Search

Background: Contemporary outcomes for aortic stenosis (AS) and the association between physician-assessed AS severity and quantitative parameters is poorly understood. We aimed to evaluate AS natural history, compare outcomes for physicians' AS assessment vs. quantitative parameters, and identify AS parameters with the most explanatory power., Methods: We ascertained physician-assessed AS severity, echocardiographic parameters, and clinical data for 546,769 patients from 2008-2018, examined multivariable associations of physician-assessed AS severity and number of quantitative severe AS parameters with death, cardiovascular hospitalization, and aortic valve replacement, and estimated the relative contribution of different quantitative AS parameters on outcomes., Results: Among 49,604 AS patients (mean [SD] age 77 [11] years), 17.6% had moderate, 3.6% moderate-severe, and 9.4% severe AS. During median 3.7 [IQR 1.7-6.8] years, physician-assessed AS severity strongly correlated with outcomes, with moderate AS patients tracking closest to mild AS, and moderate-to-severe AS patients more comparable to severe AS. Although the number of quantitative severe AS parameters strongly predicted outcomes (adjusted HR [95% CI] for death 1.40 [1.34-1.46], 1.70 [1.56-1.85], and 1.78 [1.63-1.94] for 1, 2, and 3 parameters, respectively), aortic valve area <1.0 cm 2 was the most frequent severe AS parameter, explained the largest relative contribution (67%), and was common in patients classified as moderate (21%) or moderate-severe (56%) AS., Conclusions: Physician-assessed AS severity predicts outcomes, with cumulative effects for each severe AS parameter. Moderate AS includes a wide spectrum of patients, with discordant AVA <1.0 cm 2 being both common and predictive. Better identification of non-classical severe AS phenotypes may improve outcomes., Competing Interests: Disclosures Dr Solomon reports relevant research support from Edwards Lifesciences (Irvine, CA). Dr Ambrosy reports relevant research support from Abbott Vascular (Santa Clara, CA) and Edwards Lifesciences (Irvine, CA). Dr Go reports research support from Abbott Vascular (Santa Clara, CA) and Edwards Lifesciences (Irvine, CA). All remaining authors have nothing to disclose. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Data on the epidemiology of aortic stenosis (AS) are primarily derived from single center experiences and administrative claims data that do not delineate by degree of disease severity., Methods: An observational cohort study of adults with echocardiographic AS was conducted January 1st, 2013-December 31st, 2019 at an integrated health system. The presence/grade of AS was based on physician interpretation of echocardiograms., Results: A total of 66,992 echocardiogram reports for 37,228 individuals were identified. The mean ± standard deviation (SD) age was 77.5 ± 10.5, 50.5% (N = 18,816) were women, and 67.2% (N = 25,016) were non-Hispanic whites. The age-standardized AS prevalence increased from 589 (95% Confidence Interval [CI] 580-598) to 754 (95% CI 744-764) cases per 100,000 during the study period. The age-standardized AS prevalences were similar in magnitude among non-Hispanic whites (820, 95% CI 806-834), non-Hispanic blacks (728, 95% CI 687-769), and Hispanics (789, 95% CI 759-819) and substantially lower for Asian/Pacific Islanders (511, 95% CI 489-533). Finally, the distribution of AS by degree of severity remained relatively unchanged over time., Conclusions and Relevance: The population prevalence of AS has grown considerably over a short timeframe although the distribution of AS severity has remained stable., Competing Interests: Declaration of Competing Interest APA is supported by a Mentored Patient-Oriented Research Career Development Award (K23HL150159) through the National Heart, Lung, and Blood Institute and has received relevant research support through grants to his institution from Abbott, Edwards Lifesciences, Lexicon, and Novartis. ASG has received relevant research support through grants to his institution from the National Heart, Lung and Blood Institute; National Institute of Diabetes, Digestive and Kidney Diseases; National Institute on Aging; Amarin Pharma, Inc.; Novartis; Janssen Research & Development; and CSL Behring. All other authors have no relevant conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) may be used to urgently or emergently treat severe aortic stenosis, but outcomes for this high-risk population have not been well-characterized. We sought to describe the incidence, clinical characteristics, and outcomes of patients undergoing urgent or emergent vs. elective TAVR., Methods: We identified all adults who received TAVR for primary aortic stenosis between 2013 and 2019 within an integrated health care delivery system in Northern California. Elective or urgent/emergent procedure status was based on standard Society of Thoracic Surgeons definitions. Data were obtained from electronic health records, the Society of Thoracic Surgeons-American College of Cardiology Transcatheter Valve Therapy Registry, and state/national reporting databases. Logistic regression and Cox proportional hazard models were performed., Results: Among 1564 eligible adults that underwent TAVR, 81 (5.2%) were classified as urgent/emergent. These patients were more likely to have heart failure (63.0% vs. 47.4%), reduced left ventricular ejection fraction (21.0% vs. 11.8%), or a prior aortic valve balloon valvuloplasty (13.6% vs. 5.0%) and experienced higher unadjusted rates of 30-day and 1-year morbidity and mortality. Urgent/emergent TAVR status was independently associated with non-improved quality of life at 30-days (hazard ratio, 4.87; p < 0.01) and acute kidney injury within 1-year post-TAVR (hazard ratio, 2.11; p = 0.01). There was not a significant difference in adjusted 1-year mortality with urgent/emergent TAVR., Conclusions: Urgent/emergent TAVR status was uncommon and associated with high-risk clinical features and higher unadjusted rates of short- and long-term morbidity and mortality. Procedure status may be useful to identify patients less likely to experience significant short term improvement in health-related quality of life post-TAVR., Competing Interests: Andrew P. Ambrosy is supported by a Mentored Patient-Oriented Research Career Development Award (K23HL150159) through the National Heart, Lung, and Blood Institute and has received research support through grants to his institution from Abbott, Amarin Pharma, Edwards Lifesciences, Esperion, Lexicon, and Novartis. Alan S. Go has received research support through grants to his institution from the National Heart, Lung and Blood Institute; National Institute of Diabetes, Digestive and Kidney Diseases; National Institute on Aging; Amarin Pharma, Inc.; Novartis; Janssen Research & Development; and CSL Behring. All other authors have no potential conflicts of interest to declare., (© 2023 The Authors.)

Purpose: The long-term outcomes of surgery followed by delirium after multimodal prehabilitation program are largely unknown. We conducted this study to assess the effects of prehabilitation on 1-year mortality and of postoperative delirium on 1-year mortality and functional outcomes., Methods: The subjects of this study were patients aged ≥ 70 years who underwent elective surgery for abdominal aortic aneurysm (AAA) or colorectal cancer (CRC) between January 2013, and June 2018. A prehabilitation program was implemented in November 2015, which aimed to optimize physical health, nutritional status, factors of frailty and preoperative anemia prior to surgery. The outcomes were assessed as mortality after 6 and 12 months, compared between the two treatment groups; and mortality and functional outcomes, compared between patients with and those without delirium., Results: There were 627 patients (controls N = 360, prehabilitation N = 267) included in this study. Prehabilitation did not reduce mortality after 1 year (HR 1.31 [95% CI 0.75-2.30]; p = 0.34). Delirium was significantly associated with 1-year mortality (HR 4.36 [95% CI 2.45-7.75]; p < 0.001) and with worse functional outcomes after 6 and 12 months (KATZ ADL p = 0.013 and p = 0.004; TUG test p = 0.041 and p = 0.011, respectively)., Conclusions: The prehabilitation program did not reduce 1-year mortality. Delirium and the burden of comorbidity are both independently associated with an increased risk of 1-year mortality and delirium is associated with worse functional outcomes., Trial Registration: Dutch Trial Registration, NTR5932. https://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5932 .

Background: Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients., Methods: A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients' physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality., Result: A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32-0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes., Conclusion: Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation., Trial Registration: Dutch Trial Registration, NTR5932., Competing Interests: The PhD program of the corresponding author (T.L. Janssen) is funded by an ‘unrestricted grant’ by Amphia Fund for innovation. Limited financial support has been provided by Vifor Pharma Nederland B.V. All other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Due to the increase in elderly patients who undergo major abdominal surgery there is a subsequent increase in postoperative complications, prolonged hospital stays, health-care costs and mortality rates. Delirium is a frequent and severe complication in the 'frail' elderly patient. Different preoperative approaches have been suggested to decrease incidence of delirium by improving patients' baseline health. Studies implementing these approaches are often heterogeneous, have a small sample and do not provide high-quality or successful strategies. The aim of this study is to prevent postoperative delirium and other complications by implementing a unique multicomponent and multidisciplinary prehabilitation program., Methods: This is a single-center controlled before-and-after study. Patients aged ≥70 years in need of surgery for colorectal cancer or an abdominal aortic aneurysm are considered eligible. Baseline characteristics (such as factors of frailty, physical condition and nutritional state) are collected prospectively. During 5 weeks prior to surgery, patients will follow a prehabilitation program to optimize overall health, which includes home-based exercises, dietary advice and intravenous iron infusion in case of anaemia. In case of frailty, a geriatrician will perform a comprehensive geriatric assessment and provide additional preoperative interventions when deemed necessary. The primary outcome is incidence of delirium. Secondary outcomes are length of hospital stay, complication rate, institutionalization, 30-day, 6- and 12-month mortality, mental health and quality of life. Results will be compared to a retrospective control group, meeting the same inclusion and exclusion criteria, operated on between January 2013 and October 2015. Inclusion of the prehabilitation cohort started in November 2015; data collection is ongoing., Discussion: This is the first study to investigate the effect of prehabilitation on postoperative delirium. The aim is to provide evidence, based on a large sample size, for a standardized multicomponent strategy to improve patients' preoperative physical and nutritional status in order to prevent postoperative delirium and other complications. A multimodal intervention was implemented, combining physical, nutritional, mental and hematinic optimization. This research involves a large cohort, including patients most at risk for postoperative adverse outcomes., Trial Registration: The protocol is retrospectively registered at the Netherlands National Trial Register (NTR) number: NTR5932 . Date of registration: 05-04-2016.

Background: Prehospital ECG-based cardiac catheterization laboratory (CCL) activation for ST-segment-elevation myocardial infarction reduces door-to-balloon times, but CCL cancellations (CCL X ) remain a challenging problem. We examined the reasons for CCL X , clinical characteristics, and outcomes of patients presenting as ST-segment-elevation myocardial infarction activations who receive emergent coronary angiography (EA) compared with CCL X ., Methods and Results: We reviewed all consecutive CCL activations between January 1, 2012, and December 31, 2014 (n=1332). Data were analyzed comparing 2 groups stratified as EA (n=466) versus CCL X (n=866; 65%). Reasons for CCL X included bundle branch block (21%), poor-quality prehospital ECG (18%), non-ST-segment-elevation myocardial infarction ST changes (18%), repolarization abnormality (13%), and arrhythmia (8%). A multivariate logistic regression model using age, peak troponin, and initial ECG findings had a high discriminatory value for determining EA versus CCL X (C statistic, 0.985). CCL X subjects were older and more likely to be women, have prior coronary artery bypass grafting, or a paced rhythm ( P<0.0001 for all). All-cause mortality did not differ between groups at 1 year or during the study period (mean follow-up, 2.186±1.167 years; 15.8% EA versus 16.2% CCL X ; P=0.9377). Cardiac death was higher in the EA group (11.8% versus 3.0%; P<0.0001). After adjusting for clinical variables associated with survival, CCL X was associated with an increased risk for all-cause mortality during the study period (hazard ratio, 1.82; 95% CI, 1.28-2.59; P=0.0009)., Conclusions: In this study, prehospital ECG without overreading or transmission lead to frequent CCL X . CCL X subjects differ with regard to age, sex, risk factors, and comorbidities. However, CCL X patients represent a high-risk population, with frequently positive cardiac enzymes and similar short- and long-term mortality compared with EA. Further studies are needed to determine how quality improvement initiatives can lower the rates of CCL X and influence clinical outcomes.

Background: Postoperative delirium is a common and serious adverse event in the elderly patient and is associated with significant morbidity and mortality. It is of great importance to identify patients at risk for delirium, in order to focus preventive strategies. The aim of this article is to systematically review current available literature on pre-operative risk factors for delirium after vascular surgery., Methods: A systematic literature search was conducted using PubMed and EMBASE, using the MeSH terms and key words "delirium", "surgery" and "risk factor". Studies were retained for review after meeting strict inclusion criteria that included only prospective studies evaluating risk factors for delirium in patients who had elective vascular surgery. Diagnosis of delirium needed to be confirmed using the Diagnostic and Statistical Manual of Mental Disorders (DSM) or ICD-10., Results: Fifteen articles were selected for inclusion, incidence of delirium across the studies ranged from 5% to 39%. Many factors have been associated with increased risk of delirium, including age, cognitive impairment, comorbidity, depression, smoking, alcohol, visual and hearing impairment, ASA-score, biochemical abnormalities, operative strategies and blood loss., Conclusions: Delirium is a common complication after elective vascular surgery in elderly. The highest delirium incidence was observed after open aortic surgery as well as after surgery for critical limb ischemia. A picture starts to form of which predisposing factors lead to increased risk of delirium. The leading risk factors consistently identified in this systematic review were advanced age and cognitive impairment. Multi-disciplinary specialist-led interventions in the preoperative phase could decrease incidence and severity of delirium and should be focused on identified high-risk patients., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

First-medical-contact-to-device (FMC2D) times have improved over the past decade, as have clinical outcomes for patients presenting with ST-elevation myocardial infarction (STEMI). However, with improvements in FMC2D times, false activation of the cardiac catheterization laboratory (CCL) has become a challenging problem. The authors define false activation as any patient who does not warrant emergent coronary angiography for STEMI. In addition to clinical outcome measures for these patients, STEMI systems should collect data regarding the total number of CCL activations, the total number of emergency coronary angiograms, and the number revascularization procedures performed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A 78-year-old woman with a history of rheumatoid arthritis has been developing progressive speech and swallowing problems since 3 weeks. A CT scan of her head and neck showed a subluxation of the dens, which caused basilar invagination. This severe complication of rheumatoid arthritis is rare. Dynamic imaging and neurologic survey are recommended in patients with rheumatoid arthritis.

Over the past 20 years, care for patients with ST-elevation myocardial infarction (STEMI) has rapidly evolved, not just in terms of how patients are treated, but where patients are treated. The advent of regional STEMI systems of care has decreased the number of "eligible but untreated" patients while improving access to primary percutaneous coronary intervention for patients. These regional STEMI systems of care have consistently demonstrated that rapid transport of STEMI patients is safe and effective, and have shown marked improvements in a variety of clinical outcomes. However, no two STEMI systems are alike, and each must be tailored to the unique geographic, political, and socioeconomic challenges of the region. This article takes an in-depth look at two of the earliest STEMI systems within the United States: the Minneapolis Heart Institute and the Los Angeles County STEMI receiving network.

Fractional flow reserve (FFR) is a well-validated tool for determining the functional significance of a coronary artery stenosis, facilitating clinical decisions regarding the need for revascularization. FFR-guided revascularization improves clinical and economic outcomes. However, its application remains challenging in certain complex anatomic subsets, including left main coronary artery stenosis, bifurcation disease, and saphenous vein graft disease. This article reviews recent data supporting the use of FFR in these complex anatomic subsets.

Objectives: This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality., Background: HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information., Methods: Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index., Results: Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy., Conclusions: Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: HIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals., Methods and Results: We studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty-five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell's C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age- and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all)., Conclusion: In HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death.

Background: Ventilatory inefficiency (high volume of expired air/volume of carbon dioxide eliminated [Ve/Vco2] slope), and impaired exercise tolerance (low peak volume of oxygen consumption) obtained from cardiopulmonary exercise testing (CPX) strongly predict mortality in heart failure (HF) patients; however, other CPX variables may also contain prognostic information. Therefore, the purpose of this study was to determine the prognostic power of the aggregate of CPX data., Methods: The study prospectively monitored 390 patients referred for cardiac transplantation evaluation for 10 years for events (death, urgent transplant, left ventricular assist devices). Cox regression was used to analyze 18 CPX variables to identify the best survival model., Results: Ve/Vco2 slope was the most powerful mortality predictor, and only resting systolic blood pressure (SBP) added additional independent prognostic power when expressed at its threshold effect value as SBP ≤ 100 mm Hg. Patients with low SBP had a greater risk than those who were within the next higher quartile of Ve/Vco2 slope with SBP > 100 mm Hg. A very high-risk cohort included 9% of the population that had a Ve/Vco2 slope > 41 and SBP ≤ 100 mm Hg and an associated 2-year event rate of 67%; conversely, a low-risk cohort had a Ve/Vco2 slope ≤ 30 and SBP >100 mm Hg and associated 2-, 5-, and 10-year event rates of 5%, 12%, and 30%, respectively., Conclusions: Ve/Vco2 slope was the best individual predictive CPX variable and its interpretation was significantly altered by the presence of hypotension. An algorithm combining these CPX variables identifies a HF population at very high risk of early death and warranting advanced therapies., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

A patient with known asbestosis and a recent chorea was admitted for analysis of increasing disturbances of mobility, memory and social unacceptable behavior. At physical examination only minor neurological signs were seen. Additional investigations (among others CT-brain and PET-scan) suggested early M. Alzheimer. Two months later, the patient was readmitted with pneumonia and delirium. A literature review revealed some reports of vague neurological symptoms. An association between asbestos and the disorders in this patient was considered unlikely . An approach is proposed for asbestosis patients with vague neurological and/or psychiatric symptoms.

Purpose: Significant healthcare disparities exist between the developed world and low and middle income countries (LMIC), specifically in the field of cardiac electrophysiology. As a result, pacemaker reutilization has been proposed as a viable option for those in LMIC and no other means of obtaining a device. Little data exist regarding the feasibility of establishing a reuse program in addition to understanding the views of society on device reutilization. This study investigated the views of funeral directors, patients with cardiac devices, and members of the general population regarding reutilization of previously implanted pacemakers., Methods: Ninety funeral directors in Michigan were surveyed regarding current practice as well as preferences for post-mortem device disposal. One hundred and fourteen patients with devices and 1,009 members of the general population were surveyed regarding post-mortem device handling., Results: Funeral directors had an average of 21 years of experience with an annual volume of 120 deceased persons per year, with a cremation rate of 35%. When asked about disposal methods of explanted devices, the majority of devices (84%) were discarded as medical waste or stored with no intended purpose, with a total of 171 devices currently in possession at the funeral homes. Eighty-nine percent of funeral directors expressed a desire to donate devices for reuse in LMIC and 10% acknowledged previous device donation. Eighty-seven percent of device patients and 71% of the general population also expressed a desire to donate devices., Conclusions: The results of our survey show that a large percentage of funeral directors, patients with implantable devices, and members of the general population support a pacemaker reutilization initiative. This study lends further evidence that collection of devices for reuse is feasible and that establishing a framework for regional pacemaker reutilization program is warranted. If successful, the feasibility of this model should be investigated in other parts of the country in order to alleviate the burden of untreated symptomatic bradycardia in our world.

Background: Frequent idiopathic premature ventricular complexes (PVCs) can result in a reversible form of left ventricular dysfunction. The factors resulting in impaired left ventricular function are unclear. Whether a critical burden of PVCs can result in cardiomyopathy has not been determined., Objective: The objective of this study was to determine a cutoff PVC burden that can result in PVC-induced cardiomyopathy., Methods: In a consecutive group of 174 patients referred for ablation of frequent idiopathic PVCs, the PVC burden was determined by 24-hour Holter monitoring, and transthoracic echocardiograms were used to assess left ventricular function. Receiver-operator characteristic curves were constructed based on the PVC burden and on the presence or absence of reversible left ventricular dysfunction to determine a cutoff PVC burden that is associated with left ventricular dysfunction., Results: A reduced left ventricular ejection fraction (mean 0.37 +/- 0.10) was present in 57 of 174 patients (33%). Patients with a decreased ejection fraction had a mean PVC burden of 33% +/- 13% as compared with those with normal left ventricular function 13% +/- 12% (P <.0001). A PVC burden of >24% best separated the patient population with impaired as compared with preserved left ventricular function (sensitivity 79%, specificity 78%, area under curve 0.89) The lowest PVC burden resulting in a reversible cardiomyopathy was 10%. In multivariate analysis, PVC burden (hazard ratio 1.12, 95% confidence interval 1.08 to 1.16; P <.01) was independently associated with PVC-induced cardiomyopathy., Conclusion: A PVC burden of >24% was independently associated with PVC-induced cardiomyopathy., (Copyright 2010 Heart Rhythm Society. All rights reserved.)

As disparities in healthcare between the industrialized world and low- and middle-income countries (LMIC) continue to widen, novel methods of delivering cardiovascular therapies-specifically electrophysiological devices-must be explored. Post-mortem pacemaker donation is a safe and effective method of decreasing the morbidity associated with cardiovascular disease in LMIC.

The existence of dimers and higher oligomers of G-protein-coupled receptors (GPCRs) has been frequently reported using strategies based on coimmunoprecipitation or Western blot assays. These methods rely on highly artificial systems with overexpressed receptors, resulting in conflicting observations on the question of whether GPCR dimers are preformed or are formed in response to agonist treatment. Fluorescence resonance energy transfer (FRET) microscopy is a superior and less perturbing technique which can be performed on selected cell regions, e.g., plasma membrane of intact cells with a sensitivity high enough to allow study under physiological levels of receptor expression. Here we describe the application of photobleaching (pb) FRET microscopy for investigating ligand-dependent oligomerization of somatostatin receptors. Procedures for the introduction of suitable donor-acceptor fluorophores in a given GPCR are described. The competitive nature of FRET and photobleaching is exploited to enable the indirect measurement of FRET via its effect on donor photobleaching lifetimes on a pixel-by-pixel basis. The method allows enhanced resolution between 10 and 100A and represents a sensitive and specific biophysical tool for characterizing the assembly and regulation of GPCR oligomers on the cell surface.

Background: The optimum method for inguinal hernia repair has not yet been determined. The recurrence rate for non-mesh methods varies between 0.2 and 33 per cent. The value of tension-free repair with prosthetic mesh remains to be confirmed. The aim of this study was to compare mesh and non-mesh suture repair of primary inguinal hernias with respect to clinical outcome, quality of life and cost in a multicentre randomized trial in general hospitals., Methods: Between September 1993 and January 1996, all patients scheduled for repair of a unilateral primary inguinal hernia were randomized to non-mesh or mesh repair. The patients were followed up at 1 week and at 1, 6, 12, 18, 24 and 36 months. Clinical outcome, quality of life and costs were registered., Results: Three hundred patients were randomized of whom 11 were excluded. Three-year recurrence rates differed significantly: 7 per cent for non-mesh repair (n = 143) and 1 per cent for mesh repair (n = 146) (P = 0.009). There were no differences in clinical variables, quality of life and costs., Conclusion: Mesh repair of primary inguinal hernia repair is superior to non-mesh repair with regard to hernia recurrence and is cost-effective. Postoperative complications, pain and quality of life did not differ between groups.

Background: Incisional hernia is an important complication of abdominal surgery. Procedures for the repair of these hernias with sutures and with mesh have been reported, but there is no consensus about which type of procedure is best., Methods: Between March 1992 and February 1998, we performed a multicenter trial in which we randomly assigned to suture repair or mesh repair 200 patients who were scheduled to undergo repair of a primary hernia or a first recurrence of hernia at the site of a vertical midline incision of the abdomen of less than 6 cm in length or width. The patients were followed up by physical examination at 1, 6, 12, 18, 24, and 36 months. Recurrence rates and potential risk factors for recurrent incisional hernia were analyzed with the use of life-table methods., Results: Among the 154 patients with primary hernias and the 27 patients with first-time recurrent hernias who were eligible for the study, 56 had recurrences during the follow-up period. The three-year cumulative rates of recurrence among patients who had suture repair and those who had mesh repair were 43 percent and 24 percent, respectively, with repair of a primary hernia (P=0.02; difference, 19 percentage points; 95 percent confidence interval, 3 to 35 percentage points). The recurrence rates were 58 percent and 20 percent with repair of a first recurrence of hernia (P=0.10; difference, 38 percentage points; 95 percent confidence interval, -1 to 78 percentage points). The risk factors for recurrence were suture repair, infection, prostatism (in men), and previous surgery for abdominal aortic aneurysm. The size of the hernia did not affect the rate of recurrence., Conclusions: Among patients with midline abdominal incisional hernias, mesh repair is superior to suture repair with regard to the recurrence of hernia, regardless of the size of the hernia.

Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.

The existence of receptor dimers has been proposed for several G protein-coupled receptors. However, the question of whether G protein-coupled receptor dimers are necessary for activating or modulating normal receptor function is unclear. We address this question with somatostatin receptors (SSTRs) of which there are five distinct subtypes. By using transfected mutant and wild type receptors, as well as endogenous receptors, we provide pharmacological, biochemical, and physical evidence, based on fluorescence resonance energy transfer analysis, that activation by ligand induces SSTR dimerization, both homo- and heterodimerization with other members of the SSTR family, and that dimerization alters the functional properties of the receptor such as ligand binding affinity and agonist-induced receptor internalization and up-regulation. Double label confocal fluorescence microscopy showed that when SSTR1 and SSTR5 subtypes were coexpressed in Chinese hamster ovary-K1 cells and treated with agonist they underwent internalization and were colocalized in cytoplasmic vesicles. SSTR5 formed heterodimers with SSTR1 but not with SSTR4 suggesting that heterodimerization is a specific process that is restricted to some but not all receptor subtype combinations. Direct protein interaction between different members of the SSTR subfamily defines a new level of molecular cross-talk between subtypes of the SSTR and possibly related receptor families.

Objective: To obtain an impression of the tissue donor potential in Dutch nursing homes and of the knowledge and the attitude of nursing home physicians and nursing home directors with regard to tissue donation. Also, to gain insight into the problems associated with activating tissue donation in nursing homes., Design: Descriptive and inventory., Method: The donor potential was calculated from data derived from the National nursing home registration system (SIVIS) in 1995. A questionnaire on the knowledge and attitude with regard to organ/tissue donation was sent to 400 randomly chosen nursing home physicians and all 323 nursing home directors., Results: Out of the 10,619 somatic patients deceased in nursing homes in 1995, 2670 (25%) would have been suitable for skin and/or cornea donation. Other patients had comorbidity regarded as a contraindication for donorship or were over 80 years of age. Of the 9771 deceased psychogeriatric patients, virtually none were suitable as tissue donors. The response to the questionnaire was 55% among nursing home physicians and 66% among nursing home directors. Both groups showed inadequate knowledge with regard to tissue donation. Most nursing home physicians (85%) took a neutral position on tissue donation in nursing homes; most directors (88%) would support tissue donation in their nursing home. The two problems that were mentioned most in having a negative influence on tissue donation in nursing homes, were: the lack of knowledge of physicians and the refusal of donation by patients., Conclusion: Some 2700 somatic nursing home patients annually would be suitable for tissue donation. Determination of their willingness is necessary. Activating of tissue donation in nursing homes requires solving of the lack of knowledge.

Two potential ligand binding sites in the lipocalin beta-lactoglobulin have been postulated for small hydrophobic molecules such as retinol or retinoic acid. An agreement on one of the two alternatives, an interior cavity or a surface cleft, however, has not been achieved. In order to discriminate between these two possibilities, we measured the efficiency of fluorescence resonance energy transfer between the two intrinsic Trp-residues of beta-lactoglobulin and the ligands retinol, retinoic acid and bis-ANS. Using the crystallographic coordinates of beta-lactoglobulin, this efficiency could be accurately computed for both the interior cavity and the surface cleft as ligand binding sites. For the surface cleft, the theoretical value was found to be in excellent agreement with the measured value, whereas for the interior cavity any reasonable agreement would require a dramatic ligand-induced conformational change that can be ruled out due to the protein's known structural stability. Our conclusion that these ligands bind to the surface pocket rather than the interior cavity was further confirmed by competitive binding studies.

Objective: The authors determined the prevalence of foreign body granulomas in intra-abdominal adhesions in patients with a history of abdominal surgery., Patients and Methods: In a cross-sectional, multicenter, multinational study, adult patients with a history of one or more previous abdominal operations and scheduled for laparotomy between 1991 and 1993 were examined during surgery. Patients in whom adhesions were present were selected for study. Quantity, distribution, and quality of adhesions were scored, and adhesion samples were taken for histologic examination., Results: In 448 studied patients, the adhesions were most frequently attached to the omentum (68%) and the small bowel (67%). The amount of adhesions was significantly smaller in patients with a history of only one minor operation or one major operation, compared with those with multiple laparotomies (p < 0.001). Significantly more adhesions were found in patients with a history of adhesions at previous laparotomy (p < 0.001), with presence of abdominal abscess, hematoma, and intestinal leakage as complications after former surgery (p = 0.01, p = 0.002, and p < 0.001, respectively), and with a history of an unoperated inflammatory process (p = 0.04). Granulomas were found in 26% of all patients. Suture granulomas were found in 25% of the patients. Starch granulomas were present in 5% of the operated patients whose surgeons wore starch-containing gloves. When suture granulomas were present, the median interval between the present and the most recent previous laparotomy was 13 months. When suture granulomas were absent, this interval was significantly longer--i.e., 30 months (p = 0.002). The percentage of patients with suture granulomas decreased gradually from 37% if the previous laparotomy had occurred up to 6 months before the present operation, to 18% if the previous laparotomy had occurred more than 2 years ago (p < 0.001)., Conclusions: The number of adhesions found at laparotomy was significantly larger in patients with a history of multiple laparotomies, unoperated intra-abdominal inflammatory disease, and previous postoperative intra-abdominal complications, and when adhesions were already present at previous laparotomy. In recent adhesions, suture granulomas occurred in a large percentage. This suggests that the intra-abdominal presence of foreign material is an important cause of adhesion formation. Therefore intra-abdominal contamination with foreign material should be minimized.