indian Population

Decoding the Prevalent High-Risk Breast Cancers: Demographics, Pathological, Imaging Insights, and Long-Term Outcome.

Objective: To investigate the features and outcomes of breast cancer in high-risk subgroups. Materials and Methods: REB approved an observational study of women diagnosed with breast cancer from 2010 to 2019. Three radiologists, using the BI-RADS lexicon, blindly reviewed mammogram and MRI screenings without a washout period. Consensus was reached with 2 additional reviewers. Inter-rater agreement was measured by Fleiss Kappa. Statistical analysis included Mann-Whitney U, Chi-square tests for cohort analysis, and Kaplan-Meier for survival rates, with a Cox model for comparative analysis using gene mutation as a reference. Results: The study included 140 high-risk women, finding 155 malignant lesions. Significant age differences noted: chest radiation therapy (median age 44, IQR: 37.0-46.2), gene mutation (median age 49, IQR: 39.8-58.0), and familial risk (median age 51, IQR: 44.5-56.0) (P = .007). Gene mutation carriers had smaller (P = .01), higher-grade tumours (P = .002), and more triple-negative ER- (P = .02), PR- (P = .002), and HER2- (P = .02) cases. MRI outperformed mammography in all subgroups. Substantial to near-perfect inter-rater agreement observed. Over 10 years, no deaths occurred in chest radiation group, with no significant survival difference between gene mutation and familial risk groups, HR = 0.93 (95% CI: 0.27, 3.26), P = .92. Conclusion: The study highlights the importance of age and specific tumour characteristics in identifying high-risk breast cancer subgroups. MRI is confirmed as an effective screening tool. Despite the aggressive nature of cancers in gene mutation carriers, early detection is crucial for survival outcomes. These insights, while necessitating further validation with larger studies, advocate for a move toward personalized medical care, strengthening the existing healthcare guidelines.

Discovery of a T cell proliferation-associated regulator signature correlates with prognosis risk and immunotherapy response in bladder cancer.

The efficacy of immunotherapy is heavily influenced by T cell activity. This study aimed to examine how T cell proliferation regulators can predict the prognosis and response to immunotherapy in patients with bladder cancer (BCa). T cell proliferation-related subtypes were determined by employing the non-negative matrix factorization (NMF) algorithm that analyzed the expression patterns of T cell proliferation regulators. Subtypes were assessed for variations in prognosis, immune infiltration, and functional behaviors. Subsequently, a risk model related to T cell proliferation was created through Cox and Lasso regression analyses in the TCGA cohort and then confirmed in two GEO cohorts and an immunotherapy cohort. BCa patients were categorized into two subtypes (C1 and C2) according to the expression profiles of 31T cell proliferation-related genes (TRGs) with distinct prognoses and immune landscapes. The C2 subtype had a shorter overall survival (OS), with higher levels of M2 macrophage infiltration, and the activation of cancer-related pathways than the C1 subtype. Following this, thirteen prognosis-related genes that were involved in T cell proliferation were utilized to create the prognostic signature. The model's predictive accuracy was confirmed by analyzing both internal and external datasets. Individuals in the high-risk category experienced a poorer prognosis, increased immunosuppressive factors in the tumor microenvironment, and diminished responses to immunotherapy. Additionally, the immunotherapeutic prediction efficacy of the model was further confirmed by an immunotherapy cohort (anti-PD-L1 in the IMvigor210 cohort). Our study characterized two subtypes linked to T cell proliferation in BCa patients with distinct prognoses and tumor microenvironment (TME) patterns, providing new insights into the heterogeneity of T cell proliferation in BCa and its connection to the immune landscape. The signature has prospective clinical implications for predicting outcomes and may help physicians to select prospective responders who prioritize current immunotherapy.

Value of 24h ambulatory ECG for prediction of sufficient number of premature ventricular complexes during catheter ablation

Abstract Introduction Successful catheter ablation (CA) of premature ventricular complexes (PVCs) depends on identification of the site of origin (SOO), but no parameter suggested for prediction of success from CA have been sufficiently validated in previous studies. Activation mapping and pace-mapping are invasive methods for the identification of SOO, and the burden of PVCs is critical for activation mapping to identify SOO. The number of PVCs in 24h ambulatory ECGs is claimed to predict occurrence of PVCs during the procedure, and hence procedural success, but the predictive value remains unknown. Purpose The primary objective of this study was to quantify the predictive value of pre-procedural of 24h ambulatory ECG with regard to sufficient number of PVCs during the CA procedure. Methods Patients admitted for CA of PVCs at our hospital from 2011-2020 were included. Data were retrospectivity collected from electronic health records. Clinical characteristics, results from clinical pre-procedural examinations, including 24h ambulatory ECG, exercise testing and echocardiogram, as well as acute outcomes were recorded. Results A total of 332 patients were included, CA was performed in 285 (86 %) patients, while 47 (14 %) patients had insufficient number of PVCs to allow adequate identification of SOO. Neither clinical characteristics nor results of cardiac imaging separated patients with sufficient and insufficient number of PVCs for CA, respectively. Patients with sufficient number of PVCs had nominally more PVCs in the preceding 24h ambulatory ECG, although the difference was not statistically significant (16007 (6509-26205) vs. 8332 (3066-20974), p = 0.055). A receiver operating characteristics (ROC) curve analysis of sufficient number of PVCs during CA and number of PVCs in the preceding 24h ambulatory ECG had an area under curve (AUC) of 0.610 (0.95% CI 0.498-0.722, p = 0.055). The commonly clinically used cut-off of &amp;gt;10 000 PVCs/24h had a positive predictive value of 67 % and a negative predictive value of 57 % for sufficient number of PVCs during CA. The median period from the 24h ambulatory ECGs to CA was 183 days (6 months). The positive and negative predicative values for &amp;gt;10 000 PVCs in 24h ambulatory ECG performed &amp;gt;6 months prior to the procedure were 67 % and 71 %, respectively, compared to 53 % and 61 % for 24h ECGs performed &amp;lt;6 months prior to the procedure. The ROC curve for sufficient number of PVCs during the procedure and number of PVCs in a 24h ambulatory ECG performed &amp;gt;6 months and &amp;lt;6 months prior to the procedure did not differ, with had AUC values of 0.665 and 0.584, respectively (p = 0.4). Conclusion In this retrospective analysis of a large cohort of patients admitted for CA of PVCs, number of PVCs in 24h ambulatory ECGs recorded prior to the procedure had a low predictive value for presence of PVCs during CA. Others parameters need to be evaluated to improve prediction.

Association between Dietary Patterns and All-Cause Mortality in the Chinese Old: Analysis of the Chinese Longitudinal Healthy Longevity Survey Cohort

Diet is one of the most important ways to intervene and promote the health of older adults and reduce all-cause mortality. This study aimed to investigate the association between dietary patterns and all-cause mortality in the Chinese old. This study involved 11,958 subjects aged 65–116 years in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. Dietary patterns were derived from principal component analysis (PCA) with varimax rotation. Four dietary patterns were derived: the ‘milk–egg–sugar pattern’, ‘carnivorous pattern’, ‘healthy pattern’, and ‘northeastern pattern’. Cox proportional hazard models were built for males and females separately to estimate the relationship between different dietary patterns and all-cause mortality. After adjusting for all covariates, the milk–egg–sugar pattern played a reverse role in mortality risk in males and females in different quartiles. In the carnivorous pattern, only males in the fourth quartile were observed to have a significantly reduced mortality risk (HR = 0.84 (95% CI: 0.77–0.93)). Both genders benefited from the healthy pattern, which consistently lowered mortality risk across all quartiles (males: HR = 0.87 (95% CI: 0.84–0.89); females: HR = 0.95 (95% CI: 0.92–0.97)). The northeastern pattern also showed an inverse association with all-cause mortality in males (HR = 0.94 (95% CI: 0.92–0.97)) and females (HR = 0.96 (95% CI: 0.93–0.98)). This study showed the association between dietary patterns and all-cause mortality in the Chinese old, which is significant for further quantitative studies.

Clinical findings and outcomes of Brugada syndrome in women

Abstract Introduction Brugada syndrome (BrS) is a genetic disorder characterized by typical ECG changes and association with spontaneous ventricular tachyarrhythmia (VTA) and sudden death in young patients. BrS has been widely established to be particularly prevalent in men, however less information exists regarding female patients and their long-term risk. Objectives The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS. Methods This study includes a retrospective analysis of a single-center cohort of patients followed and observed for relevant clinical outcomes. The data collected included demographic data, severity of symptoms (e.g. syncope, VTA), cardioverter-defibrillator logs and occurrence of sudden cardiac death. Results 317 patients were diagnosed with BrS between 1998 and 2023. Among those, 112 (36%) were female. At presentation, 5 patients (4%) were symptomatic with history of survived cardiac arrest and/or documented VTA. 29 (26%) had history of unexplained syncope and 78 (70%) were asymptomatic. The average age at diagnosis was 42.1±15.1 yrs. as opposed to 40.1±14.2 yrs. in men. Females presented less frequently with a type 1 ECG pattern (5% vs 21%; p&amp;lt;0.01), had a trend to a higher rate of family history of sudden cardiac death (31% vs 25%; p=n.s.), and had less sustained VTA during programmed ventricular stimulation (4% vs 19%; p&amp;lt;0.01). Genetic testing was performed in 89 females (79% of the sample) and pathogenic variants were present in 36 (40%) women. An implantable cardioverter defibrillator was inserted in 24 (31%) females for primary prevention. During mean follow-up of 138±72 months, 11 women had cardiovascular events (syncope, VT/VF or death). Syncope was most common and occurred in 8 cases. No VTA were documented in any female patient. In the group of ICD patients, 8 shocks have occurred. None of these were deemed appropriate by medical controls. There were 3 deaths. Two were considered non-arrhythmic due to pulmonary embolism and breast carcinoma. One ICD patient died suddenly during sleep. Unfortunately, no device interrogation data was available. Conclusion Women typically present less symptomatic and demonstrate a reduced incidence of life-threatening arrhythmias during follow-up , often experiencing a frequent occurrence of inappropriate implantable defibrillator therapy. The less frequent prevalence of the BrS ECG pattern in women adds complexity to the diagnostic process. Further studies are still needed to elucidate gender differences for risk stratification of BrS.

Selective nonoperative versus operative management of liver gunshot injuries: a retrospective cohort study.

Experience accumulated over the last decades suggests nonoperative management (NOM) of civilian gunshot liver injuries can be safely applied in selected cases. This study aims to compare the outcomes of selective NOM versus operative management (OM) of patients sustaining gunshot wounds (GSW) to the liver. A registry-based retrospective cohort analysis was performed for the period of 2008 to 2016 in a Brazilian trauma referral. Patients aged 16-80 years sustaining civilian GSW to right-sided abdominal quadrants and liver injury were included. Baseline data, vital signs, grade of liver injury, associated injuries, injury severity scores, blood transfusion requirements, liver- and non-liver-related complications, length-of-stay (LOS), and mortality were retrieved from individual registries. A total of 54 patients were eligible for analysis, of which 37 underwent NOM and 17 underwent OM. The median age was 25 years and all were male. No statistically significant differences were observed between groups regarding patients' demographics, injury scores, grade of liver injury and associated lesions. NOM patients tended to sustain higher-grade injuries (86.5% vs 64.7%; p = 0.08), and failure of conservative management was recorded in two (5.4%) cases. The rate of complications was 48% with no between-group statistically significant difference. Blood transfusion requirements were significantly higher in the OM group (58.8% vs 21.6%; p = 0.012). The median LOS was seven days. No deaths were recorded. Patients with liver GSW who are haemodynamically stable and without peritonitis are candidates for NOM. In this study, NOM was safe and effective even in high-grade injuries.