Cox Proportional Hazards Analysis Research Articles

General anaesthesia compared to conscious sedation for first-time atrial fibrillation catheter ablation-a Danish nationwide cohort study.

Catheter ablation (CA) is a well-established treatment option for atrial fibrillation (AF), where sedation and analgesia are pivotal for patient comfort and lesion formation. The impact of anaesthesia type on AF recurrence rates remains uncertain. This study aimed to examine AF recurrence rates depending on conscious sedation (CS) vs. general anaesthesia (GA) during CA. Utilizing nationwide data from the Danish healthcare registries, we conducted this cohort study involving adults (≥18 years) undergoing first-time CA for AF between 2010 and 2018. Patients were categorized by anaesthesia type (CS or GA), with the primary endpoint being AF recurrence, defined by a composite endpoint of either antiarrhythmic drug (AAD) prescriptions, AF-related hospital admissions, electrical cardioversions, or AF re-ablation. The impact of anaesthesia type was evaluated using multivariable Cox proportional hazards analysis. The study cohort comprised 7957 (6421 CS and 1536 GA) patients. Persistent AF, hypertension, and heart failure, as well as use of AAD, were more prevalent in the GA group. Cumulative incidences of recurrent AF were higher in the CS group at 1 (46% vs. 37%) and at 5 (68% vs. 63%) years. Multivariate analysis revealed CS as significantly associated with increased risk of AF recurrence at 5-year follow-up [hazard ratio 1.26 (95% confidence interval 1.15-1.38)], consistent across paroxysmal and persistent AF subtypes. This nationwide cohort study suggests a higher risk of AF recurrence with CS during CA compared to GA. These results advocate for considering GA as the preferred anaesthesia type for improved CA outcomes.

Gene Expression Changes Associated With Recurrence After Gross Total Resection of Newly Diagnosed World Health Organization Grade 1 Meningioma.

Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a "low-risk" group, but some low-risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression values in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence. This was a retrospective, international, multicenter cohort study that included WHO grade 1 meningiomas that underwent GTR, as first treatment, based on postoperative magnetic resonance imaging. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low-risk meningiomas. In total, 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. The median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence was 90.5%, and median time to recurrence was 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. Of these genes, PGK1 had the largest effect size. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low-risk meningiomas with significant differences in local freedom from recurrence (hazard ratio 2.5, 95% CI 1.2-5.1, P = .016). Gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

Addressing the Neck: An NCDB Study of Clinically Node-Negative Supraglottic Squamous Cell Carcinoma.

Identify the proportion of patients undergoing elective neck dissection (END) in surgically managed supraglottic squamous cell carcinoma (SCCa), assess associations between patient, tumor, and treatment factors with END, and assess associations between neck management and overall survival (OS). Retrospective study. National Cancer Database (NCDB) 2019 Participant User File. Patients with previously untreated, clinically node-negative (cN0) supraglottic SCCa treated with partial laryngectomy were queried from NCDB. Patients without known neck management and who underwent total laryngectomy were excluded. Patient and tumor factors associated with END were evaluated by logistic regression analysis. Univariable Cox proportional hazard analysis was used to examine associations between patient factors and OS, and factors with P < .05 were included on multivariable analysis. A total of 1352 patients met eligibility criteria. Eight hundred eleven (60%) patients had END performed with occult nodal metastasis identified in 177 (22%) patients. END was more likely to be performed at academic centers than nonacademic centers (odds ratio: [1.66], 95% confidence interval [CI]: 1.32-2.09, P < .001). On multivariable analysis, patients who underwent adjuvant radiation had worse OS (hazard ratio [HR]: 1.45, 95% CI: 1.13-3.29, P = .017). END was associated with improved OS overall on univariable analysis (HR: 0.83, 95% CI: 0.69-0.98, P = .026), but not on multivariable analysis. In this NCDB study, 22% of cN0 supraglottic SCCa patients had occult nodal metastatic disease. Despite this, 40% of patients do not receive END at the time of primary resection. Patients who receive END for supraglottic SCCa are more likely to avoid adjuvant radiation without impacting OS.

Concomitant sarcopenia and undernutrition: Impact on clinical outcomes in patients undergoing hemodialysis

BackgroundSarcopenia and undernutrition are crucial in the cycle of frailty in patients requiring hemodialysis therapy, and their deleterious clinical consequences are well documented. However, little attention has been directed towards examining their combined impact on clinical outcomes. ObjectiveThis study aimed to elucidate the effects of concomitant sarcopenia and undernutrition on clinical outcomes in patients undergoing hemodialysis. MethodsThis prospective cohort study recruited outpatients undergoing hemodialysis from four facilities. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia, 2019. Undernutrition was determined using the Geriatric Nutritional Risk Index, with a score of < 92 classified as undernutrition. Patients were classified into four groups according to the presence or absence of sarcopenia and undernutrition. Cox proportional hazards analysis was used to assess the independent association between concomitant sarcopenia and undernutrition, all-cause mortality, and cardiovascular (CV) events after adjusting for baseline characteristics. ResultsWe included 450 patients in this analysis. Of the 450 patients, 69 (15.3%) had concomitant sarcopenia and undernutrition. The mean follow-up period was 1,067 days, and there were 61 deaths and 60 CV events. The cumulative survival rate was significantly lower in the sarcopenia with undernutrition group (P=0.011). The overlap of sarcopenia and undernutrition was significantly associated with a risk of mortality (hazard ratio 2.10; 95% confidence interval 1.05-4.21; P=0.037). However, no association was observed between the co-occurrence of sarcopenia and undernutrition and the risk of CV events. ConclusionsConcomitant sarcopenia and undernutrition were significantly associated with an increased mortality risk among patients undergoing hemodialysis. This finding reaffirms the importance of managing sarcopenia and undernutrition in patients undergoing hemodialysis in daily clinical practice.

Impact of pharmacist-driven antimicrobial stewardship interventions in a secondary care facility in Japan: A pragmatic quasi-experimental study

BackgroundEfforts to promote antimicrobial stewardship aimed at reducing antimicrobial resistance are necessary regardless of hospital scale owing to delays in new antimicrobial development. We aimed to evaluate the effects of pharmacist-driven interventions on broad-spectrum antimicrobial usage and the prognosis of patients with bacteremia in a medium-sized hospital lacking infectious disease physicians and a microbiology laboratory. MethodsThis single-center, retrospective, pragmatic, quasi-experimental study was conducted to compare pre- and post-intervention effects at Saiseikai Futsukaichi Hospital. We analyzed the days of therapy (DOT) for carbapenems and days of antibiotic spectrum coverage (DASC) for antimicrobials using an interrupted time series analysis. Cox proportional hazards analysis was performed to assess 30-day mortality using propensity score and inverse probability of treatment weighting in patients with bacteremia. ResultsPharmacist-driven interventions significantly reduced the DOT (incidence rate ratio [IRR]: 0.53, 95 % confidence intervals [CI]: 0.33−0.81, p = 0.003) and DASC (IRR: 0.87, 95 % CI: 0.78−0.97, p = 0.016). The 30-day mortality due to bacteremia did not significantly differ between pre- and post-intervention in all patients (adjusted hazard ratio [HR]: 0.92, 95 % CI: 0.56−1.51, p = 0.74). Conversely, pharmacist-driven interventions significantly reduced the 30-day mortality owing to bacteremia with Pitt bacteremia score (PBS) ≥4 (adjusted HR: 0.52, 95 % CI: 0.28−0.99, p = 0.047). ConclusionsPharmacist-driven interventions may represent a valuable approach for optimizing antimicrobial treatment and improving prognosis, especially in patients with PBS ≥4, which will potentially benefit patients in similar healthcare environments facing challenges related to antimicrobial stewardship and patient prognosis.

Optimal Medical Therapy and Outcomes Among Patients With Chronic Heart Failure With Reduced Ejection Fraction

BackgroundOptimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF. ObjectivesThe purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups. MethodsCHAMP-HF (Change the Management of Patients with Heart Failure) included U.S. outpatients with chronic HFrEF receiving ≥1 GDMT. OMT subgroups were defined as suboptimal (score <3), acceptable (score = 3), and optimal (score ≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates. ResultsThe authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P < 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95% CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95% CI: 0.65-0.96) than those with suboptimal treatment. ConclusionsAcross a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death.

Non-adherence to recommended adjuvant radiation after total laryngectomy

ObjectivesInvestigate trends and associated factors in guideline adherence to adjuvant radiation therapy in locally advanced laryngeal and hypopharyngeal cancer after primary total laryngectomy (TL). MethodsPreviously untreated, non-metastatic patients who underwent TL for pathologic T4 larynx or hypopharynx squamous cell carcinoma (SCC) were queried using the National Cancer Database (NCDB). Patients were excluded if they had regional or distant metastasis or positive margins. Patient characteristics were evaluated for association with non-adherence to adjuvant radiation by logistic regression analysis. Association between non-adherence and overall survival (OS) was investigated by Cox proportional hazard analysis. ResultsAmong 2823 eligible T4 N0 patients, 841 (29.8 %) did not receive adjuvant radiation. Associated factors include increasing age, a Charlson Comorbidity Index of 2, greater per-mile distance to treatment center, and treatment at an academic cancer center. Delivery of adjuvant radiation was associated with improved OS on multivariable (HR 0.82, 95 % CI 0.72–0.93) analysis. ConclusionsWithin the NCDB, non-adherence to adjuvant radiation treatment after TL for pathologically T4 N0 larynx and hypopharynx SCC is common. Older patients with more comorbidities and greater travel distance may be at higher risk for non-adherence. Treatment at an academic cancer center is associated with non-adherence to recommended adjuvant radiation. Lack of adjuvant radiation is associated with worse overall survival.

Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study

Functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg)-seroconversion. We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients, who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg-seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per perperson-year, and increased to 0.96% per person-year after HBeAg-seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg-seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazard analysis of the cohort revealed that HBeAg-seroconversion at < 18 years of age, high genetic barrier nucleos(t)ide analogue(s) therapy before HBeAg-seroconversion, and a serum HBsAg titer < 1,000 IU/mL at 18 months after HBeAg-seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg-seroconversion in childhood, high genetic barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg-seroconversion were significant predictors of functional cure.

Recompensation of Chronic Hepatitis C-related decompensated cirrhosis following direct-acting antiviral therapy: Prospective Cohort study from an HCV elimination program.

Background and AimsChronic hepatitis C(CHC) related decompensated cirrhosis is associated with lower SVR-12 rates and variable regression of disease severity following direct-acting antiviral agents (DAAs). We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. MethodsBetween July 2018-July 2023, patients with decompensated CHC-related cirrhosis post DAAs treatment, were evaluated for SVR-12 and then had 6-monthly follow-up. ResultsOf 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2±11.5 years,63% men, MELD-Na:16.5± 4.6,87% genotype 3) were enrolled. SVR-12 was 81.8% after one course; ultimately SVR was 90.8% following additional treatment. Decompensation events included ascites (1098,95.3%), hepatic encephalopathy (191,16.6%), and variceal bleeding (284,24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284(24.7%) at a median time of 16.5(IQR-14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin(aHR-0.6,95%CI-0.5-0.8,P<0.001), INR(aHR-0.2,95%CI:0.1-0.3,P<0.001), absence of large esophageal varices(aHR-0.4,95%CI:0.2-0.9,P=0.048), or gastric varices (aHR-0.5,95%CI:0.3-0.7,P=0.022) predicted recompensation. Portal hypertension (PHT) progressed in 158(13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR-1.6,95%CI:1.2-2.8, P=0.042), and presence of large varices (aHR-2.9,95%CI:1.3-6.5,P<0.001) were associated with PHT progression. Further decompensation was seen in 221(19%);145 patients died and 6 underwent liver transplant. A decrease in MELDNa of ≥3 was in 409(35.5%) and a final MELDNa score of <10 was in 335(29%), but 2.9% developed HCC despite SVR-12. ConclusionsSVR-12 in HCV-related decompensated cirrhosis in a predominant genotype 3 population, led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and HCC developed in 2.9% of patients.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. In this prospective community-based cohort, participants with normal kidney function were analysed (N=5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. The participants' mean age was 57.2±8.3years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] μg/ng, P<0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI<23.0kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI≥23.0kg/m2 and those without sarcopenia. A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI<23.0kg/m2 and sarcopenia.

Gender-Dependent Association of Pulmonary Hypertension with Adverse Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement.

The relationship between pulmonary hypertension (PH) and outcomes after transcatheter aortic valve replacement (TAVR) has been shown to be unfavorable. The impact of gender on TAVR outcomes remains controversial. There have been no studies evaluating the simultaneous effects of both factors on TAVR outcomes. We retrospectively analyzed a prospective cohort of patients who underwent TAVR between January 2016 and December 2022. The patients were stratified by gender and the presence of PH. The primary outcome of the study was all-cause mortality. Secondary outcome was a composite of all-cause mortality and heart failure hospitalization. We identified a total of 133 female patients without PH, 179 males without PH, 87 females with PH, and 122 males with PH. The median follow-up period was 18 months. Female patients without PH demonstrated a lower cumulative mortality rate compared to those with male gender and/or PH. Adjusted multivariate Cox proportional hazard analyses revealed that male gender and PH status, either individually or in combination, were independently associated with long-term mortality when compared to female patients without PH. Specifically, females with PH (HR 6.80, 95% confidence interval (CI): 1.49-31.12, P=0.013), males without PH (HR 6.45, 95% CI: 1.47-28.22, P=0.013), and males with PH (HR 7.2, 95% CI: 1.63-31.81, P=0.009) demonstrated significantly higher risk for mortality. Patients who were male or had PH status had a higher risk of mortality. However, there was no synergistic effect between being male and having PH on the prognosis after TAVR.

Prognostic Impact of Sarcopenia Assessed Using Modified Asian Working Group for Sarcopenia 2019 Criteria in Heart Failure

BackgroundSarcopenia is a substantial therapeutic target, yet the validity of risk stratification values per the latest Asian Working Group for Sarcopenia in 2019 (AWGS 2019) remains unconfirmed in patients with heart failure. We hypothesized that using the 6-minute walk test (6MWT) to assess physical performance improves risk stratification. MethodsThe study included 832 hospitalized patients with heart failure who could walk at discharge. Sarcopenia was diagnosed using both the original AWGS 2019 criteria (AWGS 2019 model) and an alternative method in which physical performance components were replaced with the 6MWT (modified model). An < 300 m 6MWT indicated low physical performance in the modified model. The primary outcome was 2-year mortality. ResultsSarcopenia and severe sarcopenia were identified in 45 and 150 patients with the AWGS 2019 model and in 75 and 108 patients with the modified model, respectively. Over the 2-year follow-up period, 145 (17.4%) deaths occurred. Adjusted Cox proportional hazard analysis showed both sarcopenia and severe sarcopenia were significantly associated with 2-year mortality in the modified model. In the AWGS 2019 model, only severe sarcopenia was significantly related to 2-year mortality. The modified model demonstrated significant net reclassification improvement (NRI) over the AWGS 2019 model (NRI, 0.396; 95% CI, 0.214-0.578; P < 0.001). ConclusionsIn patients with heart failure who were ambulatory at discharge, sarcopenia assessment with the modified AWGS 2019 model using the 6MWT as a physical performance component improved risk stratification compared with the original AWGS 2019 model. Reconsidering the current criteria to improve risk stratification is necessary to ensure timely, appropriate treatment. Clinical Trial RegistrationUMIN000023929

The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.

To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart. Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R. Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59). When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression.

Five-Repetition Sit-to-Stand Test as Predictor of Mortality in High Risk COPD Patients

ObjectiveTo determine if adding performance on the five-repetition sit-to-stand test (5-STS) to chronic obstructive pulmonary disease (COPD) high-risk criteria, proposed by the Spanish COPD guidelines (GesEPOC), affects mortality prognosis. MethodsObservational study of COPD outpatients involved prospective follow-up for 5 years. Patients were classified based on 5-STS performance and risk criteria proposed by GesEPOC version 2021. Outcome measures were 5-year mortality timing and rate. Kaplan–Meier curves and univariate and multivariate Cox proportional-hazard analyses, analysis of variance, and univariate and multivariate linear and logistic regression models were used. ResultsOne hundred and thirty-seven patients were included. Mean age was 66±8.3 years, and 87.6% were men. Of them, 115 (83.9%) were classified as high risk, 43 (34.4%) of whom had poor performance on the 5-STS. Overall mortality at 5 years was 27% and was significantly higher in the high-risk (29.6%) compared with the low-risk (13.6%) group. Among high-risk patients, mortality at 5 years was significantly worse with poor 5-STS performance (60.5%) compared with non-poor performance (11.1%). Poor performance on the 5-STS was independently associated with increased 5-year mortality risk (HR 4.70; 95% CI: 1.96–11.27) in a model adjusted for history of heart disease and dyspnea. ConclusionAmong high-risk COPD patients, those with poor performance on the 5-STS have a significantly higher mortality at 5 years than those with non-poor 5-STS performance.

Machine learning-derived prognostic signature for progression-free survival in non-metastatic nasopharyngeal carcinoma.

Early detection of high-risk nasopharyngeal carcinoma (NPC) recurrence is essential. We created a machine learning-derived prognostic signature (MLDPS) by combining three machine learning (ML) models to predict progression-free survival (PFS) in patients with non-metastatic NPC. A cohort of 653 patients with non-metastatic NPC was divided into a training (n = 457) and validation (n = 196) dataset (7:3 ratio). The study included clinicopathological characteristics, hematologic markers, and MRI findings in three machine learning models-random forest (RF), extreme gradient boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO)-to predict progression-free survival (PFS). A Venn diagram identified the overlapping signatures from the three ML algorithms. Cox proportional hazard analysis determined the MLDPS for PFS. The RF, XGBoost, and LASSO algorithms identified six consensus factors from the 33 signatures. Cox proportional hazards analysis showed that the MLDPS includes age, lymphocyte count, number of positive lymph nodes, and regional lymph node density. Additionally, MLDPS effectively stratified prognosis, with low-risk individuals showing better PFS than high-risk individuals (p < 0.001). MLDPS, based on clinicopathological characteristics, hematologic markers, and MRI findings, is crucial for guiding clinical management and personalizing treatments for patients with non-metastatic NPC.

Outcome 1 year after ICH: Data from the Tranexamic acid for IntraCerebral Haemorrhage 2 (TICH-2) trial.

The Tranexamic acid for IntraCerebral Haemorrhage-2 (TICH-2) trial reported no significant improvement in death and dependency at day 90 despite reductions in haematoma expansion, early neurological deterioration and early death. However, significant recovery after stroke, particularly intracerebral haemorrhage (ICH), may take more than 3 months. Here we report the participant outcomes at 1 year after stroke. TICH-2 was a prospective randomised controlled trial that tested the efficacy and safety of tranexamic acid in spontaneous ICH when given within 8 h of onset. Patients with ICH on anticoagulation were excluded. Centralised blinded telephone follow up was performed for patients from the United Kingdom at 1 year. The primary outcome was modified Rankin Scale at 1 year. Secondary outcomes included Barthel index, Telephone Interview Cognitive Status-modified, EuroQoL-5D and Zung Depression Scale. This was a prespecified secondary analysis of the TICH-2 trial. About 2325 patients were recruited into the trial (age 68.9 ± 13.8 years; 1301 male, 56%). About 1910 participants (82.2%) were eligible for day 365 follow up. 57 patients (3.0%) were lost to follow up. Tranexamic acid did not reduce the risk of poor functional outcome at 1 year (adjusted OR 0.91 95% CI 0.77-1.09; p = 0.302). However, Cox proportional hazard analysis revealed significant survival benefit in the tranexamic acid group (adjusted HR 0.83, 95% CI 0.70-0.99; p = 0.038). There was no difference in functional outcome at 1 year after ICH. Tranexamic acid may reduce mortality at 1 year without an increase in severely dependent survivors. But this should be interpreted with caution as this is a result of secondary analysis in a neutral trial.

Elevated resting heart rate is associated with mortality in patients with chronic kidney disease

A higher heart rate is recognized as an independent risk factor for all-cause mortality and cardiovascular events in the general population. However, the association between elevated heart rate and clinical adverse outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD) has not been sufficiently investigated. A total of 1353 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between resting heart rate and clinical adverse outcomes using Cox proportional hazards analysis. The primary outcome of the present study was all-cause mortality, with cardiovascular events as the secondary outcome. Participants were stratified into four groups based on resting heart rate levels at baseline (heart rate < 70/min, ≥ 70 and < 80/min, ≥ 80 and < 90/min, and ≥ 90/min). During the median observation period of 4.9 years, 123 participants died, and 163 cardiovascular events occurred. Compared with the reference level heart rate < 70/min group, the adjusted hazard ratios (HRs) for all-cause mortality were 1.74 (1.05–2.89) and 2.61 (1.59–4.29) for the heart rate ≥ 80 and < 90/min group and heart rate ≥ 90/min group, respectively. A significantly higher risk of cardiovascular events was observed in the heart rate ≥ 80/min and < 90/min group (adjusted HR 1.70, 1.10–2.62), but not in the heart rate ≥ 90/min group (adjusted HR 1.45, 0.90–2.34). In patients with non-dialysis-dependent CKD, a higher resting heart rate was associated with increased all-cause mortality.

The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score-Matched Study.

Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.

Tumour budding, MELF-pattern and tumour-infiltrating lymphocytes as possible pathomorphological parameters of the course of endometrioid adenocarcinoma of the uterine corpus

Aim. To evaluatethe role tumour budding (TB), MELF-pattern and tumour-infiltrating lymphocytes (TILs) as possible prognostic factors of endometrioid adenocarcinoma of the uterine corpus.Materials and methods. A single-centre, retrospective, observational study was conducted involving 188 patients with endometrioid adenocarcinoma of the uterine body. 40 patients who had disease recurrence or died directly from progression of endometrioid adenocarcinoma of the uterine body were the unfavourable outcome group, 148 patients without progression and death from this tumour were the favourable outcome group. Fisher, Yates exact two-sided criteria were used to analyze the data. Survival analysis was performed using log-rank test. The hazard ratio (HR) and its 95 % confidence interval (CI) were estimated using single-factor analysis with log-rank test and multivariate Cox proportional hazards analysis. p &lt;0.05 was considered statistically significant.Results. TB was observed predominantly in the group of patients with unfavourable outcome (р &lt;0.0001) Survival analysis revealed statistically significant decreased survival in cases with TB (HR 5.3; 95 % CI 2.2–12.7; р &lt;0.0001). MELF-pattern was statistically significantly more frequent in the group of patients with unfavourable outcome (р &lt;0.0001), a decreased survival of patients was observed in the presence of MELF-pattern (HR 5.8; 95 % CI 2.1–16.2; р &lt;0.0001). Comparison of groups according to the number of TILs revealed statistically significant differences (р = 0.0242). When analyzing survival relative to the threshold value of the number of TILs, statistically significant differences were also observed (HR 3.7; 95 % CI 1.7–7.9; р = 0.021). Multivariate Cox proportional hazards analysis revealed that only TB and MELF-pattern had prognostic significance for recurrence-free survival (HR 3.7; 95 % CI 1.8–7.4; р &lt;0.001).Conclusion. TB and MELF-pattern are specific changes in the stroma of endometrioid adenocarcinoma stroma of the uterine corpus that can be used as pathomorphological predictors of clinical outcome.

High antinuclear antibody titer is associated with increased mortality risk in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a diagnosis of exclusion, requiring that potential etiologies of interstitial lung disease be ruled out. Antinuclear antibody (ANA) testing is commonly performed in individuals with IPF, but the clinical significance of ANA positivity remains uncertain. A retrospective search identified 161 patients diagnosed with IPF between May 2010 and January 2021. Data on ANA titers at the time of diagnosis were available in all cases. Mean age of the patients was 66.4 ± 9.6 years; 70.8% were male. ANA titers were high (≥ 1:160) in 25.4% of the cohort. Baseline characteristics were comparable between those with high and low ANA titers. During follow-up (median 28 months), 93 patients (57%) died. On Cox proportional-hazards analysis with lung transplantation entered as a competing risk and adjusting for potential confounders (age, sex, and baseline forced vital capacity and diffusing lung capacity for carbon monoxide), ANA ≥ 1:160, as a dichotomized variable, was significantly associated with case-specific mortality (HR 2.25, 95% CI 1.14−4.42, P = 0.02) and older age (for each 10-year increment, HR 1.55, 95% CI 1.07−2.25, P = 0.02). High ANA titers appear to be associated with increased mortality in IPF. This finding emphasizes the potential prognostic value of ANA testing. Further studies are needed to validate these findings and explore their implications for patient management.