The Role of Sleep in Cardiovascular Disease.

PURPOSE OF REVIEW: Sleep is an important component of cardiovascular (CV) health. This review summarizes the complex relationship between sleep and CV disease (CVD). Additionally, we describe the data supporting the treatment of sleep disturbances in preventing and treating CVD. RECENT FINDINGS: Recent guidelines recommend screening for obstructive sleep apnea in patients with atrial fibrillation. New data continues to demonstrate the importance of sleep quality and duration for CV health. There is a complex bidirectional relationship between sleep health and CVD. Sleep disturbances have systemic effects that contribute to the development of CVD, including hypertension, coronary artery disease, heart failure, and arrhythmias. Additionally, CVD contributes to the development of sleep disturbances. However, more data are needed to support the role of screening for and treatment of sleep disorders for the prevention of CVD.

Long-term outcomes after transcatheter aortic valve replacement with minimal contrast in chronic kidney disease.

BACKGROUND: Patients with renal insufficiency have poor short-term outcomes after transcatheter aortic valve replacement (TAVR). METHODS: Retrospective chart review identified 575 consecutive patients not on hemodialysis who underwent TAVR between September 2014 and January 2017. Outcomes were defined by VARC-2 criteria. Primary outcome of all-cause mortality was evaluated at a median follow-up of 811 days (interquartile range 125-1,151). RESULTS: Preprocedural glomerular filtration rate (GFR) was ≥60 ml/min in 51.7%, 30-60 ml/min in 42.1%, and < 30 ml/min in 6.3%. Use of transfemoral access (98.8%) and achieved device success (91.0%) did not differ among groups, but less contrast was used with lower GFR (23 ml [15-33], 24 ml [14-33], 13 ml [8-20]; p < .001). Peri-procedural stroke (0.7%, 2.1%, 11.1%; p < .001) was higher with lower GFR. Core lab analysis of preprocedural computed tomography scans of patients who developed a peri-procedural stroke identified potential anatomic substrate for stroke in three out of four patients with GFR 30-60 ml/min and all three with GFR <30 ml/min (severe atheroma was the most common subtype of anatomical substrate present). Compared to GFR ≥60 ml/min, all-cause mortality was higher with GFR 30-60 ml/min (HR 1.61 [1.00-2.59]; aHR 1.61 [0.91-2.83]) and GFR <30 ml/min (HR 2.41 [1.06-5.48]; aHR 2.34 [0.90-6.09]) but not significant after multivariable adjustment. Follow-up echocardiographic data, available in 63%, demonstrated no difference in structural heart valve deterioration over time among groups. CONCLUSIONS: Patients with baseline renal insufficiency remain a challenging population with poor long-term outcomes despite procedural optimization with a transfemoral-first and an extremely low-contrast approach.

Boundaries of eliminated heterochromatin of Tetrahymena are positioned by the DNA-binding protein Ltl1.

During differentiation of the Tetrahymena thermophila somatic nucleus, its germline-derived DNA undergoes extensive reorganization including the removal of ∼50 Mb from thousands of loci called internal eliminated sequences (IESs). IES-associated chromatin is methylated on lysines 9 and 27 of histone H3, marking newly formed heterochromatin for elimination. To ensure that this reorganized genome maintains essential coding and regulatory sequences, the boundaries of IESs must be accurately defined. In this study, we show that the developmentally expressed protein encoded by Lia3-Like 1 (LTL1) (Ttherm_00499370) is necessary to direct the excision boundaries of particular IESs. In ΔLTL1 cells, boundaries of eliminated loci are aberrant and heterogeneous. The IESs regulated by Ltl1 are distinct from those regulated by the guanine-quadruplex binding Lia3 protein. Ltl1 has a general affinity for double stranded DNA (Kd ∼ 350 nM) and binds specifically to a 50 bp A+T rich sequence flanking each side of the D IES (Kd ∼ 43 nM). Together these data reveal that Ltl1 and Lia3 control different subsets of IESs and that their mechanisms for flanking sequence recognition are distinct.

The presence of thrombus in spontaneous coronary artery dissection: A systematic review of autopsy findings.

Background: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome in young women. There is no consensus on optimal treatment, though a conservative approach including antiplatelet agents is commonly used. We hypothesized that most cases of SCAD would not demonstrate true lumen thrombus in the dissected artery, suggesting that anti-platelet agents might not have a role in the treatment of SCAD. Methods: We conducted a systematic review of the published literature through March 2022 to identify pathology images from individuals who died of SCAD. The images were independently reviewed by a pathologist to assess for the presence of thrombus and inflammatory cells. Results: We identified 40 cases from 34 publications with available pathology images and found only one case of true lumen thrombus. Additionally, we found that 53% of cases involved eosinophilic inflammation. Conclusion: The role of antiplatelet agents in the treatment of SCAD should be re-evaluated. Further studies are needed to better understand the significance and treatment implications of eosinophilic inflammation.

The impact of anthropometric parameters on colorectal cancer prognosis: A systematic review and meta-analysis.

BACKGROUND & AIMS: Our study aims to clarify the relationship between weight parameters and colorectal cancer outcomes. METHODS: NCBI, Embase, Cochrane, and Web of Science were searched from inception to December 2019. Studies reporting colorectal cancer (CRC) mortality, recurrence, disease-free survival, overall survival, overall mortality stratified by pre-diagnosis BMI or post-diagnosis weight change, were included in the analysis. Random effects analysis was performed for all outcomes, with heterogeneity assessed by the I2 statistic. RESULTS: Our meta-analysis included 45 studies encompassing 607,266 patients. Obesity was associated with increased odds of overall mortality and CRC-specific mortality compared to normal weight (p < 0.001). Patients with underweight BMI had increased odds of CRC-specific mortality compared to normal BMI but were not significantly different from obese BMI. CONCLUSIONS: Obese and underweight BMI are associated with increased CRC-specific and overall mortality compared to normal BMI. Long term prognosis was similar for patients with obese and underweight BMI.

Lessons in clinical reasoning ‒ pitfalls, myths and pearls: a case of recurrent pancreatitis.

OBJECTIVES: Cognitive biases can result in clinical reasoning failures that can lead to diagnostic errors. Autobrewery syndrome is a rare, but likely underdiagnosed, condition in which gut flora ferment glucose, producing ethanol. It most frequently presents with unexplained episodes of inebriation, though more case studies are necessary to better characterize the syndrome. CASE PRESENTATION: This is a case of a 41-year old male with a past medical history notable only for frequent sinus infections, who presented with recurrent episodes of acute pancreatitis. In the week prior to his first episode of pancreatitis, he consumed four beers, an increase from his baseline of 1-2 drinks per month. At home, he had several episodes of confusion, which he attributed to fatigue. He underwent laparoscopic cholecystectomy and testing for genetic and autoimmune causes of pancreatitis, which were non-revealing. He was hospitalized 10 more times during that 9-month period for acute pancreatitis with elevated transaminases. During these admissions, he had elevated triglycerides requiring an insulin drip and elevated alcohol level despite abstaining from alcohol for the prior eight months. His alcohol level increased after consumption of complex carbohydrates, confirming the diagnosis of autobrewery syndrome. CONCLUSIONS: Through integrated commentary on the diagnostic reasoning process, this case underscores how overconfidence can lead to premature closure and anchoring resulting in diagnostic error. Using a metacognitive overview, case discussants describe the importance of structured reflection and a standardized approach to early hypothesis generation to navigate these cognitive biases.

Vascular Complications Associated with Transfemoral Aortic Valve Replacement.

Background Transfemoral aortic valve replacement (TAVR) is a novel technique for treating aortic stenosis, yet vascular complications are yet to be delineated. Objectives This study aims to study the vascular complications of TAVR with Edwards Sapien valves (Edwards Lifesciences Corp., Irvine, CA). Methods We performed a retrospective evaluation of TAVR patients. Standard demographics, femoral vessel and sheath size, access type (femoral cut-down [FC], percutaneous access [PFA], and iliac conduit [IC]), and treatment method were recorded. Complications were defined by the Valve Academic Research Consortium Criteria. Logistic regression was used for statistical analysis. Results A total of 99 patients underwent TAVR between February 15, 2012 and July 17, 2013 with an Edwards Sapien valve. Out of which, 48 were males with a mean age of 83 ± 7 years. Overall, 33 had FC, 58 had PFA, and 6 had an IC. A total of 17 major (2 aortic and 15 iliac) and 38 minor complications (36 access and 2 emboli) occurred. Aortic complications were managed by open repair (OR, 1) or percutaneous repair (PR, 1). Overall, 12 iliac injuries were managed by PR and 3 by OR. Out of the 33 groin complications in FC patients 8 (24%) were treated by OR, whereas 30 (52%) of the 58 groin complications in PTA patients were treated by PR. There were no differences in transfusion requirements or length of stay. Conclusion Vascular complications of TAVR are common with most being minor, related to access site and causing no immediate sequelae. Iliac injury can be managed by PR or OR. Aortic injury is associated with significant mortality. These findings increase vascular surgeons' awareness of these complications and how to manage them.

The Current Status of Tissue-Engineered Vascular Grafts.

Tissue-engineered vascular grafts (TEVGs) are currently being developed to overcome the limitations and complications associated with traditional synthetic grafts. This article aims to review the current status of research into the production and use of tissue-engineered grafts. TEVGs have a number of theoretical advantages over synthetic grafts. The results of animal and human studies have been promising, but more work must be done before TEVGs can replace traditional grafts.