Proportional Hazards Regression Analysis Research Articles

Impact of triglyceride-glucose index on the long-term prognosis of advanced gastric cancer patients receiving immunotherapy combined with chemotherapy

BACKGROUND Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of death worldwide. Despite advancements in immunotherapies, patient prognosis remains poor, necessitating the identification of key prognostic factors to optimize the treatment approaches. Insulin resistance, as indicated by the triglyceride glucose (TyG) index, is increasingly recognized for its impact on cancer progression and immune modulation, and its potential role in GC prognosis is of particular interest. AIM To investigate whether the TyG index, a surrogate marker of insulin resistance, can predict the prognosis of patients with advanced GC receiving immunotherapy combined with chemotherapy. METHODS This retrospective study included 300 patients with advanced GC who received sintilimab combined with chemotherapy. The patients were categorized into two groups according to high or low TyG index, and independent prognostic factors for overall survival (OS) were determined using Cox proportional hazards regression analysis, which led to the development of a nomogram model. RESULTS Of the included patients, 136 had a high TyG index and 164 had a low TyG index. The median progression-free survival of the high TyG index group was significantly longer than that of the low TyG index group. Similarly, the median OS of the high TyG index group was significantly longer than that of the low TyG index group. The objective response and disease control rates in the two groups were 18.38% vs 9.15% and 58.82% vs 46.95%, respectively. No significant difference was noted in the incidence of adverse reactions at any level between the two groups (P > 0.05). In multivariate analysis, the Eastern Cooperative Oncology Group score, programmed cell death ligand 1 expression, and TyG index acted as independent prognostic factors for OS. Of these factors, the hazard ratio of the TyG index was 0.36 (95% confidence interval: 0.36-0.55, P < 0.001), and the nomogram model re-emphasized its importance as the main predictor of patient prognosis, followed by programmed cell death ligand 1 expression and the Eastern Cooperative Oncology Group score. CONCLUSION The TyG index is a long-term predictor of the efficacy of immunotherapy combined with chemotherapy, and patients with a high index have a better prognosis.

Risk factors for distal stent graft-induced new entry after frozen elephant trunk procedure in chronic aortic dissection.

The frozen elephant trunk (FET) procedure has emerged as an effective single-stage treatment for complex aortic pathologies. However, it carries a risk of distal stent graft-induced new entry (dSINE) in patients with chronic aortic dissection (CAD). This study investigated risk factors associated with dSINE development. Between 2009 and 2021, 160 FET procedures were performed, including 48 cases of CAD (mean time from onset: 5.6 ± 3.8years). After excluding five patients due to incomplete 6-month postoperative computed tomography (CT) data, 43 patients were included. A multivariable stepwise Cox proportional hazards regression analysis was conducted to identify predictors of dSINE. During a mean follow-up period of 5.9 ± 3.9years, dSINE occurred in 22 of 43 patients (51.1%). Univariate analysis identified three significant risk factors for dSINE: total aortic diameter (TAD) > 45mm at the distal stent-graft level (HR 5.88, 95% CI 1.35-25.52, p = 0.018), True lumen (TL) perimeter-based diameter (HR 1.22, 95% CI 1.03-1.46; p = 0.021), and TL ovality (HR 1.31, 95% CI 1.04-1.65, p = 0.022). Multivariate analysis revealed TAD > 45mm as an independent risk factor for dSINE (HR 4.60, 95% CI 1.01-20.85, p = 0.048). The 5-year freedom from dSINE was significantly higher in patients with TAD ≤ 45mm compared to those with TAD > 45mm (87.5% vs. 20.8%, p < 0.01). Although FET remains an important therapeutic option for CAD, dSINE represents a significant postoperative complication. TAD > 45mm was identified as an independent risk factor. These findings may guide surgical planning for FET procedures.

Multiparameter body composition analysis on chest CT predicts clinical outcomes in resectable non-small cell lung cancer.

This study investigates the association between baseline CT body composition parameters and clinical outcomes in patients with resectable non-small cell lung cancer (NSCLC). Patients who underwent surgical resection for NSCLC between January 2006 and December 2017 were retrospectively enrolled in this multicenter study. Body composition metrics, including the area of skeletal muscle, intermuscular adipose tissue, subcutaneous adipose tissue, visceral adipose tissue, muscle radiodensity, and derivative parameters from five basic metrics mentioned before, were calculated based on preoperative non-contrast-enhanced chest CT images at L1 level. The Cox proportional hazards regression analysis was used to evaluate the association between body composition metrics and survival outcomes including overall survival (OS) and disease-free survival (DFS). A total of 2712 patients (mean age, 61.53 years; 1146 females) were evaluated. A total of 635 patients (23.41%) died. 465 patients (19.51%) experienced recurrence and/or distant metastasis. After multivariable adjustment, skeletal muscle index (SMI, HR = 0.86), intermuscular adipose index (IMAI, HR = 1.49), and subcutaneous adipose index (SAI, HR = 0.96) were associated with OS. Similar results were found after stratification by gender, TNM stage, and center. There was no significant association between all body composition metrics and DFS (all p > 0.05). The body composition metrics significantly enhance the model including clinicopathological factors, resulting in an improved AUC for predicting 1-year and 3-year OS, with AUC values of 0.707 and 0.733, respectively. SMI, IMAI, and SAI body composition metrics have been identified as independent prognostic factors and may indicate mortality risk for resectable NSCLC patients. Our findings emphasize the significance of muscle mass, quality, and fat energy storage in clinical decision-making for patients with non-small cell lung cancer (NSCLC). Nutritional and exercise interventions targeting muscle quality and energy storage could be considered for patients with NSCLC. Multiparameter body composition analysis is associated with the clinical outcome in NSCLC patients. Assessing muscle mass, quality, and adipose tissue helps predict overall survival in NSCLC. The quantity and distribution of body composition can contribute to unraveling the adiposity paradox.

Low transthyretin is associated with the poor prognosis of colorectal cancer

ObjectiveTo determine whether transthyretin (TTR) influences the prognosis of patients with colorectal cancers and establish a predictive model based on TTR.MethodsBetween January 2013 and February 2019, the clinical data of 1322 CRC patients aged from 18 years to 80 years who underwent surgical treatment were retrospectively analyzed. The preoperative TTR level, clinicopathological data, and follow-up data were recorded. The X-tile program was used to determine the optimal cut-off value. Cox proportional hazard regression analysis was conducted to evaluate the correlation between the TTR and the cumulative incidence of cancer-specific survival (CSS). Nomograms were then developed to predict CSS. Furthermore, an additional cohort of 377 CRC patients enrolled between January 2014 and December 2015 was included as an external validation.ResultsBased on the optimal cut-off value of 121.3 mg/L, we divided the patients into the TTR-lower group (&amp;lt;121.3 mg/L) and the TTR-higher group (≥121.3 mg/L). Comparative analysis revealed that the TTR-higher group exhibited a younger demographic, a higher prevalence of low colorectal cancers, an elevated R0 resection rate, superior differentiation, earlier stage and lower levels of carcinoembryonic antigen (CEA) in contrast to the TTR-lower group. The Cox multivariable analysis underscored the significance of TTR and various clinicopathological factors, encompassing age, tumor location, R0 resection status, differentiation grade, disease stage, postoperative chemoradiotherapy, and preoperative CEA levels, as substantial prognostic indicators. The postoperative survival nomogram, when internally and externally assessed, demonstrated commendable performance across multiple metrics, including the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). Compared with other models, the proportional hazards model combined with TTR demonstrates superior performance in terms of C-index, AUC, calibration chart, and DCA within the prognostic column chart.ConclusionsThe preoperative TTR was identified as a prognostic factor for predicting the long-term prognosis of CRC patients who underwent surgical treatment, supporting its role as a prognostic biomarker in clinical practice.

Comparative efficacy of cetuximab combined with FOLFOX or CAPEOX in first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer: a multicenter case-control study.

FOLFOX combined with cetuximab is a recommended first-line treatment regimen for RAS/BRAF wild-type metastatic colorectal cancer (mCRC). CAPEOX combined with cetuximab differs from the FOLFOX regimen by using oral capecitabine instead of continuous infusion of fluorouracil, offering greater convenience and cost-effectiveness with higher patient acceptance. However, the comparative efficacy of these two regimens remains debatable, necessitating further evidence to explore any differences in their efficacy. This study collected medical records of mCRC patients who were treated with CAPEOX or FOLFOX combined with cetuximab from 1 October 2021 to 16 October 2023 at Harbin Medical University Cancer Hospital and the First Hospital of Shanxi Medical University. Eligible patients were selected based on inclusion criteria and followed up through the hospital's follow-up system and telephone interviews. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were used to assess patients' progression-free survival (PFS) and overall survival (OS). A total of 71 eligible patients were enrolled in this study; 43 patients received CAPEOX combined with cetuximab (Group A, n = 43), and 28 patients received FOLFOX combined with cetuximab (Group B, n = 28). The two groups achieved similar median PFS (mPFS) and median OS (mOS), with mPFS of 18 months and 12 months, respectively (P = 0.23), and mOS of 33 months and 20 months, respectively (P = 0.21), with no statistically significant differences. The results of this study demonstrated that CAPEOX combined with cetuximab is an equally viable option for first-line treatment of RAS/BRAF wild-type mCRC as FOLFOX combined with cetuximab.

Growth differentiation factor-15 and N-terminal pro-BNP in acute heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) continues to be an increasingly common health problem associated with a high mortality rate. Elevated levels of Growth differentiation factor-15 (GDF15) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are reportedly associated with poor clinical outcomes in a broad range of cardiovascular diseases. The aim of the present study was to examine the effect of the combined assessment of these markers on clinical outcomes in patients with HFpEF. This study is the prospective observational study. We measured the serum levels of GDF15 and NT-proBNP in 643 patients (mean age 73±12, 42% females). All patients were prospectively followed up for a median period of 1998days. Total 132 HF-related events and 88 all-cause deaths occurred during the follow-up period. Multivariate Cox proportional hazards regression analysis demonstrated that both serum GDF15 and NT-proBNP levels were independently associated with HF-related events after adjustment for confounding risk factors (GDF15: hazard ratio, 1.72; 95% confidence interval, 1.35-2.19; P<0.0001 and NT-proBNP: hazard ratio, 1.63; 95% confidence interval, 1.25-2.13; P=0.0003). Serum GDF15 levels improved the prediction capacity for HF-related events (0.7405 vs. 0.7190; P=0.0422), with a significant net reclassification index (0.2724) and integrated discrimination improvement (0.0246). The C indices of GDF15 for HF-related events and all-cause deaths were significantly larger than those of NT-proBNP in men (HF-related events: 0.7389 vs. 0.6721; P=0.0393, and all-cause deaths: 0.6922 vs.0.6109; P=0.0262) but not in women. The combination of GDF15 and NT-proBNP levels stratified patients with HFpEF, identifying those at a high risk for HF-related events and all-cause deaths. Serum GDF15 could be an additional prognostic information to NT-proBNP in patients with HFpEF. The prognostic abilities of serum GDF15 and NT-proBNP differed according to sex. These markers were the feasible markers for patients with HFpEF, identifying those at a high risk for HF-related events and all-cause deaths.

Intubation Versus Tracheotomy Outcomes in Critically Ill COVID-19 Patients in Low-Resource Settings: What Do We Know?

Background: Patients undergoing prolonged mechanical ventilation commonly require tracheotomy. The main aim of this study was to evaluate the outcomes of tracheotomy for patients with acute respiratory distress syndrome (ARDS) associated with COVID-19 in low-resource settings. Methods: A retrospective, single-center, observational cohort study was performed on patients with ARDS associated with COVID-19. Patients who underwent intubation alone were compared with those who received both intubation and subsequent tracheotomy. The analysis included patient demographics, comorbidities, and outcomes. Results: Patients undergoing tracheotomy (n = 89) were compared with intubated patients (n = 622). The median time from intubation to tracheotomy was 10 days (IQR: 6–15 days). Overall, 608 patients (85.5%) died in the hospital. Thirty-seven patients (35.9%) in the survival group had tracheostomy compared with fifty-two patients (8.5%) in the non-survival group (p &lt; 0.001). The Kaplan–Meier curve shows a higher probability of survival in the tracheotomy group compared with the non-tracheotomy group (log-rank test: p &lt; 0.001). Tracheotomy was found to be independently associated with lower in-hospital mortality (HR = 0.16 [95% CI: 0.11–0.23], p &lt; 0.001) in the multivariable Cox proportional hazards regression analysis after adjusting for potential confounding factors. Furthermore, tracheotomy was associated with a higher cumulative incidence of being alive and off the ventilator at day 28 (SHR = 2.87 [95% CI: 1.88–4.38], p &lt; 0.001). Conclusions: Tracheotomy was associated with reduced in-hospital mortality and longer ventilator-free days.

Long-Term Clinical Relevance of Hyponatremia Identified During Acute Phase of Myocardial Infarction

Background/Objectives: Hyponatremia is associated with increased mortality in the general hospital population. We sought to investigate whether hyponatremia affects the long-term survival of patients following a myocardial infarction (MI) in both ST-segment elevation (STEMI) and non-ST elevation (NSTEMI) presentations. Methods: In this study, 862 MI patients who were hospitalized between 2012 and 2017 were retrospectively followed-up within the median time period of 41.9 [28.2–73.5] months. All participants were assigned to a hyponatremic or normonatremic group with hyponatremia defined as a sodium level of less than 135 mEq/L on admission. Results: In the acute phase of an MI, hyponatremia was diagnosed in 31 (3.6%) patients. The patients with hyponatremia were less often male (38.7 vs. 70.4%, p &lt; 0.001), and less frequently had Killip class I (63.3 vs. 80%) but more often had Killip class IV on admission (16.7 vs. 4.2%, p = 0.024) and more often had a history of impaired renal function (32.3 vs. 15.5%, p = 0.013) than those with normonatremia. Hyponatremic patients had higher troponin T levels on admission by 75.1% (p = 0.003), a higher isoenzyme MB of creatine kinase level by 34.4% (p = 0.006), and lower hemoglobin (by 8.5%, p = 0.001) levels as compared to the normonatremia group. Long-term mortality was significantly higher in the patients with hyponatremia versus normonatremia (18 [58.1%] vs. 243 [29.2%], log-rank p &lt; 0.001). This was driven by differences in the NSTEMI population (65 vs. 30.5%, p &lt; 0.001). By a Cox proportional hazard regression analysis, hyponatremia was associated with a higher long-term mortality (hazard ratio [HR] of 2.222, a 95% confidence interval [CI] of 1.309–3.773, and p = 0.003). Conclusions: Hyponatremia rarely identified in acute phase of MI was associated with higher long-term mortality, particularly in the NSTEMI population.

Prognosis of Fragment Reattachment in Anterior Crown Fractures: A Retrospective Study.

Although several studies have compared fragment attachment with resin build-ups in anterior crown fractures, none have specifically investigated the outcome of reattached fragments. This retrospective study aimed to evaluate long-term outcomes of fragment reattachment in anterior crown fractures and determine the prognostic affecting their success. We retrospectively analyzed clinical records of patients who underwent fragment reattachment for crown fractures in anterior teeth (maxillary and mandibular central and lateral incisors) between 2008 and 2023. All procedures were performed by experienced professors and residents following a standardized protocol. Kaplan-Meier survival curves and Cox proportional hazards regression analyses were performed to evaluate fragment retention outcomes and identify potential prognostic factors. Among 75 anterior crown fractures, the estimated fragment retention rates were 83.7% at 2 years, 75.2% at 5 years, and 56.4% at 10 years. Multivariate Cox regression analyses identified patient age and extent of crown fracture as significant factors affecting outcomes. The 5-year estimated fragment retention rates were 82.8% and 67.0% for uncomplicated and complicated crown fractures, respectively. Fragment reattachment remains a viable treatment option for anterior crown fractures. Treatment success decreased with patient age, and complicated crown fractures demonstrated lower retention rates than uncomplicated ones. Fragment reattachment can provide predictable outcomes in anterior crown fractures when cases are carefully selected, particularly considering the patient's age and the type of crown fracture.

Oral microbiome alpha diversity and all-cause, cardiovascular, and non-cardiovascular mortality in US adults: Evidence from the NHANES 2009-2019

Knowledge about the association between oral microbiome diversity within individuals and cardiovascular disease (CVD) and non-CVD mortality is scarce. Besides, variation by sex and racial and ethnic groups, and the potential mediators of these associations remain unclear. We aimed to investigate the associations of oral microbiome alpha diversity with all-cause, CVD, and non-CVD mortality, and the interaction effects of sex and racial and ethnic groups and potential mediators in the associations. The National Health and Nutrition Examination Survey (NHANES) is a population-based observational study, conducted periodically in Mexican American, Other Hispanic, Non-Hispanic (NH) White, NH Black, and other racial/ethnic participants. We linked 2009-12 survey data of 8199 adults to the mortality data until 2019. By analyzing RNA gene sequences from oral rinse samples, microbiome alpha diversity within individuals was assessed using operational taxonomic unit (OTU) richness. Potential mediators included obesity, diabetes mellitus, dyslipidemia, hypertension, and periodontitis. Multivariable Cox proportional hazards regression and causal mediation analysis were used. Baseline mean±standard deviation (SD) age was 42.1±15.1 years. Over a median follow-up of 9.1 years, 405 all-cause mortality occurred (CVD, 105; non-CVD, 300). Each 1-SD increment in OTU richness was inversely associated with all-cause mortality (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95), CVD mortality (HR, 0.92; 95% CI, 0.90-0.95), and non-CVD mortality (HR, 0.92; 95% CI, 0.90-0.95). With evidence of significant racial and ethnic groups-interaction (p <0.05), these associations were evident in Mexican American, NH White, and others racial/ethnic participants. None of the potential mediators significantly mediated the associations of OTU richness with all-cause, CVD, and non-CVD mortality. Lower oral microbiome alpha diversity is associated with higher risk for all-cause, CVD, and non-CVD mortality, and the associations are varied by racial and ethnic groups.

A comprehensive molecular and clinical study of patients with young-onset CRC.

235 Background: Young-onset colorectal cancer (YO-CRC), defined as colorectal cancer diagnosed in individuals under 50 years of age, has emerged as a distinct clinical entity, often presenting at advanced stages. Despite the increasing incidence, molecular and clinical underpinnings of YO-CRC remain underexplored. This study aims to characterize the clinical and molecular features of YO-CRC and to evaluate their impact on OS. Methods: We retrospectively reviewed 110 patients diagnosed with YO-CRCfrom our institution’s molecular database. All patients underwent next-generation sequencing. Demographic, clinical, and molecular data, including age, gender, race, tumor location, cancer stage, and mutation status (KRAS, NRAS, BRAF, POLE, ERBB-2/HER2, microsatellite status), were collected by reviewing electronic medical records. For OS analysis, we focused on patients diagnosed with de novo Stage 4. Cox proportional hazards regression and Kaplan-Meier survival analysis were utilized to assess the association of these factors with OS, with statistical significance determined by a p-value threshold of &lt;0.05. Results: Among 110 patients, N=44 (40%) presented with local disease (stage 1-3), while N=66 (60%) patients presented with de novo metastatic disease at the time of diagnosis. The median age at diagnosis was 44.5 years. The cohort consisted of 64% males and 36% females, with 84% of patients identified as White. Most tumors were left-sided (77%), including the distal colon/sigmoid (44%) and rectum (33%). KRAS and BRAF mutations were present 36% and 5.5%, respectively. ERBB-2/HER2 amplification and microsatellite instability were observed in 4.5% and 6.4% respectively. Tumor mutation burden (TMB) was &lt;10 in 57% of patients, with 14% having TMB &gt;20. CNV analysis revealed that 14% of patients had copy gains, 12% had concurrent gains/losses, and 31% had copy losses. Among the 66 Stage 4 patients, 44% had died by the time of analysis, with a median overall survival (OS) of 43.6 months (95% CI, 28.7 - not reached). KRAS mutation was found to be significantly associated with worse survival outcomes. Cox regression analysis reveals the prognostic significance of KRAS status, with a hazard ratio (HR) of 3.52 (95% CI: 1.59-7.76, P = 0.002 &lt; 0.05), indicating a significantly higher risk of death for KRAS-mutant YO-CRC patients. Conclusions: KRAS mutations are a key prognostic factor in YO-CRC, highlighting the need for therapeutic need to improve outcomes in this high-risk group.

The relationship between depression and cardiovascular disease in older people: results from a large-scale epidemiological cohort study in Japan.

Depression is known to be associated with a greater risk of developing cardiovascular disease (CVD) in middle-aged people. However, it is not certain how depression would influence incident CVD in older people aged ≥ 75years. We investigated the association between depression and CVD in older people. We analyzed 146,085 individuals aged ≥ 75years including 7581 individuals (5.2%) with depression registered in the DeSC database from April 2014 to November 2022. We excluded those with a prior history of CVD. The incidence of composite CVD events, comprising ischemic heart disease (IHD), heart failure, and stroke was documented. A Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HR) associated with the presence of depression. The median age was 79years and 41.0% were men. During the mean follow-up period of 3.4 ± 1.5years, 39,552 composite CVD events (IHD: n = 10,916; heart failure: n = 26,719; stroke: n = 13,090) were recorded. Multivariable Cox regression analyses showed that older individuals with depression had a greater risk of composite CVD events than those without (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.24-1.34). The HR (95% CI) of depression was 1.26 (1.17-1.37) for IHD, 1.25 (1.19-1.31) for heart failure, and 1.30 (1.21-1.39) for stroke, respectively. While considering the limitations of real-world data, we conducted multiple sensitivity analyses, which confirmed the results of the primary analysis. The presence of depression was independently associated with a greater risk of developing CVD even in older individuals.

The relationship between hypomagnesemia and ICU mortality in severe hemorrhagic stroke patients: an observational multicentre study on eICU database

BackgroundHemorrhagic stroke is a potentially fatal condition with high mortality and morbidity. However, there is a lack of evidence for this relationship in critically ill patients with hemorrhagic stroke. This study aims to explore the relationship between hypomagnesemia and ICU mortality in severe hemorrhagic stroke patients.MethodsThe study included 2,026 severe hemorrhagic stroke patients from the Electronic Intensive Care Unit Collaborative Study database, categorized into hypomagnesemia and non-hypomagnesemia groups based on serum magnesium levels. Primary outcome was ICU mortality. Secondary outcome was mechanical ventilation use. Multivariate Cox proportional hazards regression analyses were used to study the relationship between hypomagnesemia and the outcomes. We also performed a cumulative survival rate analysis by Kaplan–Meier curves.ResultsA total of 2,026 severe hemorrhagic stroke patients, aged over 16 and hospitalized in the ICU for more than 24 h, were enrolled. Among them, 277 (13.7%) died in the ICU, and hypomagnesemia was observed in 489 patients. Multivariable Cox regression analyses demonstrated that hypomagnesemia was related to a 28% increased risk of ICU mortality (HR 1.28, 95% CI [1.02–1.68], p = 0.035) and a 15% increased risk of mechanical ventilation use (HR 1.15, 95% CI [1.04—1.33], p = 0.010) in severe hemorrhagic stroke patients.ConclusionsOur findings suggested that hypomagnesemia is associated with increased risks of ICU mortality and mechanical ventilation use in severe hemorrhagic stroke patients. Future randomized, prospective studies are needed to elucidate the role of hypomagnesemia and explore potential interventions.

Vaccination against measles-mumps-rubella and rates of non-targeted infectious disease hospitalisations: Nationwide register-based cohort studies in Denmark, Finland, Norway, and Sweden.

To investigate if receipt of measles-mumps-rubella (MMR) vaccine following the third dose of diphtheria-tetanus-acellular pertussis (DTaP3) is associated with reduced rates of non-targeted infectious disease hospitalisations. Register based cohort study following 1,397,027 children born in Denmark, Finland, Norway, and Sweden until 2 years of age. Rates of infectious disease hospitalisations with minimum one overnight stay according to time-varying vaccination status were compared using Cox proportional hazards regression analysis with age as the underlying timescale and including multiple covariates. Summary estimates were calculated using random-effects meta-analysis. Compared with DTaP3 and no MMR vaccine, MMR after DTaP3 was associated with reduced rates of infectious disease hospitalisations: aHR was 0.86 (0.83-0.89) in Denmark, 0.70 (0.64-0.75) in Finland, 0.71 (0.68-0.74) in Norway, and 0.71 (0.65-0.77) in Sweden: summary estimate was 0.75 (0.65 to 0.84). A beneficial association was also seen in a negative control exposure analysis (3 vs. 2 DTaP doses): summary estimate aHR was 0.81 (0.75-0.87). Having MMR as the most recent vaccine was consistently associated with reduced rated of infectious disease hospitalization. However, bias may account for at least some of the observed association. Randomised controlled trials are warranted to inform the optimal timing of MMR for both its specific and potential non-specific effects.

Effect of homologous recombination deficiency on survival in patients with metastatic colorectal cancer with KRAS mutations.

252 Background: Metastatic colorectal cancer (mCRC) patients exhibit intertumoral genetic heterogeneity, making it difficult to apply precision medicine. In the molecular genetic profile of mCRC, there are relatively few other gene alterations that significantly impact treatment decisions beyond KRAS and MSI status. We aim to investigate the prognostic impact of Homologous recombination deficiency (HRD)-related genetic alterations in mCRC patients, focusing on how mutation status influences on patient outcomes. Methods: The analysis included 364 mCRC patients who underwent comprehensive genomic profiling at Korea University Anam Hospital from Sep. 2016 to Dec. 2020. HRD was defined by the presence of pathogenic variants in genes including ATM, ATR, BARD1, BRCA1/2, BRIP1, CDK12, CHEK2, FANCA, MRE11A, PALB2, RAD50/51. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate Cox proportional hazards regression analyses were performed to assess the independent impact of HRD status. Results: Of the total cohort, 181 of patients (49.78%) harbored KRAS mutations. HRD gene mutations were identified in 38 of patients (10.4%) of patients, predominantly in ATM, BRCA 1/2, ARID1A genes. KRAS-HRD co-mutations were present in 18 of patients (4.7%). There is no significant difference in HRD status between the KRAS mutant and wild-type groups (p=0.73). While first-line treatment PFS was independent of KRAS mutational status (wt 10.8 vs. mut 9.6 months, p=0.31), it was significantly associated with HRD gene mutation status (16.2 vs. 10.6 months, p=0.001). OS was similar with KRAS mutations (34.7 vs. 32.9 months, p=0.72) and HRD mutations (34.7 vs. 39.1 months, p=0.73). However, patients with both KRAS and HRD mutations had significantly worse OS compared to those with either KRAS and HRD mutation (21.3 vs. 36.7 vs. 65.3 months, p=0.034, &lt;0.001). A multivariate analysis was performed to evaluate factors affecting OS in mCRC patients. Among the variables, metastasectomy, which 44% of patients underwent, had a significantly low HR (=0.28) and would contributed to more favorable outcomes when evaluating OS. Neither KRAS nor HRD mutation alone was a significant prognostic factor, but their co-mutation was significantly associated with poor survival (HR=2.39, p=0.048). Conclusions: Poor OS in patients with KRAS-HRD co-mutations, despite metastasectomy, highlights the need for additional treatment strategies beyond surgery. Future studies with larger sample sizes and analyses stratified by metastasectomy status are necessary to strengthen these findings. Variables HR (95% CI) p-value Metastasis site Liver 2.16 (1.60 – 2.92) &lt; 0.001 Peritoneum 1.52 (1.01 – 2.11) 0.013 Bone 1.69 (0.96 – 2.97) 0.067 Metastasectomy 0.28 (0.47 – 0.74) &lt; 0.001 KRAS 1.03 (0.77 – 1.37) 0.826 HRD 0.75 (0.40 – 1.41) 0.367 Co-mutation 2.39 (1.01 – 5.66) 0.048

Prognostic significance of anti-gliadin and anti-F-actin immunoglobulin A antibodies in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a biliary disorder associated with a high risk of end‑stage liver disease and cholangiocarcinoma (CCA). Currently, prediction of unfavorable outcomes is hindered by a lack of valuable prognostic biomarkers. The aim of the study was to assess the prevalence of autoantibodies in PSC and define their potential use as the predictors of the disease progress and CCA in a large, prospective cohort of PSC patients. Enzyme‑linked immunosorbent assay was applied for detection of serum immunoglobulin (Ig) A anti‑gliadin antibodies at a concentration equal to or above 30 U and anti‑F‑actin antibodies at a concentration equal to or above 20 U in 624 patients with PSC and 305 healthy controls. Poor PSC outcomes were defined as liver transplantation or / and liver disease‑related death, that is, transplantation‑free survival, and CCA. Anti‑gliadin and anti‑F‑actin IgA antibodies were more frequent in the PSC patients than in the healthy controls (P <0.001 for both). The autoantibodies were associated with laboratory indices of the liver disease severity, including the model of end‑stage liver disease score, and anti‑F‑actin was associated with cirrhosis (P <0.001). During a median (interquartile range) follow‑up of 18.5 (8-33) months, 17.2% patients were transplanted, 4.6% died due to their liver disease, and 5.2% were diagnosed with CCA. Associations between anti‑F‑actin and anti‑gliadin and a shorter transplantation‑free survival (P <0.001 for both) were found. In the multivariable Cox proportional hazards regression analysis anti‑gliadin was an independent predictor of poor survival. No association between the analyzed antibodies and the incidence of CCA was detected. Anti‑gliadin and anti‑F‑actin IgA identify the subgroup of PSC patients with a more severe disease and at a risk of shortened transplantation‑free survival.

Comparison of 3 Aging Metrics in Dual Declines to Capture All-Cause Dementia and Mortality Risk: Cohort Study.

The utility of aging metrics that incorporate cognitive and physical function is not fully understood. We aim to compare the predictive capacities of 3 distinct aging metrics-motoric cognitive risk syndrome (MCR), physio-cognitive decline syndrome (PCDS), and cognitive frailty (CF)-for incident dementia and all-cause mortality among community-dwelling older adults. We used longitudinal data from waves 10-15 of the Health and Retirement Study. Cox proportional hazards regression analysis was employed to evaluate the effects of MCR, PCDS, and CF on incident all-cause dementia and mortality, controlling for socioeconomic and lifestyle factors, as well as medical comorbidities. Discrimination analysis was conducted to assess and compare the predictive accuracy of the 3 aging metrics. A total of 2367 older individuals aged 65 years and older, with no baseline prevalence of dementia or disability, were ultimately included. The prevalence rates of MCR, PCDS, and CF were 5.4%, 6.3%, and 1.3%, respectively. Over a decade-long follow-up period, 341 cases of dementia and 573 deaths were recorded. All 3 metrics were predictive of incident all-cause dementia and mortality when adjusting for multiple confounders, with variations in the strength of their associations (incident dementia: MCR odds ratio [OR] 1.90, 95% CI 1.30-2.78; CF 5.06, 95% CI 2.87-8.92; PCDS 3.35, 95% CI 2.44-4.58; mortality: MCR 1.60, 95% CI 1.17-2.19; CF 3.26, 95% CI 1.99-5.33; and PCDS 1.58, 95% CI 1.17-2.13). The C-index indicated that PCDS and MCR had the highest discriminatory accuracy for all-cause dementia and mortality, respectively. Despite the inherent differences among the aging metrics that integrate cognitive and physical functions, they consistently identified risks of dementia and mortality. This underscores the importance of implementing targeted preventive strategies and intervention programs based on these metrics to enhance the overall quality of life and reduce premature deaths in aging populations.

Reassessing the Role of Low PSA in Prognosis Across Grades of Prostate Cancer: A Cohort Study.

Prior studies have concentrated exclusively on how different prostate-specific antigen (PSA) levels affect the prognosis of high-grade prostate cancer (PCa), often overlooking the prognosis of low-grade PCa. The present cohort study included individuals diagnosed with PCa from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2021. The all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) for each treatment group was calculated stratified by the four PSA levels (≤ 4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL). Fine and Gray competing-risks analyses were conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Cox proportional hazards regression analyses using PSA as a continuous variable with restricted cubic splines (RCS) were conducted to allow for potential nonlinear relationships. This study encompassed 416,825 male patients diagnosed with PCa. Compared to individuals with PSA value between 4.1 and 10.0 ng/mL, a significant association between low levels of PSA (≤ 4.0 ng/mL) and an increased risk of ACM (AHR = 1.15, 95% CI: 1.12-1.19; p < 0.001) and PCSM (AHR = 1.49, 95% CI: 1.38-1.61; p < 0.001) was observed. Additionally, the increased risk of ACM (AHR = 1.35, 95% CI: 1.29-1.40; p < 0.001) and PCSM (AHR = 1.84, 95% CI: 1.67-2.02; p < 0.001) are more pronounced within the first 5 years post-diagnosis. In most subgroups, similar results were observed. The RCS curves further corroborated the correlation between PSA value and the risk of mortality. Low PSA levels are notably linked to a heightened risk for both ACM and PCSM, irrespective of the grade of PCa being high or low. There is a need to initiate new studies that tackle novel diagnostics and therapeutics.

Prognostic scores for predicting overall survival in patients with metastatic renal and urothelial cancer undergoing immunotherapy - which one to use?

PurposeEvaluation of the prognostic significance of four different scoring systems in a real-world cohort of patients with metastatic urothelial carcinoma (mUC) or renal cell carcinoma (mRCC) undergoing immunotherapy (IO).MethodsFor 120 patients with mUC (n = 67) and mRCC (n = 53) who received IO between July 2016 and December 2020 at the tertiary Urological University Medical Centre Mannheim, the following scores were recorded at pre-treatment baseline: modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER). Overall survival (time between the beginning of IO until the patients’ death or last contact) was determined for every patient.ResultsKaplan-Meier analyses revealed that high baseline mGPS, SII (> 979) and NLR (> 3) were associated with poor overall survival (OS) (p < 0.05). Cox proportional hazards regression analyses showed that baseline mGPS and NLR had a significant independent prognostic influence on OS (p < 0.05), of which mGPS had a greater significance (p < 0.001, mGPS Score 2 vs. Score 0: HR 4.1, 95% CI 1.9–8.8). Although a high baseline NER (63.9) was associated with poor OS, it did not reach statistical significance. Baseline NER was also not identified as a significant score in the regression analyses.ConclusionmGPS, SII and NLR are scoring systems that are easy to record in routine clinical practice. As they provide good prediction of OS in patients with mUC and mRCC under IO, they may allow identification of patients at high-risk and monitor them more cautiously in addition to imaging.

Association of healthy sleep patterns with incident sepsis: a large population-based prospective cohort study

BackgroundThe role that sleep patterns play in sepsis risk remains poorly understood.ObjectivesThe objective was to evaluate the association between various sleep behaviours and the incidence of sepsis.MethodsIn this prospective cohort study, we analysed data from the UK Biobank (UKB). A total of 409,570 participants who were free of sepsis at baseline were included. We used a composite sleep score that considered the following five sleep behaviours: sleep chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Cox proportional hazards regression analysis was used to estimate the associations between healthy sleep scores and incident sepsis.ResultsDuring a mean follow-up of 13.54 years, 13,357 (3.26%) incident sepsis cases were recorded. Among the 409,570 participants with a mean age of 56.47 years, 184,124 (44.96%) were male; 9942 (2.43%) reported 0 to 1 of the five healthy sleep behaviours; 46,270 (11.30%) reported 2 behaviours; 115,272 (28.14%) reported 3 behaviours; 150,522 (36.75%) reported 4 behaviours; and 87,564 (21.38%) reported 5 behaviours at baseline. Each one-point increase in the sleep score was associated with a 5% lower risk of developing sepsis (hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.93–0.97). Compared with a healthy sleep score of 0–1, for a sleep score of 5, the multivariate-adjusted HR (95% CI) for sepsis was 0.76 (0.69–0.83). In addition, we found that the negative correlation was stronger in participants who were aged < 60 years than in their older counterparts (p for interaction < 0.001). However, healthy sleep pattern was not associated with sepsis-related death and critical care admission.ConclusionsFindings from this cohort study suggest that a healthy sleep pattern may reduce the risk of developing sepsis, particularly among younger individuals.