UNASSIGNED: Immune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in randomised controlled trials (RCTs). We aimed to compare the efficacy and safety of different treatments in newly diagnosed adult primary immune thrombocytopenia.
UNASSIGNED: We did a systematic review and network meta-analysis of RCTs involving treatments for newly diagnosed primary immune thrombocytopenia. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched up to April 31, 2022. The primary outcomes were 6-month sustained response and early response. Secondary outcome was grade 3 or higher adverse events. This study is registered with PROSPERO (CRD42022296179).
UNASSIGNED: Eighteen RCTs (n = 1944) were included in this study. Pairwise meta-analysis showed that the percentage of patients achieving early response was higher in the dexamethasone-containing doublet group than in the dexamethasone group (79.7% vs 68.7%, odds ratio [OR] 1.82, 95% CI 1.10-3.02). The difference was more profound for sustained response (60.5% vs 37.4%, OR 2.57, 95% CI 1.95-3.40). Network meta-analysis showed that dexamethasone plus recombinant human thrombopoietin ranked first for early response, followed by dexamethasone plus oseltamivir or tacrolimus. Rituximab plus prednisolone achieved highest sustained response, followed by dexamethasone plus all-trans retinoic acid or rituximab. Rituximab plus dexamethasone showed 15.3% of grade 3 or higher adverse events, followed by prednis(ol)one (4.8%) and all-trans retinoic acid plus dexamethasone (4.7%).
UNASSIGNED: Our findings suggested that compared with monotherapy dexamethasone or prednis(ol)one, the combined regimens had better early and sustained responses. rhTPO plus dexamethasone ranked top in early response, while rituximab plus corticosteroids obtained the best sustained response, but with more adverse events. Adding oseltamivir, all-trans retinoic acid or tacrolimus to dexamethasone reached equally encouraging sustained response, without compromising safety profile. Although this network meta-analysis compared all the therapeutic regimens up to date, more head-to-head RCTs with larger sample size are warranted to make direct comparison among these strategies.
UNASSIGNED: National Natural Science Foundation of China, Major Research Plan of National Natural Science Foundation of China, Shandong Provincial Natural Science Foundation and Young Taishan Scholar Foundation of Shandong Province.

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Arterial thromboembolism, including myocardial infarction and stroke, is also prevalent. Risk differs in subgroups, with higher rates observed in specific cancers including pancreas, stomach, and multiple myeloma. Thromboprophylaxis is recommended for most patients with active cancer hospitalized for medical illnesses and after major cancer surgery. Outpatient thromboprophylaxis is not routinely recommended, but emerging data suggest that a high-risk population that benefits from pharmacological thromboprophylaxis can be identified using a validated risk tool. Direct oral anticoagulants are emerging as the preferred new option for the treatment of cancer-associated VTE, although low-molecular-weight heparin remains a standard for patients at high bleeding risk. Management of VTE beyond the first 6 months and challenging clinical situations including intracranial metastases and thrombocytopenia require careful management in balancing the benefits and risks of anticoagulation and remain major knowledge gaps in evidence.

Apoptosis, especially the intrinsic mitochondrial cell death pathway, is regulated by the BCL-2 family of proteins. Defects in apoptotic machinery are one of the main mechanisms that cells employ to evade cell death and become cancerous. Targeting the apoptotic defects, either by direct inhibition of BCL-2 family proteins or through modulation of regulatory pathways, can restore cell sensitivity to cell death. This review will focus on the aspects of BCL-2 family proteins, their interactions with kinase pathways, and how novel targeted agents can help overcome the apoptotic blockades. Furthermore, functional assays, such as BH3 profiling, may help in predicting responses to chemotherapies and aid in the selection of combination therapies by determining the mitochondrial threshold for initiating cell death.