Kidneys influence the production of red blood cells by secreting most of the erythropoietin (EPO) in adults. Consequently, renal diseases often impact erythropoiesis and hemoglobin levels. Chronic kidney diseases lead to anemia due to EPO deficiency. However, erythrocytosis can occur in patients with cystic diseases of the kidney and renal artery stenosis due to upregulation of hypoxia-inducible factors (HIFs) and increased EPO production. Here, we present a patient with secondary polycythemia who was found to have atonic bladder and hydronephrosis. Resolution of hydronephrosis led to the reversal of erythrocytosis, highlighting the intricate regulation of red cell production.
Introduction Patients with refractory or relapsed diffuse large B cell lymphoma (DLBCL) have very limited treatment options. Axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel are the Anti-CD-19 chimeric antigen receptor T-cell (CAR-T) therapy have been recently approved for refractory or relapsed DLBCL patients who have failed at least two lines of treatment. CAR-T therapy has significant adverse effects, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), limiting its use, particularly in the elderly population. In this meta-analysis, we analyzed the safety of CAR-T therapy in the elderly population compared to the younger patients with DLBCL. Methods Randomized controlled trials and observational studies in adult patients with DLBCL treated with anti-CD-19 CAR-T therapy were included in the meta-analysis. Case reports, case series, and review articles were excluded. We searched PubMed for studies published before 1st July 2021 using keywords "tisagenlecleucel," "axicabtagene ciloleucel," and "lisocabtagene maraleucel." The study selection process is shown in figure 1. Statistical analysis was performed with Comprehensive meta-analysis version 3. The fixed-effect model was used for pooled analysis. Heterogeneity across studies was analyzed using I2 statistics. Results Three studies, comprising of 616 patients, were included in the analysis. Characteristics of the study population and the number of events in each study are shown in figure 2. Two studies used a cut-off of 65 years, while one study used a cut-off of 70 years for the older population. The mean age in the younger population was 55, while the mean age in the elderly population ranged from 69 to 76. Mean follow-up ranged widely in the three studies ranging from 7 months to 27.1 months. Incidence of CRS ranged from 36% to 84% in the elderly population compared to 34% to 83% in younger patients. Grade 3 or 4 CRS ranged from 1 to 14% in the elder compared to 2 to 14% in younger patients. The pooled analysis shown in figure 3 revealed an odd ratio of 1.11 with a confidence interval ranging from 0.76 to 1.63 (p=0.58), implying there is no statistical difference between the two groups. The incidence of ICANS ranged from 27% to 65% in elderly patients compared to 8.5% to 47% in younger patients. Grade 3 or 4 ICANS ranging from 2 to 47% in elderly patients compared to 2% to 18% in younger patients. The pooled analysis shown in figure 4 showed an odd ratio of 1.59 with a confidence interval ranging from 1.09 to 2.34 (p=0.02), suggesting the risk of ICANS is higher in older patients. Conclusion CRS and ICANS are the most common adverse effects limiting the use of CAR-T therapy in the elderly. Our analysis showed that age does not impact the risk of CRS in DLBCL patients treated with anti-CD19 CAR-T treatment. However, older patients are at a higher risk of ICANS as compared to younger, suggesting CAR-T therapy should be used with caution in patients older than 65 years of age, especially if they have baseline neurological impairment. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
Introduction US Food and Drug Administration has recently approved the use of rivaroxaban 2.5mg BID in patients with coronary heart disease based on Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. However, it's unclear whether there is net clinical benefit with use of rivaroxaban in such patients. Therefore, we did a systematic review and meta-analysis to evaluate the effects of rivaroxaban on clinical outcomes in coronary heart disease patients. Methods: Embase, Ovid, Pubmed and Scopus were extensively searched from inception of these databases to April 2019 by two independent reviewers. Only randomized controlled trials of low dose rivaroxaban (2.5 mg BID) reporting mortality and cardiovascular outcomes of interest in baseline coronary heart disease patients (≥ 18 years) with at least 1000 patients and follow-up of ≥ 1 year were included. The co-primary outcomes were cardiovascular mortality and all-cause mortality. The secondary endpoints were myocardial infarction (MI), stroke, major adverse cardiovascular events, major bleeding and cerebral nervous system (CNS) bleeding. Cochrane Collaboration's tool was used for risk of bias assessment. Statistical heterogeneity was quantified using I2 statistics whereas publication bias was assessed with Eggers regression test. We combined estimates using DerSimonian and Laird random effects models. Outcomes were reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: Five randomized control trials including 39,979 patients were included in our meta-analysis. Trials ATLAS and Commander HF used placebo as their control while COMPASS and GEMINI ACS-1 used aspirin as control. Pioneer AF-PCI used vitamin K antagonist as the control. Mean age (SD) of the patients was 65.6 ± 3.7 years with 74.3% females. Mean follow up in years was 1.6 ±0.5. Majority of the patients in each trial had hypertension. Our pooled analysis showed reduction in all-cause mortality (HR, 0.85, 95% CI, 0.72-1.00, P=0.05), cardiovascular mortality (HR, 0.83, 95% CI, 0.70-1.00, P=0.05), MI (HR, 0.88, 95% CI, 0.78-1.00, P=0.05) and stroke (HR, 0.70, 95% CI, 0.53-0.94, P=0.02) with low dose rivaroxaban. No significant difference in risk of bleeding was observed (HR, 1.45, 95% CI, 0.83-2.51, P=0.19). Our pooled analysis also showed reduction in major cardiovascular events (HR, 0.91, 95% CI, 0.85-0.98, P=0.01). CNS bleeding was only reported by ATLAS and COMPASS trials and net effect showed no statistically significant bleeding risk (HR, 1.63, 95% CI, 0.70-3.79, P=0.26). Conclusion: Our data suggest that the use of rivaroxaban is associated with reduction in all-cause and cardiovascular mortality in coronary heart disease patients without significantly increasing the risk of bleeding. To further decrease the residual risk of cardiovascular events in coronary heart disease patients, low dose rivaroxaban can be considered by clinicians. Disclosures No relevant conflicts of interest to declare.
Background: Direct oral anticoagulants (DOACS) were recently approved for anticoagulation in patients with atrial fibrillation for prevention of stroke and patient with venous thromboembolism (VTE) for the prevention of recurrent VTE. They have shown comparable efficacy and safety compared to vitamin K antagonist (VKA). DOACS have uniform pharmacokinetics and pharmacodynamics; hence, regular monitoring is not required. The morbidly obese patients may have increased volume of distribution and altered clearance which may alter the pharmacokinetics and consequently efficacy and safety of DOACS in these patients. 2016 International Society of Thrombosis and Hemostasis guideline recommends avoiding DOACS in a patient with body mass index (BMI) >40 kg/m2 or with body weight >120 kg due to lack of clinical trials. There is no sizeable randomized control trial to study the outcome of DOACS in morbidly obese patients, but subgroup analysis of a major randomized control trials and observational studies may provide the data on the efficacy and safety of DOACS. We intend to utilize this data in this meta-analysis to study the effectiveness and safety of DOACS in morbidly obese patients. Methods: Eligibility Criteria- Randomized control trial, observational studies including patients above 18 years with BMI>40kg/m2, body weight>120 kg and history of atrial fibrillation or VTE who are taking DOACS or warfarin for therapeutic purpose were included in the analysis. Study Selection- We searched Medline and Cochrane database. 52 studies were identified and 43 remained after removing duplicates. After assessing full text for eligibility 5 studies were included in the meta-analysis. Statistical analysis- Statistical analysis was performed with Review manager 5.3 by the Cochrane Collaboration. Forest plot was used to analyze publication bias. Heterogeneity in the studies were analyzed with Cochran Q analysis and I2 statistics. Results: Population characteristics were available in four studies. The mean age of the population ranged from 61.7 to 66.8 years, and mean BMI ranged from 44.8 to 46.7 kg/m2 . I2 analysis showed that the studies included were homogeneous, so fixed-effect model was applied. The incidence of recurrent VTE, stroke, or death ranged from 1.5% to 7.3% in DOACS compared to 1.2% to 7.9% in warfarin except in one study by Kalani et al. where it was 26% in DOACS vs. 20% in warfarin. Relative risk was 0.96 (confidence interval 0.75 - 1.28, p 0.78) indicating there was no significant difference in the primary efficacy outcome between the two groups. The incidence of major bleeding ranged from 1.5% to 4.8% in DOACS compared to 2.6% to 6.1% in warfarin. Relative risk was 0.72 (confidence interval 0.56 - 0.93, p 0.01) indicating that the risk of major bleeding was low among patient using DOACS. Conclusion: Efficacy of DOACS is similar compared to VKA when used for prevention of recurrence in VTE or prevention of stroke in atrial fibrillation in the patients with BMI>40 kg/m2 or bodyweight >120 kg. There was a trend towards a lower risk of bleeding in the patients with DOACS which is similar to the risk of major bleeding reported in non-obese patients in landmark randomized clinical trials. Only two studies included the patients with VTE, and additional studies are required to assess the safety and efficacy of DOACS among morbidly obese individuals with VTE. Figure Disclosures No relevant conflicts of interest to declare.
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