Treatment of AL amyloidosis in the era of novel immune and cellular therapies

Light chain (AL) amyloidosis is a plasma cell disorder distinguished from multiple myeloma (MM) by the degree of organ involvement due to tissue deposition of misfolded proteins. Treatments for AL amyloidosis have largely been borrowed from those developed for patients with MM. High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has historically been associated with the best outcomes. The recent incorporation of daratumumab into up front therapy represents a significant advance and has changed the treatment paradigm, calling into question the role of ASCT. The development of very active novel immune and cellular therapies, specifically B cell maturation antigen (BCMA)-directed therapies, has similarly been transformative for patients with MM and is now being studied in patients with AL amyloidosis. These include chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody drug conjugates. Although limited, preliminary data in patients with relapsed and refractory AL amyloidosis are showing promising results, and it is expected that the treatment landscape for AL amyloidosis will continue to evolve. Particular attention to safety, potential for organ recovery, and quality of life will be important when evaluating new treatments and/or treatment paradigms

Ethnic and Gender Disparities in the Uptake of Transcatheter Aortic Valve Replacement in the United States

Introduction: Little is known about ethnic and gender disparities for transcatheter aortic valve replacement (TAVR) procedures in the United States. Methods: We queried the Nationwide Inpatient Sample (NIS) database (2011–2014) to identify patients who underwent TAVR. We described the temporal trends in the uptake of TAVR procedures among various ethnicities and genders. Results: Our analysis identified 39,253 records; 20,497 (52.2%) were men and 18,756 (47.8%) were women. Among all TAVRs, 87.2% were Caucasians, 3.9% were African Americans (AA), 3.7% were Hispanics, and 5.2% were of other ethnicities. We found a significant rise in the trend of TAVRs in all groups: in Caucasian men (coefficient = 0.946, p \u3c 0.001), Caucasian women (coefficient = 0.985, p \u3c 0.001), AA men (coefficient = 0.940, p \u3c 0.001), AA women (coefficient = 0.864, p \u3c 0.001), Hispanic men (coefficient = 0.812, p = 0.001), Hispanic women (coefficient = 0.845, p \u3c 0.001). Hence, the uptrend was most significant among Caucasian women, and relatively least significant among Hispanic men. Multivariate regression analysis was conducted to evaluate in-hospital mortality among different groups after adjusting for demographics and baseline characteristics. After multivariable regression for baseline characteristics overall, the in-hospital mortality per 100 TAVRs was highest among Hispanic men 5.5%, followed by Caucasian women 5.0%, Hispanic women 4.6%, AA women 3.7%, AA men 3.4%, and Caucasian men 3.38% (adjusted p value = 0.004). Conclusions: In this observational study, we demonstrated that there is evidence of ethnic and gender differences in the overall uptake and adjusted mortality of TAVRs in the United States

Critical Review and Meta-Analysis of Postoperative Sedation after Adult Cardiac Surgery: Dexmedetomidine Versus Propofol

Objective: To evaluate reports from the published literature of all randomized clinical trials (RCT) comparing postoperative sedation with dexmedetomidine versus propofol in adult patients, after open cardiac surgery.Design: A computerized search on Medline, EMBASE, Web of Science, and Agency for Healthcare Research and Quality databases was completed through June 2020. Meta-analysis of all published RCT comparing dexmedetomidine versus propofol utilization in the postoperative phase, using the standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.Setting: Assemblage and critical discussion of 11 RCTs comparing postoperative sedation from standard published reports from 2003 to 2019.Participants: The study comprised 1,184 patients and analyzed critical discussion of time-based parameters (time to extubation, intensive care unit length of stay, and hospital length of stay) and nontime-dependent factors (delirium, bradycardia, and hypotension).Measurements and Main Results: Time to extubation was significantly reduced in the dexmedetomidine group (standardized mean difference [SMD] = -0.70, 95% confidence interval [CI] -0.98 to -0.42, p < 0.001); however, no difference in mechanical ventilation time was observed (SMD = -0.72, 95% CI -1.60 to 0.15, N.S.). Dexmedetomidine significantly reduced the intensive care unit length of stay (SMD = 0.23, 95% CI -1.06 to -0.16, p = 0.008), but this did not translate into a reduced hospital length of stay (SMD = -1.13, 95% CI -2.43 to 0.16, N.S). For nontime-dependent factors, incidence of delirium was unaffected between groups (odds ratio [OR]: 0.68, 95% CI 0.43-1.06, N.S), and higher rates of bradycardia (OR: 3.39, 95% CI: 1.20-9.55, p = 0.020) and hypotension (OR: 1.68, 95% CI 1.09-2.58, p = 0.017) were reported with propofol.Conclusions: Despite the ICU time advantages afforded by dexmedetomidine over propofol, the former did not seem to contribute to an overall reduction in hospital length of stay or improvement in postoperative outcomes of heart valve surgery and CABG patients. (C) 2020 Published by Elsevier Inc

Quality Improvement Project of a Massive Transfusion Protocol (MTP) to Reduce Wastage of Blood Components

Massive transfusion protocols (MTPs) facilitate the organized delivery of blood components for traumatically injured patients. MTPs vary across institutions, and ratios of blood components can change during clinical management. As a result, significant amounts of components can be wasted. We completed a review of all MTP activations from 2015 to 2018, providing an in-depth analysis of waste in our single Level 1 trauma center. An interdepartmental group analyzed patterns of blood component wastage to guide three quality improvement initiatives. Specifically, we (1) completed a digital timeline for each MTP activation and termination, (2) improved communications between departments, and (3) provided yearly training for all personnel about MTP deployment. The analysis identified an association between delayed MTP deactivations and waste (RR = 1.48, CI 1.19-1.85, p = 0.0005). An overall improvement in waste was seen over the years, but this could not be attributed to increased closed-loop communication as determined by the proportion of non-stop activations (F(124,3) = 0.98, not significant). Delayed MTP deactivations are the primary determinant of blood component waste. Our proactive intervention on communications between groups was not sufficient in reducing the number of delayed deactivations. However, implementing a digital timeline and regular repetitive training yielded a significant reduction in wasted blood components

Meta-Analysis of Trials on Prophylactic Use of Levosimendan in Patients Undergoing Cardiac Surgery

BACKGROUND: The role of prophylactic levosimendan in patients undergoing cardiac surgery is controversial. METHODS: We performed a computerized search of Medline, Embase, and Cochrane databases through September 2017 for randomized trials evaluating the prophylactic use of levosimendan in patients undergoing cardiac surgery (ie, patients without low cardiac output syndrome). The main study outcome was mortality at 30 days. RESULTS: The final analysis included 16 randomized trials with total of 2,273 patients. There was no statistically significant difference in mortality at 30 days between levosimendan and control groups (relative risk 0.68, 95% confidence interval [CI]: 0.45 to 1.03). Subgroup analysis showed no statistically significant difference in mortality at 30 days for patients with reduced left ventricular ejection fraction compared with patients having preserved left ventricular ejection fraction (p for interaction = 0.12). Further analysis suggested that levosimendan might be associated with improved mortality at 30 days when compared with active-control but not when compared with placebo (p for interaction = 0.01). The levosimendan group had a significant reduction in acute kidney injury (relative risk 0.59, 95% CI: 0.38 to 0.92), intensive care unit stay (standardized mean difference = -0.21, 95% CI: -0.29 to -0.13), and ventilation time (standardized mean difference = -0.43, 95% CI: -0.61 to -0.25), whereas it had higher rates of atrial fibrillation (relative risk 1.11, 95% CI: 1.00 to 1.24). No statistically significant differences were observed between groups in mortality beyond 30 days, postoperative dialysis, or myocardial infarction. CONCLUSIONS: Prophylactic use of levosimendan does not appear to reduce the mortality at 30 days or beyond 30 days in patients undergoing cardiac surgery. This lack of benefit was noted irrespective of the LVEF

Assessment of Bleeding Risk in Hospitalized COVID-19 Patients: A Tertiary Hospital Experience during the Pandemic in a Predominant Minority Population-Bleeding Risk Factors in COVID-19 Patients

INTRODUCTION: In the wake of the SARS-CoV-2 (COVID-19) pandemic, our world has faced multiple challenges. Infection with this virus has commonly been associated with thrombotic events. However, little is known about bleeding risk and anticoagulation therapy. This study aims to determine factors that are associated with increased risk of bleeding in COVID-19 patients. METHODS: A retrospective cohort study was conducted using the records of COVID-19 patients admitted during the COVID-19 pandemic from March 2020 through May 2020. Using patient charts, investigators manually collected data regarding patient characteristics and bleeding. Patients were included in the analysis if they had a confirmed COVID-19 PCR test, were older than 18 years of age and were admitted to the hospital. Patients who were pregnant or had incomplete charts were excluded from the study. ANOVA and logistic regression were used to determine the statistical significance of the data using SPSS version 27. RESULTS: A total of 651 patients were included in the analysis out of 685 patients located in the database of COVID-19 infected patients during that time frame. The general characteristics of the patients were as follows: 54.2% were males; females 45.8% ages ranged from 28 to 83 years old (median age = 66 years old). There were 31 patients (4.9%) who required more than 1 unit of packed red blood cell (PRBC). A total of 16 (2.85%) patients had a documented gastrointestinal bleed (GIB), of which 8 received a total of 29 units of PRBC transfusions. The HAS-BLED score (without alcohol/drug due to inadequate charting) is calculated for patients who had a documented GI bleed and who received more than one unit of PRBC. It was noted that the higher the HAS-BLED score the greater the likelihood of having a GI bleed ( \u3c 0.001). The HAS-BLED score (not including alcohol/drug) was also predictive for patients who received more than one unit of PRBC during their hospital stay ( \u3c 0.001). DISCUSSION: Using the HAS-BLED score without alcohol/drugs, patients with COVID-19 can be stratified in regard to their risk of GI bleeding and their risk of transfusion while in the hospital. When administering anticoagulation therapy, cautious monitoring should be carried out. Decisions regarding anticoagulant therapy should be based on individual patient characteristics