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ImportancePathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS).ObjectiveTo examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response.Design, Setting, and ParticipantsThe study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence.InterventionsParticipants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery.Main Outcomes and MeasuresThe presence of DCIS and EFS, DRFS, and LRR.ResultsThe study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS.Conclusions and RelevanceThe analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS.Trial RegistrationClinicalTrials.gov Identifier NCT01042379.

Abstract Refractory post‐operative chylothorax in congenital heart disease is difficult to treat. We present a case of intractable neonatal chylothorax after cardiac surgery due to central lymphatic flow disorder that was treated by creating a lymphovenous anastomosis of the thoracic duct to the left external jugular vein for definitive treatment.

Abstract Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

OBJECTIVES: To describe hospital variation in use of “guideline-based care” for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Retrospective, observational study. SETTING: The Society of Critical Care Medicine’s Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS: Hospital-level use of “guideline-based care” for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao 2/Fio 2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in “guideline-based care.” A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1–3.4) for receipt of “guideline-based care” compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47–62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use “guideline-based care” quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3–1.9; p = 0.49). CONCLUSIONS: During the first year of the COVID-19 pandemic, only half of patients received “guideline-based care” for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

AbstractBackgroundLung transplant recipients are at increased risk of candidemia, especially in the early posttransplant period. However, the specific predisposing factors have not been established. The natural history of candidemia after lung transplantation, in the absence of universal antifungal prophylaxis, is not known.MethodsWe retrospectively examined the epidemiology of candidemia at any time posttransplant in patients who underwent lung transplantation at our center between 2016 and 2019. We undertook a case‐control study and used logistic regression to evaluate the risk factors for candidemia during the first 30 days posttransplantation.ResultsDuring the study period 712 lung transplants were performed on 705 patients. Twenty‐five lung transplant recipients (LTRs) (3.5%) experienced 31 episodes of candidemia. The median time to candidemia was 19.5 days (IQR 10.5–70.5), with 61.2% (n = 19) episodes of candidemia occurring within the first 30 days posttransplantation. Pretransplant hospitalization, posttransplant ECMO, and posttransplant renal replacement therapy were associated with an increased risk of candidemia in the first 30 days posttransplant. Of those with candidemia in the first 30 days, 31.2% died within 30 days of the index positive blood culture. Candidemia was associated with decreased survival within 30 days posttransplant.ConclusionThis study highlights the greatest risk period of lung transplant recipients for development of candidemia and identifies several factors associated with increased risk of candidemia. These findings will help guide future studies on antifungal prophylaxis.

Refractory post-operative chylothorax in congenital heart disease is difficult to treat. We present a case of intractable neonatal chylothorax after cardiac surgery due to central lymphatic flow disorder that was treated by creating a lymphovenous anastomosis of the thoracic duct to the left external jugular vein for definitive treatment

ABSTRACT Background The COVID-19 pandemic displaced newly matched emergency medicine “pre-interns” from in-person educational experiences at the end of medical school. This called for novel remote teaching modalities. Objective This study assesses effectiveness of a multisite Accreditation Council for Graduate Medical Education (ACGME) sub-competency-based curricular implementation on Slack during the first wave of the COVID-19 pandemic in the United States. Methods Emergency medicine residency programs were recruited via national organization listservs. Programs designated instructors to manage communications and teaching for the senior medical students who had matched to their programs (pre-interns) in spring/summer 2020. Pre- and post-surveys of trainees and instructors assessed perceived preparedness for residency, perceived effectiveness of common virtual educational modalities, and concern for the pandemic's effects on medical education utilizing a Likert scale of 1 (very unconcerned) to 5 (very concerned). Data were analyzed using descriptive statistics and the t test. Results Of 276 possible residency programs, 28 enrolled. Of 324 possible pre-interns, 297 (91.7%) completed pre-surveys in April/May and 249 (76.9%) completed post-surveys in June/July. The median weeks since performing a physical examination was 8 (IQR 7–12), since attending in-person didactics was 10 (IQR 8–15) and of rotation displacement was 4 (IQR 2–6). Perceived preparedness increased both overall and for 14 of 21 ACGME Milestone topics taught. Instructors reported higher mean concern (4.32, 95% CI 4.23–4.41) than pre-interns (2.88, 95% CI 2.74–3.02) regarding the pandemic's negative effects on medical education. Conclusions Pre-interns reported improvements in residency preparedness after participating in this ACGME sub-competency-based curriculum on Slack.

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.