Despite significant evidence implicating an important role for neutrophils in thrombosis, their impact on the thrombotic process has remained a matter of controversy. Until 2010, platelets, coagulation factors, fibrinogen and monocytes were implicated in the thrombotic process. Several studies conducted over the last decade now support the growing notion that neutrophils indeed do contribute significantly to this process. Neutrophils can contribute to pathologic venous and arterial thrombosis or 'immunothrombosis' by the release of neutrophil extracellular traps (NETs) and NET release is emerging as a major contributor to thrombogenesis in pathologic situations such as sepsis and malignancy. Further, blood-cell derived microparticles, including those from neutrophils, have been implicated in thrombus formation. Finally, inflammasome activation in the neutrophil identifies another important mechanism that may be operative in neutrophil-driven risk for thrombosis. The knowledge of these roles of neutrophils in thrombosis may pave the road for novel anti-thrombotic agents in the future that do not affect hemostasis.
Wound healing is a complex process that consists of multiple phases, each of which are indispensable for adequate repair. Timely initiation and resolution of each of these phases namely, hemostasis, inflammation, proliferation and tissue remodeling, is critical for promoting healing and avoiding excess scar formation. While platelets have long been known to influence the healing process, other components of blood particularly coagulation factors and the fibrinolytic system also contribute to efficient wound repair. This review aims to summarize our current understanding of the role of platelets, the coagulation and fibrinolytic systems in cutaneous wound healing, with a focus on how these components communicate with immune and non-immune cells in the wound microenvironment. We also outline current and potential therapeutic strategies to improve the management of chronic, non-healing wounds.
Introduction. Cutaneous paraneoplastic syndromes are a heterogeneous group of skin manifestations that occur in relation to many known malignancies. Paraneoplastic occurrence of SCLE has been noted but is not commonly reported. SCLE association with cholangiocarcinoma is rare. Case Presentation. A 72-year-old man with a history of extrahepatic stage IV cholangiocarcinoma presented with a pruritic rash. Cholangiocarcinoma had been diagnosed three years earlier and was treated. Five months after interruption of his chemotherapy due to a semiurgent surgery, he presented with explosive onset of a new pruritic rash, arthralgias, and lower extremity edema. Physical exam revealed a scaly erythematous rash on his arms, hands, face, neck, legs, and trunk. It was thick and scaly on sun exposed areas. Skin biopsy revealed vacuolar interface dermatitis. Immunofluorescence revealed IgM positive cytoid bodies scattered along the epidermal basement membrane zone. PET-CT scanning revealed metabolically active recurrent disease in peripancreatic and periportal region with hypermetabolic lymph nodes. Oral steroids and new regimen of chemotherapy were started. Rash improved and steroids were tapered off. Discussion. Paraneoplastic syndromes demonstrate the complex interaction between the immune system and cancer. Treatment resistant SCLE should raise a suspicion for paraneoplastic etiology.
Background There are acute settings where assessing the anticoagulant effect of direct oral anticoagulants (DOACs) can be useful. Due to variability among routine coagulation tests, there is an unmet need for an assay that detects DOAC effects within minutes in the laboratory or at the point of care. Methods We developed a novel dielectric microsensor, termed ClotChip, and previously showed that the time to reach peak permittivity (T peak) is a sensitive parameter of coagulation function. We conducted a prospective, single-center, pilot study to determine its clinical utility at detecting DOAC anticoagulant effects in whole blood. Results We accrued 154 individuals: 50 healthy volunteers, 49 rivaroxaban patients, 47 apixaban, and 8 dabigatran patients. Blood samples underwent ClotChip measurements and plasma coagulation tests. Control mean T peak was 428 seconds (95% confidence interval [CI]: 401–455 seconds). For rivaroxaban, mean T peak was 592 seconds (95% CI: 550–634 seconds). A receiver operating characteristic curve showed that the area under the curve (AUC) predicting rivaroxaban using T peak was 0.83 (95% CI: 0.75–0.91, p < 0.01). For apixaban, mean T peak was 594 seconds (95% CI: 548–639 seconds); AUC was 0.82 (95% CI: 0.73–0.91, p < 0.01). For dabigatran, mean T peak was 894 seconds (95% CI: 701–1,086 seconds); AUC was 1 (p < 0.01). Specificity for all DOACs was 88%; sensitivity ranged from 72 to 100%. Conclusion This diagnostic study using samples from “real-world” DOAC patients supports that ClotChip exhibits high sensitivity at detecting DOAC anticoagulant effects in a disposable portable platform, using a miniscule amount of whole blood (<10 µL).
Introduction: The risk of venous thromboembolism (VTE) is increased in patients with cancer and contributes to significant morbidity, treatment delays and mortality. The Khorana score is the most well-validated VTE risk prediction tool that guides use of prophylactic anticoagulation in patients with cancer. The Khorana score includes cancer type, body mass index (BMI), hemoglobin, platelet count and leukocyte count but not a prior history of VTE which may increase the risk of recurrent VTE. Scant published data have suggested that a personal history of VTE increases the risk of VTE recurrence by 2 to 7-fold after cancer diagnosis. In this study, we examine the impact of history of VTE on VTE recurrence in a large cohort of patients with cancer. Methods: We performed a retrospective cohort study of patients diagnosed with cancer using aggregated de-identified data from electronic medical record of >300 major hospitals in US (IBM Watson Explorys). Patients with a personal history of VTE (deep vein thrombosis and/ or pulmonary embolism) more than one year prior to the diagnosis of cancer were included. Within this cohort, patients who developed recurrent VTE within 180 days of diagnosis of cancer were identified. The primary end-point was the incidence of cancer associated VTE (CVTE) in patients with prior history of VTE as compared to patients without history of VTE. Baseline characteristics including age, race, gender, BMI, prothrombotic mutations (Factor V Leiden, prothrombin gene 20210A mutation), antineoplastic agent use, cancer type and laboratory values (as included in Khorana risk score) were compared in all patients. Results: A total of 4,159,400 patients with a diagnosis of cancer were included. Of these, 138,820 patients (3.3%) had a history of VTE >1 year prior to being diagnosed with cancer. The incidence of CVTE at 180 days was 10-fold higher in those with prior history of VTE compared to those without (36.9% vs 3.66%; OR 15.4, 95% CI 15.22-15.6, P value <0.0001). While the inherent risk of CVTE varied based on cancer type (highest risk of 10.5% in pancreatic cancer), the risk of recurrent VTE in patients with prior VTE history is magnified to a similar degree across all cancer types as shown in Figure 1. Baseline characteristics including age, race, gender and cancer type distribution were similar in all groups, as shown in Table 1. Factor V Leiden mutation or activated protein C resistance (FVL/APC) was more prevalent in patients with prior history of VTE and subsequent CVTE (3%) as compared to all patients with CVTE regardless of history (1%), as shown in Table 1. A higher BMI was noted in patients with prior history of VTE (49% and 71% respectively in patients with and without CVTE) as compared to 41% in all patients with CVTE. Greater use of antineoplastic agents (41%) was noted in the group of patients with prior history of VTE and subsequent CVTE as compared to patients with prior VTE but no CVTE (36%). Conclusion: Our study highlights that a prior personal history of VTE >1 year before cancer diagnosis significantly increases the risk of cancer associated VTE independently, regardless of other established risk factors for VTE suggesting that this group of patients, especially those undergoing anti-cancer treatment may benefit from prophylactic anticoagulation. Increased incidence of FVL/ APC in patients with prior history of VTE and recurrent CVTE may reflect increased testing for prothrombotic mutations in this cohort. Our ongoing efforts include examining the effect of addition of history of VTE to the Khorana score. Finally, large prospective observational studies would be key to assess the impact of history of VTE on cancer thrombosis. Disclosures No relevant conflicts of interest to declare.
Cancer survivors often indicate a preference to receive long-term follow-up care from their oncologist. These findings suggest that long-term cancer survivorship care represents only a small component of care at a comprehensive cancer center and also that alternative models for long-term survivorship health care need to be considered.
Colorectal cancer is the third most common malignancy and the second leading cause of cancer death in the United States. Approximately 20 to 25% of patients have clinically detectable colorectal liver metastases (CLM) at the initial diagnosis, and nearly 50% of patients with colorectal cancer develop hepatic metastases at some point during the course of their disease. Patients with untreated CLM have a median survival time of approximately 4.5 months. For the resectable cases, surgical resection is the first-choice treatment. However, only 10 to 30% of patients with CLM are eligible for resection at presentation. There are several nonsurgical treatment options for patients with CLM who are not candidates for initial or potentially curative resection. These include systemic chemotherapy, locoregional therapy that includes thermal and nonthermal ablation, external beam radiation therapy, regional chemotherapy via the hepatic artery, and selective radioembolization using yttrium-labeled glass or resin microspheres. In this review, we discuss the nonsurgical treatment options described earlier that are part of the current multidisciplinary algorithm in the management of CLM and focus on the expanding role of interventional radiology.
Background This study analyzes the pattern of use of single agent anticancer therapy (SAACT) in the treatment and survival of advanced hepatocellular carcinoma (aHCC) before and after sorafenib was FDA approved in 2007. Methods Adult patients diagnosed with HCC and treated with only ACT from 2004 – 2014 were identified in NCDB database. Patients were analyzed during three time frames: 2004–2006 (pre‐sorafenib (PS)), 2007–2010 (early sorafenib (ES)) and 2011–2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan‐Meier method were used for analyses. Results The NCDB contained 31,107 patients with HCC diagnosed from 2004–2014 and treated with ACT alone. Patients were generally men (78.0%), >50 years of age (92.5%). A significant increase in the rate of adaption of SAACT was observed over time: 6.2% PS, 15.2% ES, and 22.2% LS (p < 0.0001). During this later period, the highest proportion of SAACT is among academic and integrated network facilities (23.3%) as compared to community facilities (17.0%, p < 0.0001). The median overall survival of patients with aHCC treated only with SAACT improved significantly over time from 8.0 months (m) (95% CI: 7.4–8.8) to 10.7 m (10.4–11.2) to 15.6 m (15.2–16.0, p < 0.001). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.28, (5% CI: 1.23–1.32), patients without insurance (HR 1.11, 1.06–1.16) and estimated household income of <$63,000 (HR 1.09, 1.05–1.13). Conclusion aHCC patients treated only with ACT have experienced an overall improvement in survival, but significant differences exist between facility type, insurance status, and income.
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