Citations

BackgroundThe Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) offers a six‐tiered diagnostic scheme for thyroid Fine Needle Aspiration (FNA): Benign, Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS), suspicious for follicular neoplasm, suspicious for malignancy, malignant, and unsatisfactory with an aim to standardize diagnostic criteria. Reported rate of AUS/FLUS category in the literature has varied from 3% to 20.5%.MethodsThe aim of this study was to assess interobserver variability among cytopathologists to assess reproducibility of the AUS/FLUS category. Seven cytopathologists brought FNA cases (a mixture of atypical and non‐atypical FNA diagnosis) diagnosed using TBSRTC from their respective institutions which were reviewed and diagnosed by the participants. The analysis assessed interobserver variability among 7 cytopathologists and determined characteristics on the slides which were associated with concordance to the institutional diagnosis.ResultsSeventy eight of 125 (62.4%) benign cases were classified as benign by the reviewers and 26 (21%) were called AUS/FLUS on review. A third of the AUS/FLUS cases were called benign on review and 28.2% were classified as suspicious for neoplasia/malignancy. Roughly a third each of the suspicious for follicular neoplasm/suspicious for malignancy cases were classified as AUS/FLUS.DiscussionWhen pathologists from different institutions shared their slides, concordance was high for specimens with adequate cellularity and those that were clearly benign but thresholds varied for the other indeterminate categories. Most definite categorization of the AUS/FLUS category was seen on review. Diagn. Cytopathol. 2017;45:399–405. © 2017 Wiley Periodicals, Inc.

Background Soluble ST2 is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity‐driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction ( HF p EF ) pathophysiology, but data on how sST 2 relates to clinical characteristics or inflammatory conditions or biomarkers in HF p EF are limited. We sought to determine circulating levels and clinical correlates of sST 2 in HF pEF. Methods and Results At enrollment, patients (n=174) from the Phosphodiesterase‐5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HF p EF had sST 2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST 2 levels. Median sST 2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9–49.2 ng/mL; reference range 4–31 ng/mL) and 30.8 ng/mL (range 25.3–39.3 ng/mL; reference range 2–21 ng/mL), respectively. Among HF p EF patients, higher sST 2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis ( P <0.05 for all). sST 2 was not associated with left ventricular structure or left ventricular systolic or diastolic function. Conclusions In HF p EF , sST 2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that sST2 may be a marker of systemic inflammation in HF p EF and potentially of extracardiac origin. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00763867.

Abstract Welander distal myopathy is a rare autosomal dominant disorder characterized by muscle weakness in the hands and feet. Exome sequencing of affected families discovered a segregating p.Glu384Lys pathogenic variant in TIA-1 as the main genetic cause of Welander distal myopathy. TIA-1 encodes an RNA-binding protein which serves as a key component of stress granules. This protein also regulates splicing and translation of mRNA. Our patient developed progressive weakness in his hands and feet during his late 40s that was misdiagnosed as a neuropathy that caused muscle atrophy. Follow-up genetic testing revealed a p.Glu384Lys pathogenic variant in TIA-1, and he was then diagnosed with Welander distal myopathy. Our case report underlines the importance of electrodiagnostic and genetic testing of patients.

Abstract Stem cell-based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. Therapeutic effects of bone-marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d-galactosamine/tumor necrosis factor-α (TNF-α). Systemically administered EV derived from MSC accumulated within the injured liver following systemic administration, reduced hepatic injury, and modulated cytokine expression. Moreover, survival was dramatically increased by EV derived from either murine or human MSC. Similar results were observed with the use of cryopreserved mMSC-EV after 3 months. Y-RNA-1 was identified as a highly enriched noncoding RNA within hMSC-EV compared to cells of origin. Moreover, siRNA mediated knockdown of Y-RNA-1 reduced the protective effects of MSC-EV on TNF-α/ActD-mediated hepatocyte apoptosis in vitro. These data support a critical role for MSC-derived EV in mediating reparative responses following hepatic injury, and provide compelling evidence to support the therapeutic use of MSC-derived EV in fulminant hepatic failure.

The authors report a case of a developmentally normal child with a congenital complex torcular dural arteriovenous fistula (DAVF) who later, in his teenage years, developed several vermian cavernomas within a large cerebellar developmental venous anomaly (DVA). The patient had initially presented with an abnormally large head circumference but no neurological deficits. He underwent several partial embolization procedures in an attempt to decrease the blood supply of the fistula over the course of 8 years. Nine years following initial presentation, he presented with a fourth ventricular hemorrhage, due to development of a new vermian cavernoma adjacent to a previously known vermian DVA and suffered subsequent mild left-sided hemiataxia from which he later recovered. CT angiographic images demonstrated that the vermian DVA drained into the left transverse sinus, which also drained the torcular arteriovenous fistula. A routine follow-up MRI examination 10 years following initial presentation demonstrated interval development of several large cavernomas in the cerebellum, all within the DVA. The patient had no new symptoms at that time and was neurologically intact. This case report highlights the de novo development of multiple cavernous malformations potentially secondary to DAVF-induced venous congestion in a preexisting DVA.