A scoping review protocol on diagnostic strategies to detect occult malignancies in individuals with ischemic stroke.

BACKGROUND: Emerging data show an increased risk of ischemic stroke in patients with a new diagnosis of cancer. As the risk of stroke begins to increase 150 days before cancer is diagnosed, stroke may be the first clinical manifestation of undiagnosed cancer. About 6% of patients with cryptogenic ischemic stroke (unknown etiology after diagnostic evaluations) are diagnosed with cancer within one year. However, the optimal cancer screening strategy in this population is not known. We aim to conduct a scoping review of screening strategies for occult cancer in individuals with ischemic stroke. METHODS: Electronic databases including MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost) and Scopus will be systematically searched to identify articles that report on screening strategies for occult cancer in individuals with ischemic stroke. At least two investigators will independently perform two-stage study selection consisting of title/abstract screening and full-text review, followed by data extraction. Thereafter, a thematic analysis will be conducted to provide an overview of what diagnostic tests/strategies have been used, and their clinical utility in terms of positive and negative predictive value (when available). CONCLUSION: We anticipate that the findings of this scoping review will identify strategies used to detect occult cancer in individuals with ischemic stroke and summarize their clinical utility (if reported). Addressing this knowledge gap will help guide the development of future clinical trials on occult cancer screening patients with ischemic stroke.

Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations.

INTRODUCTION: Severe and recurrent gastrointestinal (GI) bleeding caused by angiodysplasia is a significant problem in patients with von Willebrand disease (VWD) and in those with acquired von Willebrand syndrome (AVWS). At present, angiodysplasia-related GI bleeding is often refractory to standard treatment including replacement therapy with von Willebrand factor (VWF) concentrates and continues to remain a major challenge and cause of significant morbidity in patients despite advances in diagnostics and therapeutics. AREAS COVERED: This paper reviews the available literature on GI bleeding in VWD patients, examines the molecular mechanisms implicated in angiodysplasia-related GI bleeding, and summarizes existing strategies in the management of bleeding GI angiodysplasia in patients with VWF abnormalities. Suggestions are made for further research directions. EXPERT OPINION: Bleeding from angiodysplasia poses a significant challenge for individuals with abnormal VWF. Diagnosis remains a challenge and may require multiple radiologic and endoscopic investigations. Additionally, there is a need for enhanced understanding at a molecular level to identify effective therapies. Future studies of VWF replacement therapies using newer formulations as well as other adjunctive treatments to prevent and treat bleeding will hopefully improve care.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It is caused by problems with von Willebrand factor (VWF), a protein in blood that helps stop bleeding. People with VWD either have low levels of VWF or VWF that does not work properly. The disease causes bleeding symptoms in 1 in 1000 individuals. Three main types of VWD exist. Depending on the type, people can have minimal symptoms or serious bleeding that needs hospital care.Patients with severe VWD may often experience repeated bleeding from the gastrointestinal tract. This is usually due to the formation of abnormal fragile vessels (malformations) called angiodysplasia, which have been linked to the absence or abnormal function of VWF. These fragile vessels are very difficult to find and diagnose. At present, available treatments for angiodysplasia, including long-term VWF replacement therapy, are not very effective. As a result, VWD patients with angiodysplasia have a poor quality of life.More research is needed to better evaluate current treatments and explore the contribution of abnormal VWF in the development of angiogenesis and angiodysplasia in VWD which may reveal new targets for treatment.

Special considerations in GI bleeding in VWD patients.

Gastrointestinal (GI) bleeding is an important cause of morbidity and mortality in von Willebrand disease (VWD). It has been noted that GI bleeding caused by angiodysplasia is overrepresented in VWD patients compared to other causes. The bleeding from angiodysplasia is notoriously difficult to treat; recurrences and rebleeds are common. A growing body of basic science evidence demonstrates that von Willebrand factor negatively regulates angiogenesis through multiple pathways. VWD is clinically highly associated with angiodysplasia. The predisposition to angiodysplasia likely accounts for many of the clinical difficulties related to managing GI bleeding in VWD patients. Diagnosis and treatment are challenging with the current tools available, and much further research is needed to further optimize care for these patients with regard to acute treatment, prophylaxis, and adjunctive therapies. In this review we provide an overview of the available literature on GI bleeding in VWD and explore the molecular underpinnings of angiodysplasia-related GI bleeding. Considerations for diagnostic effectiveness are discussed, as well as the natural history and recurrence of these lesions and which therapeutic options are available for acute and prophylactic management.

All-cause mortality after major gastrointestinal bleeding among patients receiving direct oral anticoagulants: a protocol for a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal (GI) bleeding represents the single most frequent site of anticoagulant-related bleeding. Adverse outcomes after major GI bleeding including mortality are not well characterized and, as a result, may be underappreciated in clinical practice. We aim to conduct a systematic review and meta-analysis of the risk for 30-day all-cause mortality after major GI bleeding among patients receiving DOACs. METHODS: Electronic databases including MEDLINE, EMBASE, and Cochrane CENTRAL will be systematically searched to identify randomized controlled trials and prospective and retrospective cohort studies reporting 30-day all-cause mortality in adults with DOAC-related major GI bleeding. At least two investigators will independently perform study selection, risk of bias assessment, and data extraction. The proportion of deaths following a major GI event relative to the number of major GI bleeding events will be calculated for each individual study, and results across studies will be pooled using random-effects meta-analysis. We will assess risk of bias using criteria proposed by the GRADE group for prognostic studies. DISCUSSION: The findings of this systematic review and meta-analysis will provide clinicians and patients with estimates of mortality after the most common major bleeding event to support shared decision making about anticoagulation management. TRIAL REGISTRATION: PROSPERO CRD42022295815.

Tranexamic acid evidence and controversies: An illustrated review.

Tranexamic acid (TXA) is an antifibrinolytic agent commonly used for the treatment or prevention of bleeding. Indications for TXA are diverse, including heavy menstrual bleeding, trauma, postpartum hemorrhage, traumatic brain injury, and surgical site bleeding. Despite decades of use and a robust body of evidence, hesitancy using TXA persists in many clinical settings. This illustrated review describes the history, pharmacology, and practical considerations of TXA use. We also describe the major landmark randomized controlled trials of TXA and their implications. Finally, we review the evidence around common controversies surrounding TXA such as the risk of thrombosis, prescription along with combined hormonal contraceptives, and use in patients with gross hematuria.

Detection of right ventricular dysfunction in acute pulmonary embolism by computed tomography or echocardiography: A systematic review and meta-analysis.

BACKGROUND: Right ventricular (RV) dysfunction predicts worse outcomes in acute pulmonary embolism (PE). Because computed tomography (CT) pulmonary angiography visualizes cardiac structures, it is a potential method for assessing RV function without the delays associated with inpatient echocardiography. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of CT scan findings for detecting RV dysfunction compared with echocardiography. METHODS: We searched MEDLINE and EMBASE from inception to April 2020 for studies comparing RV dysfunction on CT scan with echocardiography standard. Study quality was assessed with the QUADAS-2 risk of bias tool. Meta-analysis was performed using a bivariate mixed effects regression framework. RESULTS: After screening, 26 studies (3508 patients) were included. In a pooled analysis, septal deviation (5 studies; 459 patients) had a sensitivity of 0.31 (95% CI 0.25-0.38; I2  = 0%), specificity of 0.98 (95% CI 0.90-1.00; I2  = 59.4%), and positive likelihood ratio of 13.6 (95% CI 3.1-60.4) for RV dysfunction compared with echocardiography. The pooled sensitivity of increased RV/left ventricular ratio (21 studies; 3111 patients) was 0.83 (95% CI 0.78-0.87; I2  = 81.8%), whereas the pooled specificity was 0.75 (95% CI 0.66-0.82; I2  = 94.2%) and negative likelihood ratio was 0.23 (0.18-0.29). CONCLUSIONS: Overall, RV dysfunction can be detected by CT imaging but the diagnostic accuracy when compared with echocardiography varies depending on specific findings. The presence of septal bowing appears to be highly specific for RV dysfunction. Our findings suggest that multiple CT findings of RV dysfunction may improve diagnostic accuracy and further studies are warranted.

Vascular abnormalities in patients with von Willebrand disease: A scoping review.

BACKGROUND: Qualitative or quantitative defects of von Willebrand factor (VWF) such as in von Willebrand disease (VWD) are associated with vascular abnormalities, especially in the gastrointestinal (GI) tract. However, the locations, extent, and natural history of vascular abnormalities in patients with VWD is not well understood. To summarize the existing literature on the topic, we conducted a scoping review of vascular abnormalities in patients with VWD. METHODS: We searched MEDLINE and EMBASE from inception to September 1, 2020, for studies clinically describing vascular abnormalities in VWD patients. Screening and data extraction was completed independently and in duplicate and each abnormality was documented individually. RESULTS: After screening, 54 studies that reported patient level data comprising 146 patients were included. Type 2A (39%) and type 3 (14.4%) were the most common VWD subtypes. The most common site of vascular malformation was the GI tract, occurring in 124 patients (84.9%), whereas 18 (12.3%) had non-GI vascular abnormalities and 4 (2.7%) had both GI and non-GI vascular abnormalities. With respect to outcomes, the clinical course was not specified in the majority (55.5%) of patients. Survey and population level data were reported in nine studies, demonstrating vascular abnormalities occurred at higher rates in VWD and that VWD patients are overrepresented among those with those abnormalities. CONCLUSION: Vascular malformations in patients with VWD occur primarily in the gastrointestinal tract. Type 2A and type 3 VWD are the most common subtypes affected. The clinical treatment and natural history of these abnormalities remains understudied and further research is needed.