BACKGROUND. Understanding outcomes and immunologic characteristics of cellular therapy recipients with SARS-CoV-2 is critical to performing these potentially life-saving therapies in the COVID-19 era. In this study of recipients of allogeneic (Allo) and autologous (Auto) hematopoietic cell transplant and CD19-directed chimeric antigen receptor T cell (CAR T) therapy at Memorial Sloan Kettering Cancer Center, we aimed to identify clinical variables associated with COVID-19 severity and assess lymphocyte populations. METHODS. We retrospectively investigated patients diagnosed between March 15, 2020, and May 7, 2020. In a subset of patients, lymphocyte immunophenotyping, quantitative real-time PCR from nasopharyngeal swabs, and SARS-CoV-2 antibody status were available. RESULTS. We identified 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days; IQR, 354-1611 days). Overall survival at 30 days was 78%. Clinical variables significantly associated with the composite endpoint of nonrebreather or higher oxygen requirement and death (n events = 25 of 77) included number of comorbidities (HR 5.41, P = 0.004), infiltrates (HR 3.08, P = 0.032), and neutropenia (HR 1.15, P = 0.04). Worsening graft-versus-host disease was not identified among Allo recipients. Immune profiling revealed reductions and rapid recovery in lymphocyte populations across lymphocyte subsets. Antibody responses were seen in a subset of patients. CONCLUSION. In this series of Allo, Auto, and CAR T recipients, we report overall favorable clinical outcomes for patients with COVID-19 without active malignancy and provide preliminary insights into the lymphocyte populations that are key for the antiviral response and immune reconstitution.

Purpose: SMARCA4 mutations are among the most common recurrent alterations in non-small cell lung cancer (NSCLC), but the relationship to other genomic abnormalities and clinical impact has not been established.Experimental Design: To characterize SMARCA4 alterations in NSCLC, we analyzed the genomic, protein expression, and clinical outcome data of patients with SMARCA4 alterations treated at Memorial Sloan Kettering.Results: In 4,813 tumors from patients with NSCLC, we identified 8% (n ¼ 407) of patients with SMARCA4-mutant lung cancer. We describe two categories of SMARCA4 mutations: class 1 mutations (truncating mutations, fusions, and homozygous deletion) and class 2 mutations (missense mutations). Protein expression loss was associated with class 1 mutation (81% vs. 0%, P < 0.001). Both classes of mutation co-occurred more frequently with KRAS, STK11, and KEAP1 mutations compared with SMARCA4 wild-type tumors (P < 0.001). In patients with metastatic NSCLC, SMARCA4 alterations were associated with shorter overall survival, with class 1 alterations associated with shortest survival times (P < 0.001). Conversely, we found that treatment with immune checkpoint inhibitors (ICI) was associated with improved outcomes in patients with SMARCA4mutant tumors (P ¼ 0.01), with class 1 mutations having the best response to ICIs (P ¼ 0.027).Conclusions: SMARCA4 alterations can be divided into two clinically relevant genomic classes associated with differential protein expression as well as distinct prognostic and treatment implications. Both classes co-occur with KEAP1, STK11, and KRAS mutations, but individually represent independent predictors of poor prognosis. Despite association with poor outcomes, SMARCA4-mutant lung cancers may be more sensitive to immunotherapy.

Objective To examine age–period–cohort effects on trends in gestational diabetes mellitus (GDM) prevalence in the US, and to evaluate how these trends have affected the rates of stillbirth and large for gestational age (LGA)/macrosomia. Design Retrospective cohort study. Setting USA, 1979–2010. Population Over 125 million pregnancies (3 337 284 GDM cases) associated with hospitalisations. Methods Trends in GDM prevalence were examined via weighted Poisson models to parse out the extent to which GDM trends can be attributed to maternal age, period of delivery, and maternal birth cohort. Multilevel models were used to assess the contribution of population effects to the rate of GDM. Log-linear Poisson regression models were used to estimate the contributions of the increasing GDM rates to changes in the rates of LGA and stillbirth between 1979–81 and 2008–10. Main outcome measures Rates and rate ratios (RRs). Results Compared with 1979–1980 (0.3%), the rate of GDM has increased to 5.8% in 2008–10, indicating a strong period effect. Substantial age and modest cohort effects were evident. The period effect is partly explained by period trends in body mass index (BMI), race, and maternal smoking. The increasing prevalence of GDM is associated with a 184% (95% CI 180–188%) decline in the rate of LGA/macrosomia and a 0.75% (95% CI 0.74–0.76) increase in the rate of stillbirths for 2008–10, compared with 1979–81. Conclusions The temporal increase in GDM can be attributed to period of pregnancy and age. Increasing BMI appears to partially contribute to the GDM increase in the US.

We sought to evaluate the extent of the association between placental implantation abnormalities (PIA) and preterm delivery in singleton gestations. We conducted a systematic review of English-language articles published from 1980 onward using PubMed, MEDLINE, EMBASE, CINAHL, LILACS, and Google Scholar, and by identifying studies cited in the references of published articles. Search terms were PIA defined as ≥ 1 of the following: placenta previa, placenta accreta, vasa previa, and velamentous cord insertion. Observational and experimental studies were included for review if data were available regarding any of the aforementioned PIA and regarding gestational age at delivery or preterm delivery. Case reports and case series were excluded. Studies were reviewed and data extracted. The primary outcome was gestational age at delivery or preterm delivery<37 weeks' gestation. Secondary outcomes included birthweight, 1- and 5-minute Apgar scores, neonatal intensive care unit (NICU) admission, neonatal and perinatal death, and small for gestational age. Of the 1421 studies identified, 79 met the defined criteria; 56 studies were descriptive and 23 were comparative. Based on the descriptive studies, the preterm delivery rates for low-lying/marginal placenta, placenta previa, placenta accreta, vasa previa, and velamentous cord insertion were 26.9%, 43.5%, 57.7%, 81.9%, and 37.5%, respectively. Based on the comparative studies using controls, there was decreased pregnancy duration for every PIA; more specifically, there was an increased risk for preterm delivery in patients with placenta previa (risk ratio [RR], 5.32; 95% confidence interval [CI], 4.39-6.45), vasa previa (RR, 3.36; 95% CI, 2.76-4.09), and velamentous cord insertion (RR, 1.95; 95% CI, 1.67-2.28). Risks of NICU admissions (RR, 4.09; 95% CI, 2.80-5.97), neonatal death (RR, 5.44; 95% CI, 3.03-9.78), and perinatal death (RR, 3.01; 95% CI, 1.41-6.43) were higher with placenta previa. Perinatal risks were also higher in patients with vasa previa (perinatal death rate RR, 4.52; 95% CI, 2.77-7.39) and velamentous cord insertion (NICU admissions [RR, 1.76; 95% CI, 1.68-1.84], small for gestational age [RR, 1.69; 95% CI, 1.56-1.82], and perinatal death [RR, 2.15; 95% CI, 1.84-2.52]). In singleton gestations, there is a strong association between PIA and preterm delivery resulting in significant perinatal morbidity and mortality.

Background Occupational and physical therapy (OT/PT) services seek to reduce morbidity, mortality, and improve the quality of life of individuals; however, little is known about the needs and use of OT/PT for older adults with cancer. The goal of this study was to describe the functional deficits and their associations with other factors, and to examine the use of OT/PT after a noted functional deficit. Materials and Methods This study analyzed data from an institution-based registry that included geriatric assessments of older adults with cancer linked to billing claims data. Logistic regression was used to model predictors of functional deficits. Use of OT/PT was determined and validated with medical chart review. Results 529 patients with cancer, a median age of 71, 78% were female, 87% Caucasian, 57% married, 53% post-secondary education, 63% with breast cancer were included. In a multivariable model, the odds of having any functional deficits increased with age [5 year OR: 1.31, 95% CI: (1.10, 1.57)] were higher for those with a high school diploma versus those with advanced degrees [OR: 1.66, 95% CI: (1.00, 2.77)] and were higher for patients with comorbidities [OR: 1.15, 95% CI: (1.10, 1.21)]. Of patients with functional deficits only 9% (10/111) received OT/PT within 12 months of a noted deficit. Discussion The odds of having any potentially modifiable functional deficit were higher in patients with increasing age, comorbid conditions, and with less than a college degree. Few were referred for OT/PT services suggesting major underutilization of these potentially beneficial services.