Citations

AbstractSystemic inflammation can lead to coagulopathy and disseminated intravascular coagulation (DIC). In prior studies, the recombinant A2 domain of human von Willebrand factor (VWF; A2 protein) attenuated DIC and decreased mortality in lipopolysaccharide (LPS)-treated mice. Here, we performed studies to dissect the mechanism by which the A2 protein moderates DIC. We used confocal microscopy to analyze the fibrin clot structure in plasma from healthy humans and endotoxemic mice, turbidity assays to examine fibrin polymerization, and a murine model for LPS-induced DIC and introduced a loss-of-function mutation into the A2 protein for fibrin. The mutation of the residue E1567 located in the α2 helix of the folded A2 domain of VWF inhibited binding activity for fibrin, possibly mapping a novel region containing a putative binding site for fibrin. The A2 protein increased the initial rate of change of fibrin polymerization, intercalated into the fibrin network, and modified the resultant clot structure in vitro. Furthermore, ex vivo experiments using plasma from mice with endotoxemia treated with the A2 protein revealed an increased rate of fibrin formation and an altered clot structure as compared with plasma from nontreated sick animals. Moreover, and in contrast to the A2 mutant, the A2 protein improved survival and reduced fibrin deposition and microvascular thrombosis in mice with endotoxemia-induced DIC. Importantly, in vivo and in vitro studies indicated that the A2 protein did not affect experimental thrombosis. Thus, we provide evidence for a novel treatment to attenuate systemic inflammation-induced coagulopathy/DIC via targeting fibrin formation, without an increased risk for bleeding.

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, with potential causes stemming from obesity, metabolic syndrome, genetic disorders, and drug toxicity. We report a 42-year-old woman with lipodystrophy and NAFLD due to a pathogenic variant in the LMNA (D300N) gene. This case report attempts to encourage clinicians to consider genetic diseases, specifically lipodystrophies, when working up uncommon causes of NAFLD.

Objective This study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient. Design A PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale. Results PAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test–retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale. Conclusion The PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up. Trial registration number NCT03650062

Objectives: To report long-term outcomes of nonmelanoma skin cancer (NMSC) in immunosuppressed cardiac and liver transplant recipients (CLTR). Materials and Methods: The authors reviewed CLTR at the Mayo Clinic in Arizona from 1986 to 2013. Patient and tumor characteristics were recorded. Survival rates were calculated using the Kaplan-Meier method. Patient-specific and lesion-specific analyses were performed. Univariate and multivariate cox regressions were performed for comparisons. Results: Seven-hundred and forty-seven patients underwent cardiac (138) or liver (609) transplantation and of these, 97 patients (13%) developed 382 invasive NMSC. The median follow-up was 11 (range, 3 to 27) years for surviving patients. Primary treatment was mainly surgery alone. At 10 years, the local recurrence (LR) rate was 20% (95% confidence interval, 15%-28%), and 14% of patients had multiple LRs. At 10 years, LR rates were higher for T3/T4 tumors when compared with T1/T2 tumors (32.5% vs. 20%, P=0.05). At 10 years, overall survival was 79% (95% confidence interval, 64%-88%). On multivariate analysis, age 61 years and more demonstrated inferior overall survival (P<0.01). Conclusions: This is the first study describing the AJCC 8th edition stage-based patterns of recurrence and long-term outcomes of surgically managed NMSC in a large cohort of immunosuppressed CLTRs. T3 and T4 tumors recur more often than early stage tumors. Further study is required to identify factors related to recurrence and guide upfront treatment intensification in this high-risk population.

Background: Historical and conceptual issues related to community psychiatry as an innovative approach to clinical assistance across the world, precede a more or less detailed examination of its presence, role and current accomplishments in Latin America, particularly related to child and adolescent subpopulations. Information about transition processes from the traditional hospital-centered model to the community-based approach, applicable mental health policies, levels of implementation and quality of the available reports in different countries, are duly evaluated. Objective: Within an understanding of the broader Latin American context, the paper describes the situation in Perú, a country considered representative of the Low and Middle Income (LMIC) group in the subcontinent. Methods: The situation in Perú is presented with particular emphasis on a recently established community-based mental health centers program across its territory. Results: This description includes consideration of variables such as personal, family and identity empowerment, a focus on integrated care, and clinical outcomes and community relations. The development of community mental health centers across Perú is described. Conclusion: Adolescents represent the unique future of socio-culturally diverse Latin American countries, and must be the target population of well-conceived, cohesive community mental health policies and programs. The importance of political will to promote community health centers that provide adolescents access to services is critical.