Screening for occult cancer after unprovoked venous thromboembolism: Assessing the current literature and future directions.

While significant evidence has established an increased rate of thrombosis in patients with cancer, the risk of occult malignancy in the setting of an unprovoked thrombosis is less clear. Despite continued interest in developing an effective screening system for occult malignancy following unprovoked venous thromboembolism (VTE), discrepancies in the literature and guideline recommendations leave providers uncertain whether to screen or perform further diagnostics for this patient population. Evidence suggests that screening for malignancy can detect cancer sooner in patients with unprovoked VTE, but there is a lack of high-quality evidence demonstrating improvements in survival who receive early detection. In the following manuscript, we summarize VTE in relation to cancer epidemiology and pathophysiology. Our literature review summarizes the spectrum of testing strategies for occult malignancy following unprovoked VTE, including biomarker detection methods and various imaging approaches. We evaluate the benefit of additional diagnostic strategies, review current guidelines on the issue, and provide guidance to the reader on the best practice for investigating undiagnosed malignancy in patients with unprovoked VTE.

Anticoagulation in Cirrhosis: Evidence for the Treatment of Portal Vein Thrombosis and Applications for Prophylactic Therapy.

The clinical utility of anticoagulation for patients with cirrhosis and asymptomatic portal vein thrombosis (PVT) is widely debated. Complex hemostatic derangements in cirrhosis that increase risk of both bleeding and thrombosis, as well as a lack of randomized controlled data, limit conclusive assessments regarding optimal management of anticoagulation in this setting. In this review, we summarize the relevant literature pertaining to PVT in cirrhosis, including the effect of untreated PVT on the natural progression of liver disease and the overall impact of anticoagulation on clot burden and other relevant clinical outcomes. Apart from patients who are symptomatic or listed for liver transplantation, data supporting anticoagulation for the treatment of PVT is limited and without clear consensus guidelines. In patients with cirrhosis without PVT, emerging evidence for the role of prophylactic anticoagulation to mitigate the progression of fibrosis suggests an optimal risk-benefit tradeoff with decreased rates of liver decompensation and mortality, without a heightened risk of bleeding. In summation, as our understanding of the role of both prophylactic and therapeutic anticoagulation in cirrhosis continues to evolve, ongoing risk stratification of patients with asymptomatic PVT demands further attention.

Head injury and neuropsychiatric sequelae in asylum seekers.

OBJECTIVE: Asylum seekers experience a high burden of physical and psychological trauma, yet there is a scarcity of literature regarding the epidemiology and sequelae of head injury (HI) in asylum seekers. We examined HI prevalence and association with neuropsychiatric comorbidities in asylum seekers. METHODS: A retrospective cross-sectional study was performed through review of 139 medical affidavits from an affidavit database. Affidavits written from 2010 to 2018 were included. Demographic and case-related data were collected and classified based on the presence of HI. For neuropsychiatric sequelae, the primary study outcome was headache and the secondary outcomes were depression, posttraumatic stress disorder, and anxiety. Multivariable logistic regression was performed to examine the association between HI and neuropsychiatric sequelae, adjusted for demographic and clinical characteristics. RESULTS: A total of 139 medical affidavits of asylum seekers were included. The mean age was 27.4 ± 12.1 years, 56.8% were female, and 38.8% were <19 years. Almost half (42.5%) explicitly self-reported history of HI. Compared to clients who did not report HI, clients with HI were older and more likely to report a history of headache, physical abuse, physical trauma, concussion, and loss of consciousness. After adjustment for demographic and clinical characteristics, clients with HI had greater odds for neuropsychological sequelae such as headache (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.0-8.7) and depression (OR 2.5, 95% CI 1.1-5.7). CONCLUSIONS: We observed a high prevalence of HI in asylum seekers. Comprehensive screening for HI and neuropsychiatric comorbidities is encouraged when evaluating asylum seekers.

DNA damage repair deficiency as a predictive biomarker for FOLFIRINOX efficacy in metastatic pancreatic cancer.

Patients with pathogenic germline and somatic variants in DNA damage repair (DDR) genes may derive greater benefit with platinum-based chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC). This study investigates the role of DDR genes as a predictive biomarker for response to first-line platinum chemotherapy with FOLFIRINOX in metastatic PDAC patients. Demographic, clinical, and pathologic variables were collected for patients with metastatic PDAC who received FOLFIRINOX as frontline treatment and who had germline and somatic genetic testing. Kaplan-Meier analysis of overall survival (OS) and progression free survival (PFS) were correlated to the presence of DDR pathogenic variants. Forty patients with metastatic PDAC met inclusion criteria. Germline genetic testing revealed germline pathogenic variants in DDR genes in 5 patients (12%), and somatic pathogenic variants in DDR genes in 4 patients (10%). Median PFS was significantly longer in patients with any (germline or somatic) pathogenic variant in DDR genes than in those without alterations 18.5 vs. 6.9 months (log-rank P=0.003). When restricted to the presence or absence of germline pathogenic variants in DDR genes, the median PFS was 18.5 vs. 7.4 months (log-rank P=0.005). The median OS for the entire cohort was 11.5 months was not statistically different between the two groups, however there were no deaths in the subgroup with germline pathogenic variants in DDR genes treated with frontline FOLFIRINOX. A subset of patients with metastatic PDAC and germline or somatic pathogenic variants in DDR genes have a statistically superior PFS when treated with the platinum containing regimen FOLFIRINOX. The role of DDR gene alterations as a predictive biomarker for FOLFIRINOX benefit should be further evaluated in prospective trials.

Recent Advances in Understanding the Pathogenesis of Cardiovascular Diseases and Development of Treatment Modalities.

Cardiovascular Diseases (CVDs) are a leading cause of morbidity and mortality worldwide. The underlying pathology for cardiovascular disease is largely atherosclerotic in nature and the steps include fatty streak formation, plaque progression and plaque rupture. While there is optimal drug therapy available for patients with CVD, there are also underlying drug delivery obstacles that must be addressed. Challenges in drug delivery warrant further studies for the development of novel and more efficacious medical therapies. An extensive understanding of the molecular mechanisms of disease in combination with current challenges in drug delivery serves as a platform for the development of novel drug therapeutic targets for CVD. The objective of this article is to review the pathogenesis of atherosclerosis, first-line medical treatment for CVD, and key obstacles in an efficient drug delivery.

Recent treatment modalities for cardiovascular diseases with a focus on stem cells, aptamers, exosomes and nanomedicine.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Due to the significant impact of CVD on humans, there is a need to develop novel treatment modalities tailored to major classes of cardiac diseases including hypertension, coronary artery disease, cardiomyopathies, arrhythmias, valvular disease and inflammatory diseases. In this article, we discuss recent advancements regarding development of therapeutic strategies based on stem cells, aptamers, exosomes, drug-eluting and dissolvable stents, immunotherapy and nanomedicine for the treatment of CVD. We summarize current research and clinical advances in cardiovascular therapeutics, with a focus on therapies that move beyond current oral- or sublingual-based regimens. This review article provides insight into current research and future treatment strategies that hold a great relevance for future clinical practice in pursuit of improving quality of life of patients suffering from CVD.