Biomarkers Profile in Provoked Versus Unprovoked Deep Venous Thrombosis.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Biomarkers profile in provoked versus unprovoked deep venous thrombosis

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE).

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen. RESULTS: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care. CONCLUSION: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. STUDY REGISTRATION: ClinicalTrials.gov NCT04383613.

Incisional negative pressure wound therapy decreases the frequency of postoperative perineal surgical site infections: a cohort study.

BACKGROUND: Abdominoperineal resection is a procedure associated with high rates of perineal surgical site infections, causing distress to the patient, costs to the hospital system, and delays in further treatment. OBJECTIVE: The aim of this study was to investigate the role of incisional negative pressure wound therapy in decreasing the rates of perineal surgical site infection. DESIGN: This retrospective cohort study had a historical, consecutively sampled control group. SETTINGS: This study was conducted at a single-institution tertiary care academic institution. PATIENTS: All patients undergoing an abdominoperineal resection between 2008 and 2012 were assessed. INTERVENTIONS: Perineal incisional negative pressure wound therapy was applied to all patients following an abdominoperineal resection between 2010 and 2012 at 125 mmHg continuous suction for 5 days postoperatively. MAIN OUTCOME MEASURES: The development of a perineal surgical site infection within the first 30 days postoperatively was the primary outcome measured. RESULTS: Fifty-nine patients were included: 27 in the incisional negative pressure wound therapy group and 32 in the control group. A statistically lower proportion of perineal surgical site infections were detected in the incisional negative pressure wound therapy group than in the standard dressing group (15% vs 41%; p = 0.02). Both populations were similar in perioperative risk factors, with the exception of increased levels of blood urea nitrogen, a higher proportion of hypertensive patients, and a longer mean operative time in the incisional negative pressure wound therapy group. Additionally, an increased length of stay was observed in the incisional negative pressure wound therapy group (11 vs 8 days; p = 0.03). After adjusting for confounders, including the type of perineal dissection, incisional negative pressure wound therapy was found to be an independent predictor of not developing an surgical site infection (adjusted OR, 0.11; 95% CI, 0.04-0.66; p = 0.01). LIMITATIONS: The study's retrospective nature limits the results because of the risk of interpreter bias, although this was addressed in part by reviewing data in duplicate. We controlled for the potential for selection bias with our consecutive sampling model. CONCLUSIONS: Our study demonstrates a role for incisional negative pressure wound therapy in decreasing rates of perineal surgical site infection following abdominoperineal resection. Prospective randomized trials will be required to further investigate this intervention.

Discoidin domain receptor 1 on bone marrow-derived cells promotes macrophage accumulation during atherogenesis.

RATIONALE: We described a critical role for the discoidin domain receptor (DDR)1 collagen receptor tyrosine kinase during atherosclerotic plaque development. Systemic deletion of Ddr1 in Ldlr(-/-) mice accelerated matrix accumulation and reduced plaque size and macrophage content. However, whether these effects reflected an independent role for macrophage DDR1 during atherogenesis remained unresolved. METHODS: In the present study, we performed sex-mismatched bone marrow transplantation using Ddr1(+/+);Ldlr(-/-) and Ddr1(-/-);Ldlr(-/-) mice to investigate the role of macrophage DDR1 during atherogenesis. Chimeric mice with deficiency of DDR1 in bone marrow-derived cells (Ddr1(-/--->+/+)) or control chimeric mice that received Ddr1(+/+);Ldlr(-/-) marrow (Ddr1(+/+-->+/+)) were fed an atherogenic diet for 12 weeks. RESULTS: We observed a 66% reduction in atherosclerosis in the descending aorta and a 44% reduction in plaque area in the aortic sinus in Ddr1(-/--->+/+) mice compared to Ddr1(+/+-->+/+) mice. Furthermore, we observed a specific reduction in the number of donor-derived macrophages in Ddr1(-/--->+/+) plaques, suggesting that bone marrow deficiency of DDR1 attenuated atherogenesis by limiting macrophage accumulation in the plaque. We have also demonstrated that the effects of DDR1 on macrophage infiltration and accumulation can occur at the earliest stage of atherogenesis, the formation of the fatty streak. Deficiency of DDR1 limited the appearance of 5-bromodeoxyuridine-labeled monocytes/macrophages in the fatty streak and resulted in reduced lesion size in Ldlr(-/-) mice fed a high fat diet for 2 weeks. In vitro studies to investigate the mechanisms involved revealed that macrophages from Ddr1(-/-) mice had decreased adhesion to type IV collagen and decreased chemotactic invasion of type IV collagen in response to monocyte chemoattractant protein-1. CONCLUSIONS: Taken together, our data support an independent and critical role for DDR1 in macrophage accumulation at early and late stages of atherogenesis.