Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.

Plasma cell leukemia: Retrospective review of cases at Monter Cancer Center/Northwell Health Cancer Institute, 2014-2019.

Plasma cell leukemia (PCL) is an aggressive malignancy and an area of unmet need. The diagnostic criteria for PCL are in flux and the molecular basis of disease is complex. Due to its fulminant course and lack of prospective clinical trials in PCL, the optimal therapeutic approach remains controversial. "Novel therapy" in this manuscript refers to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). "Newer agents" refers to currently approved and investigational targeted therapies such as monoclonal antibodies (mAbs), example daratumumab (Dara), bi- or tri-specific antibodies, and antibody-drug conjugate therapies (ADCs). Novel therapy and use of newer agents borrowed from treatment advances in multiple myeloma (MM), is impacting PCL outcomes. Therefore, it is crucial to analyze effects of newer agents on PCL survival with respect to disease characteristics and specific treatment regimens used. In this retrospective study, we report outcomes of eight cases of PCL, primary and secondary, the prognostic factors in each case and the impact of different treatment regimens on overall survival (OS).

Peritoneal B-1b and B-2 B-cells confer long-term protection from pneumococcal serotype 3 infection after vaccination with Prevnar-13 and are defective in sickle cell disease mice.

Long-term immunity after inoculation with the pneumococcal conjugate vaccine (Prevnar-13) is impaired in sickle cell disease (SCD) mice. We sought to determine which B-cell subsets are defective in SCD mice after vaccination with Prevnar-13, yet confer long-term immunity in wild-type (WT) mice. We vaccinated WT and SCD mice three times at three week intervals with Prevnar-13. Fourteen weeks later, 5∗104 cells of isolated peritoneal B-1a, B-1b, and B-2 cells were harvested and intraperitoneally transferred to Rag -/- recipients. A week later recipients were intraperitoneally challenged with 103CFU of Streptococcus pneumoniae (serotype 3). Recipient mice that received either B-1b or B-2 B-cells from WT mice survived challenge, whereas mice that received B-1a cells died. Recipient mice that received B-1a, B-1b, or B-2 cells from SCD mice died after challenge. Both B-1b and B-2 cells appear to confer long-term immunity after Prevnar-13 vaccination, yet neither subset functions properly in SCD mice.

Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers.

BACKGROUND: One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model. METHODS: Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro. RESULTS: Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection. CONCLUSION: Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population.