Citations

Abstract This global phase 3 study compared lisocabtagene maraleucel (liso-cel) with a standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT; N = 184) were randomly assigned in a 1:1 ratio to liso-cel (100 × 106 chimeric antigen receptor–positive T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS). In this primary analysis with a 17.5-month median follow-up, median EFS was not reached (NR) for liso-cel vs 2.4 months for SOC. Complete response (CR) rate was 74% for liso-cel vs 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel vs 6.2 months for SOC (hazard ratio [HR] = 0.400; P < .0001). Median overall survival (OS) was NR for liso-cel vs 29.9 months for SOC (HR = 0.724; P = .0987). When adjusted for crossover from SOC to liso-cel, 18-month OS rates were 73% for liso-cel and 54% for SOC (HR = 0.415). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4 or 5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel compared with SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03575351.

AbstractBackgroundAs the population ages in the United States, the prevalence of many diseases like Alzheimer disease, related dementias, and Parkinson disease disproportionately affect those already at greatest risk for premature morbidity and mortality. Aging research has an opportunity to engage and support patients, communities, and caregivers most impacted by these diseases. However, under‐resourced communities frequently lack representation in research, causing decreased generalizability of study results and health inequities among these communities.MethodsUsing a community and patient engaged framework, we conducted three community engagement studios (studios) with caregivers, patients, providers, researchers, and advocates from the St. Louis community. The studios provide community input and recommendations on project feasibility, design, and cultural appropriateness. Proposed projects were presented during each studio, followed by a facilitated discussion with a neutral facilitator. Themes were derived using traditional qualitative content analysis.ResultsStakeholders included under‐resourced community members, LGBTQIA+ participants, and those without/inadequate health insurance. The main themes included participant commitment to health, culturally appropriate research design, and incentives. In addition, participants desired collaboration between researchers and the community, including connecting with local Alzheimer’s Disease Associations, faith‐based groups, and philanthropic organizations.ConclusionOur community stakeholders provided feedback on how we could modify the research design to increase community involvement, enhance participant recruitment and commitment, and reach populations currently underrepresented in aging research, especially Alzheimer’s disease. The early inclusion of stakeholders in research design and implementation constitutes a preliminary step to building trust within under‐resourced communities and increasing the recruitment and retention of diverse populations.

PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.

Abstract Background Clostridioides difficile infection (CDI) incidence estimates vary between geographic regions; few studies have evaluated the impact of CDI test order frequency on estimated CDI incidence. We evaluated this impact in a sample of hospitals at two CDC Emerging Infections Program (EIP) sites. Methods Daily surveillance was conducted for diarrhea among inpatients at 5 acute care hospitals (2,379 beds) in EIP sites in NY (2 hospitals) and GA (3 hospitals) during two 10-workday periods in 2020 and 2021. Diarrhea onset, test orders, and specimen collection status were ascertained. Stools were tested by PCR/NAAT initially or after negative EIA toxin. Differences in diarrhea incidence, testing frequency, and CDI positivity across site, care locations and hospitals were compared using Wilcoxon rank sum test. Correlates of CDI testing and positivity were assessed using modified Poisson regression. Estimates of incidence using EIP methodology at 5 hospitals was compared between sites using Mantel-Hanzel summary rate ratio. Results Surveillance of 38,365 patient-days (PD) identified 860 diarrhea cases from 107 patient-care locations mapped to 26 unique NHSN defined location-types. Incidence of diarrhea was 22.4/1000 PD (medians 25.8 NY, 16.2 GA, P< 0.01); with similar proportions of diarrhea being hospital-onset (66%) and CDI positive (17%) by site. Overall, 35% were tested for CDI (21% NY, 49% GA, P< 0.01). Percent tested varied by NHSN location type (Figure). Regression models identified location-type (oncology, critical care), laxatives use, chemotherapy, and residing in EIP catchment area predictive of testing (Figure). Adjusting for these factors, NY was 49% less likely than GA to test (aRR 0.51, 95% CI 0.40-0.63). Simulation of EIP methods estimated NY had a 38% lower incidence of CDI than GA (summary rate ratio 0.62, 95% CI, 0.54-0.71). Figure Incidence of Diarrheal Episodes (A) and Proportions Tested (B) among Hospitalized Patients, 2021 (solid, ward; open, critical care; grey, oncology), and adjusted relative risk (solid circles) with 95% confidence intervals (whisker) of independent predictors of testing for CDI (C). Conclusion After adjusting for patient characteristics (e.g., location-type, laxative use), the likelihood of testing still differed between NY and GA sites; the magnitude of the differences in testing was similar to that observed in estimated CDI incidence. Testing practices likely influence surveillance data and is a consideration when comparing data across regions. Disclosures Scott Fridkin, MD, Pfizer: Grant/Research Support christopher J. Myers, MS, Infectious diseases, Pfizer: Grant/Research Support Udodirim N. Onwubiko, MBBS MPH, Pfizer: Grant/Research Support William C. Dube, MPH, Pfizer: Grant/Research Support Sahil Khanna, MBBS, MS, Pfizer: Grant/Research Support Joann M. Zamparo, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Frederick J. Angulo, DVM PhD, Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

ImportanceLate-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.ObjectiveTo report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age.Design, Setting, and ParticipantsThis cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks’ gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers.ExposuresCulture-confirmed LOM.Main Outcomes and MeasuresIncidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021).ResultsAmong 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection.Conclusions and RelevanceIn this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.