Short-Term Exposure to Warm Microhabitats Could Explain Amphibian Persistence with Batrachochytrium dendrobatidis

Environmental conditions can alter the outcomes of symbiotic interactions. Many amphibian species have declined due to chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), but many others persist despite high Bd infection prevalence. This indicates that Bd's virulence is lower, or it may even be a commensal, in some hosts. In the Australian Wet Tropics, chytridiomycosis extirpated Litoria nannotis from high-elevation rain forests in the early 1990 s. Although the species is recolonizing many sites, no population has fully recovered. Litoria lorica disappeared from all known sites in the early 1990 s and was thought globally extinct, but a new population was discovered in 2008, in an upland dry forest habitat it shares with L. nannotis. All frogs of both species observed during three population censuses were apparently healthy, but most carried Bd. Frogs perch on sun-warmed rocks in dry forest streams, possibly keeping Bd infections below the lethal threshold attained in cooler rain forests. We tested whether short-term elevated temperatures can hamper Bd growth in vitro over one generation (four days). Simulating the temperatures available to frogs on strongly and moderately warmed rocks in dry forests, by incubating cultures at 33°C for one hour daily, reduced Bd growth below that of Bd held at 15°C constantly (representing rain forest habitats). Even small decreases in the exponential growth rate of Bd on hosts may contribute to the survival of frogs in dry forests

Prevalence of and Risk Factors for Intracranial Abnormalities in Unprovoked Seizures

Background and objectivesProspective data are lacking to determine which children might benefit from prompt neuroimaging after unprovoked seizures. We aimed to determine the prevalence of, and risk factors for, relevant intracranial abnormalities in children with first, unprovoked seizures.MethodsWe conducted a 6-center prospective study in children aged >28 days to 18 years with seemingly unprovoked seizures. Emergency department (ED) clinicians documented clinical findings on a standardized form. Our main outcome was the presence of a clinically relevant intracranial abnormality on computed tomography (CT) or MRI, defined as those that might change management, either emergently, urgently, or nonurgently.ResultsWe enrolled 475 of 625 (76%) eligible patients. Of 354 patients for whom cranial MRI or CT scans were obtained in the ED or within 4 months of the ED visit, 40 (11.3%; 95% confidence interval [CI]: 8.0-14.6%) had clinically relevant intracranial abnormalities, with 3 (0.8%; 95% CI: 0.1-1.8%) having emergent/urgent abnormalities. On logistic regression analysis, a high-risk past medical history (adjusted odds ratio: 9.2; 95% CI: 2.4-35.7) and any focal aspect to the seizure (odds ratio: 2.5; 95% CI: 1.2-5.3) were independently associated with clinically relevant abnormalities.ConclusionsClinically relevant intracranial abnormalities occur in 11% of children with first, unprovoked seizures. Emergent/urgent abnormalities, however, occur in <1%, suggesting that most children do not require neuroimaging in the ED. Findings on patient history and physical examination identify patients at higher risk of relevant abnormalities

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery : A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents

Background: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. Methods: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. Results: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31–35 years (52.1%, 95% confidence interval (CI) 37.9–66.2%), aged 36–40 years (55.9%, 95% CI 39.2–72.6%) and aged 41–45 years (46.9%, 95% CI 33–60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. Conclusions: These data demonstrate that Bethesda categories 1–4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC

Use of High-Sensitivity Troponin T to Identify Patients With Acute Heart Failure at Lower Risk for Adverse Outcomes: An Exploratory Analysis From the RELAX-AHF Trial

14siThe aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes.nonenonePang, Peter S; Teerlink, John R; Voors, Adriaan A; Ponikowski, Piotr; Greenberg, Barry H; Filippatos, Gerasimos; Felker, G Michael; Davison, Beth A; Cotter, Gad; Kriger, Joshua; Prescott, Margaret F; Hua, Tsushung A; Severin, Thomas; Metra, MarcoPang, Peter S; Teerlink, John R; Voors, Adriaan A; Ponikowski, Piotr; Greenberg, Barry H; Filippatos, Gerasimos; Felker, G Michael; Davison, Beth A; Cotter, Gad; Kriger, Joshua; Prescott, Margaret F; Hua, Tsushung A; Severin, Thomas; Metra, Marc

Retrospective natural history of thymidine kinase 2 deficiency

Background Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. Objective To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. Methods The study was conducted by 42 investigators across 31 academic medical centres. Results We identified 92 patients with genetically confirmed diagnoses of TK2 deficiency: 67 from literature review and 25 unreported cases. Based on clinical and molecular genetics findings, we recognised three phenotypes with divergent survival: (1) infantile-onset myopathy (42.4%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); (2) childhood-onset myopathy (40.2%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years; and (3) late-onset myopathy (17.4%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults. Muscle biopsies show multiple mtDNA deletions often with mtDNA depletion. Conclusions In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form. Our observations provide essential information for planning future clinical trials in this disorder.Peer reviewe