Anshal Gupta

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.

The COVID-19 pandemic has laid bare the inadequacy of the U.S. healthcare system to deliver timely and resilient care. According to the American Hospital Association, the pandemic has created a $202 billion loss across the healthcare industry, forcing health care systems to lay off workers and making hospitals scramble to minimize supply chain costs. However, as the demand for personal protective equipment (PPE) grows, hospitals have sacrificed sustainable solutions for disposable options that, although convenient, will exacerbate supply strains, financial burden, and waste. We advocate for reusable gowns as a means to lower health care costs, address climate change, and improve resilience while preserving the safety of health care workers. Reusable gowns' polyester material provides comparable capacity to reduce microbial cross-transmission and liquid penetration. In addition, previous hospitals have reported a 50% cost reduction in gown expenditures after adopting reusable gowns; given the current 2000% price increase in isolation gowns during COVID-19, reusable gown use will build both healthcare resilience and security from price fluctuations. Finally, with the United States' medical waste stream worsening, reusable isolation gowns show promising reductions in energy and water use, solid waste, and carbon footprint. The gowns are shown to withstand laundering 75-100 times in contrast to the single-use disposable gown. The circumstances of the pandemic forewarn the need to shift our single-use PPE practices to standardized reusable applications. Ultimately, sustainable forms of protective equipment can help us prepare for future crises that challenge the resilience of the healthcare system.

Background: Clinicians typically estimate heart failure health status using the New York Heart Association Class, which is often discordant with patient-reported health status. It is unknown whether collecting patient-reported health status improves the accuracy of clinician assessments. Methods: The PRO-HF trial (Patient-Reported Outcomes in Heart Failure Clinic) is a randomized, nonblinded trial evaluating routine Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) collection in heart failure clinic. Patients with a scheduled visit to Stanford heart failure clinic between August 30, 2021 and June 30, 2022 were enrolled and randomized to KCCQ-12 assessment or usual care. In this prespecified substudy, we evaluated whether access to the KCCQ-12 improved the accuracy of clinicians’ New York Heart Association assessment or patients’ perspectives on their clinician interaction. We surveyed clinicians regarding their patients’ New York Heart Association Class, quality of life, and symptom frequency. Clinician responses were compared with patients’ KCCQ-12 responses. We surveyed patients regarding their clinician interactions. Results: Of the 1248 enrolled patients, 1051 (84.2%) attended a visit during the substudy. KCCQ-12 results were given to the clinicians treating the 528 patients in the KCCQ-12 arm; the 523 patients in the usual care arm completed the KCCQ-12 without the results being shared. The correlation between New York Heart Association Class and KCCQ-12 Overall Summary Score was stronger when clinicians had access to the KCCQ-12 (r=−0.73 versus r=−0.61, P <0.001). More patients in the KCCQ-12 arm strongly agreed that their clinician understood their symptoms (95.2% versus 89.7% of respondents [odds ratio‚ 2.27; 95% CI‚ 1.32–3.87]). However, patients in both arms reported similar quality of clinician communication and therapeutic alliance. Conclusions: Collecting the KCCQ-12 in heart failure clinic improved clinicians’ accuracy of health status assessment; correspondingly, patients believed their clinicians better understood their symptoms. Registration: URL: https://www.clinicaltrials .gov; Unique identifier: NCT04164004.

BACKGROUND AND OBJECTIVES: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial and ethnic disparities in pediatric kidney transplantation access and related outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study of children <18 years of age active on the kidney transplant list from 2008 to 2019 using the Scientific Registry of Transplant Recipients. Log-logistic accelerated failure time models were used to determine the time from first activation on the transplant list and the time on dialysis to deceased donor transplant, each with KAS era or race and ethnicity as the exposure of interest. We used logistic regression to assess odds of delayed graft function. Log-rank tests assessed time to graft loss within racial and ethnic groups across KAS eras. RESULTS: All children experienced longer wait times from activation to transplantation post-KAS. In univariable analysis, Black and Hispanic children and other children of color experienced longer times from activation to transplant compared with White children in both eras; this finding was largely attenuated after multivariable analysis (time ratio, 1.16; 95% confidence interval, 1.01 to 1.32; time ratio, 1.13; 95% confidence interval, 1.00 to 1.28; and time ratio, 1.17; 95% confidence interval, 0.96 to 1.41 post-KAS, respectively). Multivariable analysis also showed that racial and ethnic disparities in time from dialysis initiation to transplantation in the pre-KAS era were mitigated in the post-KAS era. There were no disparities in odds of delayed graft function. Black and Hispanic children experienced longer times with a functioning graft in the post-KAS era. CONCLUSIONS: No racial and ethnic disparities from activation to deceased donor transplantation were seen before or after implementation of the KAS in multivariable analysis, whereas time on dialysis to transplantation and odds of short-term graft loss improved in equity after the implementation of the KAS, without compromising disparities in delayed graft function. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_07_CJN06740521.mp3.