bluuebunny/crossref_metadata_2025_split huggingface dataset:
Condoliase for the Treatment of Lumbar Disc Herniation
Authors: Chiba Kazuhiro , Matsuyama Yukihiro , Seo Takayuki , Toyama Yoshiaki 
Published: December 2017

Study Design.
A randomized, double-blind, placebo-controlled, multicenter phase III clinical trial.

Objective.
To evaluate the efficacy and safety of chemonucleolysis with condoliase in patients with lumbar disc herniation (LDH).

Summary of Background Data.
Condoliase is a pure mucopolysaccharidase derived from a bacterium, Proteus vulgaris that has high substrate specificity for chondroitin sulfate and hyaluronic acid in the nucleus pulposus of the intervertebral disc.

Methods.
In this study, patients aged 20 to 70 years with unilateral leg pain, positive straight leg raise test, and a contained LDH were recruited in Japan. Patients were treated with a single injection of condoliase (1.25 U) or placebo and were followed for 1 year after administration. The primary endpoint was change in worst leg pain from baseline to week 13. The secondary endpoints included responder rate, and the changes from baseline up to week 52 in the worst leg pain, worst back pain, Oswestry Disability Index, 36-Item Short-Form Health Survey, neurologic examinations, and imaging parameters.

Results.
A total of 82 and 81 patients received an injection of condoliase and placebo, respectively. The average changes in worst leg pain from baseline to week 13 (primary endpoint) were −49.5 mm in the condoliase group and −34.3 mm in the placebo group, and the difference of −15.2 mm was significant (95% confidence interval, −24.2 to −6.2; P = 0.001). Significant improvements were observed in the condoliase groups, compared with the placebo group, in most secondary endpoints at 1 year after administration. In the condoliase group, back pain, Modic type 1 change, and decrease in disc height were frequently reported, without any clinically relevant consequences.

Conclusion.
Condoliase significantly improved symptoms in patients with LDH and was well tolerated. Condoliase is a novel and potent chemonucleolytic drug for the treatment of LDH.

Level of Evidence: 1
Outpatient Spine Clinic Utilization is Associated With Reduced Emergency Department Visits Following Spine Surgery
Authors: Pak Linda M. , Fogel Harold A. , Chaudhary Muhammad Ali , Kwon Nicollette K. , Barton Lauren B. , Koehlmoos Tracey , Haider Adil H. , Schoenfeld Andrew J. 
Published: December 2017

Study Design.
Review of TRICARE claims (2006–2014) data to assess Emergency Department (ED) utilization following spine surgery.

Objective.
The aim of this study was to determine utilization rates and predictors of ED utilization following spine surgical interventions.

Summary of Background Data.
Visits to the ED following surgical intervention represent an additional stress to the healthcare system. While factors associated with readmission following spine surgery have been studied, drivers of postsurgical ED visits, including appropriate and inappropriate use, remain underinvestigated.

Methods.
TRICARE claims were queried to identify patients who had undergone one of three common spine procedures (lumbar arthrodesis, discectomy, decompression). ED utilization at 30- and 90 days was assessed as the primary outcome. Outpatient spine surgical clinic utilization was considered the primary predictor variable. Multivariable logistic regression was used to adjust for confounders.

Results.
Between 2006 and 2014, 48,868 patients met inclusion criteria. Fifteen percent (n = 7183) presented to the ED within 30 days postdischarge. By 90 days, 29% of patients (n = 14,388) presented to an ED. The 30- and 90-day complication rates were 6% (n = 2802) and 8% (n = 4034), respectively, and readmission rates were 5% (n = 2344) and 8% (n = 3842), respectively. Use of outpatient spine clinic services significantly reduced the likelihood of ED utilization at 30 [odds ratio (OR) 0.48; 95% confidence interval (95% CI) 0.46–0.53] and 90 days (OR 0.55; 95% CI 0.52–0.57).

Conclusion.
Within 90 days following spine surgery, 29% of patients sought care in the ED. However, only one-third of these patients had a complication recorded, and even fewer were readmitted. This suggests a high rate of unnecessary ED utilization. Outpatient utilization of spine clinics was the only factor independently associated with a reduced likelihood of ED utilization.

Level of Evidence: 3
Update on adjuvant melanoma therapy
Authors: Dimitriou Florentia , Braun Ralph Peter , Mangana Joanna 
Published: December 2017

Purpose of review
We review the results from relevant clinical trials and discuss current strategies in the melanoma adjuvant setting.

Recent findings
The favorable therapeutic efficacy and the significant less toxicity of nivolumab compared with ipilimumab, fully substitutes today‘s approval of ipilimumab, regardless mutation status, whereas in BRAF-mutated patients, dabrafenib and trametinib seem to confirm their high efficacy also in adjuvant setting. The use of interferon is restricted to patients with ulcerated melanoma and countries with no access to the new drugs.

Summary
Systemic adjuvant treatment after complete disease resection in high-risk melanoma patients aims to increase relapse-free survival (RFS) and overall survival (OS). According to the eighth edition of melanoma classification of American Joint Committee on Cancer (AJCC), the prognosis in stage III patients is heterogeneous and depends not only on N (nodal) but also on T (tumor thickness) category criteria. Recent data from randomized, phase-3 clinical trials analyzing the use of adjuvant anti-programmed death-1 and targeted therapies ultimately affect the standard of care and change the landscape of the adjuvant treatment.
Fast and Straightforward Method for the Quantification of Pazopanib in Human Plasma Using LC-MS/MS
Authors: Verheijen Remy B. , Thijssen Bas , Rosing Hilde , Schellens Jan H. M. , Nan Lianda , Venekamp Nikkie , Beijnen Jos H. , Steeghs Neeltje , Huitema Alwin D. R. 
Published: December 2017

Background:
Pazopanib is an angiogenesis inhibitor approved for renal cell carcinoma and soft-tissue sarcoma. Studies indicate that treatment with pazopanib could be optimized by adapting the dose based on measured pazopanib plasma concentrations.

Methods:
We describe the validation and clinical application of a fast and straightforward method for the quantification of pazopanib in human plasma for the purpose of therapeutic drug monitoring and bioanalytical support of clinical trials. Stable isotopically labeled 13C,2H3-pazopanib was used as internal standard. Plasma samples were prepared for analysis by protein precipitation using methanol and diluted with 10 mmol/L ammonium hydroxide buffer. Chromatographic separation was performed on a C18 column using isocratic elution with ammonium hydroxide in water and methanol. For detection, a tandem mass spectrometer, equipped with a turbo ion spray interface was used in positive ion mode at m/z 438 → m/z 357 for pazopanib and m/z 442 → m/z 361 for the internal standard.

Results:
Final runtime was 2.5 minutes. All validated parameters were within pre-established limits and fulfilled the FDA and EMA requirements for bioanalytical method validation. After completion of the validation, the routine application of the method was tested by analyzing clinical study samples that were collected for the purpose of therapeutic drug monitoring.

Conclusions:
In conclusion, the described method was successfully validated and was found to be robust for routine application to analyze samples from cancer patients treated with pazopanib.
Association between the age-related decline in renal function and lumbar spine bone mineral density in healthy Chinese postmenopausal women
Authors: Han Wen , Bai Xiao-Juan , Han Lu-Lu , Akhtari Sebastian , Sun Xue-Feng , Chen Xiang-Mei 
Published: December 2017

Abstract

Objectives:
The relationship between the decline of renal function and bone mineral density (BMD) in healthy populations is not well-researched. The aim of this study was to investigate the association between the age-related decline in renal function and lumbar spine BMD (LBMD) in a community-based cross-sectional study of 390 healthy postmenopausal women (mean age 62.97 ± 8.79 years) from Shenyang, China.

Methods:
Dual-energy x-ray absorptiometry was used to measure LBMD. Estimated glomerular filtration rate (eGFR) was calculated using a modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for Asians and the CKD-EPI serum creatinine-cystatin c equation. Pearson's correlation analysis and binary logistic regression were used to evaluate associations.

Results:
The eGFR-ASIA and eGFR-Scys were positively correlated with LBMD (r = 0.120 and r = 0.108, respectively). After adjustments for numerous potential confounders, the odds ratio for participants with LBMD decline in eGFR-ASIA quartile 3 group and 4 group were 2.45 (95% confidence interval [CI] 1.12-5.38, P < 0.05) and 3.89 (95% CI 1.55-9.76, P < 0.01), respectively, with P = 0.003 for the trend in eGFR-ASIA compared with the lowest quartile 1 group of eGFR-ASIA, where the odds ratio of eGFR-Scys for the quartile of 3 and 4 groups were 2.47 (95% CI 1.09-5.62, P < 0.05) and 2.63 (95% CI 1.10-6.29, P < 0.05), respectively, with P = 0.016 for the trend in eGFR-Scys compared with the lowest quartile 1 group of eGFR-Scys.

Conclusions:
The renal function decline was independently associated with decreased LBMD, and it was possible that the age-related decline in kidney function was an independent risk factor for decreased LBMD in healthy Chinese postmenopausal women.
Left ventricular remodeling and arterial afterload in older women with uncontrolled and controlled hypertension
Authors: Yoo Jeung-Ki , Okada Yoshiyuki , Best Stuart A. , Parker Rosemary S. , Hieda Michinari , Levine Benjamin D. , Fu Qi 
Published: December 2017

Abstract

Objective:
The prevalence of hypertension increases with advancing age in women. Blood pressure control is more difficult to achieve in older women, and despite well-controlled blood pressure, the cardiovascular mortality remains high. However, the underlying mechanisms are not understood.

Methods:
Nineteen women with uncontrolled hypertension on drug treatment (70 ± 2 [SE] years, ambulatory awake blood pressure; 152 ± 2/84 ± 2 mm Hg), 19 with controlled hypertension (68 ± 1 years, 128 ± 2/71 ± 2 mm Hg), and 31 healthy normotensive women (68 ± 1 years, 127 ± 1/73 ± 1 mm Hg) were recruited. Participants were weaned from antihypertensive drugs and underwent 3 weeks of run-in before cardiac-vascular assessments. Left ventricular morphology was evaluated with cardiac magnetic resonance imaging. Arterial load and vascular stiffness were measured via ultrasound and applanation tonometry.

Results:
Left ventricular mass normalized by body surface area was not different between hypertension groups (uncontrolled vs controlled: 50.0 ± 1.7 vs 51.8 ± 2.3 g/m2), but it was lower in the normotensive group (41.7 ± 0.9 g/m2; one-way analysis of variance [ANOVA] P = 0.004). Likewise, central pulse wave velocity was not different between hypertension groups (11.5 ± 0.6 vs 11.1 ± 0.5 m/s) and lower in the normotensive group (9.1 ± 0.3 m/s; 1-way ANOVA P = 0.0001). Total peripheral resistance was greater in uncontrolled hypertension (HTN) compared with normotensive group (2051 ± 323 vs 1719 ± 380 dyn∗s/cm5), whereas controlled HTN group (1925 ± 527 dyn∗s/cm5) was not different to either groups.

Conclusion:
Regardless of current blood pressure control, hypertensive older women exhibited increased cardiac mass and arterial stiffness compared with normotensives. Future large-scale longitudinal studies are warranted to directly investigate the mechanisms for the high cardiovascular mortality among older hypertensive women with well-controlled blood pressure.
Diagnostic Accuracy of Mediastinal Lymph Node Staging Techniques in the Preoperative Assessment of Nonsmall Cell Lung Cancer Patients
Authors: Fréchet Benoît , Kazakov Jordan , Thiffault Vicky , Ferraro Pasquale , Liberman Moishe 
Published: December 2017

Background:
Nonsmall cell lung cancer (NSCLC) treatment is based on an accurate staging. Mediastinal lymph nodes staging has a critical impact on treatment management.

Methods:
The objective was to assess the current accuracy of preoperative tools for predicting mediastinal and hilar lymph nodes staging with NSCLC. Retrospective analysis of 997 biopsy-proven NSCLC patients treated at a single academic medical center between January 2006 and April 2012. Mediastinal lymph nodes were evaluated with preoperatively with: computed tomography (CT), positron emission tomography (PET), endobronchial ultrasound-guided fine needle aspiration, and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Results are compared with pathologic surgical biopsy.

Results:
A total of 217 cervical mediastinoscopies, 15 anterior mediastinotomies, and 952 surgical lymphadenectomies were performed. The sensitivity of CT scan for mediastinal lymph nodes detection was 18.9% and PET-CT scan was 33.8%. Specificities were 94.9% and 93.8%, respectively. For hilar lymph nodes detection, CT was less sensitive (17.0% vs. 39.7%); however, more specific (94.7% vs. 80.3%) than PET-CT. Endobronchial ultrasound-guided fine needle aspiration (72.7% sensitivity and 100% specificity) and endoscopic ultrasound-guided fine needle aspiration (51.9% sensitivity and 100% specificity) both demonstrated superior results.

Conclusions:
The majority of biopsy-proven mediastinal lymph nodes metastases are not associated with positive results on preoperative CT or PET. CT and PET have low positive predictive value for mediastinal lymph node. This study supports the routine utilization of invasive mediastinal lymph nodes staging in NSCLC, especially for patients with tumors of >4 cm diameter, regardless of CT or PET-CT results.
Driver mutations in primary myelofibrosis and their implications
Authors: Szuber Natasha , Tefferi Ayalew 
Published: December 2017

Purpose of review
Primary myelofibrosis (PMF) is one of the classic BCR-ABL1 negative myeloproliferative neoplasms (MPN). Oncogenic driver mutations in PMF include Janus kinase 2, calreticulin (CALR), and myeloproliferative leukemia virus oncogene. These mutations are not only pathogenetically relevant but might also influence disease outcome. Our objective for the current communication is to comprehensively review the distinct phenotypic, therapeutic, and prognostic implications of driver mutations in PMF.

Recent findings
The discovery of driver mutations has revolutionized our understanding of pathogenic mechanisms and clinical heterogeneity in MPN, including PMF. Recently, there have been further advances in our knowledge of the molecular pathogenesis of MPN, particularly pertaining to CALR and its mutation. Moreover, the type and number of additional mutations, their order of acquisition, and their myriad combinatorial interactions with driver mutations may have dynamic pathogenic and clinical consequences. There are also additional data supporting the role of these genetic lesions and their associated allele burdens in modulating clinical features, including outcomes following treatment.

Summary
Literature exists to support both phenotypic and prognostic correlates of conventional driver mutations in PMF. As the genetic landscape becomes increasingly complex, establishing the functional impact of these mutations and defining their interactions with other molecular, cytogenetic, and extrinsic factors will further our insight and potentially alter our clinical approach.
Preoperative Evaluation Is Not Predictive of Transpyloric Feeding Conversion in Gastrostomy‐dependent Pediatric Patients
Authors: McSweeney Maireade E. , Kerr Jessica , Amirault Janine , Fishman Eliza , Lurie Margot , Peinado‐Fabregat Maria I. , Mitchell Paul D. , Rosen Rachel 
Published: December 2017

ABSTRACTObjectives:Limited literature exists as to whether preoperative gastrostomy (GT) evaluation may predict which patients will go onto require gastrojejunostomy (GJ) tube feeding. The goal of this study was to compare the preoperative evaluations between patients maintained on GT feeds versus patients who required conversion to GJ feeds.Methods:We identified patients at Boston Children's Hospital who underwent GT tube placement and required GJ feeding between 2006 and 2012. GT patients were matched according to age, neurologic, and cardiac status with GJ‐converted patients. Preoperative characteristics, rates of total hospitalizations, and respiratory‐related admissions were reviewed.Results:A total of 79 GJ patients (median interquartile range (IQR): age 15 (4.3, 55.7) months; weight 8.8 (4.6, 14.5) kg) were matched with 79 GT patients (median (IQR): age 14.6 (4.7, 55.7) months; weight 8.5 (5, 13.6) kg). Median time from GT to GJ conversion was 8 (IQR 3, 16) months. Both groups had similar rates of successful preoperative nasogastric feeding trials (GT (84.5%) versus GJ (83.1%), P = 1.0), upper gastrointestinal series (GT (89.1%) versus GJ (93.2%), P = 0.73), abnormal videofluoroscopic swallow studies (GT (53.8%) versus GJ (62.2%), P = 0.4), and completion of gastric emptying studies (GT (10.1%) versus GJ (5.1%), P = 0.22). No differences were seen in preoperative hospitalization rates (P = 0.25), respiratory admissions (P = 0.36), although GJ patients had a mean reduction in the number of hospitalization of −1.5 ± 0.5 days, P < 0.001, after conversion.Conclusions:No differences in preoperative patient characteristics or diagnostic evaluations were seen in GT fed versus GJ converted patients. GJ patients did experience an overall decrease in total admissions after GJ conversion.
Airway Volume Simulation in Virtual Mandibular Distraction: A Cohort Study
Authors: Humphries Laura S. , Yates Essie K. , Mhlaba Julie M. , Collins John M. , Baroody Fuad M. , Reid Russell R. 
Published: December 2017

Background:The authors investigated the accuracy of virtual surgical planning in predicting airway volume changes after mandibular distraction in patients with Pierre Robin sequence and associated tongue-based airway obstruction.Methods:The authors completed a single-institution retrospective review of patients for whom virtual surgical planning was used during mandibular distraction osteogenesis for treatment of tongue-based airway obstruction. Preoperative airway volume, virtual surgical planning–predicted airway volume, and postoperative airway volume were calculated from three-dimensional computed tomographic scans using industry software. A blinded institutional radiologist also calculated pre- and post-operative airway volumes. Pre- and post-operative polysomnography was used to titrate the endpoint of mandibular lengthening.Results:Eleven patients were included in the study. Mean apnea-hypopnea index (5.42 ± 4.53 versus 44.96 ± 20.57;p< 0.001) and mean nadir oxygen saturation (70.3 ± 9.72 percent versus 82.9 ± 9.62 percent;p= 0.003) improved with mandibular distraction. There was moderate correlation between predicted and actual mandibular distraction lengths (R2= 0.65;p= 0.003). There was a strong correlation between predicted and industry-calculated actual post–distraction airway volume (R2= 0.99;p< 0.001). There was no significant correlation between actual mandibular distraction length and industry-calculated actual post–distraction airway volume for the entire cohort (R2= 0.05;p= 0.49), but correlation approached significance by institutional calculations. No significant correlation existed between industry and institutional-calculated percentage change in post–distraction airway volume (R2= 0.06;p= 0.57).Conclusions:Predictive airway volume calculation may be an effective adjunct to determine anatomic endpoint of mandibular distraction but small sample size, operator and software variability, and patient airway morphology may confound firm conclusions. Further studies are warranted.
Apathy and Cognitive Deficits in Patients with Transient Global Ischemia After Cardiac Arrest
Authors: Frisch Stefan , Thiel Friederike , Schroeter Matthias L. , Jentzsch Regina Tina 
Published: December 2017

Background and Objective:
Despite the extensive literature on cognitive deficits in the course of transient global ischemia after cardiac arrest with delayed resuscitation, apathy has been studied less frequently and systematically. We aimed to evaluate the frequency of apathy, defined as changes in drive or lack of motivation, and its relation to cognition as well as depression in people with transient global ischemia after cardiac arrest.

Methods:
In a retrospective study using the clinical data of 38 cardiac arrest survivors, we analyzed the frequency and severity of deficits in four cognitive domains (attention, memory spans, long-term memory, and executive functions) as well as apathy.

Results:
As in previous studies, long-term memory problems were predominant, but occurred rarely in isolation. Problems in drive were frequent and correlated with the severity of deficits in all cognitive domains except memory spans (and executive functions only as a trend). Influences of apathy were independent of the presence of a depressive syndrome.

Conclusions:
Transient global ischemia after cardiac arrest generally leads to a broad pattern of cognitive decline with predominating memory deficits. Apathy is a frequent sequela and is associated with cognitive deficits, independent of depression. Studies investigating the cognitive profile after cardiac arrest should account for modulating influences of apathy.
Functional Reorganization of Right Prefrontal Cortex Underlies Sustained Naming Improvements in Chronic Aphasia via Repetitive Transcranial Magnetic Stimulation
Authors: Harvey Denise Y. , Podell Jamie , Turkeltaub Peter E. , Faseyitan Olufunsho , Coslett H. Branch , Hamilton Roy H. 
Published: December 2017

Background and Objective:
While noninvasive brain stimulation techniques show promise for language recovery after stroke, the underlying mechanisms remain unclear. We applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to regions of interest in the right inferior frontal gyrus of patients with chronic poststroke aphasia and examined changes in picture naming performance and cortical activation.

Methods:
Nine patients received 10 days of 1-Hz rTMS (Monday through Friday for 2 weeks). We assessed naming performance before and immediately after stimulation on the first and last days of rTMS therapy, and then again at 2 and 6 months post-rTMS. A subset of six of these patients underwent functional magnetic resonance imaging pre-rTMS (baseline) and at 2 and 6 months post-rTMS.

Results:
Naming accuracy increased from pre- to post-rTMS on both the first and last days of treatment. We also found naming improvements long after rTMS, with the greatest improvements at 6 months post-rTMS. Long-lasting effects were associated with a posterior shift in the recruitment of the right inferior frontal gyrus: from the more anterior Brodmann area 45 to the more posterior Brodmann areas 6, 44, and 46. The number of left hemispheric regions recruited for naming also increased.

Conclusions:
This study found that rTMS to the right hemisphere Broca area homologue confers long-lasting improvements in picture naming performance. The mechanism involves dynamic bilateral neural network changes in language processing, which take place within the right prefrontal cortex and the left hemisphere more generally.

Clinical Trial Registration:
ClinicalTrials.gov (Identifier NCT00608582).