Sanguineous Pericardial Effusion and Cardiac Tamponade in the Setting of Graves’ Disease: Report of a Case and Review of Previously Reported Cases

Introduction. Pericardial effusion in the setting of hyperthyroidism is rare. We present a patient with Graves’ disease who developed a sanguineous pericardial effusion and cardiac tamponade. Case Description. A 76-year-old man presenting with fatigue was diagnosed with Graves’ disease and treated with methimazole. Two months later, he was hospitalized for uncontrolled atrial fibrillation. Electrocardiography showed diffuse low voltage and atrial fibrillation with rapid ventricular rate. Chest radiograph revealed an enlarged cardiac silhouette and left-sided pleural effusion. Thyroid stimulating hormone was undetectable, and free thyroxine was elevated. Diltiazem and heparin were started, and methimazole was increased. Transthoracic echocardiography revealed a large pericardial effusion with cardiac tamponade physiology. Pericardiocentesis obtained 1,050 mL of sanguineous fluid. The patient progressed to thyroid storm, treated with propylthiouracil, potassium iodine, hydrocortisone, and cholestyramine. Cultures and cytology of the pericardial fluid were negative. Thyroid hormone markers progressively normalized, and he improved clinically and was discharged. Discussion. We found 10 previously reported cases of pericardial effusions in the setting of hyperthyroidism. Heparin use may have contributed to the sanguineous nature of our patient’s pericardial effusion, but other reported cases occurred without anticoagulation. Sanguineous and nonsanguineous pericardial effusions and cardiac tamponade may be due to hyperthyroidism

Deficiency in Perlecan/HSPG2 During Bone Development Enhances Osteogenesis and Decreases Quality of Adult Bone in Mice

Perlecan/HSPG2 (Pln) is a large heparan sulfate proteoglycan abundant in the extracellular matrix of cartilage and the lacunocanalicular space of adult bones. Although Pln function during cartilage development is critical, evidenced by deficiency disorders including Schwartz–Jampel Syndrome and dyssegmental dysplasia Silverman-Handmaker type, little is known about its function in development of bone shape and quality. The purpose of this study was to understand the contribution of Pln to bone geometric and mechanical properties. We used hypomorph mutant mice that secrete negligible amount of Pln into skeletal tissues and analyzed their adult bone properties using micro-computed tomography and three-point-bending tests. Bone shortening and widening in Pln mutants was observed and could be attributed to loss of growth plate organization and accelerated osteogenesis that was reflected by elevated cortical thickness at older ages. This effect was more pronounced in Pln mutant females, indicating a sex-specific effect of Pln deficiency on bone geometry. Additionally, mutant females, and to a lesser extent mutant males, increased their elastic modulus and bone mineral densities to counteract changes in bone shape, but at the expense of increased brittleness. In summary, Pln deficiency alters cartilage matrix patterning and, as we now show, coordinately influences bone formation and calcification

Evidence for an FU Orionis-like Outburst from a Classical T Tauri Star

We present pre- and post-outburst observations of the new FU Orionis-like young stellar object PTF 10qpf (also known as LkHa 188-G4 and HBC 722). Prior to this outburst, LkHa 188-G4 was classified as a classical T Tauri star on the basis of its optical emission-line spectrum superposed on a K8-type photosphere, and its photometric variability. The mid-infrared spectral index of LkHa 188-G4 indicates a Class II-type object. LkHa 188-G4 exhibited a steady rise by ~1 mag over ~11 months starting in Aug. 2009, before a subsequent more abrupt rise of > 3 mag on a time scale of ~2 months. Observations taken during the eruption exhibit the defining characteristics of FU Orionis variables: (i) an increase in brightness by > 4 mag, (ii) a bright optical/near-infrared reflection nebula appeared, (iii) optical spectra are consistent with a G supergiant and dominated by absorption lines, the only exception being Halpha which is characterized by a P Cygni profile, (iv) near-infrared spectra resemble those of late K--M giants/supergiants with enhanced absorption seen in the molecular bands of CO and H_2O, and (v) outflow signatures in H and He are seen in the form of blueshifted absorption profiles. LkHa 188-G4 is the first member of the FU Orionis-like class with a well-sampled optical to mid-infrared spectral energy distribution in the pre-outburst phase. The association of the PTF 10qpf outburst with the previously identified classical T Tauri star LkHa 188-G4 (HBC 722) provides strong evidence that FU Orionis-like eruptions represent periods of enhanced disk accretion and outflow, likely triggered by instabilities in the disk. The early identification of PTF 10qpf as an FU Orionis-like variable will enable detailed photometric and spectroscopic observations during its post-outburst evolution for comparison with other known outbursting objects.Comment: 14 pages, 11 figures, ApJ accepte

PTF10fqs: A Luminous Red Nova in the Spiral Galaxy Messier 99

The Palomar Transient Factory (PTF) is systematically charting the optical transient and variable sky. A primary science driver of PTF is building a complete inventory of transients in the local Universe (distance less than 200 Mpc). Here, we report the discovery of PTF10fqs, a transient in the luminosity "gap" between novae and supernovae. Located on a spiral arm of Messier 99, PTF 10fqs has a peak luminosity of Mr = -12.3, red color (g-r = 1.0) and is slowly evolving (decayed by 1 mag in 68 days). It has a spectrum dominated by intermediate-width H (930 km/s) and narrow calcium emission lines. The explosion signature (the light curve and spectra) is overall similar to thatof M85OT2006-1, SN2008S, and NGC300OT. The origin of these events is shrouded in mystery and controversy (and in some cases, in dust). PTF10fqs shows some evidence of a broad feature (around 8600A) that may suggest very large velocities (10,000 km/s) in this explosion. Ongoing surveys can be expected to find a few such events per year. Sensitive spectroscopy, infrared monitoring and statistics (e.g. disk versus bulge) will eventually make it possible for astronomers to unravel the nature of these mysterious explosions.Comment: 12 pages, 12 figures, Replaced with published versio

PTF10nvg: An Outbursting Class I Protostar in the Pelican/North American Nebula

During a synoptic survey of the North American Nebula region, the Palomar Transient Factory (PTF) detected an optical outburst (dubbed PTF10nvg) associated with the previously unstudied flat or rising spectrum infrared source IRAS 20496+4354. The PTF R-band light curve reveals that PTF10nvg brightened by more than 5 mag during the current outburst, rising to a peak magnitude of R~13.5 in 2010 Sep. Follow-up observations indicate PTF10nvg has undergone a similar ~5 mag brightening in the K band, and possesses a rich emission-line spectrum, including numerous lines commonly assumed to trace mass accretion and outflows. Many of these lines are blueshifted by ~175 km/s from the North American Nebula's rest velocity, suggesting that PTF10nvg is driving an outflow. Optical spectra of PTF10nvg show several TiO/VO bandheads fully in emission, indicating the presence of an unusual amount of dense (> 10^10 cm^-3), warm (1500-4000 K) circumstellar material. Near-infrared spectra of PTF10nvg appear quite similar to a spectrum of McNeil's Nebula/V1647 Ori, a young star which has undergone several brightenings in recent decades, and 06297+1021W, a Class I protostar with a similarly rich near--infrared emission line spectrum. While further monitoring is required to fully understand this event, we conclude that the brightening of PTF10nvg is indicative of enhanced accretion and outflow in this Class-I-type protostellar object, similar to the behavior of V1647 Ori in 2004-2005.Comment: Accepted to the Astronomical Journal; 21 pages, 11 figures, 6 tables in emulateapj format; v2 fixes typo in abstract; v3 updates status to accepted, adjusts affiliations, adds acknowledgmen

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

Background: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods: In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). Results: Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions: Participants with a wide range of underlying kidney diseases receiving renin–angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2–4 and increased albuminuria, with and without T2D

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment