BACKGROUND The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. METHODS We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy. RESULTS At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], −0.2; 95% confidence interval, −3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy. CONCLUSIONS Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.)

Background Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. Methods In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d -dimer level. Results The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d -dimer cohort, 92.9% in the low d -dimer cohort, and 97.3% in the unknown d -dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. Conclusions In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589 , NCT04505774 , NCT04359277 , and NCT02735707 .)

BACKGROUND: Primary cardiac lymphoma (PCL) represents a rare subset of non-Hodgkin lymphoma, characterized by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication. METHODS: Individual patient data were obtained from defined cases of PCL (1949PCL ( -2009 and systematically analyzed. RESULTS: The authors report results of a review of 197 cases of PCL, with half of all cases reported since 1995. Survival was affected by 4 factors: immune status, left ventricular involvement, presence of extra-cardiac disease, and arrhythmia. Median overall survival (OS) for immunocompromised and immunocompetent was 3.5 months (m) and not reached, respectively (HR 0.29, 95% CI, 0.13-0.68; P ¼ .004). LV involvement was uncommon (26%) and associated with an OS of only 1m, whereas patients free of LV involvement had a median OS of 22m (HR 0.28, 95% CI, 0.12-0.64; P ¼ .002). Patients with extracardiac disease had shorter median OS compared with those without (6m vs 22m, HR 0.49, 95% CI, 0.26-0.91; P ¼ .02). Those patients with an arrhythmia of any type had a median OS that was not reached (n ¼ 55), whereas those without rhythm disturbances (n ¼ 41) had median OS of 6m (HR 0.51, 95% CI, 0.29-0.91; P ¼ .024). Overall response rate to therapy was 84%, with long-term OS over 40%. CONCLUSIONS: The current study presents the largest analysis of PCL to date. The data demonstrate that PCL is now more frequently diagnosed premortem and appears to have reasonable response rates. Lack of LV involvement and the presence of arrhythmias are associated with improved survival. Cancer 2011;117:581-9.

Background COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. Methods We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20–2/15/20) and COVID time-period (3/1/20–4/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. Findings A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2–2.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. Interpretation The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. Funding N/A

Adherence is one of many factors that contribute to anticoagulation control. Adequate adherence, as determined by the Morisky survey, was significantly associated with anticoagulation control. Patient demographic characteristics, knowledge about warfarin therapy, and perceived impact of warfarin on quality of life were not associated with anticoagulation control.

Background Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity. Objective We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity. Methods This is a cohort study simulating an intention-to-treat clinical trial, by analyzing the effect on mortality of anticoagulation therapy chosen in the first 48 hours of hospitalization. We analyzed 3,625 COVID-19+ inpatients, controlling for age, gender, glomerular filtration rate, oxygen saturation, ventilation requirement, intensive care unit admission, and time period, all determined during the first 48 hours. Results Adjusted logistic regression analyses demonstrated a significant decrease in mortality with prophylactic use of apixaban (odds ratio [OR] 0.46, p = 0.001) and enoxaparin (OR = 0.49, p = 0.001). Therapeutic apixaban was also associated with decreased mortality (OR 0.57, p = 0.006) but was not more beneficial than prophylactic use when analyzed over the entire cohort or within D-dimer stratified categories. Higher D-dimer levels were associated with increased mortality (p < 0.0001). When adjusted for these same comorbidities within D-dimer strata, patients with D-dimer levels < 1 µg/mL did not appear to benefit from anticoagulation while patients with D-dimer levels > 10 µg/mL derived the most benefit. There was no increase in transfusion requirement with any of the anticoagulants used. Conclusion We conclude that COVID-19+ patients with moderate or severe illness benefit from anticoagulation and that apixaban has similar efficacy to enoxaparin in decreasing mortality in this disease.

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Morbid obesity is a health problem that has been shown to be refractory to diet, exercise, and medical treatment. Surgeries designed to promote weight loss, termed bariatric surgery and typically involving a gastric bypass procedure, have recently been implemented to treat obesity with high success rates. However, longterm sequelae can result in micronutrient deficiencies. This review will focus on iron deficiency and its association with obesity and bariatric surgery. Iron deficiency develops after gastric bypass for several reasons including intolerance for red meat, diminished gastric acid secretion, and exclusion of the duodenum from the alimentary tract. Menstruating women, pregnant women, and adolescents may be particularly predisposed toward developing iron deficiency and microcytic anemias after bypass surgery. Preoperative assessment of patients should include a complete hematological work-up, including measurement of iron stores. Postoperatively, oral iron prophylaxis and vitamin C in addition to a multivitamin should be prescribed for bypass patients, especially for vulnerable populations. Once iron deficiency has developed, it may prove refractory to oral treatment, and require parenteral iron, blood transfusions, or surgical interventions. Bariatric surgery patients require lifelong follow-up of hematological and iron parameters since iron deficiency and anemia may develop years after surgery. Am. J. Hematol. 83:403-409, 2008. V