Citations

Abstract We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine our latest data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting.

Background: Post-episode tapering of Standard of Care (SoC) medication in patients with recurrent pericarditis (RP) varies considerably. Gradual tapering of corticosteroids (CS) is recommended in ESC guidelines (decreasing by 1-2.5 mg/day every 2-6 weeks over 1-2 years) to prevent recurrence. We describe successful faster tapering of SoC treatment onto rilonacept monotherapy during RHAPSODY, a Phase 3, placebo-controlled, randomized-withdrawal (RW) trial in RP. Methods: Patients with acute symptomatic RP despite stable doses of NSAIDs, colchicine, and/or CS in any combination enrolled in a 12-week run-in period in which weekly rilonacept was initiated. After 1-week of stabilization, tapering of CS began at a rate dependent on baseline dose, to be completed by Week 10 for randomization at Week 12 when clinical response was confirmed by reduced pain and normalized CRP levels. Colchicine tapering/discontinuation was initiated no earlier than Week 4. This analysis evaluates time to rilonacept monotherapy in subgroups receiving different combinations of background therapies. Results: 79 of 86 patients were receiving pharmacotherapy at run-in baseline. Median (95% CI) time to monotherapy (n=79) was 7.9 (7.0-8.1) weeks. Of the patients receiving CS at baseline (41/86 [48%]), 39 (95%) tapered to rilonacept monotherapy, and median time to monotherapy was 7.9 (7.1-8.1) weeks. Of the patients receiving colchicine at baseline (65/86 [76%]), 61 (94%) patients achieved rilonacept monotherapy, and median time to monotherapy was 8.0 (7.1-8.3) weeks. Patients receiving only one SoC therapy achieved rilonacept monotherapy faster (6.1 [0.4-8.1] weeks) than those receiving 2 (8.0 [6.7-9.9] weeks) or 3 (7.7 [7.0-8.3] weeks) therapies. All patients who did not achieve monotherapy had withdrawn from the study for reasons unrelated to pericarditis. Conclusion: All patients randomized in the RHAPSODY trial discontinued SoC and transitioned to rilonacept monotherapy (median time 7.9 weeks) without a recurrent pericarditis episode during run-in. With rilonacept, time to successful discontinuation of SoC, including high dose CS, was substantially more rapid than current treatment practices. RHAPSODY data helped support FDA approval of the first therapy for RP.

Abstract Aims Readmission is frequent among patients with cirrhosis and is a complex multifactorial process. To examine the association of alcohol use disorder (AUD) and risk of readmission in patients with alcohol-associated cirrhosis. Methods and Results National Readmission Dataset (2016–2017) was used to extract a retrospective cohort of 53,348 patients with primary or secondary discharge diagnosis code of alcohol-associated cirrhosis with their first admission (26,674 patients with vs. propensity matched 26,674 without a primary or secondary discharge diagnosis code of AUD). Readmission within 30-day was lower (43.9 vs. 48%, P < 0.001) among patients identified to have AUD at the time of discharge. In a conditional logistic regression model, a diagnosis of AUD was associated with 15% reduced odds of 30-day readmission, 0.85 (0.83–0.88). Furthermore, the reason for readmission among patients identified vs. not identified to have AUD was less likely to be liver disease complication. The findings remained similar in a matched cohort of patients where the AUD diagnosis at discharge was listed as one of the secondary diagnoses only. Conclusion Although, our study findings suggest that identification of AUD at the time of discharge among patients hospitalized for alcohol-associated cirrhosis reduces the risk of 30-day readmission, unavailable information on patient counseling, referral for mental health specialist and treatment received for AUD limit the causality assessment. Future studies are needed overcoming the inherent limitations of the database to establish the role of identification and treatment of AUD in reducing readmission and liver decompensation in patients with alcohol-associated cirrhosis.

Abstract Purpose: CALGB/SWOG 80405 was a randomized phase III trial in first-line patients with metastatic colorectal cancer treated with bevacizumab, cetuximab, or both, plus chemotherapy. We tested the effect of tumor immune features on overall survival (OS). Experimental Design: Primary tumors (N = 554) were profiled by RNA sequencing. Immune signatures of macrophages, lymphocytes, TGFβ, IFNγ, wound healing, and cytotoxicity were measured. CIBERSORTx scores of naive and memory B cells, plasma cells, CD8+ T cells, resting and activated memory CD4+ T cells, M0 and M2 macrophages, and activated mast cells were measured. Results: Increased M2 macrophage score [HR, 6.30; 95% confidence interval (CI), 3.0–12.15] and TGFβ signature expression (HR, 1.35; 95% CI, 1.05–1.77) were associated with shorter OS. Increased scores of plasma cells (HR, 0.55; 95% CI, 0.38–0.87) and activated memory CD4+ T cells (HR, 0.34; 95% CI, 0.16–0.65) were associated with longer OS. Using optimal cutoffs from these four features, patients were categorized as having either 4, 3, 2, or 0–1 beneficial features associated with longer OS, and the median (95% CI) OS decreased from 42.5 (35.8–47.8) to 31.0 (28.8–34.4), 25.2 (20.6–27.9), and 17.7 (13.5–20.4) months respectively (P = 3.48e–11). Conclusions: New immune features can be further evaluated to improve patient response. They provide the rationale for more effective immunotherapy strategies.

BACKGROUND Discharge from the NICU is a highly complex process. Multidisciplinary survey results and chart audits identified gaps in the timeliness and efficiency of discharge in our NICU. Using the define-measure-analyze-improve-control quality improvement framework, we aimed to increase the percentage of patients discharged before 11:00 am from a baseline mean of 9.4% to 50% without adversely impacting caregiver readiness to discharge. METHODS We used a fishbone diagram to identify causes of late and inefficient NICU discharge. A Pareto chart and Impact-Effort matrix were used to select targets for improvement efforts. Plan-do-study-act (PDSA) cycles established a goal unit discharge time, created a discharge checklist, prioritized rounding on discharging patients, set expectations for caregiver education completion, and increased nurse knowledge and comfort with providing caregiver education. RESULTS The mean percent of patients discharged before 11:00 am increased from 9.4% to 52.4%, exceeding our aim. Median discharge time improved from 13:30 pm to 11:15 am (P < .001). Discharge was more efficient as demonstrated by significantly earlier completion of many discharge tasks. These improvements did not adversely impact reported caregiver readiness to discharge (75% vs 77%, P = .76). CONCLUSIONS Quality improvement methods can significantly improve the timeliness and efficiency of NICU discharge. Improvement in this complex process may be facilitated by a multidisciplinary team that offers diverse perspectives, unique process and methodologic knowledge, and the ability to appeal to all unit stakeholders. Lessons learned from this project may benefit other teams working to improve their ICU discharge process.

INTRODUCTION: Despite studies showing improved safety, efficacy, and cost-effectiveness of endoscopic resection for nonmalignant colorectal polyps, colectomy rates for nonmalignant colorectal polyps have been increasing in the United States and Europe. Given this alarming trend, we aimed to investigate whether colectomy rates for nonmalignant colorectal polyps are increasing or declining in a large, integrated, community-based healthcare system with access to advanced endoscopic resection procedures. METHODS: We identified all individuals aged 50–85 years who underwent a colonoscopy between 2008 and 2018 and were diagnosed with a nonmalignant colorectal polyp(s) at the Kaiser Permanente Northern California integrated healthcare system. Among these individuals, we identified those who underwent a colectomy for nonmalignant colorectal polyps within 12 months after the colonoscopy. We calculated annual colectomy rates for nonmalignant colorectal polyps and stratified rates by age, sex, and race and ethnicity. Changes in rates over time were tested by the Cochran-Armitage test for a linear trend. RESULTS: Among 229,730 patients who were diagnosed with nonmalignant colorectal polyps between 2008 and 2018, 1,611 patients underwent a colectomy. Colectomy rates for nonmalignant colorectal polyps decreased significantly from 125 per 10,000 patients with nonmalignant polyps in 2008 to 12 per 10,000 patients with nonmalignant polyps in 2018 ( P < 0.001 for trend). When stratified by age, sex, and race and ethnicity, colectomy rates for nonmalignant colorectal polyps also significantly declined from 2008 to 2018. DISCUSSION: In a large, ethnically diverse, community-based population in the United States, we found that colectomy rates for nonmalignant colorectal polyps declined significantly over the past decade likely because of the establishment of advanced endoscopy centers, improved care coordination, and an organized colorectal cancer screening program.

Treatment with the MTOR inhibitor everolimus improves progression-free survival (PFS) in pancreatic neuroendocrine tumors (pNETs), but it is not known if the addition of a VEGF pathway inhibitor to an MTOR inhibitor enhances antitumor activity. We performed a randomized phase II study evaluating everolimus with or without bevacizumab in patients with advanced pNETs. One hundred and fifty patients were randomized to receive everolimus 10 mg daily with or without bevacizumab 10 mg/kg i.v. every 2 weeks. Patients also received standard dose of octreotide in both arms. The primary endpoint was PFS, based on local investigator review. Treatment with the combination of everolimus and bevacizumab resulted in improved progression-free survival compared to everolimus (16.7 months compared to 14.0 months; one-sided stratified log-rank P = 0.1028; hazard ratio (HR) 0.80 (95% CI 0.56–1.13)), meeting the predefined primary endpoint. Confirmed tumor responses were observed in 31% (95% CI 20%, 41%) of patients receiving combination therapy, as compared to only 12% (95% CI 5%, 19%) of patients receiving treatment with everolimus ( P = 0.0053). Median overall survival duration was similar in the everolimus and combination arm (42.5 and 42.1 months, respectively). Treatment-related toxicities were more common in the combination arm. In summary, treatment with everolimus and bevacizumab led to superior PFS and higher response rates compared to everolimus in patients with advanced pNETs. Although the higher rate of treatment-related adverse events may limit the use of this combination, our results support the continued evaluation of VEGF pathway inhibitors in pNETs.

Objectives: Limited information is available on the prevalence of cardiorespiratory arrest (CA) and its predisposing factors in patients with acute ischemic stroke. We analyzed/evaluated clinical characteristics, risk factors, access to care, and survival in stroke patients who developed a cardiac arrest. Methods: This is a multicenter cohort study including consecutive patients with acute ischemic stroke admitted to regional stroke centers participating in the Registry of the Canadian Stroke Network from July 2003 to March 2008. Patients with DNR order on admission were excluded. CA was defined as cardiac or respiratory arrest within 30 days of admission documented by a physician and identified from resuscitation records. The main outcome measures were the 30-day and 1-year survival among patients with CA vs. no CA. We also assessed the association between medical complications during hospitalization and CA. Results: Overall, 9,019 patients with acute ischemic stroke were included. Cardiac arrest was observed in 352 patients (3.9%). In patients with CA, 30-day survival (17.9% vs. 90.7%, P<0.001) and 1-year survival (4.5% vs. 80.1, p<0.001) were significantly lower. Less than 1% of stroke patients with CA were discharged home (vs. 47.3%; p<0.0001). Other outcome measures are summarized in Table 1. On multivariable analyses, older age, more severe stroke, previous history of myocardial infarction, congestive heart failure, atrial fibrillation, and diabetes were associated with CA. Conclusions: Cardiac arrest affects less than 5% of patients admitted with an acute ischemic stroke and is associated with poor outcomes. Less than 1% of patients were independent or discharged home.