Retrospective review of a Prothrombin Complex Concentrate (Beriplex P/N) for the management of perioperative bleeding unrelated to oral anticoagulation

A multicenter, retrospective, observational study of 4-factor prothrombin complex concentrate (PCC) and/or fresh frozen plasma (FFP) use within routine clinical care unrelated to vitamin K antagonists was conducted. The PCC was administered preprocedure for correction of coagulopathy (prophylactic cohort) and treatment of bleeding postsurgery (treatment cohort). Of the 445 patients included, 40 were in the prophylactic cohort (PCC alone [n ¼ 16], PCC and FFP [n ¼ 5], FFP alone [n ¼ 19]) and 405 were in the treatment cohort (PCC alone [n ¼ 228], PCC and FFP [n ¼ 123], FFP alone [n ¼ 54]). Cardiovascular surgery was the most common setting. PCC doses ranged between 500 and 5000 IU. Effectiveness (assessed retrospectively) was reported as effective in 93.0% in the PCC-only group (95% confidence interval, 89.1% to 95.9%), 78.9% (70.8% to 85.6%) with PCC and FFP, and 86.3% (76.2% to 93.2%) with FFP alone. In the treatment cohort, international normalized ratio was significantly reduced in all 3 groups. In patients who received PCC, the rate of thromboembolic events (1.9%) was below rates in the literature for similar procedures. PCCs offer a potential alternative to FFP in the management of perioperative bleeding unrelated to oral anticoagulant therapy

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Incidental pulmonary embolism in cancer patients : should we anticoagulate? Introduction

Deep Vein Thrombosis and pulmonary embolism (PE) are collectively known as venous thromboembolism (VTE). PE has been described as one of the most commonly missed deadly diagnoses. It is the cause of more than 100,000 deaths each year in the US, and the primary diagnosis or complicating condition in more than 300,000 hospitalisations

Derivation and validation of a prediction tool for venous thromboembolism : a VERITY registry study

Accurate estimation of risk for venous thromboembolism (VTE) may help clinicians assess prophylaxis needs. Only empirical algorithms and risk scores have been described; an empirical risk score (‘Kucher’) based on 8 VTE risk factors (cancer, prior VTE, hypercoagulability, surgery, age>75 yrs, BMI>29, bed rest, hormonal factor) using electronic alerts improved hospitalized patient outcome (NEJM 2005;352:969–77[Medline]). We wished to develop a multivariate regression model for VTE risk, based on Kucher, and validate its performance. The initial derivation cohort consisted of patients enrolled in ‘VERITY’, a multicentre VTE treatment registry for whom the endpoint of VTE and all 8 risk factors were known. Initial univariate analysis (n=5928; 32.4% with diagnosis of VTE) suggested VTE risk was not accounted for by the 8 factors; an additional 3 were added (leg paralysis, smoking, IV drug use [IVD]). The final derivation cohort was 5241 patients (32.0% with VTE) with complete risk data. The validation cohort (n=915) was derived from a database of 928 consecutively enrolled patients at a single DVT clinic. Model parameters were estimated using the statistical package ‘R’ using a stepwise selection procedure to choose the optimal number of main effects and pair-wise interactions. This showed that advanced age (estimated odds ratio [OR]=2.8, p<0.001); inpatient (OR=3.0, p<0.001); surgery (OR=3.1, p<0.001); prior VTE (OR=2.9, p<0.001); leg paralysis (OR=3.8, p<0.001); cancer (OR=5.3, p<0.001); IVD (OR=14.3, p<0.001); smoking (OR=1.2, p=0.009); and thrombophilia (OR=2.8; p<0.001) increased the risk of VTE. Obesity (OR=0.7; p<0.001) increased the VTE risk only in patients with a hormonal factor (OR=2.0, p=0.007). Backward stepwise regression showed prior VTE as the most important factor followed by cancer, IVD, surgery, inpatient, age, leg paralysis, hormonal factor, obesity, thrombophilia and smoking. Expressing the parameter estimates in terms of probabilities defines a risk score model for VTE. Using the model, the receiver operating characteristic (ROC) curve (see figure) area under the curve (AUC) was estimated as 0.720 (95% CI, 0.705–0.735) for the model (dashed line), indicating a good diagnostic test significantly better (p<0.001) than Kucher (AUC=0.617, 95% CI, 0.599–0.634)(solid line). For the validation cohort, AUC was estimated as 0.678 (95% CI, 0.635–0.721) for the model, which was not significantly different from AUC for the full dataset used for model development, and was 0.587 (95% CI, 0.542–0.632) for Kucher. This model to predict individual patient risk of VTE may contribute to decision making regarding prophylaxis in clinical practice