Survival In Adults Research Articles

Clinical trial participation predicts improved survival in older adults receiving allogeneic blood and marrow transplant

BackgroundOlder adults represent a large oncologic demographic and are under-represented within oncology research despite constituting nearly two-thirds of the oncologic population in the United States. Because many social factors influence research participation, those who enroll in research do not reflect the oncology population at large, introducing bias and creating issue with external validity of studies. The same factors that influence study enrollment may also impact cancer outcomes, meaning that those who enroll in studies may already have an improved chance of cancer survival, further skewing results of these studies. This study evaluates characteristics that influence study enrollment in older adults and explore to what degree these factors may influence survival after allogeneic blood or marrow transplantation.MethodsThis retrospective comparison study evaluates 63 adults aged 60 and above undergoing allogenic transplantation at one institution. Patients who elected and declined enrollment in a non-therapeutic observational study were evaluated. Demographic and clinical characteristics between groups were compared and assessed as predictors of transplant survival, including decision to enroll in the study.ResultsParticipants who chose to enroll in the parent study were not different with regard to gender, race/ethnicity, age, insurance type, donor age, and neighborhood income/poverty level compared to patients who were invited to participate but declined enrollment. The research participant group had higher proportion assessed as being fully active (23.8% vs. 12.7%, p = 0.034) and lower mean comorbidity scores (1.0 vs 2.47, p = 0.008). Enrollment in an observational study independently predicted transplant survival (HR = 0.316, 95% CI 0.12–0.82, p = 0.017). When controlling for relevant confounders of disease severity, comorbidities, and transplant age, enrolling in the parent study was associated with a lower hazards of death following transplant (HR = 0.302, 95% CI 0.10–0.87, p = 0.027).ConclusionsDespite being demographically comparable, persons who enrolled in one non-therapeutic transplant study had significantly improved survivorship than those who did not participate in observational research. These findings suggest that there are unidentified factors that influence study involvement that may also impact disease survivorship, over-estimating outcomes from these studies. Results from prospective observational studies should be interpreted with the consideration that study participants have an improved chance of survival at baseline.

Heart waitlist survival in adults with an intra-aortic balloon pump relative to other Status 2, Status 1, and inotrope Status 3 patients.

Intra-aortic balloon pump (IABP) utilization has significantly outpaced other Status 2 eligibility criteria for heart transplant. The risk of waitlist mortality of IABP-supported patients relative to other Status 2 listed patients has not been described. We performed a retrospective analysis of all adult patients listed Status 2 for heart transplantation under the current U.S. allocation policy, using data from the United Network for Organ Sharing. Patients listed status 1 and status 3 for high-dose inotropes were included for reference. Mortality and waitlist decompensation were modeled as a function of time-varying status in cause-specific Cox survival models. We identified 3638 Status 2 listings, of whom 1676 (46%) were Status 2 due to IABP. Relative to patients supported with IABP, status 2 patients with ventricular tachycardia/fibrillation [VT/VF] (HR 4.0, p < .001), right-or-biventricular assist device configurations (HR 2.3, p=.002), or temporary surgical left ventricular assist devices [LVAD] (HR 2.6, p=.003) had greater risk of waitlist mortality and decompensation. Other Status 2 subgroups had mortality comparable to IABP Status 2. Risk of waitlist mortality and decompensation for IABP Status 2 was similar to Status 3 patients listed for high-dose inotropes (HR 1.2, p=.27) and lower than Status 1 patients (HR 0.7, p=.002). Waitlist mortality varies significantly by Status 2 eligibility criteria and is highest among patients listed for VT/VF, right-or-biVAD configurations, or temporary surgical LVADs. IABP-supported patients were among those with the lowest Status 2 waitlist mortality risk and comparable to Status 3 inotrope-supported patients.

Incidence and clinical predictors of early and late complications of implantable cardioverter-defibrillators in adults with congenital heart disease.

The Implantable cardioverter-defibrillator (ICD) has been proven to improve survival in adults with congenital heart disease (ACHD), however it is associated with a high rate of complications. We aimed to quantify the incidence of early (≤3 months) and late (>3 months) complications (EC, LC) in ACHD patients implanted with an ICD and identify their clinical predictors. We retrospectively reviewed 207 patients who had ICD follow-up at Toronto General Hospital between 1996 and 2019. Most common diagnoses were Tetralogy of Fallot (32.4%), dextro-transposition of the great arteries (17.9%), congenital corrected transposition of the great arteries (13%). No intraprocedural complications were observed. Median follow up was 3.4 years (0.1-23). 24 patients (12%) developed EC (4 hematomas, 20 lead dislodgments). A total of 56 LC occurred (46% lead failure, 21% infection, 11% prophylactic lead extraction, 9% neurologic pain, 9% erosion, 4% other) with an incidence rate of LC of 18% per 5 person-years. Anatomic complexity (odds ratio 2.9,p=0.02) and CRTD implant(OR 2.5,p=0.04) were associated with EC. Survival free from LC was 92%, 86%, 65% respectively after 1,5 and 10 years. Presence of legacy leads (hazard ratio 2.9,p=0.006) and subpulmonary ejection fraction (5% increase, HR 1.35,p=0.031) were associated with LC. ACHD patients at risk of SCD continue to benefit from newer device technology. However, these patients-particularly those with greater anatomic and device complexity-remain at increased risk of developing complications over their lifetime. Given the life expectancy of this population, careful consideration needs to be given when a device for primary prevention is being contemplated.

Integrated molecular and clinical analysis of BRAF-mutant glioma in adults

BRAF mutations are a significant driver of disease in pediatric low-grade glioma, but the implications of BRAF alterations on the clinical course and treatment response in adult glioma remain unclear. Here, we characterize a multi-institutional cohort of more than 300 patients (>200 adults) with BRAF-mutated glioma using clinical, pathological/molecular, and outcome data. We observed that adult and pediatric BRAF-mutant gliomas harbor distinct clinical and molecular features, with a higher prevalence of BRAFV600E (Class I) and BRAF fusions in pediatric tumors. BRAFV600E alterations were associated with improved survival in adults with glioma overall, though not in glioblastoma. Other genomic alterations observed within functional classes were consistent with the putative roles of those BRAF mutation classes in glioma pathogenesis. In our adult cohort, BRAFV600E alterations conferred sensitivity to targeted therapies. Overall, this large cohort of BRAF-altered adult gliomas demonstrates a broad range of molecular alterations with implications for treatment sensitivity and survival.

Treatment patterns and survival in older adults with unresected nonmetastatic biliary tract cancers

IntroductionThe optimal treatment for unresected nonmetastatic biliary tract cancer (uBTC) is not well-established. The objective of this study was to analyze the treatment patterns and compare the differences in overall survival (OS) between different treatment strategies amongst older adults with uBTC. Materials and methodsWe identified patients aged ≥65 years with uBTC using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2004–2015). Treatments were classified into chemotherapy, chemoradiotherapy, and radiotherapy. The primary outcome was OS. The differences in OS were analyzed using Kaplan-Meier curves and multivariable Cox proportional hazard regression. ResultsA total of 4352 patients with uBTC were included. The median age was 80 years and median OS was 4.1 months. Most patients (67.3%, n = 2931) received no treatment, 19.1% chemotherapy (n = 833), 8.1% chemoradiotherapy (n = 354), and 5.4% radiotherapy alone (n = 234). Patients receiving no treatment were older and had more comorbidities. Chemotherapy was associated with significantly longer OS than no treatment in uBTC (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.79–0.95), but no difference was found in the subgroups of intrahepatic cholangiocarcinoma (iCCA; HR 0.87, 95% CI 0.75–1.00) and gallbladder carcinoma (GBC; HR 1.09, 95% CI 0.86–1.39). In the sensitivity analyses, capecitabine-based chemoradiotherapy showed significantly longer OS in uBTC compared to chemotherapy (adjusted HR 0.71, 95% CI 0.53–0.95). DiscussionA minority of older patients with uBTC receive systemic treatments. Chemotherapy was associated with longer OS compared to no treatment in uBTC, but not in the subgroups of iCCA and GBC. The efficacy of chemoradiotherapy, especially in perihilar cholangiocarcinoma using capecitabine-based chemoradiotherapy, may be further evaluated in prospective clinical trials.

Impact of Antibiotic Exposure Before Immune Checkpoint Inhibitor Treatment on Overall Survival in Older Adults With Cancer: A Population-Based Study.

Antibiotic exposure before immune checkpoint inhibitor (ICI) treatment can negatively affect outcomes through alteration in the gut microbiome, but large-scale evaluations are lacking. We performed a population-level retrospective cohort study to evaluate the impact of antibiotic exposure before starting ICI on overall survival (OS). Patients with cancer, age 65 years or older, who initiated treatment with ICIs between June 2012 and October 2018 in Ontario, Canada, were identified using systemic therapy administration data. The cohort was deterministically linked to other health care databases to obtain covariates and antibiotic prescription claim data at both 1 year and 60 days before ICI therapy. Multivariable Cox models evaluated the association between exposure and OS. Among the 2,737 patients with cancer who received ICIs, 59% and 19% of patients received antibiotics 1 year and 60 days before ICI therapy, respectively. Median OS was 306 days. Any antibiotic exposure within 1 year before ICI was associated with worse OS (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.12 to 1.23; P = .03). In antibiotic class analysis, exposure to fluoroquinolones within 1 year (aHR, 1.26; 95% CI, 1.13 to 1.40; P < .001) or 60 days before ICI (aHR, 1.20; 95% CI, 0.99 to 1.45; P = .06) was associated with worse OS, with a dose effect seen on the basis of total weeks of exposure over 1 year (aHR, 1.07 per week; 95% CI, 1.03 to 1.11; P < .001) and 60 days (aHR, 1.12 per week; 95% CI, 1.03 to 1.23; P = .01). In this population-level study, exposure to antibiotics and specifically fluoroquinolones before ICI therapy was observed to be associated with worse OS among older adults with cancer. Interventions aimed at altering the gut microbiome to boost immunogenicity may help improve outcomes for patients receiving ICIs with prior antibiotic exposure.

Targeted Therapy Development in Acute Myeloid Leukemia

Therapeutic developments targeting acute myeloid leukemia (AML) have been in the pipeline for five decades and have recently resulted in the approval of multiple targeted therapies. However, there remains an unmet need for molecular treatments that can deliver long-term remissions and cure for this heterogeneous disease. Previously, a wide range of small molecule drugs were developed to target sub-types of AML, mainly in the relapsed and refractory setting; however, drug resistance has derailed the long-term efficacy of these as monotherapies. Recently, the small molecule venetoclax was introduced in combination with azacitidine, which has improved the response rates and the overall survival in older adults with AML compared to those of chemotherapy. However, this regimen is still limited by cytotoxicity and is not curative. Therefore, there is high demand for therapies that target specific abnormalities in AML while sparing normal cells and eliminating leukemia-initiating cells. Despite this, the urgent need to develop these therapies has been hampered by the complexities of this heterogeneous disease, spurring the development of innovative therapies that target different mechanisms of leukemogenesis. This review comprehensively addresses the development of novel targeted therapies and the translational perspective for acute myeloid leukemia, including the development of selective and non-selective drugs.

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Impact of time to chest closure on early and late survival in adults with delayed sternal closure.

Delayed sternal closure (DSC) after cardiac surgery is a temporizing measure to address coagulopathy or haemodynamic instability after cardiac surgery. We sought to study: (i) indications and temporal trends for DSC, (ii) factors associated with time to chest closure and (iii) its impact on short-term and long-term outcomes. From January 2007 to December 2017, 494 patients (median age 67 years, 66% males) required DSC after cardiac surgery. Medical records were reviewed for indications, risk factors, time to DSC and outcomes. Multivariable Cox regression via landmark analysis of 486 5-day survivors was used to investigate the impact of time to chest closure on early and late survival. Coagulopathy and haemodynamic instability were the most common indications. Median time to chest closure was 2 days. Pre-/intraoperative extracorporeal membranous oxygenation, severe right ventricular dysfunction and diabetes mellitus were associated with longer time to chest closure. Longer time to closure was associated with increased risk of operative complications and operative mortality, but did not have a statistically significant association with late mortality. Increasing age, pulmonary hypertension and a greater number of prior sternotomies were also found to be associated with overall mortality. While longer time to chest closure was associated with increased rates of operative complications and operative mortality, it did not reveal a statistically significant association with long-term survival.

The mortality burden of cachexia in patients with colorectal or pancreatic cancer: A systematic literature review.

87 Background: Cancer-associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (WL, skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer. Methods: The SLR was conducted following PRISMA guidelines. Embase and PubMed were searched to identify articles published in English between 1 Jan 2016 and 10 Oct 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by International Consensus (IC) diagnostic criteria (Fearon et al., Lancet Oncol 2011;12:489–95) or a broader definition of any WL. Included publications were of studies in ≥100 patients with colorectal or pancreatic cancer. Results: Twenty-six publications in patients with colorectal (n=13) or pancreatic cancer (n=13) met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 studies (58%) reported any WL. An association between survival and cachexia/WL was assessed across studies using multivariate (n=23) or univariate (n=3) analyses and within each study across multiple WL categories. Cachexia/WL was associated with a statistically significantly poorer survival in at least one WL category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Conclusions: Cachexia/WL was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two-thirds of the studies. The classification of WL varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could inform early disease management strategies that may improve prognosis.

Head Injury and Long-term Mortality Risk in Community-Dwelling Adults

Head injury is associated with significant short-term morbidity and mortality. Research regarding the implications of head injury for long-term survival in community-dwelling adults remains limited. To evaluate the association of head injury with long-term all-cause mortality risk among community-dwelling adults, with consideration of head injury frequency and severity. This cohort study included participants with and without head injury in the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective cohort study with follow-up from 1987 through 2019 in 4 US communities in Minnesota, Maryland, North Carolina, and Mississippi. Of 15 792 ARIC participants initially enrolled, 1957 were ineligible due to self-reported head injury at baseline; 103 participants not of Black or White race and Black participants at the Minnesota and Maryland field centers were excluded due to race-site aliasing; and an additional 695 participants with missing head injury date or covariate data were excluded, resulting in 13 037 eligible participants. Head injury frequency and severity, as defined via self-report in response to interview questions and via hospital-based International Classification of Diseases diagnostic codes (with head injury severity defined in the subset of head injury cases identified using these codes). Head injury was analyzed as a time-varying exposure. All-cause mortality was ascertained via linkage to the National Death Index. Data were analyzed between August 5, 2021, and October 23, 2022. More than one-half of participants were female (57.7%; 42.3% men), 27.9% were Black (72.1% White), and the median age at baseline was 54 years (IQR, 49-59 years). Median follow-up time was 27.0 years (IQR, 17.6-30.5 years). Head injuries occurred among 2402 participants (18.4%), most of which were classified as mild. The hazard ratio (HR) for all-cause mortality among individuals with head injury was 1.99 (95% CI, 1.88-2.11) compared with those with no head injury, with evidence of a dose-dependent association with head injury frequency (1 head injury: HR, 1.66 [95% CI, 1.56-1.77]; 2 or more head injuries: HR, 2.11 [95% CI, 1.89-2.37]) and severity (mild: HR, 2.16 [95% CI, 2.01-2.31]; moderate, severe, or penetrating: HR, 2.87 [95% CI, 2.55-3.22]). Estimates were similar by sex and race, with attenuated associations among individuals aged 54 years or older at baseline. In this community-based cohort with more than 3 decades of longitudinal follow-up, head injury was associated with decreased long-term survival time in a dose-dependent manner, underscoring the importance of measures aimed at prevention and clinical interventions to reduce morbidity and mortality due to head injury.

Risk of early death in adolescents and young adults with cancer: a population-based study.

Advancements in treatment and supportive care have led to improved survival for adolescents and young adults (AYAs) with cancer; however, a subset of those diagnosed remain at risk for early death (within 2 months of diagnosis). Factors that place AYAs at increased risk of early death have not been well studied. The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death in AYAs with hematologic malignancies, central nervous system tumors, and solid tumors. Associations between age at diagnosis, sex, race, ethnicity, socioeconomic status, insurance status, rurality, and early death were assessed. A total of 268 501 AYAs diagnosed between 2000 and 2016 were included. Early death percentage was highest in patients diagnosed with hematologic malignancies (3.1%, 95% confidence interval [CI] = 2.9% to 3.2%), followed by central nervous system tumors (2.5%, 95% CI = 2.3% to 2.8%), and solid tumors (1.0%, 95% CI = 0.9% to 1.0%). Age at diagnosis, race, ethnicity, lower socioeconomic status, and insurance status were associated with increased risk of early death in each of the cancer types. For AYAs with hematologic malignancies and solid tumors, risk of early death decreased statistically significantly over time. A subset of AYAs with cancer remains at risk for early death. In addition to cancer type, sociodemographic factors also affect risk of early death. A better understanding of the interplay of factors related to cancer type, treatment, and health systems that place certain AYA subsets at higher risk for early death is needed to address these disparities and improve outcomes.

Post-weaning survival in kangaroos is high and constant until senescence: Implications for population dynamics.

Large herbivores typically have consistently high prime-aged adult survival and lower, more variable, juvenile, and senescent survival. Many kangaroo populations undergo greater fluctuations in density compared with other large herbivores, but age- and sex-specific survival of kangaroos and their response to environmental variation remain poorly estimated. We used long-term capture-mark-recapture data on 920 individuals to investigate the survival component of eastern grey kangaroo (Macropus giganteus) population dynamics. Forage availability and population density were monitored quarterly and included as predictors of survival in Bayesian Cormack-Jolly-Seber models. Annual survival probabilities were estimated for five age classes: 0 years (juveniles), 1-2 years (subadults), 3-6 years (prime-aged adults), 7-9 years (presenescent adults), and ≥10 years (senescent adults). Survival of juveniles varied widely during our 12-year study, ranging from 0.07 to 0.90 for females and 0.05-0.92 for males. Subadult survival was 0.80-0.93 for females and 0.75-0.85 for males, while that of prime-aged adults was ≥0.94 for females and ≥0.83 for males, despite large fluctuations in forage and density. The survival of presenescent adults spanned 0.86-0.93 for females and 0.60-0.86 for males. Senescent survival was variable, at 0.49-0.90 for females and 0.49-0.80 for males. Male survival was significantly lower than female survival in prime-aged and presenescent adults, but not in other age classes. Although most of the models supported by Watanabe-Akaike Information Criterion selection included at least one environmental covariate, none of these covariates individually had a discernible effect on survival. Temporal variability in overall survival appeared mostly due to changes in the survival of juvenile and senescent kangaroos. Kangaroo survival patterns are similar to those of ungulates, suggesting a strong role of sex-age structure on population dynamics.

Comorbidity burden and outcomes of older adults with acute promyelocytic leukemia: a National Cancer Database analysis of 2221 patients

Association between comorbidity burden and patient outcomes has not been adequately investigated in acute promyelocytic leukemia (APL). We utilized the National Cancer Database to evaluate the association of the Charlson–Deyo Comorbidity Index (CCI) with one-month mortality and overall survival (OS) in adults ≥60 years with APL. One-month mortality was 16%, 24%, and 32%, and 3-year OS was 61%, 53%, and 38% for patients with CCI 0, 1, and ≥2, respectively. One-month mortality was higher for patients with CCI 1 (OR 1.67, 95% CI 1.29–2.16, p < .001) and CCI ≥ 2 (OR 2.31, 95% CI 1.70–3.13, p < .001) compared to patients with CCI 0. Patients with CCI 1 (HR 1.27, 95% CI 1.10–1.46, p < .001) and CCI ≥ 2 (HR 1.74, 95% CI 1.48–2.06, p < .001) had worse OS compared to patients with CCI 0. In conclusion, CCI is an independent predictor of survival outcomes in patients with APL.

Astrocytoma, Diagnosis and Treatment. Literature Review

Most primary CNS tumors are astrocytic tumors. Glial tumors are classified according to histological criteria. The WHO classification for primary malignant gliomas in adults includes grades II through IV. Terms for tumors that classify in grade II are astrocytomas (A), oligodendrogliomas (ODG), or mixed gliomas (GM). Grade III tumors are named similarly, and preceded by the word anaplastic, for example, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (ODGA), or mixed anaplastic glioma (GAM). The most malignant form, the grade IV tumor, is designated glioblastoma or GBM. GBMs are diagnosed more frequently than lower grade astrocytomas. The recent GBM classifications reflect the genetic aspects involved in the tumor and have prognostic value. The most important prognostic factor in malignant gliomas is the histopathological diagnosis of the tumor. The survival of patients with AA is much higher than that of patients with glioblastoma. Other important factors that are associated with the survival of patients with malignant gliomas are the age of the patients, Karnofsky scale, surgery, radiotherapy, and chemotherapy. There is evidence suggesting an association between younger patients and longer survival in adults with supratentorial AA and glioblastoma

The Association between Frailty and Dementia-Free and Physical Disability-Free Survival in Community-Dwelling Older Adults

Introduction: Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. Methods: This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the “ASPirin in Reducing Events in the Elderly (ASPREE)” clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). Results: At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67; 95% CI: 1.50–1.86 and frail: HR: 2.80; 95% CI: 2.27–3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. Conclusion: Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.

Antibodies to varicella-zoster virus and three other herpesviruses and survival in adults with glioma.

Lifetime exposure to the varicella-zoster virus (VZV) has been consistently inversely associated with glioma risk, however, the relationship of VZV with survival in adults with glioma has not been investigated. In this study, we analyzed the survival of adults with glioma in relation to their antibody measurements to 4 common herpes viral infections, including VZV, measured post-diagnosis. We analyzed IgG antibody measurements to VZV, cytomegalovirus (CMV), herpes simplex virus 1/2 (HSV), and Epstein-Barr virus (EBV) collected from 1378 adults with glioma diagnosed between 1991 and 2010. Blood was obtained a median of 3 months after surgery. Associations of patient IgG levels with overall survival were estimated using Cox models adjusted for age, sex, self-reported race, surgery type, dexamethasone usage at blood draw, and tumor grade. Models were stratified by recruitment series and meta-analyzed to account for time-dependent treatment effects. VZV antibody seropositivity was associated with improved survival outcomes in adults with glioma (Hazard ratio, HR = 0.70, 95% Confidence Interval 0.54-0.90, P = .006). Amongst cases who were seropositive for VZV antibodies, survival was significantly improved for those above the 25th percentile of continuous reactivity measurements versus those below (HR = 0.76, 0.66-0.88, P = .0003). Antibody seropositivity to EBV was separately associated with improved survival (HR = 0.71, 0.53-0.96, P = .028). Antibody positivity to 2 other common viruses (CMV, HSV) was not associated with altered survival. Low levels of VZV or EBV antibodies are associated with poorer survival outcomes for adults with glioma. Differential immune response rather than viral exposure may explain these findings.

The association between plant and animal protein intake and disability free survival in community-dwelling older adults: the results of the ASPREE Longitudinal Study of Older Persons (ALSOP)

The association between plant and animal protein intake and disability free survival in community-dwelling older adults: the results of the ASPREE Longitudinal Study of Older Persons (ALSOP) - Volume 82 Issue OCE2

De novo Donor-specific Anti-human Leukocyte Antigen Antibody and Its Outcome in Pediatric Renal Transplant Recipients: A Single-center Experience in India

Development of de novo donor-specific anti-HLA antibody (dnDSA) is associated with poor graft survival in adults. However, there is a paucity of data about its prevalence and outcome in Indian children. We retrospectively assessed the proportion and spectrum of dnDSA and its outcome on antibody-mediated rejection (ABMR) and graft function. Children ≤18 years who were transplanted between November 2016 and October 2019 were included in this study. Pretransplant donor-specific antibody (DSA) was screened by complement-dependent cytotoxicity, flow cytometry crossmatch, and single antigen bead (SAB) class I and II by Luminex platform. Either antithymocyte globulin or basiliximab was used as induction. Tacrolimus, mycophenolate, and prednisolone were used for the maintenance of immunosuppression. SAB screening was done at 1, 3, 6 months, and yearly in seven children and at the time of acute graft dysfunction in eight. Mean fluorescence intensity ≥1000 was considered positive. Protocol biopsies were done at 3, 6, and 12 months and annually thereafter in seven children. Fifteen children, all males with a median age (interquartile range) of 13 years (11; 15.5) were analyzed. Only one child had pretransplant DSA who developed dnDSA posttransplant. Overall, 8 (53%) developed dnDSA over a median follow-up of 18 months. Seven (87%) had Class II, one Class I and 3 (37%) both Class I and II. Six had dQ and two had DR. All children with dnDSA had ABMR, of these two had subclinical rejection. DSAs persisted despite treatment, though graft function improved. Children with DSA and ABMR had lower graft function than those without DSA. The proportion of dnDSA was high in our study, majority against DQ. The detection of dnDSA prompted early diagnosis and treatment of ABMR.

Ross Procedure Versus Mechanical Versus Bioprosthetic Aortic Valve Replacement: A Network Meta-Analysis.

Background The Ross operation appears to restore normal survival in young and middle-aged adults with aortic valve disease. However, there are limited data comparing it with conventional aortic valve replacement. Herein, we compared outcomes of the Ross procedure with mechanical and bioprosthetic aortic valve replacement (M-AVR and B-AVR, respectively). Methods and Results MEDLINE and EMBASE were searched through March 2022 to identify randomized controlled trials and propensity score-matched studies that investigated outcomes of patients aged ≥16 years undergoing the Ross procedure, M-AVR, or B-AVR. The systematic literature search identified 2 randomized controlled trials and 8 propensity score-matched studies involving a total of 4812 patients (Ross: n=1991; M-AVR: n=2019; and B-AVR: n=802). All-cause mortality was significantly lower in the Ross procedure group compared with M-AVR (hazard ratio [HR] [95% CI], 0.58 [0.35-0.97]; P=0.035) and B-AVR (HR [95% CI], 0.32 [0.18-0.59]; P<0.001) groups. The reintervention rate was lower after the Ross procedure and M-AVR compared with B-AVR, whereas it was higher after the Ross procedure compared with M-AVR. Major bleeding rate was lower after the Ross procedure compared with M-AVR. Long-term stroke rate was lower following the Ross procedure compared with M-AVR and B-AVR. The rate of endocarditis was also lower after the Ross procedure compared with B-AVR. Conclusions Improved long-term outcomes of the Ross procedure are demonstrated compared with conventional M-AVR and B-AVR options. These results highlight a need to enhance the recognition of the Ross procedure and revisit current guidelines on the optimal valve substitute for young and middle-aged patients.