Anticoagulation in cancer patients with atrial fibrillation and grade 3-4 thrombocytopenia.

INTRODUCTION: Atrial fibrillation or flutter (AF) is prevalent in cancer patients. Many of these patients have an indication for anticoagulation (AC) but are also at risk for developing chemotherapy-induced thrombocytopenia. There are scarce data regarding management of AC and risk of bleeding and thrombosis in cancer patients with AF and thrombocytopenia. AIM: To assess anticoagulation management and incidence of bleeding and arterial thromboembolism (ATE) in cancer patients with AF and grade 3-4 thrombocytopenia (platelets <50 × 109/L). METHODS: A retrospective cohort study included adults with active cancer, grade 3-4 thrombocytopenia and AF with CHA2DS2-VASc score ≥ 1. Patients were stratified according to AC discontinuation (No-AC) or continuation (Continue-AC) when platelets dropped below 50 × 109/L and followed for 30 days. The study outcomes were ATE (ischemic stroke, transient ischemic attack or systemic emboli) and major bleeding. Cox proportional hazards model was used to calculate hazard ratios (HR) with death as a competing risk (Fine and Gray model). RESULTS: The cohort included 131 patients; 90 in the No-AC group and 41 in the Continue-AC group. Patient characteristics were balanced between the groups. The 30-day cumulative incidence of ATE was 2 % [95 % CI 0.4 %-7 %] in the No-AC group and 2 % [0.2 %-11 %] in the Continue-AC group (HR 0.92 [95 % CI 0.09-9.88]). The 30-day cumulative incidence of major bleeding was 7.8 % [95 % CI 3.40 %-14.52 %] and 2.44 % [95 % CI 0.18 %-11.22 %] in the No-AC and Continue-AC groups, respectively (HR 3.29 [95 % CI 0.42-26.04]). CONCLUSIONS: The high rate of bleeding and low rate of ATE in thrombocytopenic cancer patients with AF suggests that holding AC during time-limited periods may be a reasonable approach.

The Impact of Thrombocytopenia and Lymphopenia on Mortality in Patients Infected with Influenza Virus: A Retrospective Cohort Study.

INTRODUCTION: Influenza virus causes significant global annual morbidity and mortality. Thrombocytopenia is recognized as a poor prognostic factor in sepsis and is associated with mortality, while lymphopenia has been established as a poor prognostic factor in other viral infections. We aimed to assess the incidence of thrombocytopenia and lymphopenia in seasonal influenza and their effect on clinical outcomes. METHODS: This single-center, retrospective, cohort study included consecutive adult patients, hospitalized in Rabin Medical Center between October 2017 and April 2018, with laboratory-confirmed influenza. Patients were grouped according to blood counts on admission: (1) thrombocytopenia (<150 K/mL), (2) lymphopenia (<0.5 K/mL), and (3) both thrombocytopenia and lymphopenia. Patients without thrombocytopenia and lymphopenia were designated as controls. The primary outcome was 30-day all-cause mortality. Risk factors were identified by univariable and multivariable analyses, using logistic regression and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 625 patients were included, 112 (18%) had thrombocytopenia, 98 (15.6%) had lymphopenia, and 107 (17%) had both. The crude 30-day all-cause mortality was 7.6% (48/625). Mortality rates were 7.1% (8/112) for the thrombocytopenia group, 11.2% (11/98) for the lymphopenia group, and 14.9% (16/107) for patients with both versus 4.2% (13/308) in the control (p = 0.000 for all). In a multivariable regression model, significant thrombocytopenia (<100 K/µL) [OR 5.07 (95% CI 1.5-16.2)], age [OR 1.07 (95% CI 1.02-1.11)], time to oseltamivir [OR 1.006 (95% CI 1.002-1.11)], and significant respiratory support [OR 8.85 (3.4-22.6)] were associated with 30-day all-cause mortality. CONCLUSION: Patients hospitalized with seasonal influenza and thrombocytopenia <100 K/mL on admission, have an increased 30-day all-cause mortality.

Rituximab versus obinutuzumab-based first-line chemoimmunotherapy for follicular lymphoma-a real-world multicenter retrospective cohort study.

The GALLIUM study showed a progression-free survival advantage of 7% in favor of obinutuzumab vs. rituximab-based immunochemotherapies as first-line therapy in follicular lymphoma (FL) patients. Yet, the toxicity appears to be increased with obinutuzumab-based therapy. This is a multicenter retrospective-cohort study including adult FL patients comparing the toxicity of first-line rituximab vs. obinutuzumab-based chemo-immunotherapies (R and O groups, respectively). We compared the best standard-of-care therapy used per time period, before and after obinutuzumab approval. The primary outcome was any infection during induction and 6 months post-induction. Secondary outcomes included rates of febrile neutropenia, severe and fatal infections, other adverse events, and all-cause mortality. Outcomes were compared between groups. A total of 156 patients were included in the analysis, 78 patients per group. Most patients received bendamustine (59%) or CHOP (31.4%) as adjacent chemotherapy. Half of the patients received growth-factor prophylaxis. Overall, 69 patients (44.2%) experienced infections, and a total of 106 infectious episodes were recorded. Patients in the R and O groups had similar rates of any infection (44.8% and 43.5%, p = 1), severe infections (43.3% vs. 47.8%, p = 0.844), febrile neutropenia (15% vs. 19.6%, p = 0.606), and treatment discontinuation, as well as similar types of infections. No covariate was associated with infection in multivariable analysis. No statistically significant difference was evident in adverse events of grades 3-5 (76.9% vs. 82%, p = 0.427). To conclude, in this largest real-life study of first-line treated FL patients comparing R- to O-based therapy, we did not observe any difference in toxicity during the induction and 6 months post-induction period.

Direct oral anticoagulants in patients with venous thromboembolism and hematological malignancies.

Data are needed on direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in hematological malignancies (HM). Retrospective studies to date lacked a control group and did not focus on patients with VTE. Out aim was to assess the incidence of VTE recurrence and bleeding in HM patients treated with low molecular weight heparin (LMWH) or DOACs for acute VTE. This is a retrospective cohort study including patients with active HM and newly-diagnosed VTE, indexed on the first day of anticoagulation and followed for 12 months. The outcome was a composite of recurrent VTE, major bleeding or clinically relevant non-major bleeding. Cumulative incidence [95% confidence interval (CI)] was calculated for each anticoagulation group (LMWH, DOAC) and hazard ratios (HR) were calculated using cox-proportional hazards model, with death as a competing risk. 143 HM patients treated with LMWH (96) or DOACs (47) for acute VTE were included. The most common HM types were lymphoma in 83 (58%) and plasma cell dyscrasia in 32 (22.3%). The 12-month cumulative incidence of the composite outcome was 24.2% (95% CI 15.9-33.5%; n = 22) in the LMWH group and 18.5% (8.5-31.5%; n = 8) in the DOAC group (HR 1.51 [0.695-3.297]). Two recurrent VTE occurred (both in the DOAC group while off-treatment). Nine (9.4%) LMWH-treated patients had major bleeding compared to 1 (2.1%) DOAC-treated patient (HR 4.85 [0.64-36.56]). This study generates the hypothesis that DOACs may be a safe and effective alternative to LMWH for VTE in patients with HM types represented in the study.

Predictors for spontaneous resolution of classical FUO in patients undergoing PET-CT.

Spontaneous resolution is common in patients with classic fever of unknown origin (FUO). Identifying predictors of spontaneous resolution could reduce the usage of unnecessary, invasive tests or empirical therapy, and furthermore reduce patient anxiety. Identify predictors associated with spontaneous resolution of FUO. A single center, retrospective, cohort study. All hospitalized patients who underwent an [18F] FDG PET-CT scan for the investigation of classical FUO between 1/2012 and 1/2020 were included. We compared patients with spontaneous resolution of fever and clinical symptoms, to those who were diagnosed with a specific etiology of FUO (subdivided to infectious diseases, non-infectious inflammatory diseases (NIID), and malignancies). Epidemiologic characteristics as well as laboratory and PETCT study results were compared. Variables that were found to be associated with spontaneous resolution of FUO on univariate analysis (p < 0.1) were entered into a multivariable regression analysis. The results are reported as odds ratios (OR) and 95% confidence intervals (CI). A total of 303 patients were hospitalized for the investigation of classical FUO and underwent complete assessment. Fever resolved without a diagnosis in 84/303 patients (28%). Variables that were associated with spontaneous resolution of FUO on multivariable analysis included: no anemia, no hypoalbuminemia and no pathological FDG uptake on PET-CT. In 17.8% (15/84) of studies, PET-CT yielded false-positive results that led to additional unnecessary, invasive investigation. Patients without anemia or hypoalbuminemia, and those without uptake on PET-CT are more likely to have spontaneous resolution of classical FUO.

Current approaches for the diagnosis and management of immune thrombocytopenia.

Immune thrombocytopenia (ITP), is an acquired autoimmune disorder characterized by the destruction of platelets and megakaryocytes, resulting in thrombocytopenia (platelet count <100 × 109/L). This review focuses on the diagnosis and current management of ITP. The diagnosis of ITP is based principally on the exclusion of other causes of isolated thrombocytopenia using patient history, physical examination, blood count, and evaluation of the peripheral blood film. The clinical treatment goals should be to resolve bleeding events and to prevent severe bleeding episodes. The platelet count should be improved to attain a minimum of > 20-30 × 109/L. Therapy should be given as an inpatient in newly diagnosed ITP with a platelet count of > 20 × 109/L or if there is active bleeding. Corticosteroids are considered the standard initial treatment for newly diagnosed patients. Subsequent medical therapies with robust evidence include thrombopoietin receptor agonists (TPO-RAs), rituximab and fostamatinib. Surgical therapy with splenectomy may be considered for patients failing medical therapy. The choice between therapy options is highly dependent upon patient values and preferences.

The role of additional chemotherapy prior to autologous HCT in patients with relapse/refractory DLBCL in partial remission-A retrospective multicenter study.

OBJECTIVES: To evaluate the role of additional chemotherapy before autologous hematopoietic cell transplantation (HCT) in patients with relapse/refractory diffuse large B-cell lymphoma (DLBCL) who achieve partial remission following first salvage therapy. METHODS: We conducted a multicenter retrospective study of all adult patients with DLBCL who underwent HCT between 2008 and 2020 and achieved partial response (PR) after the first salvage and were either referred directly to HCT (n = 47) or received additional salvage therapy before HCT (n = 22). RESULTS: Post-HCT CR rate and progression-free survival were comparable between the two groups (66% vs. 68%, p = .86 and median not reached vs. 10.2 months [95% confidence interval, CI 7.1-12.3], p = .27, respectively). Median overall survival (OS) and estimated 3-year OS favored patients who were directly referred to HCT (105.8 [95% CI 63-148] months vs. 14.5 [95% CI 0-44] months, p = .035, and 65% [95% CI 51%-75%] vs. 40% [95% CI 21%-53%], p = .035, respectively). In Cox regression model, while International Prognostic Index and primary refractory versus relapse disease did not impact OS, allocation to a second salvage regimen and older age were both associated with inferior survival (hazard ratio [HR] = 2.57 95% CI 1.1-5.8, p = .023 and HR = 1.04 95% CI 0.99-1.2, p = .064, respectively). CONCLUSIONS: Referring patients with chemotherapy-sensitive disease in PR directly to HCT is associated with better OS compared to those receiving additional lines of treatment.

Infectious complications and long-term outcomes in patients with diffuse large B-Cell lymphoma and diabetes mellitus.

Febrile neutropenia (FN) is a major complication in patients with diffuse large B-Cell lymphoma (DLBCL). Diabetes mellitus (DM) has deleterious effects on the immune system resulting in an increased risk of infections. We evaluated patients with DLBCL who started frontline treatment with R-CHOP, and compared outcomes according to presence of DM comorbidity. Between 2013 and 2018, 218 patients with DLBCL were included. 46 patients (21%) had DM. Rate of admissions for FN was higher for patients with DM (0.7 vs. 0.46 admissions/patient, p = .016), also after age and gender-matched subgroup analysis (p = .004). Improved glycemic control during FN hospitalizations was associated with shorter hospitalizations. Metformin was associated with improved median overall survival in diabetic patients (89 vs. 64 months, p = .018). In conclusion, Patients with DLBCL and DM had higher rates of FN hospitalizations. Improved glycemic control during FN hospitalization was associated with shorter length of stay.

Effect of steroid treatment on the diagnostic yield of baseline 18f-fluorodeoxyglucose positron emission tomography in aggressive B cell lymphoma.

Aggressive B cell lymphoma often requires prompt steroid treatment, even before baseline 18f-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and definitive treatment, to alleviate symptoms or prevent organ damage. Since lymphoma is a steroid-sensitive malignancy, there are concerns that steroids might affect the results of FDG PET/CT and decrease its diagnostic yield. The aim of the current study was to evaluate the effect of steroids administered before baseline PET/CT on the maximum standardized uptake value (SUVmax) and additional PET/CT parameters. Retrospective review of the database in a tertiary medical center yielded 178 patients newly diagnosed with aggressive B cell lymphoma between January 2017 and May 2020 who had an available baseline FDG PET/CT scan. The cohort was divided into patients who received steroids before PET/CT (n = 47) and those who did not (n = 131), and the groups were compared for SUVmax and additional PET/CT parameters. The steroid-treated group had a higher disease stage and lactate dehydrogenase level compared to the steroid-naïve group, with a trend toward a higher international prognostic index. There was no significant between-group difference in SUVmax (P = 0.61). This finding remained consistent across steroid treatment durations and dosage regimens. Further evaluation revealed a significantly larger mean tumor volume and a trend toward a higher tumor metabolic burden in the steroid-treated group, yet no between-group difference in SUV mean or other PET/CT parameters. In this retrospective analysis of patients with aggressive B cell lymphoma, steroid prophase prior to baseline PET/CT did not decrease the diagnostic yield of the scan. However, further studies are required to fully appreciate the impact of steroids on PET CT parameters.

Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. Materials and methods: All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I2 > 40%), in which we used a random effects model. Results: A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55−0.95) with a number needed to treat of 20 (95% CI 11−100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01−1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88−1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76−1.57; 8 trials). Conclusions: IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.

Chimeric antigen receptor T-cell therapy is superior to standard of care as second-line therapy for large B-cell lymphoma: A systematic review and meta-analysis.

Treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered standard of care (SOC) second-line treatment for relapsed or refractory large B-cell lymphoma (LBCL). However, outcomes remain suboptimal. A systematic review and meta-analysis of randomised controlled trials comparing efficacy and safety of SOC versus chimeric antigen receptor T-cell (CAR-T) therapy as second-line for patients with LBCL refractory or relapsing within 12 months. Outcomes included overall survival (OS), event-free survival (EFS), overall response rate (ORR) and safety. Three trials published in 2021 (involving 865 participants) fulfilled the eligibility criteria. EFS as well as OS were significantly improved with CAR-T therapy as compared to SOC, hazard ratio (HR) 0.57 (95% confidence interval [CI] 0.49-0.68) and HR 0.77 (95% CI 0.60-0.98) respectively. CAR-T therapy was associated with significantly better ORR, relative risk (RR) 1.55 (95% CI 1.12-2.13, p = 0.001). The risk of Grade III/IV adverse event was comparable between the two arms, RR 1.03 (95% CI 0.93-1.14). In summary, CAR-T therapy has superior outcomes as compared to SOC in patients with LBCL refractory or relapsing within 12 months, without excess of toxicity. Longer follow-up is needed to confirm these results and determine the optimal sequencing of CAR-T therapy in the management of LBCL.

Repeat biopsy in relapsed or refractory diffuse large B cell lymphoma: a nationwide survey and retrospective study.

Almost half of patients with diffuse large B-cell lymphoma (DLBCL) have relapsed/refractory (R/R) disease after frontline immunochemotherapy. Although guidelines recommend histological confirmation of R/R disease, repeat biopsies are not always performed. We conducted a two-part study: a nationwide case-vignette survey among treating hematologists, and a single center retrospective analysis. In the survey part, all 64 participating physicians opted not to perform a repeat biopsy in at least one scenario, more often in refractory cases. In the retrospective part, 116 episodes of R/R aNHL among 61 patients were identified. Repeat biopsy was not performed in 72%, more often in refractory episodes, mostly due to low likelihood of alternative diagnoses or problematic location for biopsy. Our study suggests that many patients do not undergo repeat biopsy in R/R DLBCL, especially in refractory cases. Future studies and recommendations should address the necessity of repeat biopsy, according to patient and disease related characteristics.

A Systematic Review Assessing the Underrepresentation of Cancer Patients in COVID-19 Trials.

BACKGROUND: The new severe acute respiratory syndrome coronavirus 2 has emerged as a global pandemic that threatens thousands around the world. Observational cohort studies have demonstrated that cancer patients have inferior outcomes due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. We aimed to examine the representation of cancer patients (hematological malignancies and solid tumors) in COVID-19 therapeutic and prophylactic interventional trials. METHODS: In this review, all randomized controlled trials (RCTs) published between December 2019 and August 2021 were included. We included only trials evaluating medications that were recommended by NIH guidelines: steroids, tocilizumab, remdesivir, and REGN-COV2. RESULTS: The search yielded 541 potentially relevant RCTs, 22 of which were considered suitable. All trials included patients with solid cancer and hematological malignancies in the formal reported inclusion criteria. However, only two trials reported the accurate number of cancer patients included. Ten trials excluded neutropenic patients and seven trials excluded thrombocytopenic patients. Eleven trials excluded patients that were treated with any immunosuppression treatment. None of the two trials that included cancer patients reported separate outcomes for this population. CONCLUSION: Our systematic review shows that cancer patients are underrepresented in COVID-19 interventional therapeutic trials, and evidence regarding outcomes are lacking.

Clinical and pathological predictors for FDG-PET/CT avidity in patients with marginal zone lymphoma-a retrospective cohort study.

BACKGROUND: The clinical value of FDG-PET/CT for staging and monitoring treatment response in patients with aggressive lymphoma is well established. Conversely, its role in the assessment and management of marginal zone lymphoma (MZL) is less conclusive. We aimed to assess clinical, laboratory, and pathological predictors for FDG uptake in these patients, in an attempt to identify MZL patients whose management will benefit from this imaging modality. METHODS: In this single-center, retrospective cohort study, we included all adult patients diagnosed with MZL at the Rabin Medical Center between January 2006 and December 2020 who underwent FDG-PET/CT at the time of diagnosis. Primary outcomes were FDG avidity (defined as a visual assessment of at least moderate intensity), SUVmax, and SUVliver. Variables such as advanced clinical stage, primary disease site, hemoglobin level (Hb), platelet count (Plt), serum albumin, LDH level, ß-2 microglobulin, and Ki 67 index were evaluated univariate and multivariate analysis using logistic and linear regression models. Association between FDG avidity and progression-free and overall survival was evaluated using Kaplan-Meier curves and Cox regression analysis. RESULTS: A total of 207 MZL patients were included in this study, 76 of whom (36.7%) had FDG-avid disease. Baseline patients' characteristics such as age, gender, and comorbid conditions were similar between patients with and without significant FDG uptake. In a multivariate logistic regression model, non-gastric MALT (OR 4.2, 95% CI 1.78-10), Ki 67 index ≥ 15% (OR 3.64, 95% CI 1.36-9.76), and elevated LDH level (OR 8.6, 95% CI 3.2-22.8) were all associated with positive FDG avidity. In a multivariate linear regression model, a combination of advanced clinical stage, specific disease subtypes, LDH level, and Ki 67 index predicted the value of SUVmax (P value < 0.001; adjusted R2 = 33.8%) and SUVmax/SUVliver (P value < 0.001; adjusted R2 = 27%). Baseline FDG avidity was associated to PFS and OS only in univariate analyses. CONCLUSIONS: In this retrospective cohort study, we present prediction models for positive FDG uptake and SUVmax in MZL patients. These models aim to help clinicians choose patients suitable for incorporation of FDG-PET/CT for staging and monitoring disease and reduce the costs of redundant tests.

Tocilizumab Treatment Effect on Iron Homeostasis in Severe COVID-19 Patients.

BACKGROUND: Tocilizumab has been proposed as an effective treatment for severe COVID-19. We aimed to investigate whether tocilizumab administration is associated with increased availability of serum iron which may possibly be associated with adverse effects on clinical outcomes. METHODS: We performed an observational, retrospective cohort study. We included adults, who were hospitalized in ICU with the diagnosis of severe COVID-19 infection eligible for tocilizumab treatment. Laboratory data including serum iron, ferritin, transferrin saturation, hemoglobin, and C-reactive protein levels of all patients were collected shortly before and 24 h, 48 h, and 72 h after tocilizumab administration. RESULTS: During the study period, 15 patients fulfilled the inclusion criteria and were eligible to receive tocilizumab treatment. Tocilizumab therapy was associated with a prominent increase in serum iron and transferrin saturation levels (26 ± 13 µg/dL and 15 ± 8% before treatment and 79 ± 32 µg/dL and 41 ± 15% 72 h after treatment, respectively, p < 0.001) and decrease in serum ferritin levels (1,921 ± 2,071 ng/mL before and 1,258 ± 1,140 ng/mL 72 h after treatment, p = 0.027). CONCLUSION: Treatment of severe COVID-19 patients with tocilizumab is associated with a profound increase in serum iron and ferritin saturation levels along with a decrease in ferritin levels. This may represent an undesirable side effect that may potentiate viral replication.

Humoral serological response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies.

Patients with lymphoma, especially those treated with anti-CD20 monoclonal antibodies, suffer high COVID-19-associated morbidity and mortality. The goal of this study was to assess the ability of lymphoma patients to generate a sufficient humoral response after two injections of BNT162b2 Pfizer vaccine and to identify factors influencing the response. Antibody titers were measured with the SARS-CoV-2 IgG II Quant (Abbott ) assay in blood samples drawn from lymphoma patients 4 2 weeks after the second dose of vaccine. The cutoff for a positive response was set at 50 AU/mL. Positive serological responses were observed in 51% of the 162 patients enrolled in this cross-sectional study. In a multivariate analysis, an interval of <12 months between the last anti-CD20 monoclonal antibody dose and the second vaccine dose (odds ratio=31.3 [95% confidence interval: 8.4-116.9], P<0.001) and presence of active lymphoma (odds ratio=4.2 (95% confidence interval: 2.1- 8.2), P=0.006) were identified as negative response predictors. The rate of seropositivity increased from 3% in patients vaccinated within 45 days after the last monoclonal antibody administration to 80% in patients vaccinated >1 year after this therapy. The latter percentage was equal to that of patients never exposed to monoclonal antibodies. In conclusion, lymphoma patients, especially those recently treated with anti- CD20 monoclonal antibodies, fail to develop sufficient humoral response to BNT162b2 vaccine. While a serological response is not the only predictor of immunity, its low level could make this population more vulnerable to COVID-19, which implies the need for a different vaccination schedule for such patients.

Autoimmune and inflammatory manifestations associated with acute myeloid leukemia with Trisomy 8-Case series and review of the literature.

AML can be associated with autoimmune or inflammatory phenomena (AIP) occurring prior, concomitantly, or after its diagnosis. Trisomy 8 is one of the most common cytogenetic abnormalities associated with AML. We describe three patients with AML, trisomy 8, and associated AIP and review the known literature on this association. All of our patients had major symptomatic relief when treated with leukemia-directed therapy and corticosteroids. AIP in AML may be an underdiagnosed phenomenon, particularly in patients with trisomy 8.

Previously undiagnosed cancer in patients with arterial thrombotic events - A population-based cohort study.

BACKGROUND: Emerging data suggest increased arterial thrombosis risk in the months preceding a cancer diagnosis. OBJECTIVES: To assess whether patients without documented vascular risk factors or pre-existing cardiovascular disease have a higher relative risk of cancer 12 months after arterial thrombotic events (ATE), compared to unselected patients. PATIENTS/METHODS: A population-based cohort study of Clalit Health Services (CHS) database included CHS members ≥25 years without prior cancer or ATE (n = 2 804 584). An iterative matching process selected 10 potential controls chronologically for each consecutive exposed, age- and sex-matched (actual controls drawn 1:1 from a lot). Study exposure, ATE, was defined as ischemic stroke, transient ischemic attack, myocardial infarction or systemic arterial thromboembolism during hospitalization. The outcome was newly-diagnosed cancer within 12 months, based on Israeli national cancer registry. Cox proportional hazards multivariate regression calculated hazard ratio (HR) for outcomes, adjusted for cancer risk factors. Analysis also performed for three subgroups: age ≤50 years; no cardiovascular risk factors; no prior cardiovascular disease. RESULTS: The full ATE and matched control cohorts included 43 108 patients. The 12-month cumulative incidence of cancer (95% confidence interval) was 0.020 (0.019-0.022) in the ATE cohort and 0.012 (0.011-0.013) in controls, corresponding to an adjusted HR of 1.665 (1.489-1.862). The relative risk of cancer was high in all subgroups up to a HR of 3.754 (1.912-7.372) in patients without cardiovascular risk factors. CONCLUSION: There is an increased risk of previously undiagnosed cancer at 12 months after ATE, especially in patients without documented vascular risk factors or pre-existent cardiovascular disease.

The Importance of Abnormal Platelet Count in Patients with Clostridioides difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) causes morbidity and mortality. Platelets have been increasingly recognized as an important component of innate and adaptive immunity. We aimed to assess the incidence of thrombocytopenia and thrombocytosis in CDI and the effect of an abnormal platelet count on clinical outcomes. METHODS: This single-center, retrospective cohort study consisted of all adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression. RESULTS: A total of 527 patients with CDI were included. Among them 179 (34%) had an abnormal platelet count: 118 (22%) had thrombocytopenia and 61 (11.5%) had thrombocytosis. Patients with thrombocytosis were similar to control patients other than having a significantly higher white blood cell count at admission. Patients with thrombocytopenia were younger than control patients and were more likely to suffer from malignancies, immunosuppression, and hematological conditions. In a multivariable analysis, both thrombocytosis (OR 1.89, 95% CI 1.01-3.52) and thrombocytopenia (OR 1.70, 95% CI 1.01-2.89) were associated with 30-days mortality, as well as age, hypoalbuminemia, acute kidney injury, and dependency on activities of daily living. A sensitivity analysis restricted for patients without hematological malignancy or receiving chemotherapy revealed increased mortality with thrombocytosis but not with thrombocytopenia. CONCLUSIONS: In this retrospective study of hospitalized patients with CDI, we observed an association between thrombocytosis on admission and all-cause mortality, which might represent a marker for disease severity. Patients with CDI and thrombocytopenia also exhibited increased mortality, which might reflect their background conditions and not the severity of the CDI. Future studies should assess thrombocytosis as a severity marker with or without the inclusion of the WBC count.