A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a "Cytokine Storm Syndrome" (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.
Background Knowing the case fatality rates of recurrent venous thromboembolism (VTE) and major bleeding is important for weighing the relative risks and benefits of anticoagulation and deciding on the duration of anticoagulant therapy, but these rates are uncertain in patients with cancer-associated thrombosis. Methods We performed a systematic review and a meta-analysis to determine the incidence of recurrent VTE and major bleeding and their respective case fatality rates in patients with cancer-associated VTE. Results Our analysis included 29 studies (15 prospective cohort studies and 14 randomized controlled trials) from 1980 to January 2019. Data from 8,000 cancer patients with 4,786 patient-years of follow-up were summarized. Rates of recurrent VTE and fatal recurrent VTE were 23.7 (95% confidence interval [CI]: 20.1–27.8) and 1.9 (95% CI: 0.8–4.0) per 100 patient-years of follow-up, respectively, with a case fatality rate of 14.8% (95% CI: 6.6–30.1%). The rates of major bleeding and fatal major bleeding events were 13.1 (95% CI: 10.3–16.7) and 0.8 (95% CI: 0.3–2.1) per 100 patient-years of follow-up, respectively, with a case fatality rate of 8.9% (95% CI: 3.5–21.1%). While the estimates of case fatality vary by anticoagulation regimen and study design, the differences between them were not statistically significant. Conclusion In cancer patients receiving anticoagulation, the case fatality rate of recurrent VTE is higher than the case fatality rate of major bleeding. These findings may help to inform decisions regarding the management of anticoagulation in patients with active cancer and VTE.
Coronavirus disease‐2019 (COVID‐19) severity appears to parallel the host immune response, with a subset of patients developing COVID‐19 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID‐19,(2–5) and interleukin (IL)‐6 appears to play a central role in COVID‐19 related CSS.(6–8) Based on the success of IL‐6 receptor blockade for chimeric antigen receptor T‐cell therapy associated cytokine release syndrome (CAR T‐cell CRS), similar strategies using tocilizumab are being investigated in COVID‐19.
The McMaster Pediatric Surgery Research Collaborative is interested in investigating current non-religious community neonatal circumcision practices. This information will be valuable to understanding the current clinical opinions and decision making processes regarding neonatal circumcision.
This large cohort study demonstrates that TAVR is associated with a moderate risk of severe UGIB. The results of this study suggest that patients on triple antithrombotic therapy are at highest risk for severe UGIB. © 2016 Wiley Periodicals, Inc.
The treatment options for patients with castration-resistant prostate cancer (CRPC), until very recently, only included docetaxel. In the past 10 months, newly Federal Drug Administration (FDA) approved agents in the United States have shown survival benefit for patients with CRPC. This review takes a closer look at these newer agents: sipuleucel-T (immune therapy) and cabazitaxel (cytotoxic therapy). We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. Newer agents currently being investigated in phase III clinical trials for their potential role in metastatic CRPC are also reviewed. These agents include abiraterone (hormonal therapy), TAK-700 (hormonal therapy), MDV3100 (hormonal therapy), ipilimumab (immune therapy), zibotentan (endothelin-A receptor antagonist) and dasatinib (tyrosine kinase inhibitor). As ongoing studies using all the aforementioned agents continue to evolve, our understanding of how and where these agents fit into the treatment paradigm for patients with CRPC will become clearer. RésuméLes options thérapeutiques des patients atteints d'un cancer de la prostate résistant à la castration (CPRC), jusqu'à tout récemment, ne comprenaient que le docetaxel. Au cours des 10 derniers mois, de nouveaux agents approuvés par la Food and Drug Administration (FDA) des États-Unis ont montré un avantage lié à la survie chez les patients atteints d'un CPRC. Nous examinons ici plus étroite-ment ces nouveaux agents : le sipuleucel-T (immunothérapie) et le cabazitaxel (traitement cytotoxique). Nous passons aussi en revue les données étayant l'approbation par la FDA du dénosumab (traitement ciblant les cellules osseuses) comme option thérapeutique chez les hommes atteints d'un cancer de la prostate résistant à la castration avec métastases osseuses. Les nouveaux agents en cours d'études cliniques de phase III en raison de leur rôle potentiel dans le traitement du CPRC métastatique sont aussi examinés. Ces agents incluent l'abiratérone (hormonothérapie), le TAK-700 (hormonothérapie), le MDV3100 (hormonothérapie), l'ipilimumab (immunothérapie), le zibotentan (antagoniste des récepteurs de l'endothéline-A) et le dasatinib (inhibiteur de la tyrosine-kinase). À mesure que les études en cours sur ces agents continuent de progresser, notre compréhen-sion du rôle et de l'usage de ces agents dans le paradigme théra-peutique des patients atteints de CPRC s'approfondira.
The treatment options for patients with castration-resistant prostate cancer (CRPC), until very recently, only included docetaxel. In the past 10 months, newly Federal Drug Administration (FDA) approved agents in the United States have shown survival benefit for patients with CRPC. This review takes a closer look at these newer agents: sipuleucel-T (immune therapy) and cabazi-taxel (cytotoxic therapy). We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. Newer agents currently being investigated in phase III clinical trials for their potential role in metastatic CRPC are also reviewed. These agents include abiraterone (hormonal therapy), TAK-700 (hormonal therapy), MDV3100 (hormonal therapy), ipilimumab (immune therapy), zibotentan (endothelin-A receptor antagonist) and dasatinib (tyrosine kinase inhibitor). As ongoing studies using all the aforementioned agents continue to evolve, our understanding of how and where these agents fit into the treatment paradigm for patients with CRPC will become clearer.
Low-molecular-weight heparin (LMWH) therapy has recently been proposed as a cause of ischemic priapism. The evidence, however, remains scarce, as there are very few published cases of LMWH-induced priapism to date. The implications of such events are significant as ischemic priapism is a medical emergency. In current clinical practice we are seeing a trend towards LMWH therapies replacing unfractionated heparin (UFH). As LMWH therapies continue to gain favor, we will potentially see more cases of LMWH-induced priapism. As such, consideration should be given to determine the underlying pathophysiology and incidence of LMWH-induced priapism. Herein, we present the case of a 33-year-old male with priapism in the setting of tinzaparin treatment.
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