Hazard Ratio For Death Research Articles

Missed Follow-up is associated with worse survival in stage I lung cancer: results from a large multi-site academic hospital system

The purpose of this study is to examine the effect of early incomplete follow-up on overall survival among stage I lung cancer patients. Patients with clinical stage I lung cancer at our institution between 2007 and 2016 were identified (N = 1111). Exclusions included < 18 years of age (N = 2), missing stage or demographics (N = 56), incomplete appointment data or had only one scheduled appointment (N = 351), or did not survive for at least 1 year after diagnosis (N = 120). Missed appointments were defined as unattended follow-up appointments within the first year of diagnosis without an attended appointment in the subsequent 60 days. The primary outcome was the hazard ratio (HR) for death associated per 10% increase in missed oncology follow-up appointments. Univariable and descriptive statistics were performed, and a multivariable landmark Cox regression model was created to examine the effect of missed oncology follow-up on survival. A total of 582 patients were analyzed with median follow-up of 3.2 years and median age of 69 years. On multivariable analysis controlling for age, sex, race, insurance status, and definitive treatment type the HR for death was 1.44 (95% CI 1.05–1.97) for every 10% increase in missed appointments. Incomplete oncologic follow-up may negatively impact overall survival among survivors of early-stage lung cancer.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults

BackgroundMany older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)–negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.MethodsIn a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point.ResultsThe data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P=0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group.ConclusionsThe addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.)

Dose-response risks of all-cause, cancer, and cardiovascular disease mortality according to sex-specific cigarette smoking pack-year quantiles.

This study investigated the risks for all-cause death and death from cancer or cardiovascular diseases due to smoking status and behavior, focusing on differences in smoking duration and amount stratified by sex. The integrated Korean Genome and Epidemiology Study provided data for 209770 individuals who were classified as never, former, or current smokers, based on their current smoking status. Pack-years were computed using daily average smoking amount and total smoking duration, and were categorized into quantiles separately for men and women. Based on the number of deaths in 2018, hazard ratios (HRs) were estimated for all-cause mortality, as well as for death caused by all cancers, lung cancer, and cardiovascular diseases according to pack-years adjusted for age, household income, marital status, body mass index, physical activity, and alcohol consumption. A significant increase in the risk of all-cause mortality was observed for current smokers (men HR=1.90; 95% CI: 1.69-2.14; women HR=2.25; 95% CI: 1.68-2.99) and former smokers (men HR=1.31; 95% CI: 1.17-1.47; women HR=2.35; 95% CI: 1.63-3.39) compared with that for those who had never smoked. Among men, HR for death from lung cancer was 3.13 (95% CI: 2.06-4.75) in former smokers and tended to increase with each pack-year quantile (range HR: 5.72-17.11). Among women, the HR was estimated to be 17.20 (95% CI: 6.22-47.57) only for >3rd quantile. Smoking increases the risks of all-cause death. Considering the persistent risks post-smoking cessation, it is vital to focus on preventing smoking initiation and providing proactive support for successful smoking cessation and maintenance of a smoke-free lifestyle.

Real world results of locally advanced and metastatic lung cancer patients treated with platinum doublet chemotherapy in first line: Moroccan cohort

BackgroundDoublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown. MethodsIn this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint. ResultsOverall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167–208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405–559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142–238; hazard ratio for progression: 1.21, 95 % CI, 0.29–5.02; p = 0.27), while the median OS was 428 (95 % CI, 324–940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193–277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41–7.27; p = 0.69, while the median OS was 273 (95 % CI, 241–459) days (hazard ratio for death: 2.95; 95 % CI, 0.4–21.7; p = 0.51). Grade 3–4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients. ConclusionMoving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

Worker exit and suicide and overdose mortality in a cohort of male non-metal mine workers

BackgroundSuicides, overdoses, and drug-related liver diseases (deaths of despair) are greatly elevated in the mining and extraction industries compared to other industries. To better understand the drivers of these deaths, we examined suicide or overdose mortality in relation to age at worker exit among a retrospective cohort of 11,009 male mine workers from the Diesel Exhaust in Miners Study II. MethodsWe calculated age-adjusted mortality rates (1947–2015) and estimated hazard ratios (HRs) and 95% Confidence Intervals (CI) for suicide or overdose death in relation to age at worker exit (leaving work). The mining industry curtailed its workforce in the early 1980s due to economic downturn; therefore, separate models were fit for worker exit pre- and post-1980. ResultsSuicide deaths peaked between 1980 and 1989 at 67.2 per 100,000, more than double the rate in the general population. The hazard rate for suicide or overdose was 2.56 times higher for inactive versus actively employed workers (95% CI: 1.88, 3.50). Based on 187 suicides or overdoses, associations between younger age at worker exit and suicide or overdose death were null or protective before 1980. However post-1980, those who exited between ages 30–39 years had an elevated risk of death HR = 1.33, 95% CI (0.70, 2.53) and those who exited before age 30 had a HR for suicide or overdose of 1.57 (0.83, 2.96) compared to those who exited work after age 55. ConclusionWorker exit may contribute to the elevated mortality from suicide or overdose among male mine workers, particularly among younger age groups.

Asparaginase-like protein 1 as a prognostic tissue biomarker in clinicopathologically and molecularly characterized endometrial cancer

ObjectivePrognostic stratification of endometrial cancer involves the assessment of stage, uterine risk factors, and molecular classification. This process can be further refined through annotation of prognostic biomarkers, notably L1 cell adhesion molecule (L1CAM) and hormonal receptors. Loss of asparaginase-like protein 1 (ASRGL1) has been shown to correlate with poor outcome in endometrial cancer. Our objective was to assess prognostication of endometrial cancer by ASRGL1 in conjunction with other available methodologies. Study DesignThis was a retrospective study of patients who underwent primary treatment at a single tertiary center. Tumors were molecularly classified by the Proactive Molecular Risk Classifier for Endometrial Cancer. Expression of ASRGL1, L1CAM, estrogen receptor, and progesterone receptor was determined by immunohistochemistry. ASRGL1 expression intensity was scored into four classes. ResultsIn a cohort of 775 patients, monitored for a median time of 81 months, ASRGL1 expression intensity was related to improved disease-specific survival in a dose-dependent manner (P < 0.001). Low expression levels were associated with stage II–IV disease and presence of uterine factors, i.e. high grade, lymphovascular space invasion, and deep myometrial invasion (P < 0.001 for all). Among the molecular subgroups, low expression was most prevalent in p53 abnormal carcinomas (P < 0.001). Low ASRGL1 was associated with positive L1CAM expression and negative estrogen and progesterone receptor expression (P < 0.001 for all). After adjustment for stage and uterine factors, strong ASRGL1 staining intensity was associated with a lower risk for cancer-related deaths (hazard ratio 0.56, 95 % confidence interval 0.32–0.97; P = 0.038). ASRGL1 was not associated with the outcome when adjusted for stage, molecular subgroups, L1CAM, and hormonal receptors. When analyzed separately within the different molecular subgroups, ASRGL1 showed an association with disease-specific survival specifically in “no specific molecular profile” subtype carcinomas (P < 0.001). However, this association became nonsignificant upon controlling for confounders. ConclusionsLow ASRGL1 expression intensity correlates with poor survival in endometrial cancer. ASRGL1 contributes to more accurate prognostication when controlled for stage and uterine factors. However, when adjusted for stage and other biomarkers, including molecular subgroups, ASRGL1 does not improve prognostic stratification.

Smoking-attributable Mortality in Korea, 2020: A Meta-analysis of 4 Databases.

Estimating the number of deaths caused by smoking is crucial for developing and evaluating tobacco control and smoking cessation policies. This study aimed to determine smoking-attributable mortality (SAM) in Korea in 2020. Four large-scale cohorts from Korea were analyzed. A Cox proportional-hazards model was used to determine the hazard ratios (HRs) of smoking-related death. By conducting a meta-analysis of these HRs, the pooled HRs of smoking-related death for 41 diseases were estimated. Population-attributable fractions (PAFs) were calculated based on the smoking prevalence for 1995 in conjunction with the pooled HRs. Subsequently, SAM was derived using the PAF and the number of deaths recorded for each disease in 2020. The pooled HR for all-cause mortality attributable to smoking was 1.73 for current men smokers (95% confidence interval [CI], 1.53 to 1.95) and 1.63 for current women smokers (95% CI, 1.37 to 1.94). Smoking accounted for 33.2% of all-cause deaths in men and 4.6% in women. Additionally, it was a factor in 71.8% of men lung cancer deaths and 11.9% of women lung cancer deaths. In 2020, smoking was responsible for 53 930 men deaths and 6283 women deaths, totaling 60 213 deaths. Cigarette smoking was responsible for a significant number of deaths in Korea in 2020. Monitoring the impact and societal burden of smoking is essential for effective tobacco control and harm prevention policies.

Comparison of the Response to Geftinib between EGFR Mutations in Exon 19 and Mutations in Exon 21 in Non-Small Cell Lung Cancer Egyptian Patients

Abstract Background The management of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) has dramatically changed following the introduction of target therapy in the last 15 years. Comprehensive reflex biomarker testing, including EGFR, is recommended for all patients with a diagnosis of non-squamous NSCLCs, regardless of disease stage and should be initiated by the pathologist at the time of initial diagnosis. Objective To compare the response to Geftinib between EGFR mutation exon 19 and EGFR mutation exon 21 in non- small cell lung cancer in Egyptian patients. Methods Our retrospective analysis examined 60 patients with advanced NSCLC who had received gefitinib therapy and the specimen were available at Shefa Alorman Oncology Hospital from June 2017 to May 2020. Results Our study showed no statistically difference as regard response to first line treatment between exon 19 deletion and exon 21 mutation with P Value = 0.1273. Our study showed no statistically significance as regard progression free survival after first line treatment Gefitinib between exon 19 deletion and exon21 mutation with median PFS 12 months for patient with exon 19 deletion compared to 10 months for patients with exon 21 mutation (Hazard ratio of progression or death 1.57; 95 % confidence interval 0.87 – 2.82; P- Value= 0.1269).Median PFS of study population was 12 months. The median survival was 27 months for exon 21 group while median survival not reached for exon 19 group (Hazard ratio for death 2.95; 95 % confidence interval 0.78 – 11.20). Median survival of whole study population was 33 months. Conclusion The EGFR mutation subtype should be considered when making treatment decisions for designing new clinical trials for chemotherapy-naïve, EGFR mutation- positive patients with advanced NSCLC.

Circulating Sphingolipids and All-Cause Mortality: The Strong Heart Family Study.

A growing body of research indicates that associations of ceramides and sphingomyelins with mortality depend on the chain length of the fatty acid acylated to the backbone sphingoid base. We examined associations of 8 ceramide and sphingomyelin species with mortality among an American Indian population. The analysis comprised 2688 participants from the SHFS (Strong Heart Family Study). Plasma ceramide and sphingomyelin species carrying long-chain (ie, 16:0) and very-long-chain (ie, 20:0, 22:0, 24:0) saturated fatty acids were measured by sequential liquid chromatography and mass spectroscopy using samples from 2001 to 2003. Participants were followed for 18.8 years (2001-2020). Associations of ceramides and sphingomyelins with mortality were assessed using Cox models. The mean age of participants was 40.8 years. There were 574 deaths during a median 17.4-year follow-up. Ceramides and sphingomyelins carrying fatty acid 16:0 were positively associated with mortality. Ceramides and sphingomyelins carrying longer fatty acids were inversely associated with mortality. Per SD difference in each ceramide and sphingomyelin species, hazard ratios for death were: 1.68 (95% CI, 1.44-1.96) for ceramide-16 (Cer-16), 0.82 (95% CI, 0.71-0.95) for Cer-20, 0.60 (95% CI, 0.51-0.70) for Cer-22, 0.67 (95% CI, 0.56-0.79) for Cer-24, 1.80 (95% CI-1.57, 2.05) for sphingomyelin-16 (SM-16), 0.54 (95% CI, 0.47-0.62) for SM-20, 0.50 (95% CI, 0.44-0.57) for SM-22, and 0.59 (95% CI, 0.52-0.67) for SM-24. The direction/magnitude of associations of ceramides and sphingomyelins with mortality differs according to the length of the fatty acid acylated to the backbone sphingoid base. URL: https://www.clinicatrials.gov; Unique identifier: NCT00005134.

Do Indian men have similar oncological outcomes with abiraterone plus androgen deprivation therapy in the setting of metastatic hormone-sensitive prostate cancer? A prospective observational study.

Combination of abiraterone with androgen deprivation therapy (ADT) has better survival outcomes than ADT alone in metastatic Hormone-sensitive prostate cancer (mHSPC) in the Western population. In this prospective (Clinical Trials Registry-India [CTRI] registered) observational study, we present the comparative oncological outcomes of ADT alone and ADT + abiraterone in Indian patients, which is not available currently. This study (CTRI-number-CTRI/2020/07/026545) included newly diagnosed mHSPC patients from January 2020 to June 2023 in a tertiary care hospital, urology department. Patients fulfilling inclusion criteria were advised ADT with abiraterone (A + ADT), and those not affording received ADT monotherapy (ADT). The primary endpoint was overall survival (OS). Secondary outcomes included prostate-specific antigen (PSA) decline >90%, radiographic progression-free survival (rPFS), and PSA progression-free survival (pPFS). Out of 278 patients with mHSPC, 163 patients were excluded and 115 were analyzed (ADT = 40 vs. A + ADT = 75). After a median follow-up of 20.3 months, 11 of 40 (27.5%) in ADT-only arm and 15 of 75 (20%) in ADT + abiraterone arm had died (Hazard-ratio of death 0.72; 95% confidence interval 0.68-0.88; P < 0.001). A PSA decline of >90% was seen in 85% in the ADT alone group and 93.3% in the ADT + abiraterone group. Significantly better outcomes of the ADT + abiraterone were seen in the secondary endpoints of rPFS (P < 0.001) and pPFS (P < 0.001). The OS benefit was 28% reduction in risk of death in our study versus 37% and 38% in STAMPEDE and LATITUDE, respectively. pPFS and rPFS were also poorer in Indian subsets. Abiraterone with ADT improves OS, PSA response, rPFS, and pPFS in the Indian population akin to the Western data but with poorer OS, rPFS, and PSA progression-free survival on comparison.

Concomitant Surgical Ablation in Paroxysmal vs Persistent Atrial Fibrillation During Mitral Surgery

BackgroundDespite prospective randomized evidence supporting concomitant treatment of atrial fibrillation (AF) during mitral valve (MV) surgery, variation in surgical management of AF remains. We assessed longitudinal outcomes after surgical treatment of persistent or paroxysmal AF during MV surgery in Medicare beneficiaries. MethodsAll Medicare beneficiaries with a diagnosis of AF undergoing MV surgery (2018-2020) were evaluated. Patients were stratified by no AF treatment, left atrial appendage obliteration (LAAO) alone, or surgical ablation and LAAO (SA+LAAO). Doubly robust risk adjustment and subgroup analysis by persistent or paroxysmal AF were performed. ResultsA total of 7517 patients with preoperative AF underwent MV surgery (32.1% no AF treatment, 23.1% LAAO alone, 44.7% SA+LAAO). After doubly robust risk adjustment, AF treatment with SA+LAAO or LAAO alone were associated with lower 3-year readmission for stroke or bleeding. However, SA+LAAO was associated with reduced 3-year mortality and readmission for AF or heart failure compared with no AF treatment or LAAO alone. Compared with no AF treatment or LAAO alone, SA+LAAO was associated with lower composite end point of stroke (hazard ratio, 0.75) or death (hazard ratio, 0.83) at 3 years. Subgroup analysis identified similar longitudinal benefits of SA+LAAO in patients with persistent or paroxysmal AF. ConclusionsIn Medicare beneficiaries with AF undergoing MV surgery, SA+LAAO was associated with improved longitudinal outcomes compared with LAAO alone or no AF treatment in patients with paroxysmal or persistent AF. These contemporary real-world data further clarify the benefit of SA+LAAO during MV surgery across all types of AF.

Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML

AbstractAlthough intensive induction chemotherapy (IC) remains the standard of care for younger patients with acute myeloid leukemia (AML), hypomethylating agents + venetoclax (HMA/VEN) can lead to durable remission among older patients with nucleophosmin 1 (NPM1) mutations. Whether IC or HMA/VEN is superior in patients aged ≥60 years with NPM1-mutant AML is unknown. We performed an international, multicenter retrospective cohort study of 221 patients (147 IC and 74 HMA/VEN) with previously untreated NPM1-mutant AML. Composite complete remission (cCR) (defined as CR + CR with incomplete count recovery) rate was similar for IC and HMA/VEN (cCR, 85% vs 74%; P = .067). Although overall survival (OS) was favorable with IC in unselected patients compared with HMA/VEN (24-month OS, 59% [95% confidence interval (CI), 52-69%] vs 38% [95% CI, 27-55%]; P = .013), it was not statistically different among patients aged 60-75 years (60% [95% CI, 52-70%] vs 44% [95% CI, 29-66%]; P = .069) and patients who received an allogeneic stem cell transplant (70% [95% CI, 58-85%] vs 66% [95% CI, 44-100%]; P = .56). Subgroup analyses suggested that patients with normal cytogenetics (24-month OS, 65% [95% CI, 56-74%] with IC vs 40% [95% CI, 26-60%] with HMA/VEN; P = .009) and without FLT3 internal tandem duplication mutations might benefit from IC compared with HMA/VEN (24-month OS, 68% [95% CI, 59-79%] vs 43% [95% CI, 29-63%]; P = .008). In multivariable analysis, OS was not statistically different between patients treated with IC and HMA/VEN (hazard ratio for death with HMA/VEN vs IC, 0.71; 95% CI, 0.40-1.27; P = .25).

Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC.

Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

Temporal evolution of ascending aortic aneurysm wall stress predicts all-cause mortality.

Diameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over 3-5 years and subsequent all-cause mortality. Male veterans with <5.5 cm ascending aortic aneurysms and computed tomography at baseline and 3- to 5-year follow-up underwent three-dimensional aneurysm model construction. Peak circumferential and longitudinal wall stresses at systole were calculated using finite element analysis. Temporal trends were assessed by mixed-effects modelling. Changes in aortic wall stresses, diameter and length over time were evaluated as predictors of subsequent 3-year all-cause mortality by Cox proportional hazards modelling. Sixty-two male veterans were included in the study. Yearly changes in geometric and biomechanical measures were 0.12 mm/year (95% confidence interval, 0.04-0.20) for aortic diameter, 0.41 mm/year (0.12-0.71) for aortic length, 1.19 kPa/year -5.94 to 8.33) for peak circumferential stress, and 0.48 kPa/year (-3.89 to 4.84) for peak longitudinal stress. Yearly change in peak circumferential stress was significantly associated with hazard of death-hazard ratio for peak circumferential stress growth per 10 kPa/year, 1.27 (95% CI, 1.02-1.60; P = 0.037); hazard ratio for peak circumferential stress growth ≥ 32 kPa/year, 8.47 (95% CI, 2.42-30; P < 0.001). In this population of nonsurgical aneurysm patients, large temporal changes in peak circumferential stress, but not aortic diameter or length, was associated with all-cause mortality. Biomechanical stress and stress changes over time may be beneficial as additional risk factors for elective surgery in small aneurysms.

Long-term Outcomes After Kidney Transplantation From DBD Donors Aged 70 y and Older.

Transplantation of kidneys from elderly donations after brain death (DBD) donors has increased owing to organ shortages. We aimed to assess the impact on long-term kidney transplant outcomes from DBD donors aged 70 y and older compared with kidneys from younger donors. From 2007 to 2022, 2274 first single kidney transplantations from DBD donors were performed at our center. Data from 1417 kidney transplant recipients receiving a DBD organ were included and categorized into 3 groups according to donor age: 70 y and older (n = 444, median age 74 y), 60-69 y (n = 527, median age 64 y), and a reference group consisting of donors aged 45-54 y (n = 446, median age 50 y). Kaplan-Meier plots and multivariate Cox regression with correction for recipient, donor, and transplant characteristics were used to investigate patient and kidney graft survival outcomes. The median patient follow-up time was 9.3 y (interquartile range, 5.3-13.1). The adjusted hazard ratios for patient death in recipients of kidneys from DBD donors aged 70 y and older compared with 60-69 y and 45-54 y were 1.12 (95% confidence interval [CI], 0.92-1.36; P = 0.26) and 1.62 (95% CI, 1.26-2.07; P < 0.001), respectively. Compared with recipients of donors aged 60-69 y and 45-54 y, the adjusted hazard ratios for kidney graft loss in recipients of donors aged 70 y and older were 1.23 (95% CI, 1.02-1.48; P = 0.029) and 1.94 (95% CI, 1.54-2.45; P < 0.001), respectively. Transplantation of kidneys from DBD donors aged 70 y and older resulted in acceptable long-term outcomes and is encouraging.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database

BackgroundThere are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AimUsing a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. MethodsFrom 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. ResultsAfter adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881–1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049–1.188) remained higher in patients with lymphoma. ConclusionIn this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Extreme Humid-Heat Exposure and Mortality Among Patients Receiving Dialysis

Rationale & ObjectiveExposure to extreme heat events has been linked to increased morbidity and mortality in the general population. Patients receiving maintenance dialysis may be vulnerable to greater risks from these events, but this is not well understood. We sought to characterize the association of extreme heat events and the risk of death among patients receiving dialysis in the United States. Study DesignRetrospective cohort study. Setting & ParticipantsData from the United States Renal Data System were used to identify adults living in US urban settlements prone to extreme heat who initiated maintenance dialysis between 1997 and 2016. ExposureAn extreme heat event was defined as a time-updated heat index (a humid-heat metric) exceeding 40.6°C for ≥2 days or 46.1°C for ≥1 day. OutcomeDeath. Analytical ApproachCox proportional hazards regression to estimate the elevation in risk of death during a humid-heat event adjusted for age, sex, year of dialysis initiation, dialysis modality, poverty level, and climate region. Interactions between humid-heat and these same factors were explored. ResultsAmong 945,251 adults in 245 urban settlements, the mean age was 63 years and 44% were female. During a median follow-up of 3.6 years, 498,049 adults were exposed to at least one of 7,154 extreme humid-heat events, and 500,025 deaths occurred. In adjusted models, there was an increased risk of death (hazard ratio 1.18; 95% confidence interval 1.15-1.20) during extreme humid-heat exposure. Relative mortality risk was higher among patients living in the Southeast (P<0.001) compared with the Southwest. LimitationsPossibility of exposure misclassification, did not account for land use and air pollution co-exposures. ConclusionsThis study suggests that patients receiving dialysis face an increased risk of death during extreme humid-heat exposure.

Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study.

Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy. Patients with EGFR-mutated advanced NSCLC who progressed after osimertinib and platinum-based chemotherapy were randomly assigned 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Coprimary pharmacokinetic noninferiority end points were trough concentrations (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-D15). Key secondary end points were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory end point. Overall, 418 patients underwent random assignment (subcutaneous group, n = 206; intravenous group, n = 212). Geometric mean ratios of Ctrough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04 to 1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27 to 1.61) at cycle-4-day-1; the cycle-2 AUCD1-D15 was 1.03 (90% CI, 0.98 to 1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42 to 0.92; nominal P = .02). Fewer patients in the subcutaneous group experienced infusion-related reactions (IRRs; 13% v 66%) and venous thromboembolism (9% v 14%) versus the intravenous group. Median administration time for the first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab and to 5 hours (range, 0.2-9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; the end-of-treatment rates were 85% and 35%, respectively. Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.

The Clinical Role of Adjuvant Chemotherapy after Sublobar Resection for Non-Small-Cell Lung Cancer ≤ 20 mm with Lymph Node Metastases: A Propensity-Matched Analysis of the National Cancer Database.

Sublobar resection is a standard surgical procedure for small-sized non-small-cell lung cancer (NSCLC). However, the clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. The National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. The Kaplan-Meier method with a log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. The samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

Office measurement vs. ambulatory blood pressure monitoring: associations with mortality in patients with or without diabetes.

Guidelines suggest similar blood pressure (BP) targets in patients with and without diabetes and recommend ambulatory BP monitoring (ABPM) to diagnose and classify hypertension. It was explored whether different levels of ambulatory and office BP and different hypertension phenotypes associate with differences of risk in diabetes and no diabetes. This analysis assessed outcome data from the Spanish ABPM Registry in 59 124 patients with complete available data. The associations between office, mean, daytime, and nighttime ambulatory BP with the risk in patients with or without diabetes were explored. The effects of diabetes on mortality in different hypertension phenotypes, i.e. sustained hypertension, white-coat hypertension, and masked hypertension, compared with normotension were studied. Analyses were done with Cox regression analyses and adjusted for demographic and clinical confounders. A total of 59 124 patients were recruited from 223 primary care centres in Spain. The majority had an office systolic BP >140 mmHg (36 700 patients), and 23 128 (40.6%) patients were untreated. Diabetes was diagnosed in 11 391 patients (19.2%). Concomitant cardiovascular (CV) disease was present in 2521 patients (23.1%) with diabetes and 4616 (10.0%) without diabetes. Twenty-four-hour mean, daytime, and nighttime ambulatory BP were associated with increased risk in diabetes and no diabetes, while in office BP, there was no clear association with no differences with and without diabetes. While the relative association of BP to CV death risk was similar in diabetes compared with no diabetes (mean interaction P = .80, daytime interaction P = .97, and nighttime interaction P = .32), increased event rates occurred in diabetes for all ABPM parameters for CV death and all-cause death. White-coat hypertension was not associated with risk for CV death (hazard ratio 0.86; 95% confidence interval 0.72-1.03) and slightly reduced risk for all-cause death in no diabetes (hazard ratio 0.89; confidence interval 0.81-0.98) but without significant interaction between diabetes and no diabetes. Sustained hypertension and masked hypertension in diabetes and no diabetes were associated with even higher risk. There were no significant interactions in hypertensive phenotypes between diabetes and no diabetes and CV death risk (interaction P = .26), while some interaction was present for all-cause death (interaction P = .043) and non-CV death (interaction P = .053). Diabetes increased the risk for all-cause death, CV, and non-CV death at every level of office and ambulatory BP. Masked and sustained hypertension confer to the highest risk, while white-coat hypertension appears grossly neutral without interaction of relative risk between diabetes and no diabetes. These results support recommendations of international guidelines for strict BP control and using ABPM for classification and assessment of risk and control of hypertension, particularly in patients with diabetes. Not applicable.