bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial Titin Hypophosphorylation Importantly Contributes to Heart Failure With Preserved Ejection Fraction in a Rat Metabolic Risk Model
Authors: Hamdani Nazha , Franssen Constantijn , Lourenço André , Falcão-Pires Inês , Fontoura Dulce , Leite Sara , Plettig Luisa , López Begoña , Ottenheijm Coen A. , Becher Peter Moritz , González Arantxa , Tschöpe Carsten , Díez Javier , Linke Wolfgang A. , Leite-Moreira Adelino F. , Paulus Walter J. 
Published: September 2013

Background—
Obesity and diabetes mellitus are important metabolic risk factors and frequent comorbidities in heart failure with preserved ejection fraction. They contribute to myocardial diastolic dysfunction (DD) through collagen deposition or titin modification. The relative importance for myocardial DD of collagen deposition and titin modification was investigated in obese, diabetic ZSF1 rats after heart failure with preserved ejection fraction development at 20 weeks.

Methods and Results—

Four groups of rats (Wistar-Kyoto, n=11; lean ZSF1, n=11; obese ZSF1, n=11, and obese ZSF1 with high-fat diet, n=11) were followed up for 20 weeks with repeat metabolic, renal, and echocardiographic evaluations and hemodynamically assessed at euthanization. Myocardial collagen, collagen cross-linking, titin isoforms, and phosphorylation were also determined. Resting tension (F
passive
)–sarcomere length relations were obtained in small muscle strips before and after KCl–KI treatment, which unanchors titin and allows contributions of titin and extracellular matrix to F
passive
to be discerned. At 20 weeks, the lean ZSF1 group was hypertensive, whereas both obese ZSF1 groups were hypertensive and diabetic. Only the obese ZSF1 groups had developed heart failure with preserved ejection fraction, which was evident from increased lung weight, preserved left ventricular ejection fraction, and left ventricular DD. The underlying myocardial DD was obvious from high muscle strip stiffness, which was largely (±80%) attributable to titin hypophosphorylation. The latter occurred specifically at the S3991 site of the elastic N2Bus segment and at the S12884 site of the PEVK segment.

Conclusions—
Obese ZSF1 rats developed heart failure with preserved ejection fraction during a 20-week time span. Titin hypophosphorylation importantly contributed to the underlying myocardial DD.
Functional Significance of Elevated Mitral Gradients After Repair for Degenerative Mitral Regurgitation
Authors: Chan Kwan Leung , Chen Shin-Yee , Chan Vincent , Hay Karen , Mesana Thierry , Lam Buu Khanh 
Published: September 2013

Background—
We have observed that elevated mitral gradients can develop in some patients after mitral valve repair for degenerative mitral regurgitation.

Methods and Results—

We screened 275 patients who had mitral valve repair involving >1 leaflet scallop between October 2001 and July 2010. Mitral valve hemodynamics were assessed at rest and at peak exercise using the cycle ergometer. B-type natriuretic peptide levels were measured at rest and after exercise. The patients also performed a 6-minute walk test and short-form 36-Item Health Survey questionnaire. We enrolled 110 patients, with resting mean mitral diastolic gradient of ≤3 mm Hg in 35 patients (group 1) and >3 mm Hg indicative of elevated mitral gradients in 75 patients (group 2). Posterior mitral leaflet plication (
P
=0.04) and the use of a complete mitral annuloplasty ring (
P
<0.0001) were associated with elevated mitral gradients. Group 2 patients had larger left atrial volume (
P
=0.02), higher mitral gradients at peak exercise and higher pulmonary artery systolic pressure at rest and at peak exercise, and lower exercise capacity (101±40 versus 122±51 W;
P
=0.02). Group 2 patients also had higher B-type natriuretic peptide levels and lower scores in 3 short-form 36-Item Health Survey health concepts. Multivariate regression analyses showed that mitral valve area was an independent predictor of maximum exercise capacity (
P
=0.003).

Conclusions—
After mitral valve repair for degenerative mitral regurgitation, elevated mitral gradients is not uncommon and is associated with worse intracardiac hemodynamics, higher B-type natriuretic peptide levels, lower exercise capacity, and poorer quality of life. Further refinement in the surgical technique may reduce the incidence of this complication.
Relationship Between the Magnitude of Reduction in Mitral Regurgitation Severity and Left Ventricular and Left Atrial Reverse Remodeling After MitraClip Therapy
Authors: Grayburn Paul A. , Foster Elyse , Sangli Chithra , Weissman Neil J. , Massaro Joseph , Glower Donald G. , Feldman Ted , Mauri Laura 
Published: September 2013

Background—
MitraClip has been shown to reduce mitral regurgitation (MR) severity safely but to a lesser degree than surgery. No data exist on the magnitude of MR reduction necessary to reverse left ventricular (LV) and left atrial (LA) dilation in patients with severe MR. Therefore, an analysis was performed to evaluate the relationship between MR reduction and LV and LA volumes after MitraClip therapy.

Methods and Results—

A total of 801 patients treated with MitraClip and 80 patients treated surgically were included. All patients had severe (3–4+) MR. MR severity, LV volumes at end-diastole and end-systole, and LA volumes were measured at baseline, discharge, 30 days, 6 months, and 1 year by an independent echocardiographic core laboratory. A linear repeated measures model was developed to determine the relationship between MR severity and time of measurement postindex procedure on longitudinal LV and LA volumes. Separate models were fit for functional MR and degenerative MR. In both degenerative and functional MR, reduction in LV volumes at end-diastole was associated with degree of residual MR at 12 months (
P
<0.0001). LV volumes at end-systole was significantly reduced in functional MR but not degenerative MR. LA volumes were significantly related to reduction of MR severity in both groups.

Conclusions—
Reduction of LV volumes at end-diastole and LA volumes, but not LV volumes at end-systole in degenerative MR, is consistent with correction of volume overload from primary MR. Reduction of all 3 measurements in functional MR demonstrates reverse remodeling when MR severity is reduced to either 1+ or 2+ by MitraClip therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00209274.
Impaired Cholesterol Metabolism and Enhanced Atherosclerosis in Clock Mutant Mice
Authors: Pan Xiaoyue , Jiang Xian-Cheng , Hussain M. Mahmood 
Published: September 2013

Background—
Clock is a key transcription factor that positively controls circadian regulation. However, its role in plasma cholesterol homeostasis and atherosclerosis has not been studied.

Methods and Results—

We show for the first time that dominant-negative Clock mutant protein (Clock
Δ19/Δ19
) enhances plasma cholesterol and atherosclerosis in 3 different mouse models. Detailed analyses revealed that
Clk

Δ19/Δ19

Apoe
−/−
mice display hypercholesterolemia resulting from the accumulation of apolipoprotein B48–containing cholesteryl ester–rich lipoproteins. Physiological studies showed that enhanced cholesterol absorption by the intestine contributes to hypercholesterolemia. Molecular studies indicated that the expression of Niemann Pick C1 Like 1, Acyl-CoA:Cholesterol acyltransferase 1, and microsomal triglyceride transfer protein in the intestines of
Clk

Δ19/Δ19

Apoe
−/−
mice was high and that enterocytes assembled and secreted more chylomicrons. Furthermore, we identified macrophage dysfunction as another potential cause of increased atherosclerosis in
Clk

Δ19/Δ19

Apoe
−/−
mice. Macrophages from
Clk

Δ19/Δ19

Apoe
−/−
mice expressed higher levels of scavenger receptors and took up more modified lipoproteins compared with
Apoe
−/−
mice, but they expressed low levels of ATP binding casette protein family A member 1 and were defective in cholesterol efflux. Molecular studies revealed that Clock regulates ATP binding casette protein family A member 1 expression in macrophages by modulating upstream transcription factor 2 expression.

Conclusions—

Clock
Δ19/Δ19
protein enhances atherosclerosis by increasing intestinal cholesterol absorption, augmenting uptake of modified lipoproteins by macrophages, and reducing cholesterol efflux from macrophages. These studies establish that circadian Clock activity is crucial in maintaining low plasma cholesterol levels and in reducing atherogenesis in mice.
Surgeon Experience and Complications with Transoral Robotic Surgery (TORS)
Authors: Chia Stanley H. , Gross Neil D. , Richmon Jeremy D. 
Published: September 2013

ObjectiveTo investigate surgeon preferences for perioperative management of transoral robotic surgery (TORS) and explore the frequency of postoperative complications.Study DesignRetrospective survey.SettingMulti‐institutional.Subjects and MethodsAn electronic survey was sent to over 300 TORS‐trained surgeons in the United States identified by Intuitive Surgical, Inc. Participation was voluntary and solicited by email invitations to participate 3 times over a 1‐month period.ResultsA total of 2015 procedures were reported by 45 respondent TORS‐trained surgeons: 67% academic, 33% nonacademic. A minority of TORS procedures (n = 214, 10.6%) were performed on previously irradiated patients. Neck dissections were performed concurrently (58%) or staged (42%). Fewer than 6% of TORS procedures required tracheotomy or reconstruction. Most surgeons (62%) initiated oral intake on postoperative day 0‐1. Of the patients who required readmission, bleeding (n = 62, 3.1%) was the most common cause followed by dehydration (n = 26, 1.3%). Other complications of surgery included tooth injury (n = 29, 1.4%), percutaneous endoscopic gastrostomy (PEG) dependency >6 months (n = 21, 1.0%), temporary hypoglossal nerve injury (n = 18, 0.9%), and lingual nerve injury (n = 11, 0.6%). A total of 6 deaths (0.3%) were reported within 30 days of TORS. All reported deaths were due to postoperative hemorrhage. The complication rate decreased significantly with higher surgeon case volume (>50 cases).ConclusionsTORS is associated with a low major complication rate, early initiation of oral intake, and a low rate of long‐term PEG dependency. Postoperative hemorrhage was the most common cause of hospital readmission and postoperative mortality.
Clinical Assessment and Treatment of the Dysfunctional Larynx after Radiation
Authors: Allen Clint T. , Lee Chia‐Jung , Merati Albert L. 
Published: September 2013

ObjectiveTo review the pathophysiology of early and late radiation‐related tissue changes, methods to differentiate these changes from disease recurrence, and treatment of these changes in the irradiated larynx.Data SourcesPeer‐reviewed publications.Review MethodsPubMed database search.Conclusions/Implications for PracticeEarly and late radiation‐related changes in the larynx manifest variably between individual patients. Severe radiation‐related tissue changes in the larynx and recurrent malignancy share many clinical characteristics, and the presence of malignancy must be considered in these patients. Positron emission tomography may help select patients who need operative biopsy to rule out recurrence. In patients with a cancer‐free but dysfunctional larynx, both surgical and nonsurgical treatment options, including hyperbaric oxygen, are available for attempted salvage. Further investigation is needed before hyperbaric oxygen can be considered standard‐of‐care treatment for these patients.
Physical activity maintenance in patients with rheumatoid arthritis: a qualitative study
Authors: Loeppenthin K , Esbensen BA , Ostergaard M , Jennum P , Thomsen T , Midtgaard J 
Published: September 2013

Objective: To describe the experience of physical activity maintenance in patients with rheumatoid arthritis. Design: A qualitative salutogenic-oriented interview study. Setting: A rheumatology outpatient clinic. Subjects: A purposive sample of 16 physically active patients (mean age 50, range 37–67) diagnosed with rheumatoid arthritis on average 21 years previously (range 4–46 years). Methods: In-depth interviews were conducted using a semi-structured interview guide to illuminate how the phenomenon ‘physical activity maintenance’ was experienced by patients with rheumatoid arthritis. The interviews were analysed using systematic text condensation, inspired by Giorgi’s descriptive phenomenological methodology. Results: The analysis revealed three categories: (1) knowing and enjoying the body; (2) responsibility and challenges; (3) autonomy and social belonging. On the basis of these categories, the essential meaning of the phenomenon of physical activity maintenance for patients with rheumatoid arthritis was summarized into ‘striving for a transparent body and participation’, pointing to experiences of sensations of wellbeing, liberation from restrictions and social participation on equal terms with non-arthritis populations. Conclusion: This study demonstrates that physical activity in patients with rheumatoid arthritis may be understood as a resource to resist disability and to feel and stay healthy while creating and sustaining meaningfulness in life.
Comparison of computer tomographic volumetry versus nuclear split renal function to determine residual renal function after living kidney donation
Authors: Patankar Khalil , Low Ronny Su-Tong , Blakeway Darryn , Ferrari Paolo 
Published: September 2013

Background Living-donor kidney transplantation is an established practice. Traditionally a combination of renal scintigram and computed tomography (CT) is used to select the kidney that is to be harvested in each donor. Purpose To evaluate the ability of split renal volume (SRV) calculated from volumetric examination of CT images compared to nuclear split renal function (nSRF) derived from gamma camera scintigram to predict donor residual single kidney function after donor nephrectomy. Material and Methods This pilot study comprised a retrospective analysis of CT images and renal scintigrams from 12 subsequent live kidney donors who had at least 12 months post-donation renal function follow-up. Results nSRF derived from the renal scintigram, expressed as the right kidney’s function in percent of the total, was 50.2 ± 3.3 (range, 44.1–54.0%) and SRV estimated following analysis of CT imaging was 49.0 ± 2.9 (range, 46.4–52.3%). Although the correlation between nSRF and SRV was moderate (R = 0.46), there was 92% agreement on the dominant kidney if a difference of <2% in nSRF versus SRV was considered. Post-donation glomerular filtration rate (GFR) by CKD-EPI formula was 92 ± 10 mL/min/1.73m2 at 1 year and the correlation between estimated GFR (eGFR) at 1 year and extrapolated single kidney eGFR adjusted by nSRF (R2 = 0.69, P = 0.0007) or SRV (R2 = 0.74, P = 0.0003) was similar. Conclusion Calculation of SRV from pre-donation CT examination is a valid method to estimate nSRF with good concordance with nSRF determined by renal scintigram and could replace the latter in the assessment of potential kidney donors.
Exertional Heat Stroke Management Strategies in United States High School Football
Authors: Kerr Zachary Y. , Marshall Stephen W. , Comstock R. Dawn , Casa Douglas J. 
Published: September 2013

Background: The 5-year period of 2005-2009 saw more exertional heat stroke–related deaths in organized sports than any other 5-year period in the past 35 years. The risk of exertional heat stroke appears highest in football, particularly during the preseason. Purpose: To estimate the incidence of exertional heat stroke events and assess the utilization of exertional heat stroke management strategies during the 2011 preseason in United States high school football programs. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A self-administered online questionnaire addressing the incidence of exertional heat stroke events and utilization of exertional heat stroke management strategies (eg, removing athlete’s football equipment, calling Emergency Medical Services [EMS]) was completed in May to June 2012 by 1142 (18.0%) athletic trainers providing care to high school football athletes during the 2011 preseason. Results: Among all respondents, 20.3% reported treating at least 1 exertional heat stroke event. An average of 0.50 ± 1.37 preseason exertional heat stroke events were treated per program. Athletic trainers responding to exertional heat stroke reported using an average of 6.6 ± 1.8 management strategies. The most common management strategies were low-level therapeutic interventions such as removing the athlete’s football equipment (98.2%) and clothing (77.8%) and moving the athlete to a shaded area (91.6%). Few athletic trainers reported active management strategies such as calling EMS (29.3%) or using a rectal thermometer to check core body temperature (0.9%). Athletic trainers in states with mandated preseason heat acclimatization guidelines reported a higher utilization of management strategies such as cooling the athlete through air conditioning (90.1% vs 65.0%, respectively; P < .001), immersion in ice water (63.0% vs 45.4%, respectively; P = .01), or fans (54.3% vs 42.0%, respectively; P = .06) and monitoring the athlete’s temperature (60.5% vs 46.2%, respectively; P = .04). Conclusion: Preseason exertional heat stroke events, which are likely to be fatal if untreated, were reported by one fifth of all athletic trainers in high school football programs. The standard of care is (and should be) to treat proactively; therefore, treatment is not a perfect proxy for incidence. Nevertheless, there is an urgent need for improved education and awareness of exertional heat stroke in high school football. Areas of improvement include the greatly increased use of rectal thermometers and immersion in ice water.
Stable Surgical Repair With Accelerated Rehabilitation Versus Nonsurgical Treatment for Acute Achilles Tendon Ruptures
Authors: Olsson Nicklas , Silbernagel Karin Grävare , Eriksson Bengt I. , Sansone Mikael , Brorsson Annelie , Nilsson-Helander Katarina , Karlsson Jón 
Published: September 2013

Background: The optimal treatment for acute Achilles tendon ruptures is still a subject of debate. Early loading of the tendon is a factor that has been shown to be beneficial to recovery and to minimize complications. The main outcome of previous studies has been complications such as reruptures and deep infections, without focusing on the functional outcome relevant to the majority of patients who do not experience these complications. Purpose: To evaluate whether stable surgical repair and early loading of the tendon could improve patient-reported outcome and function after an acute Achilles tendon rupture. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 100 patients (86 men, 14 women; mean age, 40 years) with an acute total Achilles tendon rupture were randomized to either surgical treatment, including an accelerated rehabilitation protocol, or nonsurgical treatment. The primary outcome was the Achilles tendon Total Rupture Score (ATRS). The patients were evaluated at 3, 6, and 12 months for symptoms, physical activity level, and function. Results: There were no significant differences between the groups in terms of symptoms, physical activity level, or quality of life. There was a trend toward improved function in surgically treated patients; the results were significantly superior when assessed by the drop countermovement jump (95% CI, 0.03-0.15; P = .003) and hopping (95% CI, 0.01-0.33; P = .040). No reruptures occurred in the surgical group, while there were 5 in the nonsurgical group ( P = .06). There were 6 superficial infections in the surgically treated group; however, these superficial infections had no bearing on the final outcome. Symptoms, reduced quality of life, and functional deficits still existed 12 months after injury on the injured side in both groups. Conclusion: The results of the present study demonstrate that stable surgical repair with accelerated tendon loading could be performed in all (n = 49) patients without reruptures and major soft tissue–related complications. However, this treatment was not significantly superior to nonsurgical treatment in terms of functional results, physical activity, or quality of life.
Primary care quality and safety systems in the English National Health Service: a case study of a new type of primary care provider
Authors: Baker Richard , Willars Janet , McNicol Sarah , Dixon-Woods Mary , McKee Lorna 
Published: September 2013

Objectives Although the predominant model of general practice in the UK National Health Service (NHS) remains the small partnership owned and run by general practitioners (GPs), new types of provider are emerging. We sought to characterize the quality and safety systems and processes used in one large, privately owned company providing primary care through a chain of over 50 general practices in England. Methods Senior staff with responsibility for policy on quality and safety were interviewed. We also undertook ethnographic observation in non-clinical areas and interviews with staff in three practices. Results A small senior executive team set policy and strategy on quality and safety, including a systematic incident reporting and investigation system and processes for disseminating learning with a strong emphasis on customer focus. Standardization of systems was possible because of the large number of practices. Policies appeared generally well implemented at practice level. However, there was some evidence of high staff turnover, particularly of GPs. This caused problems for continuity of care and challenges in inducting new GPs in the company’s systems and procedures. Conclusions A model of primary care delivery based on a corporate chain may be useful in standardizing policies and procedures, facilitating implementation of systems, and relieving clinical staff of administrative duties. However, the model also poses some risks, including those relating to stability. Provider forms that retain the long term, personal commitment of staff to their practices, such as federations or networks, should also be investigated; they may offer the benefits of a corporate chain combined with the greater continuity and stability of the more traditional general practice.
Impact of two different health systems on the burden of type 2 diabetes
Authors: Gallagher Naomh , Bennett Kathleen , Smith Susan M , O’Reilly Dermot 
Published: September 2013

Objectives Health policy directs the management of patients with chronic disease in a country, but evaluating nationwide policies is difficult, not least because of the absence of suitable comparators. This paper examines the management of patients with type 2 diabetes in two demographically comparable populations with different health care systems to see if this represents a viable approach to evaluation. Methods A secondary analysis of centralized prescribing databases for 2010 was undertaken to compare the levels and costs of care of patients with type 2 diabetes in Northern Ireland’s National Health Service (NHS) (NI, n = 1.8 million) which has structured care, financial incentives related to diabetes care and an emphasis on generic prescribing, with that of the Republic of Ireland (ROI, n = 4.3 million) where management of diabetes care is guided solely by clinical and other guidelines. Results The prevalence of treated type 2 diabetes was 3.59% in NI and 3.09% in ROI, but there were similar and high levels of prescribing of secondary cardiovascular medications. Medication costs per person for anti-diabetic, anti-obesity and cardiovascular medication were 46% higher in ROI than NI, due to differences in levels of generic prescribing. Conclusions These different health care systems appear to be producing similar levels of care for patients with type 2 diabetes, although at different levels of cost. The findings question the need for financial incentives in NI and highlight the large cost savings potentially accruing from a greater shift to generic prescribing in ROI. Cross-country comparison, though not without difficulties, may prove a useful adjunct to within-country analysis of policy impact.