bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment Serum VEGF Is Associated with Clinical Response and Overall Survival in Advanced Melanoma Patients Treated with Ipilimumab
Authors: Yuan Jianda , Zhou Jun , Dong Zhiwan , Tandon Sapna , Kuk Deborah , Panageas Katherine S. , Wong Philip , Wu Xinqi , Naidoo Jarushka , Page David B. , Wolchok Jedd D. , Hodi F. Stephen 
Published: February 2014

AbstractIpilimumab, an antibody that blocks CTL antigen 4 (CTLA-4), improves overall survival (OS) for patients with metastatic melanoma. Given its role in angiogenesis and immune evasion, serum VEGF levels were evaluated for association with clinical benefit in ipilimumab-treated patients. Sera were collected from 176 patients treated at 3 (n = 98) or 10 mg/kg (n = 68). The VEGF levels before treatment and at induction completion (week 12) were analyzed using the Meso Scale Discovery kit. The association of the levels of VEGF with clinical responses and OS were assessed using the Fisher exact and Kaplan–Meier log-rank tests. VEGF as a continuous variable was associated with OS (P = 0.002). Using 43 pg/mL as the cutoff pretreatment VEGF value defined by maximally selected log-rank statistics, pretreatment VEGF values correlated with clinical benefit at week 24 (P = 0.019; 159 patients evaluable). Pretreatment VEGF ≥ 43 pg/mL was associated with decreased OS (median OS 6.6 vs. 12.9 months, P = 0.006; 7.4 vs. 14.3 months, P = 0.037 for 3 mg/kg; and 6.2 vs. 10.9 months, P = 0.048 for 10 mg/kg). There was no correlation between VEGF changes and clinical outcome. Serum VEGF may be a predictive biomarker for ipilimumab treatment and is worthy of prospective investigation with various forms of immunologic checkpoint blockade. Cancer Immunol Res; 2(2); 127–32. ©2014 AACR.
Sustained Complete Response to CTLA-4 Blockade in a Patient with Metastatic, Castration-Resistant Prostate Cancer
Authors: Graff Julie N. , Puri Sachin , Bifulco Carlo B. , Fox Bernard A. , Beer Tomasz M. 
Published: February 2014

Abstract
We present the case of a man with metastatic, castration-resistant prostate cancer, who had a complete prostate-specific antigen (PSA) response after 2½ doses of ipilimumab. His treatment course was complicated by diarrhea and autoimmune hepatitis, both of which resolved within 4 months. Sera and biopsy specimens were accessed, and sera from pretreatment and day 113 were analyzed. Augmented antibody responses were detected against 11 potential tumor antigens, with responses ranging from 5- to 20-fold in day 113 sera compared with baseline. Genes that were targets of a strong antibody response (arbitrarily set at 10-fold or greater increase) were analyzed by real-time PCR for expression in the tumor biopsy cDNA. Of the top 5 genes, only 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) could be identified in the amplified tumor biopsy cDNA. Using an antibody to HIBCH, immunohistochemical analysis documented strong expression of the protein. Together, these data suggest that an augmented antibody response to HIBCH, an antigen that was expressed by the patient's prostate cancer, could have contributed to the clinical response. After 16 months of PSA stability, he discontinued his androgen-suppression therapy. With the return of his testosterone, his PSA increased slightly, likely originating from his intact prostate. He has been disease free for the past 6 years without any additional therapy. Cancer Immunol Res; 2(5); 399–403. ©2014 AACR.
Suppression of Spontaneous Ca Elevations Prevents Atrial Fibrillation in Calsequestrin 2-Null Hearts
Authors: Faggioni Michela , Savio-Galimberti Eleonora , Venkataraman Raghav , Hwang Hyun Seok , Kannankeril Prince J. , Darbar Dawood , Knollmann Björn C. 
Published: February 2014

Background—
Atrial fibrillation (AF) risk has been associated with leaky ryanodine receptor 2 (RyR2) Ca release channels. Patients with mutations in RyR2 or in the sarcoplasmic reticulum Ca-binding protein calsequestrin 2 (Casq2) display an increased risk for AF. Here, we examine the underlying mechanisms of AF associated with loss of Casq2 and test mechanism-based drug therapy.

Methods and Results—

Compared with wild-type Casq2
+/+
mice, atrial burst pacing consistently induced atrial flutter or AF in Casq2
−/−
mice and in isolated Casq2
−/−
hearts. Atrial optical voltage maps obtained from isolated hearts revealed multiple independent activation sites arising predominantly from the pulmonary vein region. Ca and voltage mapping demonstrated diastolic subthreshold spontaneous Ca elevations (SCaEs) and delayed afterdepolarizations whenever the pacing train failed to induce AF. The dual RyR2 and Na channel inhibitor R-propafenone (3 μmol/L) significantly reduced frequency and amplitude of SCaEs and delayed afterdepolarizations in atrial myocytes and intact atria and prevented induction of AF. In contrast, the S-enantiomer of propafenone, an equipotent Na channel blocker but much weaker RyR2 inhibitor, did not reduce SCaEs and delayed afterdepolarizations and failed to prevent AF.

Conclusions—
Loss of Casq2 increases risk of AF by promoting regional SCaEs and delayed afterdepolarizations in atrial tissue, which can be prevented by RyR2 inhibition with R-propafenone. Targeting AF caused by leaky RyR2 Ca channels with R-propafenone may be a more mechanism-based approach to treating this common arrhythmia.
National Assessment of Warfarin Anticoagulation Therapy for Stroke Prevention in Atrial Fibrillation
Authors: Dlott Jeffrey S. , George Roberta A. , Huang Xiaohua , Odeh Mouneer , Kaufman Harvey W. , Ansell Jack , Hylek Elaine M. 
Published: February 2014

Background—
Anticoagulation control with warfarin, as assessed by the international normalized ratio (INR), is challenging. Time in the therapeutic range has been inversely correlated with major hemorrhage, thrombosis, and mortality. Quest Diagnostics offers standardized INR laboratory testing services to approximately half of US physician practices. To inform national stroke prevention strategies, we evaluated anticoagulation control in office-based community practices.

Methods and Results—

We selected individuals with ≥2 months of INR data, INR results of >1.2, and an ICD-9 diagnosis code of atrial fibrillation. Frequency of INR testing and time in the therapeutic range were analyzed by age, sex, length of testing period, number of referred patients per provider, and median household income (based on home ZIP code). We identified 138 319 individuals referred by 37 939 physicians, yielding a total of 2 683 674 INR results. Patients had a mean age of 74 years; 81% were ≥65 years of age, and 55% were ≥75 years of age. The mean time in the therapeutic range was 53.7% overall and improved with time on treatment, increasing from 47.6% for patients with <6 months of testing to 57.5% for those with ≥6 months of testing (
P
<0.0001). The number of patients tested per physician practice was positively associated with time in the therapeutic range. Younger age, female sex, and lower income were also independently associated with poorer anticoagulant control.

Conclusion—
This study demonstrates widespread suboptimal anticoagulation control, suggesting an urgent need to improve oral anticoagulation care for most patient segments in the United States.
Text Mining to Decipher Free-Response Consumer Complaints
Authors: Ghazizadeh Mahtab , McDonald Anthony D. , Lee John D. 
Published: February 2014

Objective: This study applies text mining to extract clusters of vehicle problems and associated trends from free-response data in the National Highway Traffic Safety Administration’s vehicle owner’s complaint database. Background: As the automotive industry adopts new technologies, it is important to systematically assess the effect of these changes on traffic safety. Driving simulators, naturalistic driving data, and crash databases all contribute to a better understanding of how drivers respond to changing vehicle technology, but other approaches, such as automated analysis of incident reports, are needed. Method: Free-response data from incidents representing two severity levels (fatal incidents and incidents involving injury) were analyzed using a text mining approach: latent semantic analysis (LSA). LSA and hierarchical clustering identified clusters of complaints for each severity level, which were compared and analyzed across time. Results: Cluster analysis identified eight clusters of fatal incidents and six clusters of incidents involving injury. Comparisons showed that although the airbag clusters across the two severity levels have the same most frequent terms, the circumstances around the incidents differ. The time trends show clear increases in complaints surrounding the Ford/Firestone tire recall and the Toyota unintended acceleration recall. Increases in complaints may be partially driven by these recall announcements and the associated media attention. Conclusion: Text mining can reveal useful information from free-response databases that would otherwise be prohibitively time-consuming and difficult to summarize manually. Application: Text mining can extend human analysis capabilities for large free-response databases to support earlier detection of problems and more timely safety interventions.
Laryngeal Muscle Activity in Unilateral Vocal Fold Paralysis Patients Using Electromyography and Coronal Reconstructed Images
Authors: Sanuki Tetsuji , Yumoto Eiji , Nishimoto Kohei , Minoda Ryosei 
Published: February 2014

ObjectiveTo assess laryngeal muscle activity in unilateral vocal fold paralysis (UVFP) patients using laryngeal electromyography (LEMG) and coronal images.Study DesignCase series with chart review.SettingUniversity hospital.Subjects and MethodsTwenty‐one patients diagnosed with UVFP of at least 6 months in duration with paralytic dysphonia, underwent LEMG, phonatory function tests, and coronal imaging. A 4‐point scale was used to grade motor unit (MU) recruitment: absent = 4+, greatly decreased = 3+, moderately decreased = 2+, and mildly decreased = 1+. Maximum phonation time (MPT) and mean flow rate (MFR) were employed. Coronal images were assessed for differences in thickness and vertical position of the vocal folds during phonation and inhalation.ResultsMU recruitment in thyroarytenoid/lateral cricoarytenoid (TA/LCA) muscle complex results were 1+ for 4 patients, 2+ for 5, 3+ for 6, and 4+ for 6. MPT was positively correlated with MU recruitment. Thinning of the affected fold was evident during phonation in 19 of the 21 subjects. The affected fold was at an equal level with the healthy fold in all 9 subjects with MU recruitment of 1+ and 2+. Eleven of 12 subjects with MU recruitments of 3+ and 4+ showed the affected fold at a higher level than the healthy fold. There was a significant difference between MU recruitment and the vertical position of the affected fold.ConclusionsSynkinetic reinnervation may occur in some cases with UVFP. MU recruitments of TA/LCA muscle complex in UVFP patients may be related to phonatory function and the vertical position of the affected fold.
Prevalence and Risk Factors for Central Sleep Apnea in Infants with Laryngomalacia
Authors: Tanphaichitr Archwin , Tanphaichitr Pattraporn , Apiwattanasawee Polporn , Brockbank Justin , Rutter Michael J. , Simakajornboon Narong 
Published: February 2014

ObjectiveTo identify the prevalence of and risk factors for central sleep apnea (CSA) in infants who are diagnosed with laryngomalacia.Study DesignCase series with chart review.SettingQuaternary care pediatric hospital.Subjects and MethodsWe performed a chart review in infants with laryngomalacia. All infants had diagnostic polysomnography (PSG) performed from 2003 to 2012. Infants who underwent supraglottoplasty or other upper airway surgery prior to PSG were excluded. CSA was defined as central apnea index ≥ 5. Demographic data, underlying diseases, and PSG data were reviewed and analyzed.ResultsFifty‐four patients met the inclusion criteria. The mean age at the date PSG was performed was 3.4 ± 2.7 months. The prevalence of CSA in infants with laryngomalacia was 46.3%. Odds ratio (OR) of CSA was above 2.0 in patients with the following risk factors: underlying neurologic disease, hypotonia, or syndrome (OR = 2.5, P =. 13), history of apparent life‐threatening events (OR = 2.7, P =. 19), premature infants (OR = 2.2, P =. 33), and age less than 3 months (OR = 2.3, P =. 15). However, none of the risk factors were statistically significant. Analysis of sleep architecture revealed a decrease in total sleep time (345.4 ± 70.6 minutes vs 393.5 ± 68.3 minutes, P =. 02) and sleep efficiency (67.7 ± 8.9% vs 75.2 ± 9.3%, P =. 004) in the CSA group.ConclusionCSA is relatively common in infants with laryngomalacia. There seems to be a higher prevalence of CSA in infants with certain risk factors, but none of the risk factors are statistically significant. The presence of CSA can lead to alteration in sleep architecture. In addition to clinical evaluation, polysomnography may be warranted for the evaluation of infants with laryngomalacia and associated complex medical conditions.
Aquaporin‐1 Promoter Hypermethylation Is Associated with Improved Prognosis in Salivary Gland Adenoid Cystic Carcinoma
Authors: Tan Marietta , Shao Chunbo , Bishop Justin A. , Feng Zhaoyong , Trock Bruce J. , Westra William H. , Ha Patrick K. 
Published: February 2014

ObjectivesAquaporin‐1 (AQP1) is a candidate oncogene that is epigenetically modified in adenoid cystic carcinoma (ACC). We sought to (1) assess AQP1 promoter methylation and expression in an ACC cohort, (2) identify correlations between AQP1 and clinical outcomes, and (3) explore the role of AQP1 in tumor progression in vitro.Study designLaboratory study, retrospective chart review.SettingAcademic medical center.MethodsDNA and RNA were isolated from ACC tumors and control salivary gland tissues. Quantitative methylation‐specific polymerase chain reaction (PCR) was performed on bisulfite‐treated DNA. Quantitative reverse transcription PCR was performed after cDNA synthesis. Cell lines stably overexpressing an AQP1 plasmid or empty vector were generated. Cell scratch and Matrigel invasion assays were performed. Retrospective chart review was performed for collection of clinical information.ResultsMethylation results from 77 tumors and 30 controls demonstrated that AQP1 was hypomethylated in tumors (P <. 0001). Fifty‐eight tumors (75.3%) displayed AQP1 hypomethylation compared with controls. AQP1 expression levels assessed in 58 tumors and 23 controls demonstrated a trend toward increased expression in tumors (P =. 08). Univariate analysis revealed that AQP1 hypermethylation was associated with increased overall survival. No associations between AQP1 expression level and survival were found. AQP1 overexpression did not affect cell migratory or invasive capacities in vitro.ConclusionAQP1 promoter hypomethylation is common in ACC, and AQP1 tends to be overexpressed in these tumors. Increased AQP1 methylation is associated with improved prognosis on univariate analysis, but expression is not associated with outcomes. Further in vitro studies are necessary to clarify the role of AQP1 in ACC.
Secondary Tracheoesophageal Puncture In‐Office Using Seldinger Technique
Authors: Britt Christopher J. , Lippert Dylan , Kammer Rachael , Ford Charles N. , Dailey Seth H. , McCulloch Timothy , Hartig Gregory 
Published: February 2014

ObjectiveEvaluate the safety and efficacy of in‐office secondary tracheoesophageal puncture (TEP) technique using transnasal esophagoscopy (TNE) and the Seldinger technique in conjunction with a cricothyroidotomy kit for placement.Study DesignCase series with chart review.SettingAcademic medical center.Subject and MethodsA retrospective chart review was performed on 83 subjects who underwent in‐office secondary TEP. Variables that were examined included disease site, staging, histologic diagnosis, extent of resection and reconstruction, chemoradiation, functional voice status (as assessed by speech pathologist in most recent note), and complications directly related to the procedure.ResultsEighty‐three individuals from our institution met our criteria for in‐office secondary TEP from 2005 to August 2012. Of these, 97.6% (81/83) had no complications of TEP. The overall complication rate was 2.4% (2/83). Complications included bleeding from puncture site and closure of puncture site after dislodgement of prosthesis at the time of puncture. Fluent conversational speech was achieved in 69.9% of all patients (58/83), and an additional 19.3% (16/83) achieved functional/intelligible speech; of those, 3.6% (3/83) were unable to achieve fluent conversational speech due to anatomic defects from previous surgery.ConclusionAn in‐office TEP can be safely performed using the Seldinger technique with direct visualization using TNE, despite the extent of resection or reconstruction, with functional speech outcomes comparable to other studies available in the literature.
The Interrater and Intrarater Reliability of the Philpott‐Javer Staging System Based on Level of Training
Authors: Parhar Harman S. , Thamboo Andrew , Habib Al‐Rahim , Chang Brent , Gan Eng Cern , Javer Amin R. 
Published: February 2014

ObjectiveThe Philpott‐Javer postoperative endoscopic mucosal staging system for allergic fungal rhinosinusitis has previously demonstrated acceptable interrater reliability among rhinologists. There are, however, numerous learners involved in patient care at tertiary centers. This study aims to analyze the interrater and intrarater reliability of this system among learners in otolaryngology at different stages in training.Study DesignA prospective analysis of retrospectively collected endoscopic photographs.SettingA tertiary care teaching hospital (January 2013).SubjectsFifty patients undergoing routine follow‐up.MethodThree photographs from each of 50 patients undergoing routine postsurgical nasoendoscopy were reviewed. Images were played twice, 1 week apart, in 2 differently randomized cycles and scored according to Philpott‐Javer criteria by a rhinologist, a rhinology fellow, a senior otolaryngology resident, a junior otolaryngology resident, and a medical student. Interobserver reliability was assessed using the intraclass correlation coefficient, while intrarater reliability was assessed by Shrout‐Fleiss κ values. Agreement between each learner and the rhinologist was also assessed using κ values.ResultsThe interclass correlation among the 5 raters was 0.7600 (95% confidence interval, 0.6917‐0.8161) for the Philpott‐Javer scoring system, suggesting substantial reliability. Intrarater data showed substantial to almost‐perfect reliability (κ values between 0.668 and 0.815) among all raters using this system. There was also moderate to substantial agreement between the learners and the rhinologist (κ values between 0.534 and 0.710).ConclusionResults suggest that the Philpott‐Javer staging system has acceptable intrarater and interrater reliability among learners of differing levels of clinical experience and is suitable for evaluating progress following surgery.
Diagnostic accuracy of 3D color volume-rendered CT images for peroneal tendon dislocation in patients with acute calcaneal fractures
Authors: Ohashi Kenjirou , Sanghvi Tina , El-Khoury Georges Y , Ahn Joong Mo , Bennett D Lee , Geijer Mats , Inaoka Tsutomu , Berbaum Kevin 
Published: February 2014

Background Use of three-dimensional (3D) color volume-rendered (VR) images has been reported to be more time-efficient compared to that of cross-sectional computed tomography (CT) images for the diagnosis of peroneal tendon dislocation. However, the diagnostic performance of this technique has not been studied. Purpose To test diagnostic accuracy of 3D color VR CT images of ankle for peroneal tendon dislocation in patients with acute calcaneal fractures. Material and Methods The study consisted of 121 ankle CT studies from 105 consecutive patients (85 men, 20 women; mean age, 42 years; age range, 16–75 years) with acute calcaneal fractures. Peroneal tendon dislocation was diagnosed on multiplanar CT images by consensus of two experienced musculoskeletal radiologists, which served as the reference standard. Three other musculoskeletal radiologists independently reviewed 3D images alone on a workstation. The readers determined whether or not there was peroneal tendon dislocation using three degrees of certainty (definite, probable, and possible). Diagnostic performance of 3D images for peroneal tendon dislocation was evaluated by calculating the sensitivities, specificities, and area under the receiver-operating characteristic (ROC) curves. Results Forty-eight (40%) out of 121 studies showed peroneal tendon dislocation based on the expert readings using multiplanar reformatted images. Sensitivities/specificities of 3D images measured 0.92/0.81, 0.88/0.90, and 0.81/0.92 for three readers, respectively. The area under the proper binormal ROC curve based on all three readers (0.93, 0.94, and 0.92) measured 0.93 with a 95% confidence interval of 0.89–0.98. Conclusion Diagnostic accuracy of 3D images is comparable to, but not as good as that of MPR images for the diagnosis of peroneal tendon dislocation in patients with acute calcaneal fractures.
Hepatitis C prevalence in HIV-infected individuals: a comparison of inpatient and outpatient care
Authors: Zhu Ziqiang , Dhir Teena , Soe Myat , Green Linda , Jiang Ning 
Published: February 2014

Summary Due to the shared risk factors for viral transmission, coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. This study examined the seroprevalence of HCV among HIV–infected patients in inpatient and outpatient settings. A retrospective chart review of 256 HIV–infected patients was conducted in Prince George's Hospital Center (inpatients from 1 September 2011 to 1 March 2012) and Glenridge Medical Center (outpatients from 1 January 2011 to 31 December 2012). The mean age of the population was 46 ± 12 and 44 ± 11 for inpatients and outpatients, respectively. HIV–infected men comprised 61.9% inpatients and 64.8% outpatients. The overall prevalence of HCV infection in HIV/AIDS patients was 12.5% (32/256), with a higher prevalence in the inpatient group than that in the outpatient group (24.6% vs 11.2%, p < 0.01). The percentages of drug abuse (43.8% vs 16.5%, p < 0.01) and alcoholism (25.0% and 14.3%, p < 0.05) in HCV/HIV–coinfected patients were higher than those in HIV–monoinfected patients. In addition, only 64.9% of HIV–infected and 50.0% of HCV/HIV–coinfected inpatients were followed up with outside care after discharge. To our knowledge, this study, for the first time, revealed that HCV/HIV coinfection was significantly higher in inpatients compared to outpatients. Considering the high prevalence and comorbidities associated with HCV/HIV coinfection, it is recommended that evaluation of hepatic damage, especially fibrosis, should be initiated during hospitalization as well as outpatient care.