Trends in rheumatoid arthritis associated cardiovascular mortality in the United States from 1999 to 2020.

INTRODUCTION: Rheumatoid Arthritis (RA) is a risk enhancing factor for cardiovascular diseases (CVD). However, data regarding the magnitude and trends of RA associated CVD-related mortality in the United States (U.S) remains scarce. METHODS: A retrospective analysis was conducted using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) dataset. We extracted age-adjusted mortality rates (AAMR) per 100,000 persons and calculated the annual percentage change (APC) through Joinpoint regression. The outcomes were stratified to discern temporal, sex-based, racial, and geographic patterns in RA-associated CVD mortality. RESULTS: Between 1999 and 2020, 128,058 deaths related to CVD in RA patients aged 25 and above were recorded. The AAMR decreased from 3.50 in 1999 to 2.79 in 2020. However, sex disparities persisted, with females consistently experiencing a higher AAMR (3.35) compared to males (1.74). Non-Hispanic (NH) American Indian/Alaska Native had the highest AAMR (4.44) followed by NH White (2.83), NH Black or African American (2.47) and Hispanic or Latino (2.13), while NH Asian/Pacific Islander had the lowest AAMR (1.28). Geographically, the Midwestern region had the highest AAMR (3.12), while the Northeast had the lowest (2.19) with micropolitan (3.47) and nonmetropolitan (3.37) areas exhibiting higher AAMRs compared to large metropolitans (2.28). Notably, states with the highest AAMRs included North Dakota, South Dakota, Vermont, Minnesota and Wyoming. CONCLUSION: Recent trends reveal an upward incline in RA-associated CVD-related mortality with profound disparities related to sex, race, geography and regions. Redressing these disparities necessitates the implementation of targeted population level interventions.

Selinexor for the treatment of patients with relapsed or refractory multiple myeloma.

OBJECTIVE: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. DATA SOURCE: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. DATA SUMMARY: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%. CONCLUSION: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

Immune Checkpoint Inhibitor-Associated Myocarditis: A Literature Review.

Recently in the field of oncology, immune checkpoint inhibitors (ICI) are being increasingly utilized both in clinical trials and in clinical practice. It is a form of biological therapy that targets tumors by activating the immune system, which in turn eliminates proliferating cancer cells. These have numerous immune-related adverse events (irAEs), one of which is myocarditis, which has high rates of mortality. This article was a narrative review of myocarditis related to ICI use.  Studies from the PubMed, Cochrane, and American Society of Clinical Oncology (ASCO) databases were used in writing this review. The databases were searched for original publications for adverse effects related to ICI use and myocarditis specifically. There are numerous published instances of cancer immunotherapy causing myocarditis. ICI therapy has numerous benefits, as it upregulates the immune system to target cancer cells, utilizing the body's own defense mechanisms to target proliferating cells. Myocarditis is a serious side effect, however. Therefore, on balance, these monotherapies are worth using. While this literature review primarily identifies cross-reaction as the main mechanism of myocarditis, there are other possible mechanisms. One proposed mechanism involves a shared antigen between the myocardial tissue and the tumor. This mechanism is called molecular mimicry, where the monoclonal antibody attacks both the myocardial tissue and the tumor cell. Management of ICI-induced myocarditis has not been studied by randomized controlled trials or prospective studies, but based on previous case reports and case series it is mostly treated with steroids initially. An ICI rechallenge after temporary discontinuation appears conceivable in many cases, especially given its therapeutic effects, but only limited data are available on the safety of a rechallenge after an irAE. The lack of RCTs regarding rechallenge with an ICI after irAE, more so specifically about myocarditis, along with the overall results and the complexity involved in such cases once again emphasize the need to make decisions on an individual basis by a multidisciplinary expert working group. At the same time, the focus should also be on publishing more data as the need will grow along with the indications for ICI therapies.

Use of venetoclax in t(11;14) positive relapsed/refractory multiple myeloma: A systematic review.

BACKGROUND: The plasma cell malignancy, multiple myeloma (MM), remains incurable despite advanced treatment protocols. Overexpression of Bcl-2 (an anti-apoptotic protein), in MM harboring the translocation (11;14), contributes to resistance to prior therapy. Venetoclax, a selective oral inhibitor of BCL-2 is a novel agent that shows promise as a therapeutic agent. AIMS: The objective of this systematic review is to address how the use of venetoclax, alone or as a combination regimen, contributed to the treatment of patients with t(11:14) positive relapsed/refractory multiple myeloma (RRMM). DATA SOURCES: This systematic review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was done on 5th June 2022. A literature search was conducted on PubMed and Scopus, 145 articles were screened and 10 studies were included. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. DATA SUMMARY: Across the studies reviewed, a total of 311 patients were identified with t(11;14) positive RRMM. The overall response rate achieved ranged between 33% and 95.5%. Furthermore, the use of venetoclax has exhibited a favorable adverse effect profile. Side effects included hematological side effects, nausea, vomiting, and diarrhea. CONCLUSION: Venetoclax demonstrates promising results. When given with drugs like dexamethasone, daratumumab and carfilzomib, a synergistic effect is seen in treating translocation (11:14) positive relapsed/refractory MM. The use of venetoclax in clinical practice can potentially improve outcomes and quality of life in RRMM patients, and future research should continue to explore this promising treatment option.

An Analysis of the Predictors of Major Bleeding After Transcatheter Aortic Valve Transplantation Using the National Inpatient Sample (2015-2018).

Background Transcatheter aortic valve replacement (TAVR) is now a common procedure to treat and improve quality of life, clinical outcomes, and self-sufficiency in high-risk patients with aortic stenosis, and its use has been expanding rapidly in younger and low-risk populations. The aim of this study was to evaluate the outcomes, trends, and predictors of major bleeding in patients undergoing TAVR. Methodology We utilized the National Inpatient Sample (NIS) data from the year 2015 to 2018. International Classification of Disease 10 codes were utilized to extract data. Baseline characteristics were compared using Pearson's chi-square test for categorical variables and independent samples t-test for continuous variables. A multivariable logistic regression model was used to evaluate the predictors of major bleeding. Propensity matching was done for adjusted analysis to compare outcomes in TAVR with and without major bleeding. The outcomes of interest in this study were (1) predictors of major bleeding after TAVR; (2) in-hospital mortality; and (3) resource utilization in terms of cost and length of stay. Results A total of 34,752 weighted hospitalizations for TAVR were included in the analysis. Of the patients undergoing the procedure, 2,294 (6.6%) had a major bleed while 32,458 (93.3%) did not. At baseline, patients with coagulopathy (odds ratio [OR]: 2.03; 95% confidence interval [CI]: 1.82-2.27), congestive heart failure (OR: 1.26; 95% CI: 1.13-1.40), chronic obstructive pulmonary disease (OR: 1.41; 95% CI: 1.29-1.55), liver disease (OR: 1.96; 95% CI: 1.61-2.39), peripheral vascular disease (OR: 1.29; 95% CI: 1.17-1.43), cerebrovascular disease (OR: 1.22; 95% CI: 1.07-1.38), end-stage renal disease (ESRD) (OR: 2.17; 95% CI: 1.82-2.59), and coronary artery disease (OR: 1.17; 95% Cl: 1.06-1.30) had higher adjusted rates of odds of major bleeding. Patients who had major bleeding had a higher median cost of stay (US$60,326 vs. US$45490) and length of stay (seven vs. three days). Conclusions Mortality is higher in patients with major bleeding, and at baseline, coagulopathy and ESRD are significant predictors of a major bleed in patients undergoing TAVR.

Acute Kidney Injury in Transcatheter Aortic Valve Replacement.

Introduction Transcatheter aortic valve replacement (TAVR) has been established as a standard of care for patients with severe aortic stenosis. We aim to study the predictors of acute kidney injury (AKI) after TAVR from a contemporary analysis using the National Inpatient Sample (NIS) database. Methods We performed a national analysis using the NIS database to evaluate predictors of acute kidney injury (AKI) after TAVR. Our study period was from 2015 to 2018, and we identified TAVR patients in all procedure fields. Patients aged less than 18 years were excluded from the study. Results We report data of 173,760 TAVR patients, of which 20,045 (11.5%) had AKI and 153,715 (88.4%) did not. There were three principal findings of our study. First, mortality was higher in patients with AKI compared to patients who did not have AKI (8% vs. 0.8%; p<0.01). Second, patients with chronic kidney disease, weight loss, liver disease, congestive heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, metastatic cancer, and peripheral vascular disease had higher adjusted odds of AKI. Third, length of stay and cost of stay were significantly higher in patients who had AKI during the index admission.  Conclusion Patients with AKI had higher in-hospital mortality. We also report that at baseline, chronic kidney disease, weight loss, liver disease, congestive heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, metastatic cancer, and peripheral vascular disease were important predictors of AKI in patients after TAVR. Length of stay and cost of stay were higher with AKI, which result in higher burden on the health care system due to increased resource utilization.

Predictors of Mortality in Patients With Transcatheter Aortic Valve Implantation: A National Inpatient Sample Database Analysis.

Introduction In recent decades, transcatheter aortic valve implantation (TAVI) has become a treatment of choice for aortic stenosis. The purpose of this study was to evaluate predictors of mortality in patients undergoing TAVI. Methods The National Inpatient Sample database from the year 2011 to 2018 was used to identify all patients undergoing TAVI during the study period. Results A total of 215,983 weighted hospitalizations for TAVI were included in the analysis. We report the following three main findings from our contemporary analysis of the NIS: (1) despite TAVI patients having a high comorbidity burden, mortality remains low at 2.2%, (2) in terms of baseline characteristics, end-stage renal disease, liver disease, congestive heart failure, chronic obstructive pulmonary disease, atrial fibrillation, and lung cancer remain significant predictors of mortality in patients undergoing TAVI, and (3) length of stay and cost of stay are significantly higher in patients who died during the hospitalization. Conclusion In conclusion, we report that at baseline, end-stage renal disease, liver disease, atrial fibrillation, and lung cancer are significant predictors of mortality in patients undergoing TAVI.

Trends, predictors, and outcomes of major bleeding after transcatheter aortic valve implantation, from national inpatient sample (2011-2018).

INTRODUCTION: Major bleeding remains one of the most frequent complications seen in transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate outcomes, trends, and predictors of major bleeding in patients undergoing TAVI. METHODS: We utilized the National Inpatient Sample (NIS) data from the year 2011 to 2018. Baseline characteristics were compared using a Pearsonχ2 test for categorical variables and Mann-Whitney U-Test for continuous variables. A multivariable logistic regression model was used to evaluate predictors of major bleeding. Propensity Matching was done for adjusted analysis to compare outcomes in TAVI with and without major bleeding. RESULTS: A total of 215,938 weighted hospitalizations for TAVI were included in the analysis. Of the patient undergoing the procedure, 20,102 (9.3%) had major bleeding and 195,836 (90.7%) patients did not have in-hospital bleeding events. Patients in the major bleeding cohort were older and had greater female gender representation. At baseline patients with thrombocytopenia (Odds Ratio [OR], 1.47[confidence interval (CI), 1.36-1.59]), colon cancer (OR, 1.70[CI, 1.27-2.28]), coagulopathy (OR, 1.17[CI, 1.08-1.27]), liver disease (OR, 1.31[CI, 1.21-1.41]), chronic obstructive pulmonary disease (OR, 1.29[CI, 1.25-1.33]), congestive heart failure (OR, 1.12[CI, 1.08-1.16]), and end-stage renal disease (ESRD) (OR, 1.47[CI, 1.38-1.57]) had higher adjusted rates of major bleeding. The percentage of adjusted in-hospital mortality (14.4% vs. 4.2%, P < 0.01) was significantly higher in the major bleeding group Patients with major bleeding had higher median cost of stay ($235,274 vs. $177,920) and length of stay (7 vs 3 days). CONCLUSION: In conclusion, we report that mortality is higher in patients with major bleeding and that baseline comorbidities like ESRD, liver disease, coagulopathy and colonic malignancy are important predictors of this adverse event.

Traumatic brain injury causing intestinal dysfunction: A review.

Traumatic brain injuries (TBI) and its sequelae are becoming one of the most pressing public health concerns worldwide. It is one of the leading causes of increased morbidity and mortality. The primary insult to the brain can cause ischemic brain injury, paralysis, concussions, death, and other serious complications. Brain injury also involves other systems through a secondary pathway resulting in multiple complications during and after hospitalization. The focus of our article is to assess the literature available on traumatic brain injury and intestinal dysfunctional to highlight the aspects of epidemiology, pathophysiology, and different diagnostic approaches for early diagnosis of gut dysfunction. We review studies done in both humans and animals, to better understand this underrated topic, as it costs billions of dollars to the healthcare industry because of delayed diagnosis.