Quantification of recirculation as an adjuvant to transthoracic echocardiography for optimization of dual-lumen extracorporeal life support

Proper cannula positioning in single site veno-venous extracorporeal life support (vv-ELS) is cumbersome and necessitates image guidance to obtain a safe and stable position within the heart and the caval veins. Importantly, image-guided cannula positioning alone is not sufficient, as possible recirculation cannot be quantified. We present an ultrasound dilution technique allowing quantification of recirculation for optimizing vv-ELS. We suggest quantification of recirculation in addition to image guidance to provide optimal vv-ELS

Craniodental Morphology and Systematics of a New Family of Hystricognathous Rodents (Gaudeamuridae) from the Late Eocene and Early Oligocene of Egypt

BACKGROUND: Gaudeamus is an enigmatic hystricognathous rodent that was, until recently, known solely from fragmentary material from early Oligocene sites in Egypt, Oman, and Libya. Gaudeamus' molars are similar to those of the extant cane rat Thryonomys, and multiple authorities have aligned Gaudeamus with Thryonomys to the exclusion of other living and extinct African hystricognaths; recent phylogenetic analyses have, however, also suggested affinities with South American caviomorphs or Old World porcupines (Hystricidae). METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the oldest known remains of Gaudeamus, including largely complete but crushed crania and complete upper and lower dentitions. Unlike younger Gaudeamus species, the primitive species described here have relatively complex occlusal patterns, and retain a number of plesiomorphic features. Unconstrained parsimony analysis nests Gaudeamus and Hystrix within the South American caviomorph radiation, implying what we consider to be an implausible back-dispersal across the Atlantic Ocean to account for Gaudeamus' presence in the late Eocene of Africa. An analysis that was constrained to recover the biogeographically more plausible hypothesis of caviomorph monophyly does not place Gaudeamus as a stem caviomorph, but rather as a sister taxon of hystricids. CONCLUSIONS/SIGNIFICANCE: We place Gaudeamus species in a new family, Gaudeamuridae, and consider it likely that the group originated, diversified, and then went extinct over a geologically brief period of time during the latest Eocene and early Oligocene in Afro-Arabia. Gaudeamurids are the only known crown hystricognaths from Afro-Arabia that are likely to be aligned with non-phiomorph members of that clade, and as such provide additional support for an Afro-Arabian origin of advanced stem and basal crown members of Hystricognathi

Short-term Outcomes for Patients and Providers After Elective Tracheostomy in COVID-19–Positive Patients

Background Urgent guidance is needed on the safety for providers of percutaneous tracheostomy in patients diagnosed with COVID-19. The objective of the study was to demonstrate that percutaneous dilational tracheostomy (PDT) with a period of apnea in patients requiring prolonged mechanical ventilation due to COVID-19 is safe and can be performed for the usual indications in the intensive care unit. Methods This study involves an observational case series at a single-center medical intensive care unit at a level-1 trauma center in patients diagnosed with COVID-19 who were assessed for tracheostomy. Success of a modified technique included direct visualization of tracheal access by bronchoscopy and a blind dilation and tracheostomy insertion during a period of patient apnea to reduce aerosolization. Secondary outcomes include transmission rate of COVID-19 to providers and patient complications. Results From April 6th, 2020 to July 21st, 2020, 2030 patients were admitted to the hospital with COVID-19, 615 required intensive care unit care (30.3%), and 254 patients required mechanical ventilation (12.5%). The mortality rate for patients requiring mechanical ventilation was 29%. Eighteen patients were assessed for PDT, and 11 (61%) underwent the procedure. The majority had failed extubation at least once (72.7%), and the median duration of intubation before tracheostomy was 15 d (interquartile range 13-24). The median positive end-expiratory pressure at time of tracheostomy was 10.8. The median partial pressure of oxygen (PaO2)/FiO2 ratio on the day of tracheostomy was 142.8 (interquartile range 104.5-224.4). Two patients had bleeding complications. At 1-week follow-up, eight patients still required ventilator support (73%). At the most recent follow-up, eight patients (73%) have been liberated from the ventilator, one patient (9%) died as a result of respiratory/multiorgan failure, and two were discharged on the ventilator (18%). Average follow-up was 20 d. None of the surgeons performing PDT have symptoms of or have tested positive for COVID-19. Conclusions and relevance: PDT for patients with COVID-19 is safe for health care workers and patients despite higher positive end-expiratory pressure requirements and should be performed for the same indications as other causes of respiratory failure

Associations between subspecialty fellowship interest and knowledge of internal medicine: A hypothesis-generating study of internal medicine residents

<p>Abstract</p> <p>Background</p> <p>Little is known about whether and how medical knowledge relates to interest in subspecialty fellowship training. The purpose of this study was to examine the relationships between residents' interest in subspecialty fellowship training and their knowledge of internal medicine (IM).</p> <p>Methods</p> <p>A questionnaire was emailed to 48 categorical postgraduate-year (PGY) two and three residents at a New York university-affiliated IM residency program in 2007 using the Survey Monkey online survey instrument. Overall and content area-specific percentile scores from the IM in-training examination (IM-ITE) for the same year was used to determine objective knowledge.</p> <p>Results</p> <p>Forty-five of 48 residents (response rate was 93.8%) completed the survey. Twenty-two (49%) were PG2 residents and 23(51%) were PGY3 residents. Sixty percent of respondents were male. Six (13%) residents were graduates of U.S. medical schools. Eight (18%) reported formal clinical training prior to starting internal medicine residency in the U.S. Of this latter group, 6 (75%) had training in IM and 6 (75) % reported a training length of 3 years or less. Thirty-seven of 45 (82%) residents had a subspecialty fellowship interest. Residents with a fellowship interest had a greater mean overall objective knowledge percentile score (56.44 vs. 31.67; p = 0.04) as well as greater mean percentile scores in all content areas of IM. The adjusted mean difference was statistically significant (p < 0.02) across three content areas.</p> <p>Conclusions</p> <p>More than half of surveyed residents indicated interest in pursuing a subspecialty fellowship. Fellowship interest appears positively associated with general medical knowledge in this study population. Further work is needed to explore motivation and study patterns among internal medicine residents.</p

Aneurysmal disease is associated with lower carotid intima-media thickness than occlusive arterial disease

Objective: Patients with aneurysmal and occlusive arterial disease have overlapping cardiovascular risk profiles. The question remains how atherosclerosis is related to the formation of aortic aneurysms. Common carotid artery intima-media thickness (CIMT) is an easily accessible and objective marker of early atherosclerosis. The aim of the current study was to investigate whether there is a difference in atherosclerotic burden as measured by CIMT between patients with aneurysmal and those with occlusive arterial disease. Methods: From 2004 to 2011, the CIMT was measured using B-mode ultrasound scanning in patients undergoing vascular surgery for aortic aneurysmal or occlusive arterial disease at the Erasmus University Medical Center. Cardiovascular risk factors, comorbidities, and medication were recorded. Patients treated for combined aneurysmal and occlusive arterial disease and patients diagnosed with a genetic aneurysm syndrome were excluded. Univariable and multivariable analyses wer

The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population

The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] ∼4%) and Gly2385Arg variants (PAR ∼6%) yields a total PAR of ∼10%

Broadening the phenotype of TARDBP mutations: the TARDBP Ala382Thr mutation and Parkinson’s disease in Sardinia

Mutations in the TARDBP gene are a cause of autosomal dominant amyotrophic lateral sclerosis (ALS) and of frontotemporal lobar degeneration (FTLD), but they have not been found so far in patients with Parkinson’s disease (PD). A founder TARDBP mutation (p.Ala382Thr) was recently identified as the cause of ~30% of ALS cases in Sardinia, a Mediterranean genetic isolate. We studied 327 consecutive Sardinian patients with clinically diagnosed PD (88 familial, 239 sporadic) and 578 Sardinian controls. One family with FTLD and parkinsonism was also included. The p.Ala382Thr heterozygous mutation was detected in eight unrelated PD patients (2.5%). The three patients from the FTLD/parkinsonism family also carried this mutation. Within the control group, there were three heterozygous mutation carriers. During follow-up, one of these individuals developed motoneuron disease and another, a rapidly progressive dementia; the third remains healthy at the age of 79 but two close relatives developed motoneuron disease and dementia. The eight PD patients carrying the p.Ala382Thr mutation had all sporadic disease presentation. Their average onset age was 70.0 years (SD 9.4, range 51–79), which is later but not significantly different from that of the patients who did not carry this mutation. In conclusion, we expand the clinical spectrum associated with TARDBP mutations to FTLD with parkinsonism without motoneuron disease and to clinically definite PD. The TDP-43 protein might be directly involved in a broader neurodegenerative spectrum, including not only motoneuron disease and FTLD but also PD

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