Hospital Cohort Research Articles

Impact of sensitization and ABO blood types on the opportunity of deceased-donor kidney transplantation with prolonged waiting time

The waiting time to deceased-donor kidney transplantation (DDKT) is long in Asian countries. We investigated the impact of sensitization and ABO blood type (ABO) on DDKT opportunity using two Korean cohorts: a hospital cohort from two centers and a national database. The impact of panel reactive antibody (PRA) based on the maximal PRA% and ABO on DDKT accessibility was analyzed using a competing risks regression model. In the hospital cohort (n = 4722), 88.2%, 8.7%, and 3.1% of patients belonged to < 80%, 80–99%, and ≥ 99% PRA groups, respectively, and 61.1%, 11.6%, and 27.3% belonged to A or B, AB, and O blood types, respectively. When PRA and ABO were combined, PRA < 80%/A or B and 80 ≤ PRA < 99%/AB had fewer DDKT opportunities (median, 12 years; subdistribution hazard ratio [sHR], 0.71) compared with PRA < 80%/AB (median, 11 years). Also, PRA < 80%/O, 80 ≤ PRA < 99%/A or B, and PRA ≥ 99%/AB had a much lower DDKT opportunity (median, 13 years; sHR, 0.49). Furthermore, 80 ≤ PRA < 99%/O and PRA ≥ 99%/non-AB had the lowest DDKT opportunity (sHR, 0.28). We found similar results in the national cohort (n = 18,974). In conclusion, an integrated priority system for PRA and ABO is needed to reduce the inequity in DDKT opportunities, particularly in areas with prolonged waiting times.

Abstract WMP19: A Brain Care Score for Risk of Late-Life Depression: Data From the UK Biobank Cohort

Introduction: The 21-point Brain Care Score (BCS), developed via a modified Delphi process with practitioners and patients, is a novel instrument designed to motivate behavioral and lifestyle changes, ultimately aiming to decrease incidence of dementia and stroke (Fig 1). Whether or not BCS components are associated with longitudinal changes in mood disorders is not clear. For this study, we tested the hypothesis that the BCS also significantly correlates to late-life depression incidence in the UK Biobank (UKB). Design / Methods: The BCS was derived from UKB participants (using both the hospital and general practitioners cohort) aged 40-69 years, at baseline (2006-2010). After excluding patients with prevalent psychiatric disorders, we performed multivariable Cox proportional hazard regression models between the BCS and risk of incident late-life depression, adjusting for sex and stratified by age groups (&lt;50, 50-59, &gt;59 years). Results: The total BCS (median: 12; IQR:11-14) was derived for 416,370/502,408 (83%) UKB participants with complete data (mean age: 57; females: 54%). After exclusion of 50,395 participants who had mood or psychiatric disorders other than depression, a total of 365,975 participants were included in our analysis. In total, 6,628 incident cases of late-life depression were documented during the median follow-up period of 13 years. Each five-point increase in BCS was associated with a 59% (HR: 0.41, 95% CI: -0.03-0.85) decreased incidence of late-life depression among UKB participants aged &lt;50, 35% (HR: 0.65, 95% CI: 0.57-0.74) among those aged 50-59; and 28% (HR: 0.72, 95% CI: 0.65-0.79) lower risk among those aged &gt;59). Conclusions: In addition to its associations with dementia and stroke incidence, the BCS strongly correlates with late-life depression incidence in the UK Biobank. Additional research is needed to understand the association between BCS elements and late life depression in additional, diverse cohorts.

POLQ identifies a better response subset to immunotherapy in muscle-invasive bladder cancer with high PD-L1.

Though programmed cell death-ligand 1 (PD-L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology-mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy. A total of 1304 patients with muscle-invasive bladder cancer (MIBC) from six independent cohorts were included in this study. The Zhongshan Hospital (ZSHS) cohort (n = 134), The Cancer Genome Atlas (TCGA) cohort (n = 391), and the Neo-cohort (n = 148) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n = 234) and the UNC-108 cohort (n = 89) were used for the assessment of immunotherapeutic response. In addition, the relationship between POLQ and the immune microenvironment was assessed, and GSE32894 (n = 308) was used only for the evaluation of the immune microenvironment. We identified POLQhigh PD-L1high patients could benefit more from immunotherapy and platinum-based chemotherapy. Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules. The study demonstrated that high POLQ expression was correlated with chromosome instability and antitumor immune microenvironment in MIBC, and the combination of POLQ and PD-L1 could be used as a superior companion biomarker for predicting the efficacy of immunotherapy.

The changing profile of infective endocarditis: A multi-year retrospective study for dentists.

Infective endocarditis (IE) has high morbidity and mortality and is often attributed to dental procedures. This study characterized variables related to paediatric IE in a paediatric hospital cohort. A retrospective review of medical records, from January 1, 2008, to January 1, 2020, to examine demographic, medical and dental history, and risk factors associated with children diagnosed with IE at Nationwide Children's Hospital. Of the 242 patients who were admitted with tentative IE diagnoses, 67 met the inclusion criteria: 46 (69%) had underlying cardiac conditions and 21 (31%) had not. One-third had an infection with S. aureus and viridans streptococci. Age was significantly associated with intracardiac devices in children with IE. Mean hospitalization was 25 days, and the mortality was 6 (9%); 41(61%) required surgery for causative defects, and 24 (32%) had dental consultation during admission. Although cardiac-related conditions were present in most cases, IE occurred in patients without cardiac factors.

DOP26 Metagenomic and metabolomic profiles in IBD: understanding microbial and metabolic shifts from a large deeply phenotyped cohort

Abstract Background Alterations in gut microbiota composition and functions are involved in the pathogenesis of Inflammatory Bowel Disease (IBD) and the role of specific bacterial taxa has been particularly pointed out. The role of microbiota-derived metabolites, including those produced from tryptophan, are major actors in host-microbiota interactions in health and in IBD. Large studies analyzing both gut microbiota and metabolomics data are scarce. Methods In the current study, we analyzed a total of 764 individuals from Saint Antoine Hospital cohort, including 447 patients with Crohn's disease (CD), 262 patients with Ulcerative Colitis (UC) and 55 healthy subjects. We performed shotgun metagenomic sequencing on fecal samples and integrated the results with deep clinical phenotyping and targeted metabolomics data encompassing 294 different molecules. Results We observed strong changes in the taxonomic composition and functional capabilities of the microbiota in CD and UC patients compared to healthy subjects. Besides disease itself, the most important drivers of microbiota composition were the disease location (Montreal classification), recent antibiotic treatment, disease activity (flare vs remission) and history of ileocecal resection. Interestingly, IBD diagnosis explained much more the variations of microbiota functions than taxonomy. The decrease in microbiota diversity was stronger in CD than in UC. In parallel to a decreased amount of Faecalibacterium in IBD, we also observed a decrease in the diversity of Faecalibacterium strains, with a stronger decrease in CD. Our multifactorial analysis revealed specific microbial taxa and functions affected by disease-related factors. We particularly identified many correlations between tryptophan metabolites and microbial abundance. Targeted gene analysis of tryptophan-related enzymes in metagenomes further supported these findings. A network analysis considering bacterial taxa and metabolites revealed profound alterations in IBD with some specificities between CD and UC. Conclusion We pointed out new microbiome and metabolome alterations associated with IBD, with some phenotype specificities. Overall, our findings provide crucial information and a substantial resource for understanding the interactions between the host and microbiome in the context of IBD.

Do Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Need to Be Stratified for Age and Comorbidities in COVID-19 Disease? A Subgroup Analysis of Two Distinct Cohorts over Disease Course.

Several studies described neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as markers of COVID-19 severity. In a recently published study, age and frailty affected NLR and PLR more than disease severity. The study compared two distinct cohorts. The first comprised older frailer patients positive for SARS-CoV-2, with mild or asymptomatic disease, admitted to designated COVID-19 departments in a large geriatric medical center (GMC). The second cohort comprised COVID-19 patients admitted to a large general hospital (GH) for symptomatic disease. This was a follow-up study comparing a subgroup of patients who had NLR and PLR values measured a week after admission. Only 100 of 177 patients in the original GMC cohort had a second NLR test compared to almost all (287 of 289) patients in the general hospital (GH) cohort. The subgroup baseline characteristics did not change significantly from that of the original cohort. Disease symptoms were more prevalent in the GH cohort. In the GMC group, the median second NLR rose from 3.9 to 4.6, while in the GH cohort, the NLR value dropped from 3.5 to 2.8, enhancing the NLR differences between the groups. Smaller changes were observed in the second PLR. These results strengthen the prior results that age and frailty seem to have a stronger impact on NLR and PLR than disease severity.

Clinical characteristics and survival analysis in patients with isolated pulmonary metastases from colorectal cancer (CRC).

60 Background: Recent studies seem to indicate that patients with metastatic colorectal cancer (mCRC) with exclusive pulmonary metastatic disease have better outcomes than those with other metastatic sites. The aim of this study is to identify differences in clinical and survival characteristics between the two groups in a cohort of a third level hospital. Methods: We retrospectively analyzed a sample of 569 patients with mCRC in a tumor registry from 2015 to 2021, studying clinical and molecular characteristics, as well as overall survival data of patients with isolated pulmonary metastases, versus the rest of patients. Results: Of the total sample analyzed, 61 patients (10.7%) had isolated pulmonary metastases. In these patients, several clinical characteristics were more frequent: primary rectal tumor (52.5% vs 23.4%, p &lt; 0.000), resected primary tumor (95.1% vs 78.9%, p = 0.0026), metachronous metastatic disease (62.3% vs 42%, p = 0.0025) and complete response rate to the first line of treatment (19.3% vs 9.9%, p = 0.026). Furthermore, analytically, these patients were more likely to have normal CEA (75% vs 38.3%, p &lt; 0.000), CA 19.9 (84.3% vs 57.7%, p = 0.0002) and LDH (91.1% vs 66.5%, p = 0.0007) levels. In our cohort, we found no statistically significant differences in tumor mutational status (KRAS, NRAS, BRAF, PI3K and HER2). There were no patients with exclusive pulmonary metastatic disease and microsatellite instability (MSI). 70.3% of patients with isolated pulmonary metastases received lung metastasectomy, and up to 58.3% received a second metastases surgery. We also found a numerical benefit in terms of overall survival (OS) in patients with exclusive metastatic lung disease, although it did not reach statistical signification (median OS 77.3 vs 58.1 months, HR for death 0.70, 95% CI, 0.49 – 1.01, p = 0.083). Conclusions: In our cohort, patients with isolated pulmonary metastases were more likely to have rectal tumors, primary tumor resection, metachronous metastatic disease, higher rate of complete responses and normal CEA, CA 19.9 and LDH levels, with a possible benefit in terms of OS.

A 12-month follow-up study of patients with systemic lupus erythematosus after immunization against SARS-CoV-2.

To identify all post-BNT162b2 vaccination (BioNTech and Pfizer) events during the ensuing 12months in patients with systemic lupus erythematosus (SLE) from the Immuno-Rheumatology Department at Cayetano Heredia Hospital's cohort, Lima, Perú. A 12-month follow-up study was conducted from the first dose of immunization with the BNT162b2 vaccine, which was given between May and June 2021, to SLE patients from this cohort. The initial population was constituted by 100 patients (100 patients received the 1st dose, 90 the 2nd dose, and 85 the 3rd dose of this vaccine); 33 patients presented a SLE reactivation (flare), 9% (9/100) post 1st dose, 26.6% (24/90) post 2nd dose, and 16.4% (14/85) post 3rd dose. The most common types of flare were articular (26) and renal (14) with 5/33 (15.1%) requiring hospitalization for flare management. A negative association with flare occurrence was found between the use of hydroxychloroquine RR 0.43 (0.21-0.85) and the opposite was the case for azathioprine RR 2.70 (1.39-5.25). During follow-up, 26 patients developed SARS-CoV-2 infection of whom three required hospitalization, one of whom died. 33 of 100 SLE patients immunized with BNT162b2 vaccine against SARS-CoV-2, presented SLE flares (47 episodes in total); 5 of these patients required in-hospital management and all fully recovered; 26 patients had SARS-CoV-2 infection; three required hospitalization, one died.

Systemic lupus erythematosus is associated with increased risk of mortality and acute kidney injury in patients with COVID-19 hospitalization: Insights from a National Inpatient Sample analysis.

The COVID-19 pandemic has significantly impacted global health, especially for patients with chronic diseases that may compromise the immune system. This study investigates the association between systemic lupus erythematosus (SLE) and COVID-19 outcomes. Data from the National Inpatient Sample (NIS) were analyzed to create a retrospective cohort of COVID-19 hospitalizations, comparing patients with and without SLE. Propensity-score matched analysis was conducted to assess the association between SLE and clinical outcomes in COVID-19 hospitalizations. The study included over a million COVID-19 hospitalizations, with approximately 0.5% having a secondary diagnosis of SLE. The SLE-COVID hospitalizations were predominantly female and younger, with a median age of 57.2, while the non-SLE-COVID group had a median age of 64.8 years. Comorbidities such as chronic obstructive pulmonary disease, renal failure, liver disease, and others were more prevalent in the SLE-COVID group. Patients with SLE and COVID-19 had a significantly higher incidence of acute kidney injury requiring dialysis than those without SLE. In-hospital mortality was higher in the SLE group, particularly in the 18-44 year age group (6.15% vs 2.47%, p = .022). COVID-19 patients with SLE are at an increased mortality risk, especially in the younger age group, and a higher incidence of acute kidney injury requiring dialysis. The elevated risk of adverse outcomes underscores the vulnerability of SLE patients to COVID-19. These findings emphasize the importance of special precautions and patient education for individuals with SLE to mitigate the risks associated with COVID-19.

Construction of the miRNA/Pyroptosis-Related Molecular Regulatory Axis in Abdominal Aortic Aneurysm: Evidence From Transcriptome Data Combined With Multiple Machine Learning Approaches Followed by Experiment Validation.

Background: Abdominal aortic aneurysm (AAA) represents a permanent and localized widening of the abdominal aorta, posing a potentially lethal risk of aortic rupture. Several recent studies have highlighted the role of pyroptosis, a pro-inflammatory programed cell death, as critical molecular regulators in AAA occurrence, progression, and rupture. However, the potential effects of pyroptosis in AAA and its upstream microRNA (miRNA) have not been comprehensively clarified. Methods: Through a search of the gene expression omnibus (GEO) database, the expression profiles of mRNAs (GSE7084, GSE57691, and GSE98278) and miRNAs (GSE62179) and corresponding clinical features were downloaded, respectively. Expression profiles of 15 AAA and 10 normal vascular samples were consecutively collected for in vitro experimentation and subsequent analysis. Various machine learning techniques were employed to identify hub pyroptosis-related genes (PRGs), leading to the development of a predictive model termed the PRG classifier. Quantitative real-time-polymerase chain reaction (qRT-PCR), western blot (WB), and enzyme-linked immunosorbent assay (ELISA) were used to confirm the expression of the hub PRGs. The diagnostic and predictive capabilities of the model were comprehensively evaluated in GEO and hospital cohorts. Then, the crucial immune cell infiltration and molecular pathways implicated in the initiation and rupture of AAA and their association with pyroptosis were explored. Lastly, a miRNA/hub pyroptosis-related molecular regulatory axis was constructed using the TargetScan dataset, which was further explored through loss-of-function assays. Results: Differential analysis, enrichment score analysis, and principal component analysis (PCA) revealed that pyroptosis-related molecules were significantly involved in the occurrence of AAA. Utilizing multiple machine learning algorithms, eight key PRGs (cysteinyl aspartate specific proteinase [CASP]1, infiltrating lymphocyte [IL]1B, IL18, IL6, NOD-, LRR- and pyrin domain-containing protein [NLRP]1, NLRP2, NLRP3, and tumor necrosis factor [TNF]) were integrated to establish a PRG classifier. Demonstrating robust diagnostic capabilities (area under curve [AUC] > 0.90), the PRG classifier provided clinical insights across two GEO datasets and effectively differentiated small AAA from large AAA, elective stable AAA (eAAA), and ruptured AAA (rAAA), respectively. qRT-PCR, WB, and ELISA verified the mRNA and protein expression of the hub PRGs. Notably, in hospital cohorts, a substantial positive link was unveiled between the PRG classifier and AAA risk factors (hypertension history, diastolic pressure, triglyceride levels, and aneurysm diameter). Furthermore, immune cell infiltration and functional enrichment analysis revealed significant associations of the PRG classifier/PRGs with M2 macrophage infiltration, activated dendritic cells, and enrichment scores of the cytosolic deoxyribonucleic acid (DNA) sensing pathway and tryptophan metabolism, potentially mediating AAA onset and rupture. Finally, based on 90 differentially expressed miRNAs (DEmiRNAs) and eight hub PRGs through TargetScan dataset, a hsa-miR-331-3p/TNF regulatory axis was constructed, wherein upregulation of hsa-miR-331-3p expression significantly reduced TNF and CASP1 protein levels. Conclusion: A predictive model (PRG classifier) incorporating eight PRGs through multiple machine learning algorithms was developed and validated. This model may stand as a potent tool for diagnosing AAA and assessing disease severity. The identification of the cytosolic DNA sensing pathway and the hsa-miR-331-3p/TNF interaction axis may represent crucial targets for AAA treatment, offering deeper insights into its potential pathogenesis.

Renal replacement therapy prior to liver transplant and inpatient mortality in patients without advanced kidney disease: A nationwide study.

The utility of renal replacement therapy (RRT) before liver transplant (LT) in patients without end-stage renal disease (ESRD) or advanced chronic kidney disease (CKD-IV/V) is debatable and lacks data support. We aimed to evaluate the impact of RRT on patients undergoing LT. We used the National Readmission Database (2016-2019) to identify all index hospitalizations undergoing RRT before LT (cases). A matched comparison cohort of similar hospitalizations without RRT before LT was identified (controls) after 1:1 propensity score matching for age, gender, and available comorbidities. We matched 364 cases (RRT before LT) to 364 controls (LT without prior RRT). There was no statistical difference in all-cause inpatient mortality (4.9% vs 3.6% P = 0.4). A significantly greater proportion of cases were associated with ICU admission (40.7% vs 17.0%, P < 0.001) and RRT requirement post LT (100% vs 17%, P < 0.001). There was no difference in 30- (hazard ratio [HR] 1.1, 0.4-2.6), 60- (HR 0.9, 0.4-1.8), or 90-day (HR 0.8, 0.4-1.6) inpatient mortality between the groups. Also, 180-day survival estimates were comparable (P = 0.5). The results were similar in patients with no chronic kidney disease (CKD) and CKD-III. RRT prior to LT, in patients without advanced CKD or ESRD, was associated with greater instances of ICU stay and need for future RRT. Also, 30-, 60-, and 90-day inpatient mortality rates were similar, and 180-day survival estimates were comparable.

Hospital cohort study on survival predictors for intubated coronavirus disease 2019 patients.

The objective of this study was to assess the predictors of survival among patients with coronavirus disease 2019 who underwent tracheal intubation, as part of a hospital cohort study. This retrospective cohort study in the Rio do Sul County Hospital, Santa Catarina, Brazil, from April 2020 to May 2021, focused on patients aged 18 years or older intubated for coronavirus disease 2019. We assessed the 90-day survival of intubated patients by estimating the hazard ratio using a Cox proportional hazards regression model. The study included 132 participants, with an average age of approximately 60 years. Tracheal intubation was successfully accomplished in 97% of cases within two attempts. The overall mortality rate was 62.9%. Notably, mortality rates were significantly higher in patients aged over 60 years (hazard ratio=2.57; 95%CI 1.54-4.29; p<0.001), those with blood oxygen saturation below 85% (hazard ratio=1.92; 95%CI 1.03-3.57; p=0.04), instances where tracheal intubation was carried out using a conventional laryngoscope (hazard ratio=2.59; 95%CI 1.22-5.48; p=0.013), and when performed by emergency physicians (hazard ratio=3.96; 95%CI 1.51-10.4; p=0.005). Our analysis unveiled that the risk of death in intubated coronavirus disease 2019 patients is four times higher when an emergency physician, as opposed to an anesthesiologist, leads the tracheal intubation team.

Evolutionary relationship between antimitochondrial antibody positivity and primary biliary cholangitis in Taiwan: a 16-year hospital cohort study.

How antimitochondrial antibody (AMA)-positive patients evolve to have primary biliary cholangitis (PBC) in viral hepatitis-endemic areas is unknown. We aimed to investigate this evolution in Taiwan. A 16-year medical center-based cohort study of 2,095,628 subjects was conducted in Taiwan, an Asian country endemic to viral hepatitis. AMA-positive subjects were those with positive AMA with alkaline phosphatase (ALP) ⩽1.5 times the upper limit of normal (ULN), and PBC was defined as positive AMA with ALP >1.5 × ULN. AMA-positive subjects had a lower average age- and sex-adjusted prevalence than PBC patients (4.68/105 versus 11.61/105, p = 0.0002), but their incidence was comparable (0.99/105 versus 1.12/105, p = 0.36). The former group had a borderline significantly lower mean age (56.59 years versus 58.10 years, p = 0.06) and a lower female-to-male ratio (2.85:1 versus 5.44:1, p < 0.0001). Both AMA-positive subjects (prevalence change: 20.0%, p < 0.01; incidence change: -9.2%, p < 0.01) and PBC patients (prevalence change: 14.6%, p < 0.01; incidence change: -4.7%, p < 0.01) prevalence rate increased but the incidence rate decreased. Among the 423 AMA-positive subjects, 77 (18.2%) developed PBC, for a mean duration of 1.757 years. Compared with AMA-positive subjects, PBC patients had similar concurrent chronic hepatitis B (CHB) rates (2.7% versus 4.3%, p = 0.197) but lower chronic hepatitis C (CHC) rates (3.69% versus 15.60%, p < 0.01). PBC was more prevalent than AMA-positive subjects, and PBC patients had a higher female-to-male ratio than AMA-positive subjects, of whom 18.2% developed PBC (mean lag: 1.757 years). Upward trends in prevalence rates and downward trends in incidence rates were noted for both AMA-positive subjects and PBC. CHB was rare, CHC was more prevalent among PBC patients than the general population, and CHC was less prevalent among PBC than among AMA-positive subjects.

Individual and contextual factors associated with the survival of patients with severe acute respiratory syndrome by COVID-19 in Brazil.

To analyze the influence of individual and contextual factors of the hospital and the municipality of care on the survival of patients with Severe Acute Respiratory Syndrome due to COVID-19. Hospital cohort study with data from 159,948 adults and elderly with Severe Acute Respiratory Syndrome due to COVID-19 hospitalized from January 1 to December 31, 2022 and reported in the Influenza Epidemiological Surveillance Information System. The contextual variables were related to the structure, professionals and equipment of the hospital establishments and socioeconomic and health indicators of the municipalities. The outcome was hospital survival up to 90 days. Survival tree and Kaplan-Meier curves were used for survival analysis. Hospital lethality was 30.4%. Elderly patients who underwent invasive mechanical ventilation and were hospitalized in cities with low tax collection rates had lower survival rates compared to other groups identified in the survival tree (p<0.001). The study indicated the interaction of contextual factors with the individual ones, and it shows that hospital and municipal characteristics increase the risk of death, highlighting the attention to the organization, operation, and performance of the hospital network.

Calcified Neurocysticercosis: Demographic, Clinical, and Radiological Characteristics of a Large Hospital-Based Patient Cohort.

Neurocysticercosis (NCC), the infection of the central nervous system caused by Taenia solium larvae (cysticerci), is a major cause of acquired epilepsy worldwide. Calcification in NCC is the most common neuroimaging finding among individuals with epilepsy in T. solium-endemic areas. We describe the demographic, clinical, and radiological profiles of a large hospital cohort of patients with calcified NCC in Peru (during the period 2012-2022) and compared profiles between patients with and without a previous known diagnosis of viable infection. A total of 524 patients were enrolled (mean age at enrollment: 40.2 ± 15.2 years, mean age at symptom onset: 29.1 ± 16.1 years, 56.3% women). Of those, 415 patients (79.2%) had previous seizures (median time with seizures: 5 years, interquartile range (IQR): 2-13 years; median number of seizures: 7 (IQR: 3-32)), of which 333 (80.2%) had predominantly focal to bilateral tonic-clonic seizures; and 358 (68.3%) used antiseizure medication). Patients had a median number of three calcifications (IQR: 1-7), mostly located in the frontal lobes (79%). In 282 patients (53.8%) there was a previous diagnosis of viable infection, while 242 only had evidence of calcified NCC since their initial neuroimaging. Most patients previously diagnosed with viable infection were male, had previous seizures, had seizures for a longer time, had more calcifications, and had a history of taeniasis more frequently than patients without previously diagnosed viable infection (all p < 0.05). Patients with calcified NCC were heterogeneous regarding burden of infection and clinical manifestations, and individuals who were diagnosed after parasites calcified presented with milder disease manifestations.

Clinical outcome and molecular landscape of patients with ARID1A-loss gastric cancer.

Chromatin remodelers are commonly altered in human cancer. The mutation of AT-rich interactive domain 1A (ARID1A) in gastric cancer (GC), a component of the SWI/SNF chromatin remodeling complex, was proven associated with treatment response in our previous study. However, ARID1A loss of function was caused not only by mutations but also copy number deletions. The clinicopathologic, genomic, and immunophenotypic correlates of ARID1A loss is largely uncharacterized in GC. Here, 819 patients with clinicopathological information and sequencing data or formalin-fixed paraffin-embedded tissues from four cohorts, Zhongshan Hospital (ZSHS) cohort (n = 375), The Cancer Genome Atlas (TCGA) cohort (n = 371), Samsung Medical Center (SMC) cohort (n = 53), and ZSHS immunotherapy cohort (n = 20), were enrolled. ARID1A loss was defined by genome sequencing or deficient ARID1A expression by immunohistochemistry. We found that ARID1A mutation and copy number deletion were enriched in GC with microsatellite instability (MSI) and chromosomal-instability (CIN), respectively. In the TCGA and ZSHS cohorts, only CIN GC with ARID1A loss could benefit from fluorouracil-based adjuvant chemotherapy. In the SMC and ZSHS immunotherapy cohorts, ARID1A loss exhibited a tendency of superior responsiveness and indicated favorable overall survival after anti-PD-1 immunotherapy. ARID1A-loss tumors demonstrated elevated mutation burden, neoantigen load, and interferon gamma pathway activation. Moreover, in CIN GC, ARID1A loss was correlated with higher homologous recombination deficiency. ARID1A loss defines a distinct subtype of GC characterized by high levels of genome instability, neoantigen formation, and immune activation. These tumors show sensitivity to both chemotherapy and anti-PD-1 immunotherapy. This study provides valuable insights for precision treatment strategies in GC.

LGR5, a prognostic stem cell target, promotes endometrial cancer proliferation through autophagy activation

Endometrial cancer (EC) is a common malignant tumor in women worldwide. Although early EC has a good prognosis, advanced endometrial cancer is still associated with the risk of drug resistance and recurrence. Cancer stem cells (CSCs), a category closely related to drug resistance and recurrence, are rarely studied at present. Here, we constructed a risk model containing ten stemness-related prognostic genes. Compared with patients in the low-risk group, patients in the high-risk group had a shorter overall survival time. The accuracy of this model was verified by ROC in the TCGA (AUC = 0.779) and Peking University People's Hospital (PKUPH, AUC = 0.864) cohorts. The risk score and stage were independent risk factors in the multivariate regression analysis, which was subsequently used to construct the nomogram and verified in the TCGA cohort. LGR5 was significantly correlated with overall survival and involvement in the Wnt signaling pathway. In addition, LGR5 was highly expressed in EC tissues and was related to age, stage, histological type, and menopause status in the TCGA database. Overexpression of LGR5 accelerated the proliferation rate of EC cells, which may be related to autophagy activation. Taken together, our study established a prognostic model based on transcription sequencing data from the TCGA database and verified it in the PKUPH cohort, which has prospective clinical implications for the prognostic evaluation of EC. We systematically studied the code gene LGR5 in EC, which may help clinicians make personalized prognostic assessments and effective clinical decisions for EC.

Detrimental effect of anemia after mechanical thrombectomy on functional outcome in patients with ischemic stroke.

Anemia can occur due to an aspiration maneuver of blood with thrombi during mechanical thrombectomy (MT) for stroke. However, the association between postoperative anemia and stroke outcomes is unknown. In a registry-based hospital cohort, consecutive patients with acute ischemic stroke who underwent MT were retrospectively recruited. Patients were divided into the following three groups according to their hemoglobin (Hb) concentrations within 24 h after MT; no anemia (Hb concentrations ≥13 g/dL for men and ≥ 12 g/dL for women), mild anemia (Hb concentrations of 11-13 g/dL and 10-12 g/dL, respectively), and moderate-to-severe anemia (Hb concentrations <11 g/dL and < 10 g/dL, respectively). A 3-month modified Rankin Scale score of 0-2 indicated a favorable outcome. Of 470 patients, 166 were classified into the no anemia group, 168 into the mild anemia group, and 136 into the moderate-to-severe anemia group. Patients in the moderate-to-severe anemia group were older and more commonly had congestive heart failure than those in the other groups. Patients in the moderate-to-severe anemia group also had more device passes than those in the other groups (p < 0.001). However, no difference was observed in the rate of final extended thrombolysis in cerebral infarction ≥2b reperfusion or intracranial hemorrhage among the groups. A favorable outcome was less frequently achieved in the moderate-to-severe anemia group than in the no anemia group (adjusted odds ratio, 0.46; 95% confidence interval, 0.26-0.81) independent of the baseline Hb concentration. A restricted cubic spline model with three knots showed that the adjusted odds ratio for a favorable outcome was lower in patients with lower Hb concentrations within 24 h after MT. Moderate-to-severe anemia within 24 h after MT is independently associated with a reduced likelihood of a favorable outcome. https://www.clinicaltrials.gov, NCT02251665.

A risk prediction model for hepatocellular carcinoma in non-alcoholic fatty liver disease without cirrhosis: HCC prediction for non-cirrhotic NAFLD.

Although non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of hepatocellular carcinoma (HCC), HCC risk in non-cirrhotic NAFLD received little attention. We aimed to develop and validate an HCC risk prediction model for non-cirrhotic NAFLD. A nationwide cohort of non-cirrhotic NAFLD patients in Korea was recruited to develop a risk prediction model and validate it internally (n = 409 088). A model using a simplified point system was developed by Cox proportional hazard model. K-fold cross-validation assessed the accuracy, discrimination and calibration. The model was validated externally using a hospital cohort from Asan Medical Center (n = 8721). An 11-point HCC risk prediction model for non-cirrhotic NAFLD was developed using six independent factors of age, sex, diabetes, obesity, serum alanine aminotransferase level and gamma-glutamyl transferase level (c-index 0.75). The average area under receiver operating curves (AUROCs) of the model was 0.72 at 5 years and 0.75 at 10 years. In the external validation cohort, the AUROCs were 0.79 [95% confidence interval [CI], 0.59-0.95] at 5 years and 0.84 (95% CI, 0.73-0.94) at 10 years. The calibration plots showed the expected risks corresponded well with the observed risks. Risk stratification categorized patients into the low (score 0-6), moderate (7, 8) and high (9-11; estimated incidence rate >0.2%/year) risk groups. A novel HCC risk prediction model for non-cirrhotic NAFLD patients was developed and validated with fair performance. The model is expected to serve as a simple and reliable tool to assess HCC risk and assist precision screening of HCC.

Identification of Comprehensive Biomarkers in Patients With Mismatch Repair-Deficient Colon Adenocarcinoma Based on Parallel Multiomics

Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer and other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, PCR-capillary electrophoresis is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline mismatch repair (MMR) mutations, the functional redundancy of the MMR system, and abnormal methylation of MutL Homolog 1 promoter. Therefore, this study aimed to develop new biomarkers for dMMR based on artificial intelligence (AI) and pathologic images, which may help to improve the detection accuracy. To screen for the differential expression genes (DEGs) in dMMR patients and validate their diagnostic and prognostic efficiency, we used the expression profile data from the Cancer Genome Atlas (TCGA). The results showed that the expression of Immunoglobulin Lambda Joining 3 in dMMR patients was significantly downregulated and negatively correlated with the prognosis. Meanwhile, our diagnostic models based on pathologic image features showed good performance with area under the curves (AUCs) of 0.73, 0.86, and 0.81 in the training, test, and external validation sets (Jiangsu Traditional Chinese Medicine Hospital cohort). Based on gene expression and pathologic characteristics, we developed an effective prognosis model for dMMR patients through multiple Cox regression analysis (with AUC values of 0.88, 0.89, and 0.88 at 1-, 3-, and 5-year intervals, respectively). In conclusion, our results showed that Immunoglobulin Lambda Joining 3 and nucleus shape–related parameters (such as nuclear texture, nuclear eccentricity, nuclear size, and nuclear pixel intensity) were independent diagnostic and prognostic factors, suggesting that they could be used as new biomarkers for dMMR patients.