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The potential of adoptive cell therapy can be extended when combined with genome editing. However, variation in the quality of the starting material and the different manufacturing steps are associated with production failure and product contamination. Here, we present an automated T cell engineering process to produce off-the-shelf chimeric antigen receptor (CAR) T cells on an extended CliniMACS Prodigy platform containing an in-line electroporation unit. This setup was used to combine lentiviral delivery of a CD19-targeting CAR with transfer of mRNA encoding a TRAC locus-targeting transcription activator-like effector nuclease (TALEN). In three runs at clinical scale, the T cell receptor (TCR) alpha chain encoding TRAC locus was disrupted in >35% of cells with high cell viability (>90%) and no detectable off-target activity. A final negative selection step allowed the generation of TCRα/β-free CAR T cells with >99.5% purity. These CAR T cells proliferated well, maintained a T cell memory phenotype, eliminated CD19-positive tumor cells, and released the expected cytokines when exposed to B cell leukemia cells. In conclusion, we established an automated, good manufacturing practice (GMP)-compliant process that integrates lentiviral transduction with electroporation of TALEN mRNA to produce functional TCRα/β-free CAR19 T cells at clinical scale.Laboratory testing is required to distinguish coccidioidomycosis and histoplasmosis from other types of community-acquired pneumonia (CAP). In this nationwide survey of 1258 health care providers, only 3.7% reported frequently testing CAP patients for coccidioidomycosis and 2.8% for histoplasmosis. These diseases are likely underdiagnosed, and increased awareness is needed.Women with HIV (WWH) transitioning through menopause have heightened cardiovascular disease (CVD) risk. In the general population, hot flash burden relates to CVD risk indices. We found higher hot flash burden among women with vs without HIV. Further, among WWH, hot flash burden related to select CVD risk indices. NCT02874703. NCT02874703.We examined the microbial burden on hospital room environmental sites after standard (quaternary ammonium [Quat]) or enhanced disinfection (quat/ultraviolet light [UV-C], bleach, or bleach/UV-C). An enhanced terminal room disinfection reduced the microbial burden of epidemiologically important pathogens on high-touch surfaces in patient rooms, especially sites around the bed, better than standard room disinfection. Diagnosis codes are inadequate for accurately identifying herpes zoster ophthalmicus (HZO). Manual review of medical records is expensive and time-consuming, resulting in a lack of population-based data on HZO. We conducted a retrospective cohort study, including 87 673 patients aged ≥50 years who had a new HZ diagnosis and associated antiviral prescription between 2010 and 2018. We developed and validated an automated natural language processing (NLP) algorithm to identify HZO with ocular involvement (ocular HZO). We compared the characteristics of NLP-identified ocular HZO, nonocular HZO, and non-HZO cases among HZ patients and identified the factors associated with ocular HZO among HZ patients. The NLP algorithm achieved 94.9% sensitivity and 94.2% specificity in identifying ocular HZO cases. Among 87 673 incident HZ cases, the proportion identified as ocular HZO was 9.0% (n = 7853) by NLP and 2.3% (n = 1988) by codes. In adjusted analyses, older age and male sex were associated with an increased risk of ocular HZO; Hispanic and black race/ethnicity each were associated with a lower risk of ocular HZO compared with non-Hispanic white. The NLP algorithm achieved high accuracy and can be used in large population-based studies to identify ocular HZO, avoiding labor-intensive chart review. Age, sex, and race were strongly associated with ocular HZO among HZ patients. We should consider these risk factors when planning for zoster vaccination. The NLP algorithm achieved high accuracy and can be used in large population-based studies to identify ocular HZO, avoiding labor-intensive chart review. Age, sex, and race were strongly associated with ocular HZO among HZ patients. We should consider these risk factors when planning for zoster vaccination.The current severe acute respiratory syndrome coronavirus 2 testing policy and practice limits testing as a prevention tool. Radical shifts are required to increase the scale of rapid testing strategies and improve dissemination and implementation of venue-based and self-testing approaches. Attention to the full translation pipeline is required to reach high-risk segments of the population. The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, = .136). Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation. Long-term survival with IM among HM and HCT populations remains poor. https://www.selleckchem.com/products/Decitabine.html However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.
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