Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis.

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices-such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass-require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.

Breaking down tumor thrombus: Current strategies for medical management.

Tumor thrombus, the intravascular extension of tumor into adjacent blood vessels, is frequently encountered in patients with renal cell carcinoma and hepatocellular carcinoma, and often involves the abdominal vasculature including the renal vein, portal vein, and the inferior vena cava. While a bland thrombus is composed of platelets and fibrin, in contrast, a tumor thrombus refers to an organized collection of tumor cells. Though oftentimes detected incidentally on imaging, tumor thrombus may have significant clinical implications and can be challenging to differentiate from bland thrombus. Additionally, the optimal management of tumor thrombus, including the use of anticoagulation, remains poorly described. This review summarizes common causes of tumor thrombus, as well as its impact on staging, prognosis, and treatment.

D-dimer predicts venous thromboembolism in multiple myeloma: a nested case-control study.

Background: Clinical risk assessment scores, such as IMPEDE VTE, can identify patients with multiple myeloma (MM) at high-risk of venous thromboembolism (VTE). Refinement of these scores, by including 1 or more biomarkers, could improve risk assessment. Objectives: We sought to determine the association between soluble P-selectin (sP-selectin) and D-dimer with VTE in MM. Methods: We identified 545 patients with newly diagnosed MM. Using a nested case-control design, we identified 38 cases of VTE within 6-months of MM treatment and 137 randomly selected controls. Using logistic regression, we examined the association between D-dimer and sP-selectin with VTE. We also analyzed the association after adjusting for IMPEDE VTE. Results: Each 1-point increase in IMPEDE VTE score was associated with a 27% increase in odds of VTE (odds ratio 1.27; 95% CI 1.08-1.51; c-statistic 0.61; 95% CI 0.51-0.71). There was no association between sP-selectin and VTE. Each one increase in natural log of D-dimer was associated with a 44% increase in odds of VTE, so we assigned points (ranging from -2 to +2) to D-dimer values and incorporated them into IMPEDE VTE, forming IMPEDED VTE. There was a 30% increase in odds of VTE per each 1-point increase in IMPEDED VTE (OR 1.30; 95% CI 1.12-1.52; c-statistic 0.65; 95% CI 0.55-0.75). Conclusion: Among patients with newly diagnosed MM starting chemotherapy, D-dimer was associated with increased odds of developing VTE within the subsequent 6-months. The addition of D-dimer to IMPEDE VTE-IMPEDED VTE-could improve prediction of VTE among patients with MM.

A rare case of aerococcus urinae infective endocarditis.

Introduction:Aerococcus urinae is a rare cause of infective endocarditis. Aerococcus is a gram positive cocci that is easily misidentified as Staphylococci or Streptococci. The true incidence rate of this pathogen is likely underestimated. Recent advances in laboratory diagnostic methods with matrix-associated laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) have lead to increased recognition of this pathogen in the clinical microbiology lab, and awareness as a cause of infective endocarditis in the infectious disease community. Case reports: Aerococcus usually affects males with underlying urinary tract conditions. Herein, we report a case of prosthetic aortic valve endocarditis caused by Aerococcus urinae. Discussion: Our patient was considered high risk for cardiac surgery and was treated successfully with intravenous antibiotics alone for six weeks. Conclusion: Infective endocarditis should be considered in all cases of Aerococcus bacteremia and appropriate diagnostic evaluations pursued. Abbreviations: AV: Aortic valve; IE: Infective endocarditis.

Success of photodynamic therapy in palliating patients with nonresectable cholangiocarcinoma: A systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma. METHODS: Included studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS: Ten studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups. CONCLUSION: In palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.