Gopu, Sooraj Srirangadhamu

Abstract Background: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and an increased susceptibility to infections. Sepsis remains a common and serious cause of morbidity and mortality in this population. While racial disparities in sepsis-related outcomes have been described in the general population, their presence and magnitude among patients with MDS remain poorly understood. Methods: We performed a retrospective cohort study using the National Inpatient Sample (NIS) from 2016 to 2022 to identify adult hospitalizations with co-diagnoses of MDS and sepsis. Patients were stratified by race into White (reference), Black, Hispanic, Asian, Native American, and Other categories. Multivariable logistic regression models, adjusted for demographics, comorbidities, and hospital characteristics, were used to evaluate associations between race and seven key sepsis-related complications: septic shock, acute renal failure, respiratory failure, encephalopathy, disseminated intravascular coagulation (DIC), Clostridioides difficile infection (CDI), and fungal sepsis. Results: Among 78,549 hospitalizations for MDS with sepsis, significant racial disparities were observed. Asian patients had higher odds of developing septic shock (OR 1.26, 95% CI 1.05–1.50, p = 0.014), and both Black (OR 1.24, 95% CI 1.17–1.31, p < 0.001) and Asian (OR 1.14, 95% CI 1.04–1.24, p = 0.004) patients had increased odds of acute renal failure. Respiratory failure was less likely among Black (OR 0.84, 95% CI 0.79–0.90, p < 0.001) and Hispanic (OR 0.76, 95% CI 0.70–0.82, p < 0.001) patients. Encephalopathy was significantly more common in Black (OR 1.29, 95% CI 1.18–1.41, p < 0.001) and Other (OR 1.20, 95% CI 1.01–1.42, p = 0.042) patients. DIC was more frequent in Asian (OR 2.11, 95% CI 1.37–3.27, p = 0.001) and Hispanic (OR 1.53, 95% CI 1.09–2.14, p = 0.014) patients, with a borderline association in Black patients (OR 1.35, p = 0.082). No statistically significant racial differences were noted for CDI or fungal sepsis, although Asian patients trended toward lower odds of CDI (OR 0.64, p = 0.067), and Native American patients had high but non-significant odds for fungal sepsis (OR 3.03, p = 0.287). Conclusion: Our study highlights significant racial disparities in sepsis-related complications among hospitalized MDS patients. Black and Asian patients were more likely to experience acute renal failure and encephalopathy, while Asian and Hispanic patients had higher odds of developing DIC. Conversely, Black and Hispanic patients had lower risk of respiratory failure. These findings underscore the need for race-conscious approaches in sepsis management for patients with MDS and suggest that tailored interventions may be necessary to ensure equitable outcomes across racial groups. Keywords: Myelodysplastic syndromes, sepsis, racial disparities, acute kidney injury, encephalopathy, DIC, respiratory failure, fungal sepsis, National Inpatient Sample

Abstract Background: RUNX1 mutations are established high-risk features in acute myeloid leukemia (AML), associated with poor response to induction therapy and reduced overall survival (OS). Current prognostic models, including the ELN 2022 classification, incorporate RUNX1 mutation status but are based largely on cohorts of European ancestry. This raises concerns about their generalizability to underrepresented populations, particularly African American patients, who continue to experience worse outcomes in AML across treatment settings. Methods: We analyzed publicly available datasets, including TCGA-LAML, Beat AML, and a recent multi-omic study of 100 African American AML patients (Stiff et al., Nat Genet 2024). We evaluated RUNX1 mutation frequency, OS outcomes, and co-mutation patterns, stratified by race. To contextualize survival differences by ancestry, we performed a survival analysis of adult AML patients using the SEER 17 registries (2010–2020), accessed through SEER*Stat. Kaplan-Meier estimates and median OS were compared by race using disease-specific survival. Results: RUNX1 mutations were present in approximately 10–15% of AML cases and consistently associated with inferior OS (median 16–24 months) in both de novo and AML-MRC subsets. Co-mutations in DNMT3A and TET2 further worsened the prognosis. In the African American cohort described by Stiff et al., the frequency of RUNX1 mutations was similar to that in White patients; however, African American patients showed enrichment for IDH2, RAS, and WT1 mutations and lower incidence of NPM1 mutations. Despite comparable mutation rates, African American patients demonstrated significantly worse OS, even under standardized treatment. SEER 17 survival analysis of 5,932 AML cases (683 African American) confirmed shorter median OS in African American patients compared to non-African American patients (10.4 vs. 15.7 months, p<0.01).Conclusions: RUNX1 mutations confer adverse prognosis in AML, but current risk models may not adequately reflect risk in African American patients due to differing co-mutation patterns and underrepresentation in genomic datasets. These findings highlight the need for ancestry-aware risk stratification and inclusive genomic profiling to reduce disparities in AML outcomes. References: Lew-Derivry et al. Leukemia. 2023 Jalili et al. PMCID: PMC5980915 Stiff et al. Nat Genet. 2024 Bhatnagar et al. PMCID: PMC7933110 Tang et al. Blood. 2009 Mendler et al. JCO. 2012 He et al. Scand J Clin Lab Invest. 2020 Döhner et al. Blood. 2022. PMID: 35926292

Abstract Background: Cryoprecipitate is indicated for bleeding patients with hypofibrinogenemia, typically when fibrinogen levels fall below 100–150 mg/dL. Despite established national transfusion guidelines, inappropriate use remains a persistent issue in clinical practice, especially in community hospitals where formal transfusion oversight may be limited. Unnecessary transfusions can expose patients to avoidable risks and contribute to increased healthcare costs. As part of a hospital-wide quality improvement initiative, we conducted a retrospective review of cryoprecipitate use at our institution to assess adherence to transfusion guidelines and identify areas for improvement. Methods: We performed a retrospective review of all cryoprecipitate transfusions at Landmark Medical Center, a 214-bed community hospital in Rhode Island, between January 2021 and June 2025. Transfusion episodes were identified through blood bank records. For each episode, we extracted the number of units ordered and administered, pre-transfusion fibrinogen levels, documented clinical indication in the electronic medical record (EMR), and any product wastage. Each transfusion was assessed based on institutional criteria aligned with national guidelines, which recommend cryoprecipitate only in cases of active bleeding with fibrinogen <100–150 mg/dL. Results: Twenty patients received cryoprecipitate in 23 transfusion episodes involving 32 units. Of these, 28 units were administered and 4 were wasted. The majority of patients were female (65%), and 40% were between ages 61 and 75. Only 10 of 23 episodes (43%) met established transfusion criteria. Nine episodes (39%) were given when fibrinogen levels ranged between 100–200 mg/dL, and two episodes (9%) occurred with levels >200 mg/dL. One transfusion was administered without a documented fibrinogen level. Additionally, 8 episodes (35%) lacked a clearly documented indication in the EMR. Three episodes (13%) involved product wastage, including one with no documentation and another where an order was placed but the unit was not administered. Conclusion: This review revealed that more than half of cryoprecipitate transfusions did not meet guideline-based criteria. The findings point to deficiencies in provider knowledge, inconsistent documentation, and limited transfusion oversight contributing to inappropriate use. These results highlight the need for targeted interventions, including: (1) provider education on transfusion thresholds, (2) EMR-based decision support requiring lab values prior to ordering, and (3) routine audits with feedback. Strengthening transfusion practices through structured quality improvement efforts can reduce unnecessary use, improve patient safety, and preserve limited blood product supplies for those who truly need them.