bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Tumor-Derived Prostaglandin-E2 Blocks the Induction of Myeloid-Derived Suppressor Cells and Recovers Natural Killer Cell Activity
Authors: Mao Yumeng , Sarhan Dhifaf , Steven André , Seliger Barbara , Kiessling Rolf , Lundqvist Andreas 
Published: June 2014

Abstract
Purpose: Increased frequencies of myeloid-derived suppressor cells (MDSC) correlate with poor prognosis in patients with cancers. Tumor-derived prostaglandin-E2 (PGE2) plays an important role in inducing MDSCs. However, the detailed mechanisms of this induction remain unknown. To develop targeted therapies for MDSCs, we sought to investigate the molecular basis of PGE2-regulated accumulation of MDSCs and their functional consequence on natural killer (NK) cell activity.
Experimental Design: The effects of PGE2 in inducing phenotypic, signaling, and functional alternations on monocytes were analyzed in vitro. Suppression of NK-cell activity by PGE2-treated monocytes was compared with that of freshly isolated CD14+HLA-DRlow/− monocytic MDSCs (moMDSC) from patients with melanoma. In addition, to explore the in vivo relevance of targeting PGE2 to reduce MDSC-mediated suppression of NK cells, we established a murine model, where tumor cells were disabled from cyclooxygenase-2 (COX-2) production.
Results: Patient-derived moMDSCs inhibited NK-cell activity through the production of TGFβ. In vitro, binding of PGE2 to EP2 and EP4 receptors on monocytes activated the p38MAPK/ERK pathway and resulted in elevated secretion of TGFβ. Similar to moMDSCs, PGE2-treated monocytes potently suppressed NK-cell activity through production of TGFβ. Furthermore, silencing COX-2 in murine 4T1 tumor cells reduced the accumulation of CD11b+Gr1+ MDSCs in the spleen, resulting in concomitant improved in vivo clearance of NK-cell sensitive YAC-1 cells.
Conclusions: Our results reveal an indispensable role of tumor-derived PGE2 in inducing MDSCs and suggest a favorable outcome of combining COX-2–targeted therapy and adoptive NK-cell transfer in patients with cancer. Clin Cancer Res; 20(15); 4096–106. ©2014 AACR.
Physical Activity, Obesity, Weight Change, and Risk of Atrial Fibrillation
Authors: Huxley Rachel R. , Misialek Jeffrey R. , Agarwal Sunil K. , Loehr Laura R. , Soliman Elsayed Z. , Chen Lin Y. , Alonso Alvaro 
Published: June 2014

Background—
Physical activity (PA) has previously been suggested to attenuate the risk of atrial fibrillation (AF) conferred by excess body weight and weight gain. We prospectively examined the relationship between body size, weight change, and level of PA in a biracial cohort of middle-aged men and women.

Methods and Results—

Baseline characteristics on risk factor levels were obtained on 14 219 participants from the Atherosclerosis Risk in Communities Study. AF incidence was ascertained from 1987 to 2009. Adjusted Cox proportional hazards models were used to estimate the associations between body mass index, waist circumference, relative weight change, and PA level with incident AF. During follow-up, there were 1775 cases of incident AF. Body mass index and waist circumference were positively associated with AF as was weight loss/gain of >5% initial body weight. An ideal level of PA had a small protective effect on AF risk and partially attenuated the risk of AF associated with excess weight in men but not women: compared with men with a normal body mass index, the risk of AF in obese men with an ideal, intermediate, and poor level of PA at baseline was increased by 37%, 129%, and 156% (
P
interaction
=0.04). During follow-up, PA did not modify the association between weight gain and risk of AF.

Conclusions—
Obesity and extreme weight change are risk factors for incident AF, whereas being physically active is associated with a small reduction in risk. In men only, being physically active offset some, but not all, of the risk incurred with excess body weight.
Long-Term Follow-Up Shows Excellent Transmural Atrial Lead Performance in Patients With Complex Congenital Heart Disease
Authors: Williams Matthew R. , Shepard Suzanne M. , Boramanand Nicole K. , Lamberti John J. , Perry James C. 
Published: June 2014

Background—
Many patients with congenital heart disease require permanent pacing for rhythm management but cannot undergo transvenous lead placement. In others, epicardial scarring prohibits adequate sensing and pacing thresholds using epicardial leads. This study describes long-term lead performance using a transmural atrial (epicardial to endocardial) pacing approach in patients with congenital heart disease.

Methods and Results—
For transmural atrial (TMA) lead access, a bipolar, steroid-eluting transvenous lead was placed from the epicardium via purse-string incision or atriotomy and affixed to atrial endocardium. Records were reviewed for patient data and acute and long-term lead performance for TMA leads placed 1998 to 2004. Forty-two of 48 TMA leads remain active at last follow-up. Two leads fractured, 4 were functional at >5-year follow-up but no longer active. Freedom from lead failure 98% (95% confidence interval, 86%–100%) at mean follow-up 7.8 years. TMA leads gave excellent sensing and pacing characteristics at implant and chronically. Median acute and chronic sensing thresholds were 3 and 2.8 mV, respectively; median acute and chronic pacing thresholds at 0.5 ms were 0.9 and 0.7 V, respectively. TMA leads performed similarly in Fontan patients. Overdrive pacing for intra-atrial re-entrant tachycardia was successful in 7 of 8 patients. One patient with high baseline risk died of stroke 7 years after implant. No lead-associated thrombi were observed.

Conclusions—
TMA pacing leads had excellent longevity, initial, and chronic functional properties and provide an alternative to epicardial leads in patients with congenital heart disease. Patients who cannot receive transvenous leads, have epicardial scarring or have intra-atrial re-entrant tachycardia could benefit most from routine use of this technique.
Impact of Empiric Nesiritide or Milrinone Infusion on Early Postoperative Recovery After Fontan Surgery
Authors: Costello John M. , Dunbar-Masterson Carolyn , Allan Catherine K. , Gauvreau Kimberlee , Newburger Jane W. , McGowan Francis X. , Wessel David L. , Mayer John E. , Salvin Joshua W. , Dionne Roger E. , Laussen Peter C. 
Published: June 2014

Background—
We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes.

Methods and Results—

In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0–24]; milrinone, 18 [0–23]; placebo, 20 [0–23];
P
=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events.

Conclusions—
Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00543309.
Coronary Artery Disease Detected by Coronary Computed Tomographic Angiography Is Associated With Intensification of Preventive Medical Therapy and Lower Low-Density Lipoprotein Cholesterol
Authors: Hulten Edward , Bittencourt Marcio Sommer , Singh Avinainder , O’Leary Daniel , Christman Mitalee P. , Osmani Wafa , Abbara Suhny , Steigner Michael L. , Truong Quynh A. , Nasir Khurram , Rybicki Frank F. , Klein Josh , Hainer Jon , Brady Thomas J. , Hoffmann Udo , Ghoshhajra Brian B. , Hachamovitch Rory , Di Carli Marcelo F. , Blankstein Ron 
Published: June 2014

Background—
Coronary computed tomographic angiography (CCTA) is an accurate test for the identification of coronary artery disease (CAD), yet the impact of CCTA results on subsequent medical therapy and risk factors has not been widely reported.

Methods and Results—

We identified consecutive patients aged >18 years without prior CAD who underwent CCTA from 2004 to 2011 and had complete data on medications before and after CCTA. CCTA results were categorized as no CAD, <50% stenosis, and ≥50% stenosis. Based on the number of involved segments, extent of disease was categorized as nonextensive (≤4 segments) or extensive CAD (>4 segments). Electronic medical records and patient interviews were reviewed blinded to CCTA findings to assess initiation of aspirin and intensification of lipid-lowering therapies. Survival analysis was performed to evaluate intensification of lipid therapy as a predictor of cardiovascular death or nonfatal myocardial infarction. Among 2839 patients with mean follow-up of 3.6 years, the odds of physician intensification of lipid-lowering therapy significantly increased for those with nonobstructive CAD (odds ratio, 3.6; 95% confidence interval, 2.9–4.9;
P
<0.001) and obstructive CAD (odds ratio, 5.6; 95% confidence interval, 4.3–7.3;
P
<0.001). Low-density lipoprotein cholesterol levels declined significantly in association with intensification of lipid-lowering therapy after CCTA in all patient subgroups. In a hypothesis-generating analysis, among patients with nonobstructive but extensive CAD, statin use after CCTA was associated with a reduction in cardiovascular death or myocardial infarction (hazards ratio, 0.18; 95% confidence interval, 0.05–0.66;
P
=0.01).

Conclusions—
Abnormal CCTA findings are associated with downstream intensification in statin and aspirin therapy. In particular, CCTA may lead to increased use of prognostically beneficial therapies in patients identified as having extensive, nonobstructive CAD.
Assessment of a University of California, Los Angeles 4‐Variable Risk Score for Advanced Heart Failure
Authors: Sartipy Ulrik , Goda Ayumi , Mancini Donna M. , Lund Lars H. 
Published: June 2014

Background

The 4‐variable risk score from University of California, Los Angeles (
UCLA)
demonstrated superior discrimination in advanced heart failure, compared to established risk scores. However, the model has not been externally validated, and its suitability as a selection tool for heart transplantation (HT) and left ventricular assist device (LVAD) is unknown.

Methods and Results

We calculated the
UCLA
risk score (based on B‐type natriuretic peptide, peak
VO
2
, New York Heart Association class, and use of angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker) in 180 patients referred for HT. The outcome was survival free from urgent transplantation or LVAD. The model‐predicted survival was compared to Kaplan‐Meier's estimated survival at 1, 2, and 3 years. Model discrimination and calibration were assessed. During a mean follow‐up of 2.1 years, 37 (21%) events occurred. One‐, 2‐ and 3‐year observed event‐free survival was 88%, 81%, and 75%, and the observed/predicted ratio was 0.97, 0.96, and 0.97, respectively. Time‐dependent receiver operating characteristic curve analyses demonstrated good discrimination overall (1‐year area under curve, 0.801; 2‐year, 0.774; 3‐year, 0.837), but discrimination between the 2 highest risk groups was poor. The difference between observed and predicted survival ranged from −14 to +17 percentage points, suggesting poor model calibration. Fairly similar results were found when the analyses were repeated in 715 patients after multivariate imputation of missing data.

Conclusions

The
UCLA
4‐variable risk model calibration was inconsistent and high‐risk discrimination was poor in an external validation cohort. Further model assessment is warranted before widespread use.
Saphenous vein stripping surgical technique and frequency of saphenous nerve injury
Authors: Jaworucka-Kaczorowska Aleksandra , Oszkinis Grzegorz , Huber Juliusz , Wiertel-Krawczuk Agnieszka , Gabor Elżbieta , Kaczorowski Paweł 
Published: June 2014

Objectives Saphenous nerve injury is the most common complication after surgical treatment of varicose veins. The aim of this study was to establish its frequency at great saphenous vein long stripping when four methods of surgery were applied. Methods Eighty patients were divided into four groups depending on different stripping methods. Sensory transmission in saphenous nerve and sensory perception of shank were examined before surgery and two weeks, three and six months afterwards with clinical neurophysiology methods. Results In 36% of patients, surgeries caused the injury of saphenous nerve mainly by proximal stripping without invagination (65%, group I). Transmission disturbances ceased completely after three months in patients undergoing distal stripping with invagination (group IV), while in group I they persisted for six months in 35%. Group IV patients were the least injured and group I the most. Conclusion Neurophysiological findings may suggest that distal stripping with vein invagination gives the best saphenous nerve sparing.
Prevalence of asymptomatic lower limb venous thrombosis in infertile women with thrombophilic disorders
Authors: Costanzo Luca , Di Pino Luigi , Ragusa Mario , Buccheri Sergio , Sole Andrea , Virgilio Vittorio , Tamburino Corrado , Bellanca Salvatore 
Published: June 2014

Objective We sought to assess the prevalence of asymptomatic venous thrombosis in infertile women with thrombophilic disorders (TDs). Methods and results A total of 73 infertile women with TDs underwent duplex ultrasound scan to evaluate superficial and deep venous circulation of lower limbs. A control group of 35 infertile women without TDs was included. A single TD was found in 13 (17.8%) subjects, and 40 (54.8%) women presented a combined defect (more than three alterations). No residual mural thrombosis (RT) was noted in any deep veins. We found RT in 48 (65.8%) patients of TD group, while no RT was found in the control group ( p < 0.0001). None of the clinical and prothrombotic factors were predictors of RT (all p > 0.20), and frequency of TD did not correlate with multi-vessel RT ( p = 0.252). Conclusions No signs of deep vein thrombosis but high prevalence of superficial RT is present in infertile women with TDs. Further studies are needed to assess the prognostic value of our findings.
Osteochondral Autologous Transplantation Is Superior to Repeat Arthroscopy for the Treatment of Osteochondral Lesions of the Talus After Failed Primary Arthroscopic Treatment
Authors: Yoon Hang Seob , Park Yoo Jung , Lee Moses , Choi Woo Jin , Lee Jin Woo 
Published: June 2014

Background: Several studies have reported on the outcome of arthroscopic treatment or osteochondral autologous transplantation (OAT) for osteochondral lesions of the talus (OLT), with mixed results. None of these studies has compared the results of repeat arthroscopy and OAT after failed primary arthroscopic treatment. Purpose: To compare the outcomes of OAT and repeat arthroscopy for the treatment of OLT after primary arthroscopy Study Design: Cohort study; Level of evidence, 3. Methods: This study included 22 patients who underwent OAT (group A) and 22 patients who underwent repeat arthroscopy (group B) after failed treatment of OLT among 399 patients who received primary arthroscopic marrow stimulation at single institution between 2001 and 2009. All patients were evaluated clinically using the visual analog scale (VAS) for pain and American Orthopaedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Scale. The cumulative success rates were compared by use of Kaplan-Meier life table analysis. Results: The patients’ demographic and clinical characteristics and indications for surgery were comparable between the groups. Both groups showed significantly improved ( P < .001) VAS and AOFAS scores 6 months after surgery. However, group B showed significant deterioration over a mean follow-up period of 50 months. Overall, 18 of 22 (81.8%) patients in group A and 7 of 22 (31.8%) patients in group B achieved an excellent or good (≥80) AOFAS score ( P < .001). No patient in group A and 14 of 22 (63.6%) in group B required further revisions. Conclusion: Osteochondral autologous transplantation was significantly superior to repeat arthroscopic treatment of OLT after a mean follow-up period of 48 months. Therefore, repeat arthroscopy should be used judiciously for the treatment of OLT after failed arthroscopic treatment.
Examination of the Test-Retest Reliability of a Computerized Neurocognitive Test Battery
Authors: Nakayama Yusuke , Covassin Tracey , Schatz Philip , Nogle Sally , Kovan Jeff 
Published: June 2014

Background: Test-retest reliability is a critical issue in the utility of computer-based neurocognitive assessment paradigms employing baseline and postconcussion tests. Researchers have reported low test-retest reliability for the Immediate Post Concussion Assessment and Cognitive Testing (ImPACT) across an interval of 45 and 50 days. Purpose: To re-examine the test-retest reliability of the ImPACT between baseline, 45 days, and 50 days. Study Design: Descriptive laboratory study. Methods: Eighty-five physically active college students (51 male, 34 female) volunteered for this study. Participants completed the ImPACT as well as a 15-item memory test at baseline, 45 days, and 50 days. Intraclass correlation coefficients (ICCs) were calculated for ImPACT composite scores, and change scores were calculated using reliable change indices (RCIs) and regression-based methods (RBMs) at 80% and 95% confidence intervals (CIs). Results: The respective ICCs for baseline to day 45, day 45 to day 50, baseline to day 50, and overall were as follows: verbal memory (0.76, 0.69, 0.65, and 0.78), visual memory (0.72, 0.66, 0.60, and 0.74), visual motor (processing) speed (0.87, 0.88, 0.85, and 0.91), and reaction time (0.67, 0.81, 0.71, and 0.80). All ICCs exceeded the threshold value of 0.60 for acceptable test-retest reliability. All cases fell well within the 80% CI for both the RCI and RBM, while 1% to 5% of cases fell outside the 95% CI for the RCI and 1% for the RBM. Conclusion: Results suggest that the ImPACT is a reliable neurocognitive test battery at 45 and 50 days after the baseline assessment. The current findings agree with those of other reliability studies that have reported acceptable ICCs across 30-day to 1-year testing intervals, and they support the utility of the ImPACT for the multidisciplinary approach to concussion management. Clinical Relevance: This study suggests that the computerized neurocognitive test battery, ImPACT, is a reliable test for postconcussion serial assessments. However, when managing concussed athletes, the ImPACT should not be used as a stand-alone measure.
Prevalence and Incidence of Cartilage Injuries and Meniscus Tears in Patients Who Underwent Both Primary and Revision Anterior Cruciate Ligament Reconstructions
Authors: Wyatt Ronald W.B. , Inacio Maria C.S. , Liddle Kate D. , Maletis Gregory B. 
Published: June 2014

Background: Previous studies have found differences in meniscus and cartilage injury rates between groups of patients after primary and revision anterior cruciate ligament reconstructions (ACLRs). This study examined a cohort of individual patients who underwent primary and subsequent revision ACLR to determine the incidence of cartilage and meniscus disease. Purpose: To describe the prevalence and incidence of meniscus and articular cartilage injuries in patients who underwent primary and then subsequent revision ACLR as well as indicate differences in the management of these injuries. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent primary and then revision ACLR from February 2005 to September 2011 were identified using a community-based registry. Patient and procedure characteristics were obtained, and descriptive statistics were used to evaluate the study sample. Results: There were 261 patients who underwent primary and then subsequent revision ACLR during the study period. The median age was 18 years at primary ACLR and 20 years at revision ACLR. Revision ACLR was performed for instability in 256 patients (98%) and for infection in 5 patients (2%). The prevalence of cartilage injuries increased from 14.9% at primary ACLR to 31.8% at revision ACLR. The prevalence of meniscus tears decreased from 54.8% at primary ACLR to 43.7% at revision ACLR. The prevalence of lateral meniscus tears was 32.2% at primary ACLR but only 18.4% at revision ACLR, while the prevalence of medial meniscus tears was the same at primary and revision ACLRs (32.6%). Patients who underwent meniscus tear treatment at primary ACLR had a 70.8% prevalence of meniscus tears at revision ACLR. Conclusion: In this community-based sample followed from primary ACLR to revision ACLR, the prevalence of articular cartilage injuries increased, while the prevalence of meniscus injuries decreased. The higher prevalence of articular cartilage injuries at revision ACLR may represent new injuries. The lower prevalence of meniscus tears at revision ACLR may be caused by susceptible menisci being injured and treated at primary surgery or by changes in knee kinematics or injury exposure patterns.
Routine screening for α-thalassaemia using an immunochromatographic strip assay for haemoglobin Bart's
Authors: Prayalaw Patcharawadee , Fucharoen Goonnapa , Fucharoen Supan 
Published: June 2014

Objective To evaluate an immunochromatographic (IC) strip assay for Hb Bart's as a routine screening test for α-thalassaemia in area with a high prevalence of thalassaemia and haemoglobinopathies. Methods A total of 300 adult screen positive blood specimens were collected at an ongoing thalassaemia screening programme in northeast Thailand. Routine screening was done using red blood cell indices, osmotic fragility, and dichlorophenolindophenol tests. The IC strip assay for haemoglobin Bart's was performed on all samples. The result was evaluated against thalassaemia genotypes determined using standard haemoglobin and DNA analyses. Results Of 300 subjects investigated, Hb and DNA analyses identified 32 with normal genotype. The remaining subjects carried thalassaemia with as many as 16 different genotypes. Hb Bart's was detected in all cases, with several α0-thalassaemia (SEA type) related disorders. Of cases with α+-thalassaemia, 86.1% showed a positive result; 100 out of 103 Hb E carriers, all homozygous Hb E and β-thalassaemia trait were negative. Nine out of 17 cases with β-thalassaemia/Hb E disease, and one case of double heterozygote for Hb Q-Thailand and Hb E returned positive results. The overall sensitivity and specificity of the IC strip assay for detecting α0-thalassaemia were 100% and 73.1%, respectively. Conclusion The results showed a high sensitivity for screening for α0-thalassaemia using IC strip assay for Hb Bart's. This simple method, used in combination with conventional screening protocols, should lead to a significant reduction in the number of referral cases for DNA analysis. Cost effectiveness in each population should be taken into consideration.