Joshi, Dhruvi

Complete revascularization improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD); however, the optimal timing of noninfarct-related artery intervention during the index procedure, immediate revascularization (IR) versus a staged approach (SR), remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials comparing SR and IR in patients with STEMI and MVD. The primary outcome was major adverse cardiovascular events. Secondary outcomes included all-cause and cardiovascular mortality, recurrent myocardial infarction, unplanned ischemia-driven revascularization, stent thrombosis, stroke, major bleeding, acute kidney injury, and heart failure hospitalization. Random-effects models with Hartung–Knapp adjustment were used. Trial sequential analysis assessed evidence conclusiveness, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. Eight randomized trials, including 5077 patients (2556 SR; 2521 IR), were analyzed. No significant differences were observed between SR and IR for major adverse cardiovascular events [odds ratios (ORs), 1.07; 95% confidence intervals (CI), 0.76–1.49], recurrent myocardial infarction (OR, 1.30; 95% CI, 0.80–2.14), cardiovascular mortality (OR, 0.76; 95% CI, 0.51–1.13), or all-cause mortality (OR, 0.75; 95% CI, 0.54–1.06). Rates of stent thrombosis, stroke, unplanned ischemia-driven revascularization, major bleeding, acute kidney injury, and heart failure hospitalization were also comparable. Trial sequential analysis indicated insufficient information size to draw definitive conclusions, and the certainty of evidence ranged from very low to low. In patients with STEMI and MVD, staged and immediate complete revascularization provide comparable ischemic, safety, and mortality outcomes. Current evidence supports clinical equipoise, and revascularization timing should be individualized pending results from adequately powered trials.

Abstract Background Thrombotic Thrombocytopenic Purpura (TTP) is a rare, typically acquired disorder due to an immune-mediated deficiency of ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand Factor (vWF). In the absence of ADAMTS13 activity, ultra-large vWF multimers accumulate, promoting widespread platelet aggregation and microvascular thrombosis. This consumptive cascade leads to thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and rarely renal dysfunction. Although therapeutic plasma exchange (TPE) has long been the cornerstone of TTP treatment, the FDA approved Caplacizumab as a first-line treatment for TTP in 2019. This drug is a bivalent single-domain antibody that binds to the A1 domain of vWF and prevents its interaction with platelets, thus effectively interrupting the pathogenic cascade, which is associated with a risk of bleeding. Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, comprising data from 152 healthcare organizations. Adults (≥18 years) with a diagnosis of TTP who received Caplacizumab plus TPE were compared to patients with TTP who received TPE alone. 1:1 propensity score matching (PSM) was performed to balance characteristics between cohorts. The primary outcomes assessed were all-cause mortality and major bleeding events over a period of 1 month. Results A total of 4084 patients with TTP were identified, of whom 356 received caplacizumab with TPE and 3728 received TPE. After PSM, 2 balanced cohorts were created: C+P (Caplacizumab + TPE), P only (TPE), each comprising 356 patients. The average age in C+P and P only, after PSM, was 50.4 +/- 16.2 and 50.8 +/- 16.2 years, respectively. Females formed 65.7% of both C+P and P only, and males accounted for 28.4% and 28.7% of C+P and P only, respectively. 2.8% patients in C+P and 7.06% patients in P only had all-cause mortality at the end of 1 month. One-month all-cause mortality was significantly lower in C+P (2.8%) compared to P only (7.06%), with an odds ratio (OR) of 0.385 (95% CI 0.182 to 0.814, p=0.010). Upon assessment of bleeding outcomes, no statistically significant risk difference was noted between the 2 groups, with the odds ratio being 0.974 (95% CI 0.399 to 2.379, p=0.954). Conclusion Our large database study suggests that the addition of caplacizumab to standard TPE therapy is associated with a reduction in one-month all-cause mortality in patients with TTP, without a corresponding increase in major bleeding. However, given the lack of granular clinical data, such as contraindications to caplacizumab use, it is possible that patients who received TPE alone were inherently at a higher risk. As such, while these findings support the potential benefit of early caplacizumab use, they should be interpreted with caution and warrant prospective validation to confirm causality and assess long-term outcomes.

Abstract Background: Patients with myelodysplastic syndromes (MDS) are at heightened risk for severe infections, including sepsis, due to underlying cytopenias and immune dysregulation. Hospital-level characteristics, including size and available resources, may influence clinical outcomes in these patients, but data remain limited. This study examines the association between hospital bed size and sepsis-related complications in patients with MDS using a nationally representative dataset. Methods: We conducted a retrospective cohort analysis using the National Inpatient Sample (NIS) from 2016 to 2022, identifying adult hospitalizations with co-diagnoses of MDS and sepsis. Hospitalizations were stratified by hospital bed size: small (n = 15,490), medium (n = 22,815), and large (n = 40,245). Multivariable logistic regression, adjusted for patient demographics, comorbidities, and hospital characteristics, was used to assess associations between hospital bed size and eight clinical outcomes: in-hospital mortality, septic shock, acute renal failure, respiratory failure, encephalopathy, disseminated intravascular coagulation (DIC), Clostridioides difficile infection (CDI), and fungal sepsis. Results: Compared to small hospitals, patients treated at large hospitals had significantly higher odds of in-hospital mortality (OR 1.43, p < 0.001), septic shock (OR 1.25, p < 0.001), acute renal failure (OR 1.10, p < 0.001), encephalopathy (OR 1.11, p = 0.004), DIC (OR 1.48, p = 0.007), and fungal sepsis (OR 2.13, p = 0.028). Medium-sized hospitals were also associated with increased odds of mortality (OR 1.16, p = 0.021) and septic shock (OR 1.13, p = 0.038). No statistically significant differences were found in rates of CDI across hospital sizes. Respiratory failure showed a borderline association in medium hospitals (OR 1.05, p = 0.082) but not in large hospitals. Conclusion: Hospital bed size is independently associated with important variations in sepsis-related outcomes among patients with MDS. Large hospitals demonstrated significantly increased odds of multiple complications and mortality, possibly reflecting referral bias, higher disease acuity, or institutional coding practices. These findings underscore the importance of hospital-level factors in evaluating outcomes and resource planning for high-risk hematologic populations. Keywords: Myelodysplastic syndromes, hospital bed size, sepsis, mortality, ICU complications, NIS

Abstract Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders often complicated by infections due to cytopenias. Sepsis is a frequent cause of hospitalization and mortality in MDS patients. Neutropenia, a common feature in MDS, may predispose patients to specific infectious complications, but its impact on sepsis-related outcomes remains poorly characterized. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database from 2016 to 2022. Adult hospitalizations with co-diagnoses of MDS and sepsis were identified using ICD-10-CM codes. Patients were stratified based on the presence or absence of neutropenia. Multivariable logistic regression models were used to evaluate the association between neutropenia and specific in-hospital outcomes, including Clostridioides difficile infection, fungal sepsis, and disseminated intravascular coagulation (DIC). Models were adjusted for age, sex, comorbidities, hospital characteristics, and illness severity. Results: A total of 78,549 hospitalizations involving MDS patients with sepsis were identified, including 11,295 (14.4%) with neutropenia. Neutropenic patients had significantly higher odds of C. difficile infection (adjusted odds ratio [aOR] 1.61, 95% CI 1.30–1.99, p < 0.001) and fungal sepsis (aOR 2.08, 95% CI 1.22–3.54, p = 0.007) compared to those without neutropenia. However, neutropenia was not significantly associated with DIC (aOR 0.84, 95% CI 0.59–1.19, p = 0.322). Conclusion: In this large national cohort, neutropenia was associated with a significantly increased risk of C. difficile infection and fungal sepsis among MDS patients hospitalized with sepsis. These findings highlight the need for early recognition and targeted antimicrobial strategies in neutropenic MDS patients. No significant association was observed between neutropenia and DIC. Future studies should explore preventive strategies and risk stratification tools tailored to this high-risk population. Keywords: Myelodysplastic syndromes, neutropenia, sepsis, NIS, Clostridioides difficile, fungal sepsis, outcomes

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