bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcatheter Replacement of Stenotic Aortic Valve Normalizes Cardiac–Coronary Interaction by Restoration of Systolic Coronary Flow Dynamics as Assessed by Wave Intensity Analysis
Authors: Rolandi M. Cristina , Wiegerinck Esther M.A. , Casadonte Lorena , Yong Ze-Yie , Koch Karel T. , Vis Marije , Piek Jan J. , Baan Jan , Spaan Jos A.E. , Siebes Maria 
Published: March 2016

Background—
Aortic valve stenosis (AS) can cause angina despite unobstructed coronary arteries, which may be related to increased compression of the intramural microcirculation, especially at the subendocardium. We assessed coronary wave intensity and phasic flow velocity patterns to unravel changes in cardiac–coronary interaction because of transcatheter aortic valve implantation (TAVI).

Methods and Results—

Intracoronary pressure and flow velocity were measured at rest and maximal hyperemia in undiseased vessels in 15 patients with AS before and after TAVI and in 12 control patients. Coronary flow reserve, systolic and diastolic velocity time integrals, and the energies of forward (aorta-originating) and backward (microcirculatory-originating) coronary waves were determined. Coronary flow reserve was 2.8±0.2 (mean±SEM) in control and 1.8±0.1 in AS (
P
<0.005) and was not restored by TAVI. Compared with control, the resting backward expansion wave was 45% higher in AS. The peak of the systolic forward compression wave was delayed in AS, consistent with a delayed peak aortic pressure, which was partially restored after TAVI. The energy of forward waves doubled after TAVI, whereas the backward expansion wave increased by >30%. The increase in forward compression wave with TAVI was related to an increase in systolic velocity time integral. AS or TAVI did not alter diastolic velocity time integral.

Conclusions—
Reduced coronary forward wave energy and systolic velocity time integral imply a compromised systolic flow velocity with AS that is restored after TAVI, suggesting an acute relief of excess compression in systole that likely benefits subendocardial perfusion. Vasodilation is observed to be a major determinant of backward waves.
Treatment Effect of Clopidogrel Plus Aspirin Within 12 Hours of Acute Minor Stroke or Transient Ischemic Attack
Authors: Li Zixiao , Wang Yilong , Zhao Xingquan , Liu Liping , Wang David , Wang Chunxue , Meng Xia , Li Hao , Pan Yuesong , Wang Xianwei , Wang Chunjuan , Yang Xiaomeng , Zhang Changqing , Jing Jing , Xian Ying , Johnston S. Claiborne , Wang Yongjun ,   on behalf of the CHANCE Investigators
Published: March 2016

Background
The aim of this study was to analyze the benefits and safety associated with the combination therapy of clopidogrel and aspirin among minor stroke or transient ischemic attack patients treated within 12 hours.

Methods and Results

This was a subanalysis of the
CHANCE
(Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events) trial, mainly limited to the prespecified group of patients randomized within 12 hours to either the combination of clopidogrel plus aspirin or aspirin alone. The primary outcome was ischemic stroke during 90‐day follow‐up. Recurrent ischemic stroke and progressive ischemic stroke were analyzed. Multivariable Cox modeling showed that randomization within 12 hours was an independent predictor of ischemic stroke events (hazard ratio [95%
CI
] 1.25 [1.04–1.49],
P
=0.02). Among 2573 patients randomized within 12 hours, 282 (10.96%) patients had ischemic stroke events. Among them, 158 (12.34%) of 1280 patients taking aspirin experienced ischemic stroke compared with 124 (9.59%) of 1293 patients taking clopidogrel–aspirin (
P
=0.02). The dual antiplatelet was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke (6.57% versus 8.91%,
P
=0.03) but not progressive ischemic stroke (3.02% versus 3.43%,
P
=0.28). There was no significant difference in hemorrhagic events (
P
=0.39).

Conclusions
Among patients treated within 12 hours, the combination of clopidogrel and aspirin was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke during the 90‐day follow‐up and did not increase the hemorrhagic risk.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT
00979589.
About thymic carcinomas: challenges in diagnosis and management
Authors: Mlika Mouna , Boudaya Sadok , Braham Emna , Chermiti Fatma , Sayi Ahmed , Marghli Adel , El Mezni Faouzi 
Published: March 2016

Background Thymic carcinomas are rare tumors with a challenging diagnosis. Our aim was to report our 17-year experience of these tumors and to highlight the challenges encountered and the main differential diagnoses ruled out. Methods We studied 12 (92%) men and 1 (7.7%) woman with a mean age of 37 years (range 15–60 years). All patients were symptomatic, with chest pain representing the most frequent symptom. Radiology revealed anterior mediastinal masses in all cases, with either infiltration of the adjacent organs or pulmonary parenchymal metastases. Results The diagnosis was made on surgical biopsies in 12 cases and a lymph node biopsy in one. Microscopic examination revealed squamous carcinoma in 3 cases, synovial sarcoma in 1, mucinous adenocarcinoma in 1, undifferentiated carcinoma in 2, clear cell carcinoma in 1, lymphoepithelioma-like carcinoma in 2, atypical carcinoid tumor in 2, and sarcomatoid carcinoma in 1. Total surgical resection was possible in one patient after neoadjuvant chemotherapy and radiotherapy. Follow-up was possible in only 6 patients, and the mean survival reached 13 months. Conclusion In spite of the lack of follow-up information, this study demonstrates the poor outcome associated with these tumors and the need for standardized treatment.
The Effect of Autologous Hamstring Graft Diameter on the Likelihood for Revision of Anterior Cruciate Ligament Reconstruction
Authors: Spragg Lindsey , Chen Jason , Mirzayan Raffy , Love Rebecca , Maletis Gregory 
Published: March 2016

Background: Hamstring autografts for anterior cruciate ligament (ACL) reconstruction (ACLR) have become popular in the past 2 decades; however, it is difficult to predict the diameter of the harvested tendons before surgery. Previous biomechanical studies have suggested that a smaller graft diameter leads to a lower load to failure, but clinical studies looking at various predictors for failure, including graft size, have been inconclusive. Purpose: To evaluate the relationship of hamstring graft diameter to ACL revision within a large cohort of patients, while controlling for sex, age, body mass index (BMI), and femoral and tibial fixation type. Study Design: Case-control study; Level of evidence, 3. Methods: A case-control study using patients registered in an ACLR registry was conducted. Revision was used as a marker for graft failure. A case was defined as a patient who underwent primary ACLR with a hamstring autograft that was revised during the study period (April 2006 to September 2012). Three controls, defined as patients who underwent primary ACLR with a hamstring autograft that was not revised, were matched to each of the cases according to age, sex, BMI, and femoral and tibial fixation type. Descriptive characteristics were employed, and conditional logistic regression was conducted to produce estimates of odds ratios and 95% CIs. Results: A total of 124 cases and 367 controls were identified. There were no significant differences between cases and controls in the distribution of sex (52.4% male vs 52.9% male, respectively; P = .932), median age (17.6 years [interquartile range (IQR), 15.9-20.4] vs 17.6 years [IQR, 15.9-20.4], respectively; P = .999), median BMI (23.4 kg/m2 [IQR, 21.5-26.4] vs 23.4 kg/m2 [IQR, 21.6-25.8], respectively; P = .954), femoral fixation ( P = .459), and tibial fixation ( P = .766). The mean (±SD) graft diameter was 7.9 ± 0.75 mm in the cases and 8.1 ± 0.73 mm in the controls. The likelihood of a patient needing revision ACLR in the study cohort was 0.82 times lower (95% CI, 0.68-0.98) for every 0.5-mm increase in the graft diameter from 7.0 to 9.0 mm. Conclusion: In this study, within the range of 7.0 to 9.0 mm, there was a 0.82 times lower likelihood of being a revision case with every 0.5-mm incremental increase in graft diameter.
Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study
Authors: Nottage Kerri A , Hankins Jane S , Faughnan Lane G , James Dustin M , Richardson Julie , Christensen Robbin , Kang Guolian , Smeltzer Matthew , Cancio Maria I , Wang Winfred C , Anghelescu Doralina L 
Published: March 2016

Background/aims: Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. Methods: In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical. Results: In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff. Lessons learned: Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well-trained study staff; and (4) utilizing technology to automate procedures whenever possible. Conclusion: This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies.
Recanalization treatments in basilar artery occlusion—Systematic analysis
Authors: Lindsberg Perttu J , Sairanen Tiina , Nagel Simon , Salonen Oili , Silvennoinen Heli , Strbian Daniel 
Published: March 2016

Background and aims Basilar artery occlusion is a most devastating form of stroke, and the current practice is to reverse it with revascularization therapies. Pharmacological thrombolysis, intravenous or intraarterial, has been adjuncted or replaced with invasive, endovascular thrombectomy procedures. The preferred approach remains unknown and many recanalizations are futile with no clinical benefit. We sought to determine reasons for futility and weigh the existing reports to find whether endovascular mechanical interventions provide superior outcomes over pharmacological thrombolysis alone. Methods After analyzing systematically the reports of outcomes produced by variable basilar artery occlusion recanalization protocols, information was retrieved and reconciled from 15 reports published from year 2005 comprising 803 patients in 17 cohorts. In the largest single-center cohort (162, Helsinki), predictors of futile recanalization (three-month modified Rankin Scale score 4 to 6) were determined. Results Good outcome was reported by mechanical approaches either alone or on demand more frequently than by pharmacological, intravenous or intraarterial thrombolysis protocols (35.5% versus 24.4%, p < 0.001), accompanied by higher recanalization rates (84.1% versus 70.9%, p < 0.001). Along with superior recanalization rate at 91%, good outcome was reached by primary thrombectomy in 36% at the cost of substantial futile recanalization rate at 60%, which was lower when using modern stentrievers only (52.8%). In the Helsinki cohort, the single most significant predictor was extensive baseline ischemia, increasing the odds of futility 20-fold (95%CI 4.39–92.29, p < 0.001). Other attributes of futility were ventilation support and history of atrial fibrillation or previous stroke. Conclusions Endovascular mechanical approaches have been reported to provide superior outcomes over pharmacological thrombolysis in basilar artery occlusion. Stricter patient selection, most notably to exclude victims of already extended ischemia, would assist in translating excellent recanalization rates into improved clinical outcomes and more acceptable futility rates.
Sensitivity and correlation of hypervariable regions in 16S rRNA genes in phylogenetic analysis
Authors: Yang Bo , Wang Yong , Qian Pei-Yuan 
Published: March 2016

Abstract
Background
Prokaryotic 16S ribosomal RNA (rRNA) sequences are widely used in environmental microbiology and molecular evolution as reliable markers for the taxonomic classification and phylogenetic analysis of microbes. Restricted by current sequencing techniques, the massive sequencing of 16S rRNA gene amplicons encompassing the full length of genes is not yet feasible. Thus, the selection of the most efficient hypervariable regions for phylogenetic analysis and taxonomic classification is still debated. In the present study, several bioinformatics tools were integrated to build an in silico pipeline to evaluate the phylogenetic sensitivity of the hypervariable regions compared with the corresponding full-length sequences.

Results
The correlation of seven sub-regions was inferred from the geodesic distance, a parameter that is applied to quantitatively compare the topology of different phylogenetic trees constructed using the sequences from different sub-regions. The relationship between different sub-regions based on the geodesic distance indicated that V4-V6 were the most reliable regions for representing the full-length 16S rRNA sequences in the phylogenetic analysis of most bacterial phyla, while V2 and V8 were the least reliable regions.

Conclusions
Our results suggest that V4-V6 might be optimal sub-regions for the design of universal primers with superior phylogenetic resolution for bacterial phyla. A potential relationship between function and the evolution of 16S rRNA is also discussed.
Patterns of foot complaints in systemic lupus erythematosus: a cross sectional survey
Authors: Otter Simon J. , Kumar Sunil , Gow Peter , Dalbeth Nicola , Corkill Michael , Rohan Maheswaran , Davies Kevin A. , Pankathelam Sam , Rome Keith 
Published: March 2016

AbstractBackgroundFoot complaints are common in inflammatory arthropathies such as rheumatoid arthritis and cause considerable disability. However, little is published about the nature and extent of foot complaints in systemic lupus erythematosus (SLE). We aimed to explore foot complaints among people with (SLE) and to evaluate the associations between foot pain and self‐reported activities of daily living and well‐being.MethodsWe developed and tested a new 40‐item item self‐administered questionnaire, using a five‐stage development process utilising patient involvement throughout to ensure face and content validity. The self‐administered instrument was posted to 406 people with SLE attending adult rheumatology clinics across three health boards in Auckland, New Zealand. The questionnaire enquired about symptoms of foot pain, extra‐articular features, anatomical distribution of symptoms according to validated foot‐mannequins and the impact of foot symptoms on activities of daily living and well‐being.ResultsIn total, 406 questionnaires were posted, with 131 responses (response rate 32 %). We found 89 % were women, mean (SD) age 51 (15) years, mean (SD) diagnosis 12.5 (11.1) years. Overall, 77 % of those responding to the questionnaire reported foot pain during their SLE, with 45 % reporting current foot pain. All regions of the feet were affected, with the hindfoot (32 %) and ankles (30 %) most troublesome. The most common self‐reported extra‐articular foot complaints were cold feet, swelling and numbness. Almost two‐thirds (61 %) reported foot pain adversely affected their lives; foot pain prevented sleeping in 36 % and had a negative effect on emotions for 33 %. Only 33 % of participants had seen a podiatrist. Significant association was found between foot pain and standing longer than 15 min (p < 0.001), walking (p < 0.001), climbing stairs (p < 0.001) and going shopping (p < 0.001). Pain was the primary symptom to affect quality of life (47/100).ConclusionFoot complaints in SLE are heterogeneous in nature, and may have a substantial negative impact on patient well‐being. Foot complaints need to be addressed to reduce the burden of SLE and our findings support the need for wider access to specific foot care services.
Fixed point theorems of JS-quasi-contractions
Authors: Li Zhilong , Jiang Shujun 
Published: March 2016

AbstractIn this paper, we introduce the concept of JS-quasi-contraction and prove some fixed point results for JS-quasi-contractions in complete metric spaces under the assumption that the involving function is nondecreasing and continuous. These fixed point results extend and improve many existing results since some assumptions made there are removed or weakened. In addition, we present some examples showing the usability of our results.
Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013
Authors: King Tari A. , Lyman Jaclyn P. , Gonen Mithat , Voci Amy , De Brot Marina , Boafo Camilla , Sing Amy Pratt , Hwang E. Shelley , Alvarado Michael D. , Liu Minetta C. , Boughey Judy C. , McGuire Kandace P. , Van Poznak Catherine H. , Jacobs Lisa K. , Meszoely Ingrid M. , Krontiras Helen , Babiera Gildy V. , Norton Larry , Morrow Monica , Hudis Clifford A. 
Published: March 2016

Purpose The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013. Patients and Methods TBCRC 013 was a multicenter prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. From July 2009 to April 2012, 127 patients from 14 sites were enrolled; 109 (86%) patients had pretreatment primary tumor samples suitable for 21-gene RS analysis. Clinical variables, time to first progression (TTP), and 2-year overall survival (OS) were correlated with the 21-gene RS by using log-rank, Kaplan-Meier, and Cox regression. Results Median patient age was 52 years (21 to 79 years); the majority had hormone receptor–positive/human epidermal growth factor receptor 2 (HER2)–negative (72 [66%]) or hormone receptor–positive/HER2-positive (20 [18%]) breast cancer. At a median follow-up of 29 months, median TTP was 20 months (95% CI, 16 to 26 months), and median survival was 49 months (95% CI, 40 months to not reached). An RS was generated for 101 (93%) primary tumor samples: 22 (23%) low risk (< 18), 29 (28%) intermediate risk (18 to 30); and 50 (49%) high risk (≥ 31). For all patients, RS was associated with TTP (P = .01) and 2-year OS (P = .04). In multivariable Cox regression models among 69 patients with estrogen receptor (ER)–positive/HER2-negative cancer, RS was independently prognostic for TTP (hazard ratio, 1.40; 95% CI, 1.05 to 1.86; P = .02) and 2-year OS (hazard ratio, 1.83; 95% CI, 1.14 to 2.95; P = .013). Conclusion The 21-gene RS is independently prognostic for both TTP and 2-year OS in ER–positive/HER2-negative de novo stage IV breast cancer. Prospective validation is needed to determine the potential role for this assay in the clinical management of this patient subset.
A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse
Authors: Vergote Ignace , Armstrong Deborah , Scambia Giovanni , Teneriello Michael , Sehouli Jalid , Schweizer Charles , Weil Susan C. , Bamias Aristotelis , Fujiwara Keiichi , Ochiai Kazunori , Poole Christopher , Gorbunova Vera , Wang Wenquan , O’Shannessy Daniel , Herzog Thomas J. 
Published: March 2016

Purpose Farletuzumab is a humanized monoclonal antibody that binds to folate receptor-α, which is highly expressed in ovarian carcinoma and largely absent from normal tissue. Farletuzumab was investigated in a double-blind, randomized phase III study in platinum-sensitive ovarian cancer. Patients and Methods Eligible patients had first recurrent ovarian cancer 6-24 months following completion of platinum-taxane chemotherapy. All patients received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomly assigned test products in a 1:1:1 ratio: farletuzumab 1.25 mg/kg, farletuzumab 2.5 mg/kg, or placebo). The single-agent test product was continued weekly until disease progression. The primary end point was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors. Additional analyses not outlined in the original protocol were prespecified in the final statistical analysis plan, including a subgroup analysis by baseline CA-125 and farletuzumab exposure levels. Results A total of 1,100 women were randomly assigned to treatment dose or placebo. PFS from the primary analysis was 9.0, 9.5, and 9.7 months for the placebo, farletuzumab 1.25 mg/kg, and farletuzumab 2.5 mg/kg groups, respectively. Neither farletuzumab group was statistically different from the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.81 to 1.21] and 0.86 [95% CI, 0.70 to 1.06] for farletuzumab 1.25 mg/kg and 2.5 mg/kg group v placebo, respectively). In the prespecified subgroup, baseline CA-125 levels not more than three times the upper limit of normal (ULN) correlated with longer PFS (HR, 0.49; P = .0028) and overall survival (OS) (HR, 0.44; P = .0108) for farletuzumab 2.5 mg/kg versus placebo. Subgroup analysis of farletuzumab exposure above the median, regardless of dose, showed significantly better PFS versus placebo. The most common adverse events were those associated with chemotherapy. Conclusion Neither farletuzumab dose met the study’s primary PFS end point. Prespecified subgroup analyses demonstrated that patients with CA-125 levels not more than three times the ULN and patients with higher farletuzumab exposure showed superior PFS and OS compared with placebo.