The Evolving Trends in Infective Endocarditis and Determinants of Mortality: a 10-year Experience From a Tertiary Care Epicenter.

The epidemiology of infective endocarditis (IE) continues to evolve in areas affected by the opioid epidemic. Understanding the demographics of the disease allows us to better tailor therapy towards this at-risk population. This was an observational study of adults (age ≥ 18) admitted to the University of Kentucky hospital with IE between January 2009 and December 2018. 1,255 patients were included in the final analysis. The mean age was 42 years, 45% were female and injection drug use was seen in 66% of patients. On multivariable analysis, higher Charlson comorbidity indices, left sided, and multivalve involvement were associated with increased mortality, whereas surgical intervention demonstrated a trend towards lower mortality. Our results highlight the alarming increase in injection drug use related IE and the high mortality rates despite therapeutic advances. Patients with left sided IE, multivalve involvement and a higher Charlson comorbidity index had decreased survival.

Implantable cardioverter-defibrillators with end stage renal disease: Nationwide inpatient sample database results.

BACKGROUND: When compared to patients with normal renal function, patients with chronic kidney disease develop higher in-hospital complications post implantable cardioverter-defibrillator (ICD) therapy. However, real world data on in-hospital complications post ICD therapy in patients with end stage renal disease (ESRD) is limited. In this study, we aim to explore the procedure-related complications of ICD therapy in patients with ESRD. METHODS: Using the nationwide inpatient sample (NIS) database, we conducted a retrospective analysis on ESRD patients who underwent inpatient ICD placement from 2010 to 2016. Using 1:2 propensity score matching, we compared ESRD patients to those with normal renal function. Outcomes of interest were postoperative hemorrhage and hematoma formation, blood transfusion, pericardial complications, mechanical complications requiring lead revision, vascular injury, in-hospital mortality, and length of stay. RESULTS: Our sample included 40,075 cases with subsequent propensity score matching between ESRD and normal renal function. Comparatively, patients with ESRD had higher odds of postoperative hemorrhage (Odds ratio [OR] = 1.67, 95% confidence interval [CI] 1.4-1.99, p = < .0001), blood transfusion (OR, 3.88; CI 3.29-4.56; p = < .0001), mechanical complications requiring lead revision (OR, 1.24; CI 1.01-1.51; p = .035), vascular injury (OR, 2.02; CI 1.27-3.24; p = .0027), in-hospital mortality (OR, 4.56; CI 3.08-6.76; p = < .0001), and longer hospitalization (11 vs. 7 days, p = < .0001), but without significant difference in pericardial complications (OR, 1.9; CI 0.92-1.54; p = < .18). CONCLUSION: In this large contemporary cohort, patients with ESRD undergoing inpatient ICD therapy are at higher risk of developing postprocedural complications including hemorrhage and hematoma, blood transfusion, mechanical complications requiring lead revision, and in hospital mortality, without increased risk of pericardial complications.

CHA2DS2-VASc and readmission with new-onset atrial fibrillation, atrial flutter, or acute cerebrovascular accident.

BACKGROUND: Although risk factors for atrial fibrillation (AF) and atrial flutter (AFL) are known, identifying patients who will develop AF/AFL within the near future remains challenging. We sought to evaluate if the CHA2DS2-VASc risk score (CVRS) can identify hospital readmissions with AF, AFL, or acute cerebrovascular accident (CVA) among hospitalized patients without prior history of AF/AFL. METHODS: Using the Nationwide Readmission Database, a study cohort included patients without prior AF/AFL or new diagnosis of AF/AFL at the index hospitalization from 2012 to 2014. Patients were stratified based on the CVRS into three groups: Low (CVRS ≤1), Intermediate (CVRS 2-5), and High (CVRS ≥6).The primary outcome of interest was 180-day readmission rate with a primary or secondary diagnosis of AF/AFL. Secondary outcomes of interest were acute CVA and 6-month mortality rate. RESULTS: A total of 17,820,640 patients were included in our study. Over a 6-month follow up duration from the index hospitalization, the overall re-admission rate for new onset atrial arrhythmias (AF/AFL) was 3.48% (n = 620,986), acute CVA 0.13% (n = 22,522), and all-cause mortality 0.31% (n = 55,632). When compared to other groups, patients with a higher CVRS were readmitted more frequently for AF/AFL [odds ratio (OR) 2.43; 95% confidence interval (CI) 2.41-2.45, P < .0001), acute CVA (OR 3.96; 95%CI 3.85-4.08, P < .0001), and all-cause mortality (OR 2.19; 95%CI 2.14-2.24, P < .0001). CONCLUSION: In this large contemporary cohort, a CHADS2VA2SC score ≥ 6 identified patients without known prior atrial arrhythmias at an elevated risk of developing AF/AFL or acute CVA within 6 months of hospitalization.

Cardiac Magnetic Resonance Stress Perfusion Imaging for Evaluation of Patients With Chest Pain.

BACKGROUND: Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies. OBJECTIVES: This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States. METHODS: In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates. RESULTS: In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (<1%) and coronary revascularization (1% to 3%), across all years of study follow-up. In contrast, patients with ischemia+/LGE+ experienced a >4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers. CONCLUSIONS: In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891).

Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice.

Cytosolic Malic Enzyme (ME1) provides reduced NADP for anabolism and maintenance of redox status. To examine the role of ME1 in tumor genesis of the gastrointestinal tract, we crossed mice having augmented intestinal epithelial expression of ME1 (ME1-Tg mice) with ApcMin/+ mice to obtain male ApcMin/+/ME1-Tg mice. ME1 protein levels were significantly greater within gut epithelium and adenomas of male ApcMin/+/ME1-Tg than ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice had larger and greater numbers of adenomas in the small intestine (jejunum and ileum) than male ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice exhibited greater small intestine crypt depth and villus length in non-adenoma regions, correspondent with increased KLF9 protein abundance in crypts and lamina propria. Small intestines of male ApcMin/+/ME1-Tg mice also had enhanced levels of Sp5 mRNA, suggesting Wnt/ß-catenin pathway activation. A small molecule inhibitor of ME1 suppressed growth of human CRC cells in vitro, but had little effect on normal rat intestinal epithelial cells. Targeting of ME1 may add to the armentarium of therapies for cancers of the gastrointestinal tract.

Impact of Chronic Thrombocytopenia on In-Hospital Outcomes After Percutaneous Coronary Intervention.

OBJECTIVES: This study sought to evaluate the impact of chronic thrombocytopenia (cTCP) on clinical outcomes after percutaneous coronary intervention (PCI). BACKGROUND: The impact of cTCP on clinical outcomes after PCI is not well described. Results from single-center observational studies and subgroup analysis of randomized trials have been conflicting and these patients are either excluded or under-represented in randomized controlled trials. METHODS: Using the 2012 to 2014 National (Nationwide) Inpatient Sample database, the study identified patients who underwent PCI with or without cTCP as a chronic condition variable indicator. Propensity score matching was performed using logistic regression to control for differences in baseline characteristics. The primary outcome of interest was in-hospital mortality. Secondary outcomes of interest included in-hospital post-PCI bleeding events, post-PCI blood and platelet transfusion, vascular complications, ischemic cerebrovascular accidents (CVAs), hemorrhagic CVAs, and length of stay. RESULTS: Propensity matching yielded a cohort of 65,130 patients (32,565 with and without cTCP). Compared with those without cTCP, PCI in patients with cTCP was associated with higher risk for bleeding complications (odds ratio [OR]: 2.40; 95% confidence interval [CI]: 2.05 to 2.72; p < 0.0001), requiring blood transfusion (OR: 2.10; 95% CI: 1.80 to 2.24; p < 0.0001), requiring platelet transfusion (OR: 11.70; 95% CI: 6.00 to 22.60; p < 0.0001), higher risk for vascular complications (OR: 1.94; 95% CI: 1.43 to 2.63; p < 0.0001), ischemic CVA (OR: 1.60; 95% CI: 1.20 to 2.10; p = 0.01), and higher in-hospital mortality (OR: 2.30; 95% CI: 1.90 to 2.70; p < 0.0001), but without a significant difference in hemorrhagic CVA (OR: 1.50; 95% CI: 0.70 to 3.10; p = 0.27). CONCLUSIONS: In this large contemporary cohort, patients with cTCP were at higher risk of a multitude of complications, including higher risk of in-hospital mortality.

Long Term Risk of Recurrent Atrial Fibrillation and Ischemic Stroke after Post-Operative Atrial Fibrillation Complicating Cardiac and Non-Cardiac Surgeries.

BACKGROUND: New onset post-operative atrial fibrillation (POAF) can complicate both non-cardiac(NCS) and cardiac(CS) surgeries. Long term differences in recurrence of atrial fibrillation (AF) and incidence of ischemic stroke/transient ischemic attack(CVA)between these types of POAFare lacking. OBJECTIVE: To compare thelong term recurrence rate of AF and incidence of CVAin patients withnew onset POAF after CS and NCS. METHODS: All patients who developed POAF between May 2010 and April 2014 were included in this single-center, retrospective study Exclusion criteria included a prior history of atrial tachyarrhythmias and pre-operative use of anti-arrhythmic drugs. Recurrence of atrial fibrillation and CVA was identified by review of medical records, electrocardiogram and Holter monitor. RESULTS: patients identified by the ICD9 code=523, 112 patients (61 cardiac; 51 non-cardiac) met inclusion criteria. Mean follow up was 943 days (range 32-2052 days).AF recurrence rate within 30 days after hospital discharge was higher in CS compared with NCS(10% vs 0%, p =0.03). Kaplan Meier analysis showed a trend towards higher recurrence in NCS compared with CS(HR 2.8; 95% CI 0.78-10.6, log rank p =0.03).In long term follow-up, CVA was numerically more common in patients with POAF after CS compared withNCS(10% vs 2%) though this difference was non-significant(HR 3.1; 95% CI 0.72-13.3; log rank p =0.26). CONCLUSION: The risk of recurrent AF and ischemic stroke is not different between POAF after CS or NCS. The overall high rate of AF recurrence and risk of ischemic stroke mandate careful long term follow-up.

Perioperative Heparin Bridging in Atrial Fibrillation Patients Requiring Temporary Interruption of Anticoagulation: Evidence from Meta-analysis.

BACKGROUND: Patients with atrial fibrillation (AF) often require temporary interruption of warfarin for an elective operation or invasive procedure. However, the safety and efficacy of periprocedural bridging anticoagulation with unfractionated heparin (UH) or low-molecular-weight heparin (LMWH) are still unclear. We evaluated the safety of periprocedural heparin bridging in AF patients requiring temporary interruption of oral anticoagulation. METHODS: We searched the literature for trials that compared heparin bridging with no bridging in AF patients for whom warfarin was temporarily interrupted. The incidence of all-cause mortality, thromboembolism, and major and all bleeding was included, and meta-analysis was performed. RESULTS: A total of 13,808 patients with AF were included in 4 observational studies, 1 randomized trial, and 1 subgroup analysis of a randomized trial. The mean CHADS2 score for the no heparin bridging group was 2.49 and that for the heparin bridging group was 2.34. At 30 days and up to 3 months, when compared to the heparin bridging group, the no bridging group did not have any significant difference in mortality (odds ratio [OR], 1.29; 95% confidence interval [CI], .15-11.52; P = .82) or cerebrovascular accidents (OR, .93; 95% CI, .34-2.51; P = .88), but the no bridging group had significantly less major bleeding (OR, .41; 95% CI, .24-.68; P = .0006). CONCLUSION: Among AF patients with intermediate CHADS2 scores who are anticoagulated with warfarin and who required temporary interruption of warfarin for an elective surgery or procedure, periprocedural bridging with UH or LMWH was associated with a higher rate of major bleeding with no significant difference in mortality or CVA.

The Krüppel-like factors in female reproductive system pathologies.

Female reproductive tract pathologies arise largely from dysregulation of estrogen and progesterone receptor signaling, leading to aberrant cell proliferation, survival, and differentiation. The signaling pathways orchestrated by these nuclear receptors are complex, require the participation of many nuclear proteins serving as key binding partners or targets, and involve a range of paracrine and autocrine regulatory circuits. The members of the Krüppel-like factor (KLF) family of transcription factors are ubiquitously expressed in reproductive tissues and have been increasingly implicated as critical co-regulators and integrators of steroid hormone actions. Herein, we explore the involvement of KLF family members in uterine pathology, describe their currently known molecular mechanisms, and discuss their potential as targets for therapeutic intervention.