Chiral 3-Acylglutaric Acid Derivatives from Strain-Induced Nucleophilic Retro-Claisen Ring-Opening Reactions.

A nucleophilic retro-Claisen ring-opening of donor-acceptor cyclobutenes, formed with high stereocontrol by [3 + 1]-cycloaddition of TIPS-protected enoldiazoacetates with α-acyl sulfur ylides, has been developed. Removal of the TIPS group to form the isolable ß-keto ester precedes the strain-induced ring-opening. Various amines, alcohols, thiols, and amino acid derivatives are effective nucleophiles, and their products are formed in very high yields via stoichiometric reactions. The chirality of the reactant donor-acceptor cyclobutenes is fully retained in the ring-opening reactions. The 3-acylglutaric acid products are converted to various valuable structures, including amido-diols, γ-aminobutyric acid (GABA) derivatives, and heterocycles.

Consumer-grade wearable cardiac monitors: What they do well, and what needs work.

Consumer-grade smart devices, including smartwatches and smartphones, are potentially valuable tools in detecting cardiac arrhythmias, particularly atrial fibrillation, and their use is increasing. These devices, which use photoplethys mography, show remarkably high sensitivity and specificity for detection of atrial fibrillation, with implications for stroke prevention and management in at-risk patients. The ability of the devices to detect atrial fibrillation is being compared with single-lead electrocardiography. Physicians will increasingly be asked to interpret data from these nonmedical-grade devices as they become more common. Limitations include high false-positive rates in certain populations and disparities in access.

Trends in prevalence of guideline-based use of lipid-lowering therapy in a large health system.

BACKGROUND: The 2013 ACC/AHA (American College of Cardiology/American Heart Association) cholesterol guidelines provided an evidence-based rationale for the allocation of lipid-lowering therapy based on risk for atherosclerotic cardiovascular disease (ASCVD). Adoption of these guidelines was initially suboptimal but whether this has improved over time remains unclear. HYPOTHESIS: Prevalence of guideline-based statin therapy will increase over time. METHODS: Electronic health record data were used to create two cross-sectional data sets of patients (age 40-75) served in 2013 and 2017 by a large health system. Data sets included demographics, clinical risk factors, lipid values, diagnostic codes, and active medication orders during each period. Prevalence of indications for statin therapy according to the ACC/AHA guidelines and statin prescriptions were compared between each time period. RESULTS: In 2013, of the 219 376 adults, 57.7% of patients met statin eligibility criteria, of which 61.3% were prescribed any statin and 19.0% a high intensity statin. Among those eligible, statin use was highest in those with established ASCVD (83.9%) and lowest in those with elevated ASCVD risk >7.5% (39.3%). In 2017, of the 256 074 adults, 62.3% were statin eligible, of which 62.3% were prescribed a statin and 24.3% a high intensity statin. In 2017, 66.4% of statin eligible men were prescribed a statin compared to 57.4% of statin eligible women (P < 0.001). The use of ezetimibe (3.6% in 2013, 2.4% in 2017) and protein convertase subtilisin/kexin type 9 inhibitors (<0.1% and 0.1%) was infrequent. CONCLUSION: In a large health system, guideline-based statin use has remained suboptimal. Improved strategies are needed to increase statin utilization in appropriate patients.

Characterization of Acidosis in Trauma Patient.

BACKGROUND: Recent data suggest that acidosis alone is not a good predictor of mortality in trauma patients. Little data are currently available regarding factors associated with survival in trauma patients presenting with acidosis. AIMS: The aims were to characterize the outcomes of trauma patients presenting with acidosis and to identify modifiable risk factors associated with mortality in these patients. SETTINGS AND DESIGN: This is a retrospective observational study of University of Arkansas for Medical Sciences (UAMS) trauma patients between November 23, 2013, and May 21, 2017. METHODS: Data were collected from the UAMS trauma registry. The primary outcome was hospital mortality. Analyses were performed using t-test and Pearson's Chi-squared test. Simple and multiple logistic regressions were performed to determine crude and adjusted odds ratios. RESULTS: There were 532 patients identified and 64.7% were acidotic (pH < 7.35) on presentation: 75.9% pH 7.2-7.35; 18.5% pH 7.0-7.2; and 5.6% pH ≤ 7.0. The total hospital mortality was 23.7%. Nonsurvivors were older and more acidotic, with a base deficit >-8, Glasgow Coma Scale (GCS) ≤ 8, systolic blood pressure ≤ 90, International Normalized Ratio (INR) >1.6, and Injury Severity Score (ISS) >15. Mortality was significantly higher with a pH ≤ 7.2 but mortality with a pH 7.2-7.35 was comparable to pH > 7.35. In the adjusted model, pH ≤ 7.0, pH 7.0-7.2, INR > 1.6, GCS ≤ 8, and ISS > 15 were associated with increased mortality. For patients with a pH ≤ 7.2, only INR was associated with increase in mortality. CONCLUSIONS: A pH ≤ 7.2 is associated with increased mortality. For patients in this range, only the presence of coagulopathy is associated with increased mortality. A pH > 7.2 may be an appropriate treatment goal for acidosis. Further work is needed to identify and target potentially modifiable factors in patients with acidosis such as coagulopathy.

Association of Body Mass Index With Coronary Artery Calcium and Subsequent Cardiovascular Mortality: The Coronary Artery Calcium Consortium.

BACKGROUND: Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical. METHODS: We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC. RESULTS: Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1-30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1-1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4-1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63-0.98]). CONCLUSIONS: In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.

Enoldiazosulfones for Highly Enantioselective [3 + 3]-Cycloaddition with Nitrones Catalyzed by Copper(I) with Chiral BOX Ligands.

Enoldiazosulfones undergo [3 + 3]-cycloaddition with nitrones when catalyzed by copper(I) catalysts, but not with dirhodium(II) catalysts. Under mild reaction conditions with chiral bisoxazoline ligands, copper(I) catalysts produce 1,2-oxazine-sulfone derivatives in high yields and enantioselectivities. Dirhodium(II) catalysts form stable donor-acceptor cyclopropenes that undergo uncatalyzed [3 + 2]-cycloaddition reactions with nitrones.

Radial Versus Femoral Access in Chronic Total Occlusion Percutaneous Coronary Intervention.

Background Radial access (RA) is increasingly used in chronic total occlusion (CTO) percutaneous coronary intervention with encouraging results. However, there are concerns about its safety and efficacy because of higher complexity and the need for strong guide catheter support. Methods and Results We performed a systematic review and meta-analysis of all studies published through November 2018 reporting the outcomes of RA versus femoral access in CTO percutaneous coronary intervention. Outcomes included major bleeding, access-site complications, in-hospital major adverse events, and technical success. Nine observational studies with 10 590 patients (10 617 lesions) were included in the meta-analysis. CTO lesions attempted using RA had lower Japan-CTO score (2.3±1.2 versus 2.5±1.3; P<0.001). Use of RA was associated with similar technical success (78.7% versus 78.5%; odds ratio, 1.11; 95% CI, 0.94-1.31; P=0.24; I2=23%), lower risk of access-site complications (0.73% versus 1.79%; odds ratio, 0.34; 95% CI, 0.22-0.51; P<0.001; I2=0%) and major bleeding (0.18% versus 0.9%; odds ratio, 0.22; 95% CI, 0.10-0.45; P<0.001; I2=0%), and similar risk of in-hospital adverse events and in-hospital mortality (odds ratio, 0.36; 95% CI, 0.12-1.07; P=0.07; I2=0%) as compared to femoral access. Results were similar when analyzing radial-only versus any femoral access and when excluding the largest study. Conclusions As compared with femoral access, RA is used in CTO percutaneous coronary intervention of less complex lesions and is associated with fewer access-site complications and major bleeding and comparable technical success.

Severe acute gallstone pancreatitis with diffuse hemorrhagic gastritis.

A 67-year-old male presented with acute pancreatitis secondary to gallstones, also known as acute biliary pancreatitis, and subsequently developed gastric outlet obstruction and was transferred to our hospital. A gastro-jejunal feeding tube was placed and an open cholecystectomy was performed. The patient had a pancreatic drain placed for interval increase in pancreatic necrosis and then nearly exsanguinated from gastroduodenal artery pseudoaneurysm bleed. This was managed by coiling the gastroduodenal artery. The patient underwent a pancreatic necrosectomy with malencot drain placement and developed a post-operative upper gastrointestinal bleeding. An EGD showed diffuse gastritis, but no varices. And 18 days later the patient rebled, with the same diffuse gastritis. After further complications the patient elected to receive palliative care at a hospice facility. We are presenting this unusual case of diffuse, hemorrhagic gastritis after acute necrotizing pancreatitis.

Dilated cardiomyopathy secondary to acute pancreatitis caused by hypertriglyceridemia.

A 30-year-old male presented to an outside facility with acute pancreatitis and triglycerides of 1594. He was transferred to our facility after becoming febrile, hypoxic and in acute renal failure with triglycerides of 4243. CT scan performed showed wall-off pancreatic necrosis. He underwent continuous renal replacement therapy and his acute renal failure resolved. He was treated with broad spectrum antibiotics and discharged. He developed a fever to 101 a week later and was found to have a large infected pancreatic pseudocyst. This was managed with an IR placed drain. This was continued for 6 weeks. He came to the emergency department several weeks later with shortness of breath and 3+ edema to bilateral lower extremities and lower abdomen. TTE performed showed an EF of 15%. He was diuresed 25 L during that stay. His heart failure was medically managed. We present this case of dilated cardiomyopathy secondary to acute pancreatitis.