Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.

A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe immune-mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel. We develop a simple stratification based on pre-lymphodepletion C reactive protein (CRP) and ferritin to classify patients into low-, intermediate-, and high-risk groups. We observe that patients in the high-risk category were more likely to develop grade ≥3 toxicities and had inferior overall and progression-free survival. We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low-risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy. SIGNIFICANCE: CAR T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin can identify patients at high risk of poor outcomes. This article is featured in Selected Articles from This Issue, p. 80.

Acute Chest Pain Following Bravo Device Placement.

A Bravo device is a continuous pH monitor, produced by Medtronic (Minneapolis, MN), that is placed on the esophageal mucosa during endoscopy and can be used in the evaluation of gastroesophageal reflux disease (GERD). The device detaches by itself and passes with feces in approximately 7-10 days. Because of its brief presence in the body, the device is an unusual finding on imaging and could easily be mistaken for a more ominous foreign body. The Bravo device is typically well tolerated but can be a source of severe discomfort. Its presence is an important consideration in the differential of chest pain and a contraindication to MRI. Here, we discuss a case of a patient presenting to the emergency department (ED) with acute chest pain who underwent Bravo device placement several days prior.

Reducing postoperative opioid pill prescribing via a quality improvement approach.

BACKGROUND: The opioid epidemic has been fueled by prescribing unnecessary quantities of opioid pills for postoperative use. While evidence mounts that postoperative opioids can be reduced or eliminated, implementing such changes within various institutions can be met with many barriers to adoption. OBJECTIVE: To address excess opioid prescribing within our institutions, we applied a plan-do-study-act (PDSA)-like quality improvement strategy to assess local opioid prescribing and use, modify our institutional protocols, and assess the impacts of the change. The opioid epidemic has been fueled by prescribing unnecessary quantities of opioid pills for postoperative use. While evidence mounts that postoperative opioids can be reduced or eliminated, implementing such changes within various institutions can be met with many barriers to adoption. We describe our approach, findings, and lessons learned from our quality improvement approach. METHODS: We prospectively recorded home pain pill usage after robotic-assisted laparoscopic prostatectomy (RALP) and robotic-assisted partial nephrectomy (RAPN) at two academic institutions from July 2016 to July 2019. Patients prospectively recorded their home pain pill use on a take-home log. Other factors, including numeric pain rating scale on the day of discharge, were extracted from patient records. We analyzed our data and modified opioid prescription protocols to meet the reported use data of 80% of patients. We continued collecting data after the protocol change. We also used our prospectively collected data to assess the accuracy of a retrospective phone survey designed to measure postdischarge opioid use. Our primary outcomes were the proportion of patients taking zero opioid pills postdischarge, median pills taken after discharge and the number of excess pills prescribed but not taken. We compared these outcomes before and after protocol change. RESULTS: A total of 266 patients (193 RALP, 73 RAPN) were included. Reducing the standard number of prescribed pills did not increase the percentage of patients taking zero pills postdischarge in either group (RALP: 47% vs. 41%; RAPN 48% vs. 34%). The patients in either group reporting postoperative Day 1 pain score of 0 or 1 were much more likely to use zero postdischarge opioid pills. Our reduction in prescribing protocol resulted in an estimated reduction in excess pills from 1555 excess pills in the prior protocol to just 155 excess pills in the new protocol. CONCLUSION: Our PDSA-like approach led to an acceptable protocol revision resulting in significant reductions in excess pills released into the community. Reducing the quantity of opioids prescribed postoperatively does not increase the percentage of patients taking zero pills postdischarge. To eliminate opioid use may require no-opioid pathways. Our approach can be used in implementing zero opioid discharge plans and can be applied to opioid reduction interventions at other institutions where barriers to reduced prescribing exist.

Increased thrombosis susceptibility and altered fibrin formation in STAT5-deficient mice.

To explore the effect(s) of growth hormone signaling on thrombosis, we studied signal transduction and transcription factor 5 (STAT5)-deficient mice and found markedly reduced survival in an in vivo thrombosis model. These findings were not explained by a compensatory increase in growth hormone secretion. There was a modest increase in the activity of several procoagulant factors, but there was no difference in the rate or magnitude of thrombin generation in STAT5-deficient mice relative to control. However, thrombin-triggered clot times were markedly shorter, and fibrin polymerization occurred more rapidly in plasma from STAT5-deficient mice. Fibrinogen depletion and mixing studies indicated that the effect on fibrin polymerization was not due to intrinsic changes in fibrinogen, but resulted from changes in the concentration of a circulating plasma inhibitor. While thrombin-triggered clot times were significantly shorter in STAT5-deficient animals, reptilase-triggered clot times were unchanged. Accordingly, while the rate of thrombin-catalyzed release of fibrinopeptide A was similar, the release of fibrinopeptide B was accelerated in STAT5-deficient plasma versus control. Taken together, these studies demonstrated that the loss of STAT5 resulted in a decrease in the concentration of a plasma inhibitor affecting thrombin-triggered cleavage of fibrinopeptide B. This ultimately resulted in accelerated fibrin polymerization and greater thrombosis susceptibility in STAT5-deficient animals.