bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knee Deformities in Children With Down Syndrome: A Focus on Knee Malalignment
Authors: Duque Orozco Maria del Pilar , Abousamra Oussama , Chen Brian Po-Jung , Rogers Kenneth J. , Sees Julieanne P. , Miller Freeman 
Published: June 2016

Background:
Patellofemoral instability (PFI) has been the most reported knee abnormality in people with Down syndrome. Other reported knee abnormalities have been associated with PFI and different management approaches have been described with variable outcomes. The aim of this study was to describe the anatomic variations of the knee in children with Down syndrome. A comparison between knees with and without PFI was performed and our experience in treating knee abnormalities in Down syndrome was also reported.

Methods:
Records of all children with Down syndrome were reviewed. Two groups were identified (knees with and without PFI). Radiographic measurements included the mechanical and anatomic lateral distal femoral angles, medial proximal tibial angle, angle of depression of medial tibial plateau, lateral tibial translation, and distal femoral physis-joint angle. On the lateral view, Insall-Salvati and Blackburne-Peel ratios were measured. The sulcus angle was measured on the tangential view. Measurements were compared between the 2 groups (with and without PFI).
Knees with PFI were divided into 3 subgroups based on their treatment (group A: surgical valgus correction, group B: surgical soft tissue procedures for PFI, and group C: conservative treatment). Preoperative radiographs were used for the surgical group and last available radiographs were used for the conservative group. Clinical and radiographic data were compared between the groups. For groups A and B, clinical and radiographic data were also compared between preoperative and last visits.

Results:
Of the 581 children with Down syndrome, 5% (31 children: 22 females, 9 males) had PFI in 56 knees. Mean age at diagnosis was 11.5±3.5 years. Of the remaining 550 children, 75 children had radiographs for 130 knees. Knees with PFI had significantly more valgus and a larger distal femoral physis-joint angle. Depression of the medial tibial plateau and lateral tibial translation were noted in knees with PFI. Insall-Salvati ratio was higher and the sulcus angle was larger in the PFI group.
Of the 56 knees with PFI; 10 knees were in group A, 11 knees in group B, 33 knees in group C, and the remaining 2 knees had combined procedures. Preoperative mechanical and anatomic lateral distal femoral angles were smaller in group A than in group B or C. Grades of PFI improved in group B after surgery. This improvement was not noted in group A.

Conclusions:
In children with Down syndrome, different variations of the knee anatomy can be found. Although PFI might be the most evident knee abnormality, other underlying deformities are common. Treatment of the PFI should be planned through a comprehensive anatomic approach that addresses all aspects of knee deformity.

Level of Evidence:
Level IV—prognostic and therapeutic study.
The Fibrin-Derived Peptide Bβ15–42 (FX06) Ameliorates Vascular Leakage and Improves Survival and Neurocognitive Recovery: Implications From Two Animal Models of Cardiopulmonary Resuscitation*
Authors: Bergt Stefan , Gruenewald Matthias , Beltschany Claudia , Grub Andrea , Neumann Tobias , Albrecht Martin , Vollmar Brigitte , Zacharowski Kai , Roesner Jan P. , Meybohm Patrick 
Published: June 2016

Objectives:
The fibrin-derived peptide Bβ15–42 (FX06) has been proven to attenuate ischemia/reperfusion injury. We tested the hypothesis that Bβ15–42 improves survival rate and neurocognitive recovery after cardiopulmonary resuscitation.

Design:
Pig and mouse model of cardiopulmonary resuscitation.

Setting:
Two university hospitals.

Subjects:
Pigs and mice.

Interventions:
Pigs (n = 16) were subjected to 8-minute cardiac arrest. Successful resuscitated pigs (n = 12) were randomized either to 3 mg/kg Bβ15–42 followed by a continuous infusion of 1 mg/kg/hr for 5 hours (pFX06; n = 6) or the control group (pCONTROL; n = 6). Cardiac damage, function, and hemodynamics were recorded up to 8 hours. Mice (n = 52) were subjected to 4-minute cardiac arrest followed by cardiopulmonary resuscitation, and randomized either to two boli of 2.4 mg/kg Bβ15–42 (mFX06; n = 26) or the control group (mCONTROL; n = 26). Fourteen-day survival rate, neurocognitive function, and endothelial integrity (additional experiment with n = 26 mice) were evaluated.

Measurements and Main Results:
Bβ15–42 reduced cumulative fluid intake (3,500 [2,600–4,200] vs 6,800 [5,700–7,400] mL; p = 0.004) within 8 hours in pigs. In mice, Bβ15–42 improved 14-day survival rate (mFX06 vs mCONTROL; 11/26 vs 6/26; p < 0.05) and fastened neurocognitive recovery in the Water-Maze test (15/26 vs 9/26 mice with competence to perform test; p < 0.05). Bβ15–42-treated mice showed a significant higher length of intact pulmonary endothelium and reduced pulmonary leukocyte infiltration.

Conclusions:
This study confirms the new concept of an important role of fibrin derivatives in global ischemia/reperfusion injury, which can be attenuated by the fibrin-derived peptide Bβ15–42.
Comparison of Demographics, Tumor Characteristics, and Survival Between Pancreatic Adenocarcinomas and Pancreatic Neuroendocrine Tumors
Authors: Yadav Siddhartha , Sharma Prabin , Zakalik Dana 
Published: June 2016

Objective:The objective of this study is to compare the incidence, demographics, tumor characteristics, and survival between patients with pancreatic neuroendocrine tumors (PNETs) and pancreatic adenocarcinomas.Materials and Methods:Between 2004 and 2012, all cases of pancreatic adenocarcinomas and PNETs were extracted from the population-based cancer registries of the Surveillance Epidemiology and End Results program. To identify the cases, a combination of topographical and histology codes based on ICD-O-3 were used. Incidence, demographics, tumor characteristics, and survival was then compared between these 2 histologic subtypes of pancreatic cancer.Results:A total of 57,688 patients with pancreatic cancer were identified, of which 53,753 (93%) had pancreatic adenocarcinoma and 3935 (7%) had PNET. The overall age-adjusted incidence of PNETs between 2004 and 2012 was 0.52 per 100,000 per year, whereas that for pancreatic adenocarcinomas during the same period was 7.34 per 100,000 per year. PNETs had a significantly younger median age at diagnosis (61 vs. 69 y). A significant proportion of PNETs were diagnosed at stage I (20.5% vs. 6.0%) and were well differentiated (32.8% vs. 4.5%) compared with adenocarcinomas. Five-year cause-specific survival was 51.3% and 5.0% for PNETs and pancreatic adenocarcinomas, respectively. In multivariate analysis, pancreatic adenocarcinomas had a hazard ratio for death of 4.02 (95% confidence interval, 3.79-4.28) when compared with PNETs.Conclusions:PNETs present with favorable features such as higher proportion of early-stage tumor, higher proportion of well differentiated tumors, and younger age at diagnosis. PNETs have a significantly better survival than pancreatic adenocarcinomas even after adjusting for age, sex, race, site, grade, and stage.
Utilization of Postoperative Chemoradiotherapy Among Women in the United States With High-risk Cervical Cancer
Authors: Trifiletti Daniel M. , Swisher-McClure Samuel , Showalter Timothy N. , Cantrell Leigh A. , Grover Surbhi 
Published: June 2016

Objective:
Prospective randomized data demonstrates that chemoradiotherapy (CRT) improves overall survival in women with high-risk pathologic features following radical hysterectomy. Despite this, not all high-risk patients receive adjuvant CRT and the patterns of care in this patient population are unknown. We sought to investigate the rates of adjuvant therapy utilization through analysis of the National Cancer Database.

Materials and Methods:
The National Cancer Database was queried for women with cervical cancer treated initially with hysterectomy from 2002 to 2012. Patients without high-risk pathologic features were excluded: pN+, positive surgical margins, and parametrial invasion (Peters’ criteria). Among the 5947 evaluable patients, univariable analysis and multivariable analysis were performed to investigate potential factors associated with CRT utilization and overall survival following diagnosis.

Results:
Adjuvant CRT was performed in 41.8% of women and adjuvant radiotherapy, chemotherapy, and no adjuvant therapy was utilized in 9.8%, 23.6%, and 24.8% of women, respectively. On multivariable analysis, CRT utilization was associated with younger age, race, lower facility volume, pN+, parametrial invasion, and a negative surgical margin. Residence distance to treating facility, year of diagnosis, household income, insurance status, and facility type did not predict for CRT utilization.

Conclusions:
Despite level I evidence supporting its use, less than half of women in this large US cohort with high-risk cervical cancer received adjuvant CRT. Use of adjuvant CRT for women did not significantly increase between 2002 and 2012. Patient age, race, and pathologic risk factors were associated with use of adjuvant CRT.
A Pooled Analysis of Biochemical Failure in Intermediate-risk Prostate Cancer Following Definitive Stereotactic Body Radiotherapy (SBRT) or High-Dose-Rate Brachytherapy (HDR-B) Monotherapy
Authors: Hegde John V. , Collins Sean P. , Fuller Donald B. , King Christopher R. , Demanes D. Jeffrey , Wang Pin-Chieh , Kupelian Patrick A. , Steinberg Michael L. , Kamrava Mitchell 
Published: June 2016

Objectives:
To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy.

Materials and Methods:
A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel χ2 metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure.

Results:
The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ≤3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS.

Conclusions:
With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.
Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale
Authors: Kesmodel Susan B. , Goloubeva Olga G. , Rosenblatt Paula Y. , Heiss Brian , Bellavance Emily C. , Chumsri Saranya , Bao Ting , Thompson Jennifer , Nightingale Ginah , Tait Nancy S. , Nichols Elizabeth M. , Feigenberg Steve J. , Tkaczuk Katherine H. 
Published: June 2016

Objectives:
Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy.

Methods:
Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence.

Results:
Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8).

Conclusions:
Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.
Impact of Staging With Positron-emission Tomography (PET) and Comorbidities on Management and Survival of American Veterans With Stage I-III Non–Small Cell Lung Cancer
Authors: Raghunathan Radhika , Cease Kemp , Troeschel Sandra , Zhao Lili , Gross Milton , Chen Guoan , Chopra Vineet , Ramnath Nithya 
Published: June 2016

Objectives:
The extent of whether staging by fluorodeoxyglucose positron-emission tomography (PET) impacts outcomes in American Veterans with stage I-III non–small-cell lung cancer (NSCLC) is unknown. We investigated impact of fluorodeoxyglucose PET staging and age-adjusted comorbidities (AACs) on management and survival of NSCLC in this group.

Materials and Methods:
We performed a retrospective review to identify with NSCLC who underwent initial PET scan and received care at the Ann Arbor Veterans Hospital between 2005 and 2010. Survival outcomes were estimated by Kaplan-Meier methods, quantile regressions, and Cox proportional hazards models, after accounting for age at diagnosis, sex, AAC, and initial treatment.

Results:
The number of PET scans increased from 0 in 2005 to 66 in 2010. There were 170 men, 4 women, median age 64 years. Median AAC score was 4. In CS I (n=54), initial PET upstaged 5 patients. Median survival for no change in PET stage was 27.43 versus 67 months for upstaged patients (P=0.034). For CS II (n=15), initial PET scan upstaged 1 patient. Median survival for no change in PET stage was 16.53 versus 2.8 months for upstaged patient (P=0.335). For CS III (n=104), PET scan upstaged 20 patients. Median survival for no change in PET stage was 13.3 versus 3.8 months for upstaged patients (P=0.016).

Conclusions:
PET scans resulted in upstaging in 15% in CS I-III NSCLC. AAC scores dictated therapy decisions and outcomes more than PET staging. Veterans had lower 5-year survival rates (26.3%, 15.8%/13.4%) compared with 53% and 27% in age/sex/time-period matched SEER data for stage I-II/III NSCLC.
Bifurcated Superficial Temporal Artery Island Flap for the Reconstruction of a Periorbital Burn: An Innovation
Authors: Elbanoby Tarek M. , Elbatawy Amr , Aly Gaber M. , Ayad Wael , Helmy Yasser , Helmy Emad , Sholkamy Khallad , Dahshan Hazem , Al-Hady Abdallah 
Published: June 2016

Background:
Facial burns represent between one-fourth and one-third of all burns. The long-term sequelae of periorbital burns include significant ectropion and lagophthalmos as a result of secondary burn contractures in the lower and upper eyelids, in addition to complete or incomplete alopecia of the eyebrows.

Methods:
A retrospective study of 14 reconstructive procedures for 12 postburn faces was conducted with all procedures performed since 2010 at the Department of Plastic Surgery, Al-Hussein University Hospital, and at the Craniofacial Unit, Nasser Institute Hospital. Four patients experienced chemical burns, and 8 patients experienced thermal burns. All patients underwent periorbital reconstruction using a bifurcated superficial temporal artery island flap to reconstruct the eyebrows, correct the lagophthalmos, and release the ectropion in both the upper and the lower eyelids. Two patients underwent bilateral periorbital flap reconstruction. The mean age of patients was 29 years, and the study was conducted on 8 males and 4 females. Patient satisfaction was assessed using a questionnaire completed by all patients postoperatively.

Results:
The complete release of both the upper and the lower eyelids was achieved in all cases, together with ideal replacement of brow hair; no complications were noted, apart from one case in which a loss of hair density in the new eyebrow was observed, combined with the partial loss of the flap in the lower eyelid. Patient satisfaction results were collected and assembled in a table.

Conclusion:
A bifurcated superficial temporal artery island flap is an innovative flap for reconstructing both burned eyebrows and eyelids.
Physical Activity and the Risk of Gallstone Disease
Authors: Zhang Yan-Peng , Zhao Ya-Lei , Sun Yu-Ling , Zhu Rong-Tao , Wang Wei-Jie , Li Jian 
Published: June 2016

Background:The role of physical activity in preventing gallstone disease independent of its effect on the body weight has not been well established. We performed a systematic review and meta-analysis of cohort and case-control studies to analyze this potential association.Methods:We searched PubMed and EMBASE to identify all published studies in English through April 2016. We pooled the relative risks (RRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) from individual studies using a random-effects model to investigate associations between physical activity and the risk of gallstone disease.Results:A total of 16 studies comprising 19 independent reports of approximately 260,000 participants met the inclusion criteria, including 6 case-control studies and 13 cohort studies. In a pooled analysis of cohort studies, physical activity (in a comparison of the highest-level and the lowest-level groups) was associated with a reduced risk of gallstone disease (RR=0.85; 95% CI, 0.78-0.92;I2=79.5%). For men, the RR was 0.76 (95% CI, 0.60-0.97), and for women, the RR was similar (RR=0.77; 95% CI, 0.66-0.91). In a dose-response analysis, the RR of gallstone disease was 0.87 (95% CI, 0.83-0.92;I2=1.0%) per 20 metabolic equivalent-hours of recreational physical per week. In comparison, case-control studies yielded a stronger significant risk reduction for gallstone disease (OR=0.64; 95% CI, 0.46-0.90;I2=76.6%).Conclusions:This study suggests an inverse association between physical activity and gallstone disease in both men and women; however, these findings should be interpreted cautiously because of study heterogeneity.
Identifying Consistent High-cost Users in a Health Plan
Authors: Chang Hsien-Yen , Boyd Cynthia M. , Leff Bruce , Lemke Klaus W. , Bodycombe David P. , Weiner Jonathan P. 
Published: June 2016

Background:
High-cost users in a period may not incur high-cost utilization in the next period. Consistent high-cost users (CHUs) may be better targets for cost-saving interventions.

Objectives:
To compare the characteristics of CHUs (patients with plan-specific top 20% medical costs in all 4 half-year periods across 2008 and 2009) and point high-cost users (PHUs) (top users in 2008 alone), and to build claims-based models to identify CHUs.

Research Design:
This is a retrospective cohort study. Logistic regression was used to predict being CHUs. Independent variables were derived from 2007 claims; 5 models with different sets of independent variables (prior costs, medications, diagnoses, medications and diagnoses, medications and diagnoses and prior costs) were constructed.

Subjects:
Three-year continuous enrollees aged from 18 to 62 years old from a large administrative database with $100 or more yearly costs (N=1,721,992).

Measures:
Correlation, overlap, and characteristics of top risk scorers derived from 5 CHUs models were presented. C-statistics, sensitivity, and positive predictive value were calculated.

Results:
CHUs were characterized by having increasing total and pharmacy costs over 2007–2009, and more baseline chronic and psychosocial conditions than PHUs. Individuals’ risk scores derived from CHUs models were moderately correlated (∼0.6). The medication-only model performed better than the diagnosis-only model and the prior-cost model.

Conclusions:
Five models identified different individuals as potential CHUs. The recurrent medication utilization and a high prevalence of chronic and psychosocial conditions are important in differentiating CHUs from PHUs. For cost-saving interventions with long-term impacts or focusing on medication, CHUs may be better targets.
Therapeutic drug monitoring in inflammatory bowel disease
Authors: Jossen Jacqueline , Dubinsky Marla 
Published: June 2016

Purpose of review
There are an expanding number of therapies available to treat pediatric inflammatory bowel disease (IBD). As pediatric gastroenterologists attempt to achieve complete intestinal mucosal healing for their patients, it has become more important to gain an understanding of how to maximize the efficacy of our medications while minimizing their toxicities. We aim to provide an overview of therapeutic drug monitoring in IBD with an emphasis on the biologic therapies (antitumor necrosis factor and anti-integrin monoclonal antibodies).

Recent findings
Recent findings do support optimized drug dosing for infliximab based on early trough levels, but question the utility of checking these values in patients doing well in maintenance therapy. Patients with severe colonic inflammation may be at increased risk for needing optimization with dose escalation because of medication loss in the stool. Dose escalation can recapture response in some patients with a secondary loss of response, including those with low level antibody formation. The monitoring of nontrough drug levels to allow timelier dose adjustment as well as the role of drug monitoring with anti-integrin therapy are areas of active research.

Summary
Therapeutic drug monitoring is an effective strategy in the management of pediatric IBD that can help patients achieve mucosal healing and aid the clinical decision-making of the pediatric gastroenterologist.