Successful treatment with fludarabine and cyclophosphamide in a VEXAS syndrome patient with associated myelodysplastic syndrome: a case report and systematic review.

Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.

Use of Endpoints in Phase III Randomized Controlled Trials for Hematopoietic Stem Cell Transplantation Over the Last 15 Years: A Systematic Review.

This systematic review aimed to evaluate the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and analyze their trends in time and study sponsorship status. The Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006 to 2021 reported 197 primary and 600 secondary endpoints. Overall survival (OS, 17 %), progression-free survival (PFS, 15 %), graft versus host disease (GVHD, 8 %), event-free survival (EFS, 8 %), and organ function (8 %) were the most common primary endpoints. GVHD (12.3 %, n = 74), safety/toxicity/adverse events (11.8 %, n = 71), OS (11.5 %, n = 69), PFS (9.3 %, n = 56), and relapse rate (RR; 7.5 %, n = 45) were the most common secondary endpoints during 2006-2021. After 2013, an increase was noted in the use of PFS as a primary endpoint (12 %-18 %, p = 0.196), while the use of OS as a primary endpoint declined (20 %-13 %, p = 0.170). An increase was observed in using the secondary endpoints RR (5 %-10 %, p = 0.047) and NRM (3 %-6 %, p = 0.047). EFS was used more (14 % vs. 4 %, p = 0.012) than ORR (11 % vs. 2 %, p = 0.003) as a primary endpoint in pharmaceutical-compared to non-pharmaceutical-sponsored studies. As secondary endpoints, the use of EFS (4 % vs. 1 %, p = 0.013) and ORR (4 % vs. 1 %, p = 0.028) was higher, whereas that of organ systems/functions (1.5 % vs. 5.5 %, p = 0.022) and GVHD (6.5 % vs. 15 %, p = 0.002) was lower in pharmaceutical-compared to non-pharmaceutical sponsored studies. GVHD-free relapse-free survival was reported as a primary endpoint in 2 % of studies, while only 5 % reported quality of life as a secondary endpoint. We described commonly used endpoints in HSCT phase III RCTs and patterns in their use over time by funding source and study intervention category.

Predictors of cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: Insights from a real-world experience.

BACKGROUND: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT). METHODS: We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28. Descriptive (chi-square and t-test), Kaplan-Meier and regression analyses were conducted. RESULTS: The median age was 57 years. Sixty-one percent were males and 84.3% were Caucasians. CMV serostatus was positive in 59.1% of recipients. The median follow-up was 24.4 months. CMV viremia and CMV disease were observed in 181 (40%) and 32 (7%) patients, respectively. Among CMV seropositive recipients, 65% developed CMV viremia and 11% were noted to have CMV disease compared to 4% and 1% in seronegative recipients, respectively (p < 0.001). Patients with CMV disease had significantly lower OS than those without CMV disease (median 14.1 months vs. not reached, p = 0.024); however, OS was not associated with CMV viremia (median not reached in both groups, p = 0.640). Letermovir prophylaxis was used in 66% (n = 176/267) of CMV seropositive recipients, but no impact was observed on the incidence of CMV viremia or CMV disease and OS. CONCLUSIONS: CMV disease leads to significantly inferior survival after an allogeneic hematopoietic cell transplantation. Recipient CMV seropositive status was associated with the risk of CMV viremia and CMV disease, and this was not abrogated with the use of Letermovir prophylaxis.

Geographic and Racial Disparities in Chimeric Antigen Receptor-T Cells and Bispecific Antibodies Trials Access for Diffuse Large B-Cell Lymphoma.

BACKGROUND: We investigate the geographical and racial disparities in accessing CAR-T and bispecific antibodies trials for DLBCL. MATERIALS AND METHODS: ClinicalTrials.gov was searched, and 75 trials with at least 1 open site in the US were included. 2020 US Census Bureau data was used to obtain data on race and ethnicity. SPSS version 26 was used for analysis. RESULTS: There were 62 CAR-T and 13 bispecific antibodies trials with 6221 enrolled or expected to enroll patients. Eighty-five percent of the clinical trials were only open in the US, and the majority 64% were pharmaceutical-funded. There were 126 unique study sites distributed over 31 states with 11 (0-51) mean number of trials per state and 4.5 (1-26) and 4.4 (1-24) mean number of CAR-T and bispecific antibodies trials per site, respectively. Southern states had the most number of trials 31%, followed by Midwestern 25%, Northeastern 24%, and Western 20%. The highest number of study locations were in California 13, New York 9, and Pennsylvania 9, while the highest number of open studies were in California 51, Texas 32, and New York 23. Twenty states had no open CAR-T or bispecific antibodies trials. Only 33% of African Americans (AA) lived in a county with a trial, and 7 out of 10 states with the highest proportion of AA residents (18.6%-41.4%) have no or less than 4 trial sites. Of the 62 counties analyzed, 92% were White predominant, while only 8% were AA predominant (P = .009). CONCLUSIONS: Strategies should be framed to address the observed disparities and to improve access.

How does cirrhosis impact mortality, morbidity, and resource utilization in non-variceal upper gastrointestinal bleeding? A nationwide analysis.

Introduction: Upper gastrointestinal bleeding is common in liver cirrhosis patients. Studies have described the prognostic impact of liver disease in non-variceal upper gastrointestinal bleeding (NVUGIB), but a direct subgroup comparison is lacking using a large database. Aim: To study the impact of NVUGIB on hospital-based outcomes in patients with cirrhosis. Material and methods: This is a retrospective study using Nationwide Inpatient Sample (NIS) employing International Classification of Diseases (ICD-10) codes for adult patients with a primary diagnosis of NVUGIB. Mortality, morbidity, and resource utilization were compared. Analyses were performed using STATA, proportions were compared using Fisher exact test, and continuous variables using Student's t-test. Confounding variables were adjusted using propensity matching, multivariate logistic, and linear regression analyses. Results: Of 107,001,355 discharges, 957,719 had a diagnosis of NVUGIB. Of those, 92,439 had cirrhosis upon admission. NVUGIB patients with cirrhosis had higher adjusted odds of mortality and intensive care unit (ICU) admission than patients without cirrhosis (adjusted odds ratio (AOR) for mortality 1.31, p < 0.001, ICU admission AOR = 1.29, p < 0.001). NVUGIB patients with cirrhosis had shorter length of stay (LOS) by 0.44 days (p < 0.001), greater hospital costs per day ($3114 vs. $2810, p < 0.001), and lower odds of acute kidney injury (AOR = 0.81, p < 0.001). In addition, the cirrhotic patients had higher odds of receiving endoscopic therapy (AOR = 1.08, p < 0.001). There was no difference between the 2 groups' requirements of packed red blood cell transfusion, parenteral nutrition, hypovolaemic shock, and endotracheal intubation. We also identified novel independent predictors of mortality from NVUGIB in cirrhosis patients. Conclusions: Cirrhosis presents greater mortality and morbidity burden and greater healthcare resource utilization from NVUGIB.

Acute pancreatitis secondary to tamoxifen-associated hypertriglyceridemia: A clinical update.

INTRODUCTION: Drug-induced pancreatitis has been increasingly recognized, but it is frequently encountered as an inconspicuous etiology. The underlying mechanisms of injury vary with different drugs. Tamoxifen is a frequently used anticancer drug that acts by selective modulation of the estrogen receptor in patients with breast cancer. Tamoxifen-induced hypertriglyceridemia is a relatively rare etiological factor for acute pancreatitis. However, acute pancreatitis secondary to this adverse effect remains an exceedingly important clinicopathologic entity. CASE REPORT: We hereby delineate a rare case of acute pancreatitis secondary to hypertriglyceridemia in a patient who was on tamoxifen treatment for the past 3 years. Her serum lipase and triglyceride levels were markedly elevated at 14,285 IU/L and 20,344 mg/dL, respectively. The diagnosis was considered based on the findings of a standard diagnostic workup and exclusion of alternative causes of acute pancreatitis. MANAGEMENT AND OUTCOME: The patient was instituted prompt treatment with intravenous insulin infusion and gemfibrozil. The clinical outcome was favorable with no complications. Tamoxifen was permanently discontinued and was replaced with letrozole. DISCUSSION: This article illustrates that acute pancreatitis should be considered in the differential diagnoses of abdominal pain and elevated pancreatic enzymes in patients undergoing tamoxifen treatment. It also underscores the importance of pre- and post-tamoxifen lipid screening, especially in patients with a history of dyslipidemia and diabetes mellitus. It will facilitate an expedient detection of hypertriglyceridemia, potentially saving patients from associated morbidity and mortality.

Simultaneous Left Ventricular Aneurysm and Ventricular Septal Rupture Complicating Delayed STEMI Presentation: A Case-Based Review of Post-MI Mechanical Complications Amid the COVID-19 Pandemic.

Amid the coronavirus disease 2019 (COVID-19) pandemic, there is an unprecedented increase in public avoidance of hospitals predominantly driven by fear of contracting the virus. Recent publications highlight a re-emergence of rare post-myocardial infarction complications. While mechanical complications are infrequent in the era of primary percutaneous coronary intervention, they are associated with high mortality rates. The concurrent occurrence of mechanical complications such as left ventricular aneurysm and ventricular septal rupture is an extremely rare entity. We hereby delineate a unique case of a 53-year-old Caucasian male who underwent successful concomitant closure of a ventricular septal rupture, left ventricular aneurysmectomy, and 3-vessel coronary artery bypass grafting. Due to a delayed initial presentation owing to the patient's fear of contracting COVID-19, the surgery was carried out 3 months after the myocardial infarction. His postoperative evaluation confirmed normal contractility of the left ventricle and complete closure of the ventricular septal rupture. Six months postoperatively, the patient continues to do well. We also present a literature review of the mechanical complications following delayed presentation of myocardial infarction amid the COVID-19 pandemic. This article illustrates that clinicians should remain cognizant of these extremely rare but potentially lethal collateral effects during the ongoing global public-health challenge. Furthermore, it highlights a significant concern regarding the delay in first medical contact due to the reluctance of patients to visit the hospital during the COVID-19 pandemic.