Outcomes of therapeutic plasma exchange in severe autoimmune hemolytic anemia hospitalizations: An analysis of the National Inpatient Sample.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear. STUDY DESIGN AND METHODS: We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not. RESULTS: We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001). CONCLUSION: Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes.

Delay in treatment of adult hemophagocytic lymphohistiocytosis is associated with worse in-hospital outcomes.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled activation of the immune system leading to multiorgan failure. Timely initiation of HLH-specific treatment is believed to be essential and lifesaving. Due to the rarity of the condition in adults, there is no data available in the literature to investigate the effects of treatment delay in this age group. We used data from the National Inpatient Sample (NIS) to evaluate the inpatient practices of HLH treatment initiation over 13 years (2007-2019) and their association with clinically relevant inpatient outcomes. Patients were divided into early treatment group (<6 days) and late treatment group (≥ 6 days). We compared outcomes using multivariate logistic regression models adjusting for age, sex, race, and HLH-triggering conditions. There were 1327 and 1382 hospitalizations in the early and late treatment groups, respectively. Hospitalization in the late treatment group had higher rates of in-hospital mortality (OR 2.00 [1.65-2.43]), circulatory shock (OR 1.33 [1.09-1.63]), requiring mechanical ventilation (OR 1.41 [1.18-1.69]), venous thromboembolism (OR 1.70 [1.27-2.26]), infectious complications (OR 2.24 [1.90-2.64]), acute kidney injury (OR 2.27 [1.92-2.68]), and requiring new hemodialysis (OR 1.45 [1.17-1.81]). Additionally, we observed no significant trend in the mean time to treatment over the study period. This study shows the importance of early initiation of HLH treatment and highlights the adverse outcomes of treatment delay.

Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: an analysis of the National Inpatient Sample Database.

Immune thrombocytopenia (ITP) is a known autoimmune complication of chronic lymphocytic leukemia (CLL). Currently, there is limited data regarding the risk CLL confers on hospitalization outcomes in patients admitted with ITP.The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases (ICD) codes to identify hospitalizations for ITP and then subclassified the data into hospitalizations with and without CLL. A multivariate logistic regression was designed to account for patient characteristics and comorbidities. The primary outcome was all-cause mortality. Secondary outcomes included major bleeding, gastrointestinal bleeding, intracranial bleeding, and the need for platelet transfusions, intravenous immunoglobulin, and splenectomy. Among 662,171 cases of ITP between 2005 and 2019, 15,672 had concurrent CLL. CLL patients were significantly older and had more comorbidities compared to patients without CLL. Multivariate analysis revealed CLL patients with ITP had a risk of all-cause mortality (odds ratio: 1.28, 95% CI: 1.19-1.37; p < 0.01). CLL patients also had a higher risk of complications, second-line ITP treatments, blood transfusions, and bleeding, with the exception of intracranial hemorrhage. Our study suggests CLL is an independent risk factor for increased morbidity and mortality among hospitalized patients with ITP. Prospective studies are needed to determine if refractoriness to conventional treatments for ITP can account these results.

Hemophagocytic lymphohistiocytosis in inflammatory bowel disease: a nationwide analysis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening immune dysregulation disease. Patients with inflammatory bowel disease (IBD) can become profoundly immunocompromised due to immunosuppressive therapy, hence increasing the risk of viral infections that can trigger HLH. However, data on the association between IBD and HLH remains limited. We used data from the National Inpatient Sample (2012-2019) utilizing International Classification of Diseases (ICD)-9 or ICD-10 codes to identify individuals with IBD, either Crohn's disease (CD) or ulcerative colitis (UC), and HLH. The primary outcome was to compare the prevalence of HLH among patients with IBD with those without IBD. Secondary outcomes included in-hospital mortality, mean hospital length of stay, and description of HLH-associated triggers in IBD patients. A total of 513,322 hospitalizations included a diagnosis of IBD, 188,297 had UC and 325,025 had CD. Compared to the general population, patients with IBD were older (median age of 52 vs. 49 years, p < 0.05), more likely to be male, and of Asian/Pacific Islander descent, and had a higher median household income. There was also a higher prevalence of liver disease, autoimmune diseases, tobacco abuse, and hypothyroidism (all had p-value of < 0.001) in IBD patients. There were 94 hospitalizations identified with a diagnosis of HLH in IBD patients. Compared to patients without IBD, patients with IBD had increased odds of developing HLH (0.02% vs 0.01%, p-value < 0.001). After adjusting for various demographic characteristics, co-morbidities, and HLH-related conditions, IBD was an independent predictor for developing HLH (adjusted OR, 2.3; 95% CI, 1.847-2.866, p-value of < 0.001). There was no statistical difference between CD and UC in the odds of developing HLH. Compared to IBD patients without HLH, patients with IBD and HLH had a lower mean age at diagnosis (38 vs 52, p-value of < 0.001), higher in-hospital mortality (14.9% vs 1.5%, p-value of < 0.001), and longer mean hospital length of stay (days) (17 vs 5.4, p-value of < 0.001). Prevalence of different HLH-associated illnesses was identified in HLH patient's discharge data. Lymphoma was the most common associated malignancy (18.1%) and cytomegalovirus infection was the most common associated infection (16.0%). Our population-based study suggests that IBD is independently associated with developing HLH. Early recognition of IBD patients presenting with features suggestive of HLH is warranted to aide early diagnosis and aggressive treatment.

Successful Management of Severe Hyperhaemolysis with Combined Tocilizumab and Rituximab in Non-Transfusion-Dependent Thalassaemia: A Case Report.

Introduction: This is the fourth case reporting the administration of tocilizumab to control hyperhaemolysis. It was administered with rituximab to stop hyperhaemolysis refractory to frontline therapy. Hyperhaemolysis is a rare life-threatening subtype of delayed haemolytic transfusion reaction. Refractory cases pose a clinical challenge with no standard of care to date. Case Presentation: A 29-year-old lady with non-transfusion-dependent thalassaemia presented with refractory hyperhaemolysis necessitating the administration of rituximab. This was complicated with anaemic heart failure and altered sensorium exacerbated with further transfusions. A nadir haemoglobin of 2.1 g/dL was reached after the initiation of rituximab, and her condition was too critical to wait for the slow expected improvement. Hence, tocilizumab was given as a bridging therapy to block haemolysis till the delayed onset of radical treatment. Conclusion: Tocilizumab can be effectively combined with rituximab to stop hyperhaemolytic episode refractory to first-line treatment when a prompt response is needed.

Relapsed chronic lymphocytic leukemia with a cardiac mass: A case report.

Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the USA. Extra-medullary disease is very rare and is not well characterized. In practice, clinically significant cardiac or pericardial involvement by CLL is extremely rare with only a few case reports in literature. We report a 51-year-old male patient with a past medical history of CLL in remission, who presented with fatigue, dyspnea on exertion, night sweats and left supraclavicular lymphadenopathy. Laboratory investigations were notable for leukopenia and thrombocytopenia. Due to high suspicion of an underlying malignant process, a full body computerized tomography (CT) scan was obtained and showed an 8.8 cm soft tissue mass-like lesion occupying the majority of the right atrium and extending into the right ventricle, with probable pericardial involvement. Enlarged left supraclavicular and mediastinal lymph nodes were also present and had a mild mass effect on the traversing left internal thoracic artery and left pulmonary artery. A transesophageal echocardiogram and cardiac magnetic resonance imaging (MRI) were done to better characterize the cardiac mass. They confirmed a large infiltrating mass (measuring 10 × 7.4 cm) in the right atrium and ventricle, extending into the inferior vena cava inferiorly and coronary sinus posteriorly. A left supraclavicular excisional lymph node biopsy was performed and histopathology was consistent with Small Lymphocytic Lymphoma (SLL)/CLL. This case represents one of the few known cases of cardiac extramedullary-CLL presenting with an isolated cardiac mass. Further studies are needed to characterize the course of the disease, prognosis and optimum management along with the role of surgery.

Acute venous thromboembolic events in patients with monoclonal gammopathy of undetermined significance: An analysis of the National Inpatient Sample.

BACKGROUND: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients. METHODS: We utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables. RESULTS: A total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22-1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29-1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09-1.37). CONCLUSION: Patients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS.

Toll-like receptor 4 blocker as potential therapy for acetaminophen-induced organ failure in mice.

Acetaminophen (APAP, 4-hydroxyacetanilide) is the most common cause of acute liver failure in the United States. In addition to exhibiting hepatotoxicity, APAP exerts a nephrotoxic effect may be independent of the induced liver damage. Toll-like receptors (TLRs) have been suggested as a potential class of novel therapeutic targets. The aim of the present study was to investigate the potential of the TLR-4 blocker TAK-242 in the prevention of APAP-induced hepato-renal failure. Four groups of C57BL mice were studied: Vehicle-treated/control (VEH), APAP-treated (APAP), N-acetyl cysteine (NAC)-pretreated plus APAP (APAP + NAC) and TAK-242-pretreated plus APAP (APAP + TAK) groups. Mice were clinically assessed then perfused 4 h later. Liver and kidney tissues were collected and examined histologically using basic hematoxylin and eosin staining to detect signs of necrosis and inflammation. Plasma samples were collected to measure the levels of alanine transaminase, aspartate transaminase and serum creatinine. In addition, liver and kidney tissues were assayed to determine the levels of reduced glutathione. The results of the present study indicate the potential role of TLR-4 in APAP-induced organ toxicity. In the APAP + TAK and APAP + NAC groups, histopathological examination indicated that pretreatment with TAK-242 or NAC afforded protection against APAP-induced injury. However, this protective effect was more clinically evident in the APAP + TAK group compared with the APAP + NAC group. The various biochemical parameters (serum enzymes and reduced glutathione) revealed no significant protection in either of the pretreated groups. Therefore, the present study indicated that the TLR-4 blocker had protective effects against acute APAP toxicity in liver and kidney tissues. These effects were identified clinically, histologically and biochemically. Furthermore, the TLR-4 blocker TAK-242 exhibited antioxidant properties in addition to anti-inflammatory effects.