Seegobin, Karan

Background: Cerebral venous sinus thrombosis (CVT) is a rare cause of stroke, constituting 0.5–3% of all strokes with an extremely varied spectrum of presentation, predisposing factors, neuroimaging findings, and eventual outcomes. A high index of suspicion is needed because timely diagnosis can significantly alter the natural course of the disease, reduce acute complications, and improve long-term outcomes. Due to its myriad causative factors, protean presentation, and association with several systemic diseases, CVT is encountered not only by neurologists but also by emergency care practitioners, internists, hematologists, obstetricians, and pediatricians. Discussion: Anticoagulation remains the mainstay of treatment for CVT. Heparin and warfarin previously had been the anticoagulation of choice. Recently there has been an increased interest in utilizing direct-acting oral anticoagulants in the treatment of CVT given comparable safety and efficacy with ease of utilization. However recent clinical guidelines given by multiple societies including the American Stroke guidelines and European guidelines do not include these agents so far in their treatment recommendations. Ongoing multicentric clinical trials are currently reviewing the role of these agents in both short-term as well as long-term. Our review of the literature supports the safety and reinforces the efficacy of DOAC in the treatment of CVT. Additionally, patient satisfaction has been shown to be better with the use of DOAC. In conclusion, DOAC continues to have a valid role in the management of CVT.

Introduction: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell non-Hodgkin lymphoma that originates in lymphoid tissue of epithelial lined structures. The commonest site for this lymphoma is the stomach (gastric MALT lymphoma). MALT lymphoma in other mucosal sites, including other gastrointestinal sites, lungs, salivary glands, and lacrimal glands, has been well-described. However, MALT lymphoma in urothelial organs (kidneys, ureters, and urinary bladder) has not been well-characterized. This study aimed to investigate the clinicopathological features and therapeutic outcomes in urologic MALT lymphoma (U-MALT). Methods: We identified patients with U-MALT who were treated at the Mayo Clinic Cancer Center between March 2013 and May 2022 through electronic medical chart review. Clinical, pathologic, radiologic, therapeutic, and survival data were extracted. Kaplan-Meier analysis was used to determine the survival outcomes. Results: The characteristic features of six patients (N=6) with U-MALT are summarized in Table-1. 4/6 (67%) are Caucasian, and 3/6 (50%) are males. The median age at diagnosis was 73.5 years. Urologic sites are the urinary bladder (3/6), kidneys (3/6), and ureter (1/6, this patient had both kidney and ureter involvement). 4/6 patients had primary U-MALT. Concurrent non-urologic involvement was identified in 3/6 patients and included bone marrow, lungs, stomach, and axillary lymph nodes. Bone marrow involvement was observed in 2/6 patients.Next-generation sequencing was performed on one patient's peripheral blood, revealing an ATM mutation. Regarding the initial clinical presentation, kidney-involved U-MALT patients presented with renal failure, and those with urinary bladder/ureteric involvement, U-MALT was diagnosed incidentally upon cystoscopic evaluation and biopsy. Various management strategies were used, including observation, surgical resection, and rituximab treatment. Notably, all patients achieved complete remission (CR) except one with partial response to rituximab, who subsequently achieved CR with the Bendamustine/Rituximab regimen. Median follow-up is 6 years (range, 1-10). All six patients are alive without relapse at the time of analysis, with the flat overall survival curve at 100%, indicating excellent long-term survival. Conclusions: Our study indicates that urologic MALT lymphomas are extremely rare and predominantly affect elderly people. The most common urologic sites are the kidneys and urinary bladder. Urologic manifestations are dependent on the urologic site involved. They can be primary to the urologic structures or part of the disseminated systemic marginal zone lymphoma. They can be treated like other low-grade lymphomas with observation, surgical resection, and systemic therapy. They appear to be quite responsive to CD-20 targeted therapy with Rituximab. Prognosis appears to be excellent with long overall survival. Further research with multi-institutional studies is needed to study this rare lymphoma entity and identify optimal therapy.

Introduction Acute chest syndrome (ACS) is a clinical presentation of fever, chest pain, pulmonary symptoms, and new infiltrates on lung imaging. It affects nearly 50% of patients with sickle cell disease during their lifetime and often leads to hospitalization. The mortality rate is variable ranging from 3 to 9 %. and depends on several factors. We aimed to identify the clinical and epidemiological characteristics of patients admitted with ACS on a national scale and factors affecting clinical outcomes in inpatient setting. Methods: We utilized the National Inpatient Sample (NIS) database 2019 for the purpose of this study. Using this database, we identified patients with a principle diagnosis of ACS using International Classification of Diseases (ICD-10) codes. Data on demographic characteristics such as age, sex, race, insurance type were collected. Additionally, we selected clinically significant medical comorbidities such as asthma, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), chronic kidney disease (CKD), heart failure, hypertension, diabetes mellitus (DM), sepsis, obesity, and others. The primary endpoint of this study was to identify factors influencing all-cause mortality, while the secondary endpoint was to identify factors influencing mechanical intubation, in-patient blood transfusion, and length of stay. We used multivariate logistic regression analysis to adjust for confounders. A p value of ≤0.05 considered statistically significant. Results: Baseline Characteristics Our analysis consisted of 22,459 patients who were admitted with principal diagnosis of ACS. 49.5% were female and 50.5% were male. Mean age was 30.5 years. African American race was predominant (92%) with sickle cell Hb-SS disease (87%). Major insurance payer was Medicaid (47%) followed by Medicare (27%) and then private insurance (21%). Asthma was the most common comorbidities (24%) and majority of patient had Charlson Comorbidity Index (CCI) score of zero (55%). The details of clinical and epidemiological characteristics are shown in Table 1. Clinical outcomes and factors influencing mortality Only 0.89% patient died of ACS. Average length of stay was 6.86 days. 34% of the patient required packed red blood cell (pRBC) transfusion. 3.2% needed mechanical ventilation. In multivariate analysis, factors associated with mortality included age of patient, CCI and sepsis. Younger patient had higher odds of mortality however this was not statistically significant. There was no difference in mortality with sex, race and insurance status of the patients. Factors affecting inpatient transfusion, mechanical ventilation and length of stay Female, higher CCI score and sepsis on admission were associated with higher needs of inpatient pRBC transfusion. Within race, White (OR 3.16, CI 1.44-6.93, P <0.01) and Hispanics (OR 2.68, CI 1.59-4.51, P<0.01) had higher odds of receiving transfusion compared to African Americans (OR 1.84, CI: 1.17-2.89, P <0.01). Similarly patient with sepsis, supraventricular tachycardia had more odds of needing mechanical ventilation. Patient's insurance status was also related to increased odds of intubation. Comorbidities such as asthma and CAD were not associated with need of mechanical ventilation and in fact our study shows they had less odd of needing mechanical ventilation. Length of stay was influenced by several of epidemiological and clinical comorbidities. Females had less odds of longer length of stay compared to male (OR: 0.65, P <0.01). Comorbidities such as asthma, heart failure, CAD, DM2 and hypertension did not increase the length of stay while patients with sepsis and high CCI score had higher odds of hospitalization for extended period of time. The details are in Table 2. Conclusion We found mortality was 0.89% in patients admitted with ACS compared to 3 to 9% previously reported. Sepsis and CCI were one of the predictors for odds of having higher mortality, need of blood transfusion, mechanical ventilation and increased length of stay in patient with ACS. Female, White and Hispanic had higher odds of needing transfusion then African Americans. Comorbidities such as asthma, heart failure, CAD, DM 2 and hypertension did not increase the odds of prolonged hospital stay.

Introduction: Vitamin B12 deficiency is a common nutritional issue associated with mild anemia and neurological deficits. While rare, hemolytic anemia and low platelet count can be complications of this deficiency, often misdiagnosed as thrombotic microangiopathy (TMA), specifically thrombotic thrombocytopenic purpura (TTP). Pseudo TMA features can occur with B12 deficiency and can be effectively treated with vitamin B12 supplementation. In contrast, true TMA requires plasmapheresis. This systematic review aims to differentiate between pseudo TMA and TMA cases through an analysis of published case reports, providing valuable insights to avoid unnecessary treatments. Methods: We performed systematic review from Pubmed, Web of Science, and Scopus database. Twin independent reviewers (SY and BL) performed the screening using Covidence. Search keywords included “((hemolytic anemia) AND (vitamin B12 deficiency)) OR ((cobalamin deficiency) AND (hemolytic anemia)) Filters: English” for Pubmed, “(((ALL=(Cobalamin deficiency)) OR ALL=(vitamin B12 Deficiency))) AND ALL=(hemolytic anemia) Filter: English” for Web of Science and “( vitamin AND b12 AND deficiency OR cobalamin AND deficiency ) AND hemolytic AND anemia AND ( LIMIT-TO ( LANGUAGE , ”English“ ))” from Scopus. Only case reports in English with full-text availability and adult subjects were selected. Cases without final clinical outcome after treatment were excluded. After a comprehensive review, we identified 43 case reports and series with a total 53 patients that fulfilled our criteria. The details of selection process is illustrated in the prisma diagram (Figure 1). Results: The majority of cases involved males with low hemoglobin and platelet counts upon admission. Evidence of hemolysis was observed, indicated by increased lactate dehydrogenase (LDH), undetectable haptoglobin, and elevated or normal total and direct bilirubin levels. Peripheral blood films confirmed the presence of hemolytic anemia. Due to the co-occurrence of thrombocytopenia and hemolytic anemia, some cases were initially diagnosed as TTP, leading to the initiation of plasmapheresis. In 16 out of 53 reported case reports/series, patient received plasmapheresis. However, low reticulocyte index and normal ADAMTS 13 suggested an alternative diagnosis. Once ADAMTS 13 levels were normal, plasmapheresis was discontinued as TTP was ruled out. Diagnosis of B12 deficiency was confirmed by low B12 levels and elevated methylmalonic acid (MMA) levels. Leading cause for B12 deficiency were pernicious anemia in 28/53 cases, followed by dietary deficiency, and malabsorption due to surgery. Some patients also exhibiting concurrent iron deficiency anemia and folate deficiency. Treatment with subcutaneous B12 injections showed improvement in hemolysis as early as one week. Conclusion: Many cases of Vitamin B12 deficiency presenting with hemolytic anemia and thrombocytopenia are mistakenly diagnosed as TTP, leading to unnecessary and expensive plasmapheresis. Routine B12 level checks should be performed in all patients with hemolytic anemia, as B12 deficiency can be rapidly diagnosed and effectively treated, avoiding misdiagnoses and unnecessary interventions associated with TTP. The short turnover time for B12 levels (hours) compared to ADAMTS 13 activity (1-2 days) further supports the importance of routine B12 assessment in these patients.

Abstract Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS‐IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non‐CNS‐IVL patients with abnormal FDG‐PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS‐IVL and 63.5% (35/55) had non‐CNS‐IVL. CNS‐IVL group consists of clinically isolated CNS involvement (CNS‐only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M‐IVL) (14.5%; 8/55). Non‐CNS‐IVL group consists of clinically isolated skin involvement (skin‐only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P‐IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B‐cell IVL. Rituximab + high‐dose methotrexate‐based regimen were used in 75% (12/16) of CNS‐IVL patients and RCHOP in 60% (17/28) of non‐CNS‐IVL patients. Estimated 5‐year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin‐only IVL was associated with excellent survival. Platelet count <150x10 9 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.

Effects of Crotalinae envenomation vary by geographical areas and research into coagulopathy and effects of antivenom are needed to optimize management. This was a single-center retrospective review with testing on presentation and 4 h after; antivenom administration was noted and data analyzed overall and comparing envenomations. One hundred and nineteen snakebites evaluated with 59 identified as Crotalinae and half receiving antivenom. PT/aPTT was elevated in 20% of water moccasin/copperhead and 21% of rattlesnake bites. DIC-like syndrome occurred in 8% water moccasin/copperhead and 6% rattlesnake bites. Antivenom did not seem to correct PT or aPTT at 4 h follow-up in most cases. Thrombotic microangiopathy was not seen. Coagulopathy was prevalent affecting one in five patients in this cohort and does seem to persist at short interval follow-up, even in those receiving antivenom. We support guidelines recommending clinical monitoring and serial coagulation profiles in such cases. Blood Coagul Fibrinolysis 30:000 – 000 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL. Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method. Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was &lt;2 in 66%. The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse. Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (&gt;30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29]. Conclusion: 1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected. 2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations. 3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions. 4.Overall prognosis in the literature was poor with most patients surviving &lt;1 year. Our cohort has mOS of 57 months. The reason(s) for better survival in our cohort could not be definitively determined. 5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size. 6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL. 7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. Figure 1 Figure 1. Disclosures Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

e19552 Background: Leukemic involvement (LI) in diffuse large B cell lymphoma (L-DLBCL) is very rare and has been sparsely reported. We report our experience with this entity in a large academic multi-center setting. Methods: Medical records of patients with DLBCL who received care at Mayo Clinic between 1/2003 and 6/2020 were reviewed. DLBCL patients with LI were identified. LI was defined as increased white blood cell counts and the presence of clonal B cells on peripheral blood flow-cytometry. Kaplan-Meier method was used for survival analysis. Results: Twenty patients with L-DLBCL were identified with a median follow-up of 32.5 months (CI95%, 32.5-NR). Median age at initial diagnosis was 62 (45-80) years. 60% (12/20) were male; 90% (18/20) were Caucasian. Pathologically, 90% (18/20) had DLBCL and 10% (2/20) had high-grade B cell lymphoma (HGBCL) with intermediate features between DLBCL and Burkitt lymphoma. By Hans criteria, 58% (11/19) had germinal center B-cell DLBCL (GCB-DLBCL) and 42% (8/19) had non-germinal center B-cell DLBCL (non-GCB-DLBCL). 40% (8/20) had transformed DLBCL (t-DLBCL); 36% (5/14) had double-hit lymphoma (DHL) by FISH analysis. LI was present in 55% (11/20) at initial diagnosis and 45% (9/20) at relapse. Median WBC was 39.5/ul (range, 4.3-121) with median absolute lymphocyte count of 25 k/ul (range, 0.7-117). Immunophenotypically, the leukemic lymphoma cells expressed CD19, CD20, and CD79a. Bone marrow involvement and pancytopenia were documented in all patients with a median bone marrow cellularity of 80%. Other extranodal sites of involvement with LI included spleen (65%;13/20), liver (20%;4/20), breast and soft tissue (20%;4/20), bladder or kidneys (10%;2/20), skeleton (10%;2/20), and myocardium (5%;1/20). 65% (13/20) had B-symptoms. All patients had LDH elevation (UNL 222 U/L) with a median of 2125 U/L (range, 308-10,760). 45% (5/11) of patients with LI at initial diagnosis had CNS involvement on relapse/progression. All patients with LI at initial diagnosis received anthracycline-based chemoimmunotherapy with or without CNS prophylaxis. Patients with LI at relapse had had a median of 2 prior treatments (range, 1-5) before LI. Median overall survival (OS) for the whole group was 9 months (CI 95%; 5.8-11.8). There were no long-term survivors. Median progression free survival after LI was 4.7 months (CI95%; 0.8-7.6) in the newly diagnosed group and 3 months (CI95%; 0.9-20) in the relapsed group. 90% (18/20) died due to their progressive disease. Cell of origin, DHL status, or newly diagnosed vs. relapsed status did not have a significant impact on OS in patients with L-DLBCL. Conclusions: Leukemic involvement at any time during the course of DLBCL is associated with poor prognosis. It also appears to be a major risk factor for CNS relapse. It is most frequently associated with DHL and t-DLBCL. Novel therapeutic approaches at the time of initial therapy need to be developed for L-DLBCL.

AbstractIgG4‐related disease (IgG4RD) with intracranial involvement is rare. We report a 56‐year‐old male who had an excellent response to rituximab and dexamethasone after going undiagnosed for 5 years. After 3 years of rituximab maintenance, he has no evidence of disease on brain MRI.

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT&gt;0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.