Guthrie Robert Packer Hospital

Background: The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. Purpose: To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. Data Sources: PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. Study Selection: English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Data Synthesis: Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence). Limitations: Suboptimal quality and certainty of evidence. Conclusion: Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. Primary Funding Source: None.

PURPOSE: Veliparib, a poly (ADP ribose) polymerase inhibitor, potentiated standard chemotherapy against small-cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib with cisplatin and etoposide (CE; CE+V) doublet in untreated, extensive-stage SCLC (ES-SCLC). MATERIALS AND METHODS: on days 1 through 3) along with veliparib (100 mg orally twice per day on days 1 through 7) or placebo (CE+P). The primary end point was progression-free survival (PFS). Using an overall one-sided 0.10-level log-rank test, the study had 88% power to demonstrate a 37.5% reduction in the PFS hazard rate. RESULTS: A total of 128 eligible patients received treatment on protocol. The median age was 66 years, 52% of patients were men, and Eastern Cooperative Oncology Group performance status was 0 for 29% of patients and 1 for 71%. The respective median PFS for the CE+V arm versus the CE+P arm was 6.1 versus 5.5 months (unstratified hazard ratio [HR], 0.75 [one-sided P = .06]; stratified HR, 0.63 [one-sided P = .01]), favoring CE+V. The median overall survival was 10.3 versus 8.9 months (stratified HR, 0.83; 80% CI, 0.64 to 1.07; one-sided P = .17) for the CE+V and CE+P arms, respectively. The overall response rate was 71.9% versus 65.6% (two-sided P = .57) for CE+V and CE+P, respectively. There was a significant treatment-by-strata interaction in PFS: Male patients with high lactate dehydrogenase levels derived significant benefit (PFS HR, 0.34; 80% CI, 0.22 to 0.51) but there was no evidence of benefit among patients in other strata (PFS HR, 0.81; 80% CI, 0.60 to 1.09). The following grade ≥ 3 hematology toxicities were more frequent in the CE+V arm than the CE+P arm: CD4 lymphopenia (8% v 0%; P = .06) and neutropenia (49% v 32%; P = .08), but treatment delivery was comparable. CONCLUSION: The addition of veliparib to frontline chemotherapy showed signal of efficacy in patients with ES-SCLC and the study met its prespecified end point.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents. METHODS: Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model. RESULTS: In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding. CONCLUSIONS: The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.

Acute coronary syndrome (ACS) describes the range of myocardial ischemic states that includes unstable angina, non-ST elevated myocardial infarction (MI), or ST-elevated MI. ACS is associated with substantial morbidity and mortality and places a large financial burden on the health care system. The diagnosis of ACS begins with a thorough clinical assessment of a patient's presenting symptoms, electrocardiogram, and cardiac troponin levels as well as a review of past medical history. Early risk stratification can assist clinicians in determining whether an early invasive management strategy or an initial conservative strategy should be pursued and can help determine appropriate pharmacologic therapies. Key components in the management of ACS include coronary revascularization when indicated; prompt initiation of dual antiplatelet therapy and anticoagulation; and consideration of adjuvant agents including β blockers, inhibitors of the renin angiotensin system, and HmG-coenzyme A reductase inhibitors. It is essential for clinicians to take an individualized approach to treatment and consider long-term safety and efficacy when managing patients with a history of ACS after hospital discharge.

Background Influenza infection causes considerable morbidity and mortality in patients with cardiovascular disease. We assessed the effects of the influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Methods and Results We searched PubMed, Embase, and the Cochrane Library through January 2020 for randomized controlled trials and observational studies assessing the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Estimates were reported as random effects risk ratios (RRs) with 95% CIs. Analyses were stratified by study design into randomized controlled trials and observational studies. A total of 16 studies (n=237 058), including 4 randomized controlled trials (n=1667) and 12 observational studies (n=235 391), were identified. Participants' mean age was 69.2±7.01 years, 36.6% were women, 65.1% had hypertension, 31.1% had diabetes mellitus, and 23.4% were smokers. At a median follow‐up duration of 19.5 months, influenza vaccine was associated with a lower risk of all‐cause mortality (RR, 0.75; 95% CI, 0.60–0.93 [ P =0.01]), cardiovascular mortality (RR, 0.82; 95% CI, 0.80–0.84 [ P &lt;0.001]), and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.80–0.94 [ P &lt;0.001]) compared with control. The use of the influenza vaccine was not associated with a statistically significant reduction of myocardial infarction (RR, 0.73; 95% CI, 0.49–1.09 [ P =0.12]) compared with control. Conclusions Data from both randomized controlled trials and observational studies support the use of the influenza vaccine in adults with cardiovascular disease to reduce mortality and cardiovascular events, as currently supported by clinical guidelines. Clinicians and health systems should continue to promote the influenza vaccine as part of comprehensive secondary prevention.

BACKGROUND: Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain. METHODS: In this cross-sectional study (2014-2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles. RESULTS: Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43-2.36]), ischemic heart disease (1.52 [1.09-2.13]), stroke (2.03 [1.12-3.70]), hypertension (2.71 [1.54-4.75]), and heart failure (3.38 [1.32-8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07-2.54]) and heart failure (2.42 [1.29-4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes. CONCLUSIONS: In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.

Aims: To assess whether continuous positive airway pressure (CPAP) therapy reduces major adverse cardiovascular events (MACE) in patients with moderate-to-severe obstructive sleep apnoea (OSA). Methods and results: A total of 235 articles were recovered using MEDLINE, EMBASE and Cochrane library (inception-December 2016) and references contained in the identified articles. Seven randomized controlled trials (RCTs) were selected for final analysis. Analysis of 4268 patients demonstrated non-significant 26% relative risk reduction in MACE with CPAP [risk ratio (RR) 0.74; 95% confidence interval (CI) 0.47-1.17; P = 0.19, I2 = 48%]. A series of sensitivity analyses suggested that increased CPAP usage time yielded significant risk reduction in MACE. and stroke. Subgroup analysis revealed that CPAP adherence time ≥4 hours (h)/night reduced the risk of MACE by 57% (RR 0.43; 95% CI 0.23-0.80; P = 0.01, I2 = 0%). CPAP therapy showed no beneficial effect on myocardial infarction (MI), all-cause mortality, atrial fibrillation/flutter (AF), or heart failure (HF) (P > 0.05). CPAP had positive effect on mood and reduced the daytime sleepiness [Epworth Sleepiness Scale (ESS): mean difference (MD) -2.50, 95% CI - 3.62, -1.39; P < 0.001, I2 = 81%]. Conclusion: CPAP therapy might reduce MACE and stroke among subjects with CPAP time exceeding 4 h/night. Additional randomized trials mandating adequate CPAP time adherence are required to confirm this impression.

The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the world's population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndrome's individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors.

OBJECTIVE: To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN: Network meta-analysis. DATA SOURCES: Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES: We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS: We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS: Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.

BACKGROUND: Catheter ablation is widely accepted intervention for atrial fibrillation (AF) refractory to antiarrhythmic drugs, but limited data are available regarding contemporary trends in major complications and in-hospital mortality due to the procedure. This study was aimed at exploring the temporal trends of in-hospital mortality, major complications, and impact of hospital volume on frequency of AF ablation-related outcomes. METHODS: The Nationwide Inpatient Sample database was utilized to identify the AF patients treated with catheter ablation. In-hospital death and common complications including vascular access complications, cardiac perforation and/or tamponade, pneumothorax, stroke, and transient ischemic attack, were identified using International Classification of Disease (ICD-9-CM) codes. RESULT: In-hospital mortality rate of 0.15% and overall complication rate of 5.46% were noted among AF ablation recipients (n = 50,969). Significant increase in complications during study period (relative increase 56.37%, P-trend < 0.001) was observed. Cardiac (2.65%), vascular (1.33%), and neurological (1.05%) complications were most common. On multivariate analysis (odds ratio [OR]; 95% confidence interval [95% CI]; P value), significant predictors of complications were female sex (OR = 1.40; CI = 1.17-1.68; P value < 0.001), high burden of comorbidity as indicated by Charlson Comorbidity Index ≥2 (OR = 2.84; CI = 2.29-3.52; P value < 0.001), and low hospital volume (< 50 procedures). CONCLUSION: Our study noted a decline in AF ablation-related hospitalizations and complications associated with the procedure. These findings largely reflect shifting trends of outpatient performance of the procedure and increasing safety profile due to improved institutional expertise and catheter techniques.

BACKGROUND: The Heineke-Mikulicz and Finney techniques are conventional strictureplasties that have been used to manage short (<10 cm) and medium-length (>10 cm and <20 cm) strictures from Crohn's disease. Nonconventional strictureplasty techniques have emerged to facilitate bowel conservation for atypical strictures. These techniques include the modified Finney, combined Heineke-Mikulicz and Finney, modified Heineke-Mikuliczs, Michelassi, and modifications of it and others. OBJECTIVE: The aim of this study is to compare conventional vs nonconventional strictureplasties with respect to short-term complications and long-term results. DATA SOURCES AND STUDY SELECTION: A MEDLINE search was performed using "Crohn's disease", "surgical therapy", "strictureplasty", "complications", "reoperation", and "recurrence" as medical subject headings. Studies conducted between 1975 and June 31, 2010 were found via PubMed, Ovid, Embase, and Cochrane databases and categorized into 3 groups. These groups consist of centers performing conventional strictureplasties, nonconventional strictureplasties, or both. Studies with at least 3 patients were reviewed. INTERVENTIONS: A mixed-effects meta-analysis for each outcome was performed by use of Supermix software by SSI Scientific Software International. MAIN OUTCOME MEASURES: We focused on immediate and long-term complication rates among the groups. The 6 immediate complications include small-bowel obstructions, sepsis, other infections, reoperations, early postoperative GI bleeds, and other early complications. The 5 long-term complications include recurrent strictures, small-bowel obstructions, reoperations, carcinoma, and deaths. RESULTS: We reviewed 32 studies with 1616 patients who underwent 4538 strictureplasties. One thousand one hundred fifty-seven patients underwent conventional strictureplasties with an early complication rate of 15%; 459 patients underwent nonconventional strictureplasties with an early complication rate of 8%. A late complication rate of 29% for the conventional strictureplasty group and 17% for the nonconventional strictureplasty group was noted. LIMITATIONS: We are limited by the data published with the inherent risk of finding and analyzing mostly articles with positive results. CONCLUSION: The nonconventional strictureplasty techniques were noninferior to the conventional strictureplasty procedures with respect to all prespecified outcomes.

Importance: Clinical researchers are obligated to present results objectively and accurately to ensure readers are not misled. In studies in which primary end points are not statistically significant, placing a spin, defined as the manipulation of language to potentially mislead readers from the likely truth of the results, can distract the reader and lead to misinterpretation and misapplication of the findings. Objective: To determine the level and prevalence of spin in published reports of cardiovascular randomized clinical trial (RCT) reports. Data Source: MEDLINE was searched from January 1, 2015, to December 31, 2017, using the Cochrane highly sensitive search strategy. Study Selection: Inclusion criteria were parallel-group RCTs published from January 1, 2015, to December 31, 2017 in 1 of 6 high-impact journals (New England Journal of Medicine, The Lancet, JAMA, European Heart Journal, Circulation, and Journal of the American College of Cardiology) with primary outcomes that were not statistically significant were included in the analysis. Data Extraction and Synthesis: Analysis began in August 2018. Data were extracted and verified by 2 independent investigators using a standard collection form. In cases of disagreement between the 2 investigators, a third investigators served as arbitrator. Main Outcomes and Measures: The classifications of spin type, severity, and extent were determined according to predefined criteria. Primary clinical outcomes were divided into safety of treatment, efficacy of treatment, and both. Results: Of 587 studies identified, 93 RCT reports (15.8%) met inclusion criteria. Spin was identified in 53 abstracts (57%; 95% CI, 47%-67%) and 62 main texts of published articles (67%; 95% CI, 57%-75%). Ten reports (11%; 95% CI, 6%-19%) had spin in the title, 35 reports (38%; 95% CI, 28%-48%) had spin in the results section, and 50 reports (54%; 95% CI, 44%-64%) had spin in the conclusions. Among the abstracts, spin was observed in 38 results sections (41%; 95% CI, 31%-51%) and 45 conclusions sections (48%; 95% CI, 38%-58%). Conclusions and Relevance: This study suggests that in reports of cardiovascular RCTs with statistically nonsignificant primary outcomes, investigators often manipulate the language of the report to detract from the neutral primary outcomes. To best apply evidence to patient care, consumers of cardiovascular research should be aware that peer review does not always preclude the use of misleading language in scientific articles.

Emphysematous gastritis is a condition characterized by gas within the wall of the stomach and associated systemic toxicity. We report a case of emphysematous gastritis in a 43-year-old diabetic patient receiving hemodialysis and review 41 cases published since 1889. The most common predisposing factors included ingestion of corrosive substances, alcohol abuse, abdominal surgery, diabetes, and immunosuppression. Diagnosis is based on clinical presentation of acute abdomen with associated features of systemic toxicity. The most commonly involved organisms were streptococci (nine cases), Escherichia coli (nine cases), Enterobacter species (six cases), Clostridium welchii (four cases), and Staphylococcus aureus (four cases). Computed tomography (CT) is the diagnostic procedure of choice. The mortality rate was 61% (25 of 41 patients). Gastric contractures after recovery were noted in 10% (4 of 41 patients). Antimicrobial therapy with antibiotics covering gram-negative organisms and anaerobes, and surgery in appropriate cases may enhance survival.

Background Evaluating premature (<65 years of age) mortality because of acute myocardial infarction (AMI) by demographic and regional characteristics may inform public health interventions. Methods and Results We used the Centers for Disease Control and Prevention's WONDER (Wide-Ranging Online Data for Epidemiologic Research) death certificate database to examine premature (<65 years of age) age-adjusted AMI mortality rates per 100 000 and average annual percentage change from 1999 to 2019. Overall, the age-adjusted AMI mortality rate was 13.4 (95% CI, 13.3-13.5). Middle-aged adults, men, non-Hispanic Black adults, and rural counties had higher mortality than young adults, women, NH White adults, and urban counties, respectively. Between 1999 and 2019, the age-adjusted AMI mortality rate decreased at an average annual percentage change of -3.4 per year (95% CI, -3.6 to -3.3), with the average annual percentage change showing higher decline in age-adjusted AMI mortality rates among large (-4.2 per year [95% CI, -4.4 to -4.0]), and medium/small metros (-3.3 per year [95% CI, -3.5 to -3.1]) than rural counties (-2.4 per year [95% CI, -2.8 to -1.9]). Age-adjusted AMI mortality rates >90th percentile were distributed in the Southern states, and those with mortality <10th percentile were clustered in the Western and Northeastern states. After an initial decline between 1999 and 2011 (-4.3 per year [95% CI, -4.6 to -4.1]), the average annual percentage change showed deceleration in mortality since 2011 (-2.1 per year [95% CI, -2.4 to -1.8]). These trends were consistent across both sexes, all ethnicities and races, and urban/rural counties. Conclusions During the past 20 years, decline in premature AMI mortality has slowed down in the United States since 2011, with considerable heterogeneity across demographic groups, states, and urbanicity. Systemic efforts are mandated to address cardiovascular health disparities and outcomes among nonelderly adults.

Background There are limited data on the role of temporary mechanical circulatory support ( MCS ) devices for cardiogenic shock before left ventricular assist device ( LVAD ) surgery. This study sought to evaluate the trends of use and outcomes of MCS in cardiogenic shock before LVAD surgery. Methods and Results This was a retrospective cohort study from 2005 to 2014 using the National Inpatient Sample (20% stratified sample of US hospitals). This study identified admissions undergoing LVAD surgery with preoperative cardiogenic shock. Admissions for other cardiac surgery and heart transplant were excluded. Temporary MCS was identified using administrative codes. The primary outcome was hospital mortality and secondary outcomes were hospital costs and lengths of stay in admissions with and without MCS use. In this 10-year period, 9753 admissions were identified with 40.6% requiring pre- LVAD MCS . There was a temporal increase in the frequency of cardiogenic shock associated with an increase in non-intra-aortic balloon pump MCS devices. The cohort receiving MCS had greater in-hospital myocardial infarction, ventricular arrhythmias, and use of coronary angiography. On multivariable analysis, older age, myocardial infarction, and need for MCS devices were independently predictive of higher in-hospital mortality. In 696 propensity-matched pairs, use of MCS was predictive of higher in-hospital mortality (odds ratio 1.4 [95% confidence interval 1.1-1.6]; P=0.02) and higher hospital costs, but similar lengths of stay. Conclusions In patients with cardiogenic shock bridged to LVAD therapy, there was a steady increase in preoperative MCS use. Use of MCS identified patients at higher risk for in-hospital mortality and greater resource utilization.

Pagination are not provided by the author/publisher. This work was published before the author joined Aga Khan University.

Amyloidosis, a heterogenous group of disorders, is characterized by the extracellular deposition of autologous, insoluble, fibrillar misfolded proteins. These extracellular proteins deposit in tissues aggregated in ß-pleated sheets arranged in an antiparallel fashion and cause distortion to the tissue architecture and function. In the current literature, about 60 heterogeneous amyloidogenic proteins have been identified, out of which 27 have been associated with human disease. Classified as a rare disease, amyloidosis is known to have a wide range of possible etiologies and clinical manifestations. The exact incidence and prevalence of the disease is currently unknown. In both systemic and localized amyloidosis, there is infiltration of the abnormal proteins in the layers of the gastrointestinal (GI) tract or the liver parenchyma. The gold standard test for establishing a diagnosis is tissue biopsy followed by Congo Red staining and apple-green birefringence of the Congo Red-stained deposits under polarized light. However, not all patients may have a positive tissue confirmation of the disease. In these cases additional workup and referral to a gastroenterologist may be warranted. Along with symptomatic management, the treatment for GI amyloidosis consists of observation or localized surgical excision in patients with localized disease, and treatment of the underlying pathology in cases of systemic amyloidosis. In this review of the literature, we describe the subtypes of amyloidosis, with a primary focus on the epidemiology, pathogenesis, clinical features, diagnosis and treatment strategies available for GI amyloidosis.

Background The relationship between lowering LDL (low‐density lipoprotein) cholesterol with contemporary lipid‐lowering therapies and incident diabetes mellitus ( DM ) remains uncertain. Methods and Results Thirty‐three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline , Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid‐lowering therapy. More intensive lipid‐lowering therapy was defined as the more potent pharmacological strategy ( PCSK 9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta‐analyses were conducted using a random‐effects model. No significant association was noted between 1‐mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid‐lowering therapy (risk ratio: 0.95; 95% CI , 0.87–1.04; P =0.30; R 2 =14%) or for statins or PCSK 9 inhibitors. More intensive lipid‐lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI , 1.03–1.11; P &lt;0.001; I 2 =0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI , 1.05–1.15; P &lt;0.001; I 2 =0%), whereas PCSK 9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI , 0.93–1.07; P =0.96; I 2 =0%; P =0.02 for interaction). Conclusions Among intensive lipid‐lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM . The risk of incident DM was higher with statins, whereas PCSK 9 inhibitors had no association with risk of incident DM .

BACKGROUND AND OBJECTIVES: Ventral hernia repairs continue to have high recurrence rates. The surgical literature is lacking data assessing the time trend to hernia recurrence after ventral hernia repairs and whether over time the recurrence rates change with laparoscopic technique compared to open repairs. Our aim was to carry out a long-term comparative analysis of ventral hernia repairs performed at our hospital over the last 10-y period to assess if outcomes change during the follow-up period. METHODS: We conducted a retrospective observational study analyzing electronic medical records of all consecutive patients who had a ventral hernia repair from January 2001 to February 2010 at our hospital. RESULTS: During the study period, 436 ventral hernia repairs were performed: laparoscopic repairs (n=156; 36%), laparoscopic converted to open (n=8; 2%), and open repairs (n=272; 62%). We analyzed the time distribution to hernia recurrence after surgery and found that 85% of recurrences after laparoscopic repairs and 77% of recurrences after open repairs occurred within 2 y of surgery. We did a Kaplan-Meier analysis for the subgroup of patients for whom we had a minimum 4-y follow-up and found that there continued to be a low subsequent yearly recurrence rate for open repairs after the initial 2-y follow-up. CONCLUSION: Most hernia recurrences occur within 2 y after surgery for ventral hernias. There appears to be a continued although low subsequent yearly rate of recurrence for open repairs.

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception - September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55-0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62-0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49-0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83-0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77-0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.