Cardiac Troponin Release is Associated with Biomarkers of Inflammation and Ventricular Dilatation During Critical Illness.

INTRODUCTION: Troponin release is common during critical illness. We hypothesized that there was an association between cardiac troponin T (cTnT) and biomarkers of systemic inflammation and ventricular dilatation. METHODS: In an observational prospective cohort study, we enrolled consecutive adult patients admitted for non-cardiac reasons to the Intensive Care Unit (ICU) in 2 tertiary care centers. We measured cTnT, C-reactive protein (CRP), Interleukin-6 (IL-6), procalcitonin (PCT) and N-terminal pro brain natriuretic peptide (NT-proBNP) daily in the first week, and on alternate days in the second week. Using a peak cTnT cut-off ≥15ng/L and concomitant changes on electrocardiogram (ECG), patients were categorised as "definite myocardial infarction (MI)", "possible MI", "cTnT rise only" or "no cTnT rise". Within each group, associations between CRP, IL-6, PCT, NT-proBNP and cTnT were investigated using mixed effect models. RESULTS: 172 patients were included in the analysis of whom 84% had a cTnT rise ≥15ng/L. 21 patients (12%) had a definite MI, 51 (30%) had a possible MI and 73 (42%) had a cTnT rise only. At time of peak cTnT, 71% of patients were septic and 67% were on vasopressors.Multivariable analysis showed a significant association between cTnT and IL-6 in all patients with a cTnT rise independent of age, gender, renal function and cardiovascular risk factors. In patients without a definite MI, cTnT levels were significantly associated with PCT and NT-proBNP values. In patients without elevated cTnT levels, there was no associated NT-proBNP rise. CONCLUSIONS: In ICU patients admitted for non-cardiac reasons, serial cTnT levels were independently associated with markers of systemic inflammation and NT-proBNP

Safety and efficacy of low-dose sirolimus in the PIK3CA-Related Overgrowth Spectrum

Purpose PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Methods Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. Results Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of –7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently. Conclusion This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk–benefit evaluations for sirolimus treatment in PROS

Community-based management induces rapid recovery of a high-value tropical freshwater fishery

Tropical wetlands are highly threatened socio-ecological systems, where local communities rely heavily on aquatic animal protein, such as fish, to meet food security. Here, we quantify how a ‘win-win’ community-based resource management program induced stock recovery of the world’s largest scaled freshwater fish (Arapaima gigas), providing both food and income. We analyzed stock assessment data over eight years and examined the effects of protected areas, community-based management, and landscape and limnological variables across 83 oxbow lakes monitored along a ~500-km section of the Juruá River of Western Brazilian Amazonia. Patterns of community management explained 71.8% of the variation in arapaima population sizes. Annual population counts showed that protected lakes on average contained 304.8 (±332.5) arapaimas, compared to only 9.2 (±9.8) in open-access lakes. Protected lakes have become analogous to a high-interest savings account, ensuring an average annual revenue of US$10,601 per community and US$1046.6 per household, greatly improving socioeconomic welfare. Arapaima management is a superb window of opportunity in harmonizing the co-delivery of sustainable resource management and poverty alleviation. We show that arapaima management deserves greater attention from policy makers across Amazonian countries, and highlight the need to include local stakeholders in conservation planning of Amazonian floodplains

HIV, Gender, Race, Sexual Orientation, and Sex Work: A Qualitative Study of Intersectional Stigma Experienced by HIV-Positive Women in Ontario, Canada

Mona Loutfy and colleagues used focus groups to examine experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada

Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities

PURPOSE: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. METHODS: From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. RESULTS: MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. CONCLUSION: MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex