bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors
Authors: Liu Feiyang , Zou Fengming , Chen Cheng , Yu Kailin , Liu Xiaochuan , Qi Shuang , Wu Jiaxin , Hu Chen , Hu Zhenquan , Liu Juan , Liu Xuesong , Wang Li , Ge Juan , Wang Wenchao , Ren Tao , Bai Mingfeng , Cai Yujiao , Xiao Xudong , Qian Feng , Tang Jun , Liu Qingsong , Liu Jing 
Published: May 2019

Background: cKIT kinase overexpression and gain-of-function mutations are the critical pathogenesis of gastrointestinal stromal tumors (GISTs). Although the multiple kinase inhibitors such as imatinib, sunitinib, and regorafenib have been approved for GISTs, the acquisition of polyclonal secondary resistance mutations in KIT is still a limitation for GIST treatment. Here we explored the KIT inhibitory activity of axitinib in preclinical models and describe initial characterization of its activity in GIST patient-derived primary cells. Methods: The activities of axitinib against mutant KIT were evaluated using protein-based assay and a panel of engineered and GIST-derived cell lines. The binding modes of axitinib-KIT/KIT mutants were analyzed. Four primary cells derived from GIST patients were also used to assess the drug response of axitinib. Results: Axitinib exhibited potent activities against a variety of cKIT associated primary and secondary mutations. It displayed better activity against cKIT wild-type, cKIT V559D/A/G, and L576P primary gain-of-function mutations than imatinib, sunitinib, and regorafenib. In addition, it could inhibit imatinib resistant cKIT T670I and V654A mutants in vitro and in vivo GIST preclinical models. Conclusion: Our results provide the basis for extending the application of axitinib to GISTs patients who are unresponsive or intolerant to the current therapies.
Effect of Surgical Setting on Hospital-Reported Outcomes for Elective Lumbar Spinal Procedures: Tertiary Versus Community Hospitals
Authors: Weir Tristan B. , Sardesai Neil , Jauregui Julio J. , Jazini Ehsan , Sokolow Michael J. , Usmani M. Farooq , Camacho Jael E. , Banagan Kelley E. , Koh Eugene Y. , Kurtom Khalid H. , Davis Randy F. , Gelb Daniel E. , Ludwig Steven C. 
Published: May 2019

Study Design: Retrospective cohort study. Objective: As hospital compensation becomes increasingly dependent on pay-for-performance and bundled payment compensation models, hospitals seek to reduce costs and increase quality. To our knowledge, no reported data compare these measures between hospital settings for elective lumbar procedures. The study compares hospital-reported outcomes and costs for elective lumbar procedures performed at a tertiary hospital (TH) versus community hospitals (CH) within a single health care system. Methods: Retrospective review of a physician-maintained, prospectively collected database consisting of 1 TH and 4 CH for 3 common lumbar surgeries from 2015 to 2016. Patients undergoing primary elective microdiscectomy for disc herniation, laminectomy for spinal stenosis, and laminectomy with fusion for degenerative spondylolisthesis were included. Patients were excluded for traumatic, infectious, or malignant pathology. Comparing hospital settings, outcomes included length of stay (LOS), rates of 30-day readmissions, potentially preventable complications (PPC), and discharge to rehabilitation facility, and hospital costs. Results: A total of 892 patients (n = 217 microdiscectomies, n = 302 laminectomies, and n = 373 laminectomy fusions) were included. The TH served a younger patient population with fewer comorbid conditions and a higher proportion of African Americans. The TH performed more decompressions ( P < .001) per level fused; the CH performed more interbody fusions ( P = .007). Cost of performing microdiscectomy ( P < .001) and laminectomy ( P = .014) was significantly higher at the TH, but there was no significant difference for laminectomy with fusion. In a multivariable stepwise linear regression analysis, the TH was significantly more expensive for single-level microdiscectomy ( P < .001) and laminectomy with single-level fusion ( P < .001), but trended toward significance for laminectomy without fusion ( P = .052). No difference existed for PPC or readmissions rate. Patients undergoing laminectomy without fusion were discharged to a facility more often at the TH ( P = .019). Conclusions: We provide hospital-reported outcomes between a TH and CH. Significant differences in patient characteristics and surgical practices exist between surgical settings. Despite minimal differences in hospital-reported outcomes, the TH was significantly more expensive.
Racial Differences in Perioperative Opioid Utilization in Lumbar Decompression and Fusion Surgery for Symptomatic Lumbar Stenosis or Spondylolisthesis
Authors: Davison Mark A. , Lilly Daniel T. , Desai Shyam A. , Vuong Victoria D. , Moreno Jessica , Bagley Carlos , Adogwa Owoicho 
Published: May 2019

Study Design: Retrospective cohort study. Objectives: To assess for racial differences in opioid utilization prior to and after lumbar fusion surgery for patients with lumbar stenosis or spondylolisthesis. Methods: Clinical records from patients with lumbar stenosis or spondylolisthesis undergoing primary <3-level lumbar fusion from 2007 to 2016 were gathered from a comprehensive insurance database. Records were queried by International Classification of Diseases diagnosis/procedure codes and insurance-specific generic drug codes. Opioid use 6 months prior, through 2 years after surgery was assessed. Multivariate regression analysis was employed to investigate independent predictors of opioid use following lumbar fusion. Results: A total of 13 257 patients underwent <3-level posterior lumbar fusion. The cohort racial distribution was as follows: 80.9% white, 7.0% black, 1.0% Hispanic, 0.2% Asian, 0.2% North American Native, 0.8% “Other,” and 9.8% “Unknown.” Overall, 57.8% patients utilized opioid medications prior to index surgery. When normalized by the number opiate users, all racial cohort saw a reduction in pills disbursed and dollars billed following surgery. Preoperatively, Hispanics had the largest average pills dispensed (222.8 pills/patient) and highest average amount billed ($74.67/patient) for opioid medications. The black cohort had the greatest proportion of patients utilizing preoperative opioids (61.8%), postoperative opioids (87.1%), and long-term opioid utilization (72.7%), defined as use >1 year after index operation. Multivariate logistic regression analysis indicated Asian patients (OR 0.422, 95% CI 0.191-0.991) were less likely to use opioids following lumbar fusion. Conclusions: Racial differences exist in perioperative opioid utilization for patients undergoing lumbar fusion surgery for spinal stenosis or spondylolisthesis. Future studies are needed corroborate our findings.
Arthroscopic Treatment of First-Time Shoulder Dislocations in Younger Athletes
Authors: Terra Bernardo Barcellos , Ejnisman Benno , Belangero Paulo Santoro , Figueiredo Eduardo , De Nadai Anderson , Ton Angelo , Cohen Moisés 
Published: May 2019

Background: The glenohumeral joint is characterized by its large degree of movement and consequently is the most susceptible joint to dislocations. There are few studies on the first episode of a shoulder dislocation in younger athletes. Purpose: To report the results of arthroscopic treatment for the first episode of a glenohumeral dislocation in younger athletes. Study Design: Case series; Level of evidence, 4. Methods: In this retrospective study, 53 patients younger than 40 years (N = 54 shoulders) sustained their first anterior shoulder dislocation and underwent arthroscopic surgery. Surgery was undertaken in the lateral decubitus position. Standard posterior, anteroinferior, and anterosuperior portals were used, and the number of anchors and the degree of capsular plication were individualized and based on the arthroscopic findings of each patient. The minimum follow-up was 2 years (mean, 2.31 years), and patients were evaluated with the Rowe functional score, Athletic Shoulder Outcome Rating Scale (EROE; acronym in Portuguese), and visual analog scale (VAS) for pain. Results: The mean EROE score was 93.8, with 98% of results being good or excellent, and the mean Rowe score was 95.0, with 98% good or excellent results. The mean VAS pain score was <1.0. The rate of recurrence of dislocations was 2%. The return-to-sports rate was 83%; patients with associated superior labral anterior-posterior (SLAP) lesions had a lower return-to-sports rate ( P = .001) and lower EROE ( P = .017) and Rowe ( P = .019) scores. Conclusion: The present study showed favorable results for arthroscopic surgical treatment after the first dislocation episode in young athletes. It was an effective and safe treatment option in this population.
Health outcomes and services in children with sickle cell trait, sickle cell anemia, and normal hemoglobin
Authors: Reeves Sarah L. , Jary Hannah K. , Gondhi Jennifer P. , Kleyn Mary , Dombkowski Kevin J. 
Published: May 2019

AbstractThe health effects of sickle cell trait among children are unknown. We compared select health outcomes and health services utilization among children with sickle cell trait, sickle cell anemia (SCA), and normal hemoglobin. Newborn screening records were used to identify children with sickle cell trait and SCA born in Michigan (1997-2014) who were enrolled in Michigan Medicaid for ≥1 year from 2012 to 2014. Each select health outcome (acute otitis media, acute respiratory infections, fever, invasive pneumococcal disease, pneumonia and influenza, renal complications, spleen problems, stroke) was defined as ≥1 claim with a diagnosis code for the respective outcome within a study year. Health services utilization was summarized as counts of emergency department, inpatient, and outpatient encounters. The relationship between hemoglobin status and each health outcome or utilization was assessed by logistic or negative binomial regression with generalized estimating equations. The study population consisted of 18 257 children with sickle cell trait, 368 with SCA, and 74 523 with normal hemoglobin (227 188 total person-years). Compared with those with normal hemoglobin, children with sickle cell trait had lower odds of acute otitis media (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.84-0.91), acute respiratory infections (OR, 0.94; 95% CI, 0.92-0.97), pneumonia and influenza (OR, 0.93; 95% CI, 0.87-0.99), and outpatient visits (incidence rate ratio, 0.95; 95% CI, 0.93-0.97). Children with SCA had higher or nonsignificant odds of all outcomes and types of health services utilization. These results indicate that children with sickle cell trait may not be at additional health risk for these outcomes. However, additional case-control studies may be necessary to identify rare events.
Retrospective parental assessment of childhood neurodevelopmental problems: the use of the Five to Fifteen questionnaire in adults
Authors: Lugnegård Tove , Bejerot Susanne 
Published: May 2019

Background
Attention-deficit hyperactivity disorder and autism are increasingly recognised in adults. For a diagnostic evaluation, parental information on childhood development is needed. However, no instruments that retrospectively describe neurodevelopmental problems in childhood are validated for evaluating adults. The 181-item parent-report questionnaire Five to Fifteen (FTF) is nevertheless frequently used for assessments in adulthood.

Aims
To examine if FTF is reliable for obtaining retrospective neurodevelopmental history among young adults.

Method
Details of parents who had assessed their children with the FTF for neuropsychiatric evaluation were retrieved and they were asked to complete the FTF again 10–19 years later. Agreements between original and retrospective scorings were analysed.

Results
Long-term reliability for FTF varies considerably between individual items. Several difficulties are reported as more severe at the retrospective scoring than at the original scoring. A selection of 24 items (FTF-Brief) with good agreement over time, is presented for use in adult psychiatry settings.

Conclusion
Neuropsychiatric symptoms may fluctuate over time and become more prominent when demands increase. Informants' recollections of their child's neurodevelopmental symptoms may be a selection of symptoms that are longstanding rather than present at a specific age in childhood.

Declaration of interest
None.
Sensitivity and specificity of early screening for autism
Authors: Surén Pål , Saasen-Havdahl Alexandra , Bresnahan Michaeline , Hirtz Deborah , Hornig Mady , Lord Catherine , Reichborn-Kjennerud Ted , Schjølberg Synnve , Øyen Anne-Siri , Magnus Per , Susser Ezra , Lipkin W. Ian , Stoltenberg Camilla 
Published: May 2019

Background
Early identification and diagnosis is beneficial for children with autism spectrum disorder (ASD). Universal early screening is recommended by many experts, but disputed because evidence is limited, and sensitivity and specificity in general populations are largely unknown.

Aims
To estimate the sensitivity and specificity of early population-based screening for ASDs.

Method
The study was based on the Norwegian Mother and Child Cohort Study. The 36-month cohort questionnaire included the Social Communication Questionnaire (SCQ), a 40-item screening instrument for ASD.

Results
A total of 58 520 mothers (58%) responded to the questionnaire. By the end of follow-up on 31 December 2015, 385 (0.7%) individuals with ASD had been identified among the responders' children. The distributions of SCQ scores in those with ASD and other children had large degrees of overlap. With the cut-off of 15 recommended in the SCQ manual, screening sensitivity was 20% (95% CI 16–24) for ASD overall. For children with ASD who had not developed phrase speech at 36 months, sensitivity was 46% (95% CI 35–57%), whereas it was 13% (95% CI 9–17) for children with ASD with phrase speech. Screening specificity was 99% (95% CI 99–99). With the currently recommended cut-off of 11, sensitivity increased to 42% for ASD overall (95% CI 37–47), 69% (95% CI 58–79) for ASD without phrase speech and 34% (95% CI 29–40) for ASD with phrase speech. Specificity was then reduced to 89% (95% CI 89–90).

Conclusions
Early ASD screening with a parent checklist had low sensitivity. It identified mainly individuals with ASD with significant developmental delay and captured very few children with ASD with cognitive skills in the normal range. Increasing sensitivity was not possible without severely compromising specificity.

Declaration of interest
C.L. receives royalty for the Social Communication Questionnaire, which she has co-authored.
Association of Intraoperative Ventilator Management With Postoperative Oxygenation, Pulmonary Complications, and Mortality
Authors: Douville Nicholas J. , Jewell Elizabeth S. , Duggal Neal , Blank Ross , Kheterpal Sachin , Engoren Milo C. , Mathis Michael R. 
Published: May 2019

BACKGROUND:“Lung-protective ventilation” describes a ventilation strategy involving low tidal volumes (VTs) and/or low driving pressure/plateau pressure and has been associated with improved outcomes after mechanical ventilation. We evaluated the association between intraoperative ventilation parameters (including positive end-expiratory pressure [PEEP], driving pressure, and VT) and 3 postoperative outcomes: (1) Pao2/fractional inspired oxygen tension (Fio2), (2) postoperative pulmonary complications, and (3) 30-day mortality.METHODS:We retrospectively analyzed adult patients who underwent major noncardiac surgery and remained intubated postoperatively from 2006 to 2015 at a single US center. Using multivariable regressions, we studied associations between intraoperative ventilator settings and lowest postoperative Pao2/Fio2while intubated, pulmonary complications identified from discharge diagnoses, and in-hospital 30-day mortality.RESULTS:Among a cohort of 2096 cases, the median PEEP was 5 cm H2O (interquartile range = 4–6), median delivered VTwas 520 mL (interquartile range = 460–580), and median driving pressure was 15 cm H2O (13–19). After multivariable adjustment, intraoperative median PEEP (linear regression estimate [B] = −6.04; 95% CI, −8.22 to −3.87;P< .001), median Fio2(B = −0.30; 95% CI, −0.50 to −0.10;P= .003), and hours with driving pressure >16 cm H2O (B = −5.40; 95% CI, −7.2 to −4.2;P< .001) were associated with decreased postoperative Pao2/Fio2. Higher postoperative Pao2/Fio2ratios were associated with a decreased risk of pulmonary complications (adjusted odds ratio for each 100 mm Hg = 0.495; 95% CI, 0.331–0.740;P= .001, model C-statistic of 0.852) and mortality (adjusted odds ratio = 0.495; 95% CI, 0.366–0.606;P< .001, model C-statistic of 0.820). Intraoperative time with VT>500 mL was also associated with an increased likelihood of developing a postoperative pulmonary complication (adjusted odds ratio = 1.06/hour; 95% CI, 1.00–1.20;P= .042).CONCLUSIONS:In patients requiring postoperative intubation after noncardiac surgery, increased median Fio2, increased median PEEP, and increased time duration with elevated driving pressure predict lower postoperative Pao2/Fio2. Intraoperative duration of VT>500 mL was independently associated with increased postoperative pulmonary complications. Lower postoperative Pao2/Fio2ratios were independently associated with pulmonary complications and mortality. Our findings suggest that postoperative Pao2/Fio2may be a potential target for future prospective trials investigating the impact of specific ventilation strategies for reducing ventilator-induced pulmonary injury.
Influence of Remifentanil on the Control Performance of the Bispectral Index Controlled Bayesian-Based Closed-Loop System for Propofol Administration
Authors: Neckebroek Martine , Boldingh Jan-Willem H. L. , De Smet Tom , Struys Michel M. R. F. 
Published: May 2019

BACKGROUND:This study investigated the clinical performance of a model-based, patient-individualized closed-loop (CL) control system for propofol administration using the bispectral index (BIS) as a controlled variable during the induction and maintenance of anesthesia with propofol and remifentanil and studied the influence of the targeted effect-site concentration of remifentanil (CeREMI) on its clinical performance.METHODS:In 163 patients, propofol was administered using a CL system (BIS target [BISTARGET] between 40 and 50). Initial CeREMItargets between 2 and 7.5 ng/mL were selected as deemed clinically required. Performance parameters during induction were the time required to initially cross the target BIS, the time required to reach the maximal drug effect after induction (TPEAK, BIS) and the corresponding BIS at this moment, and the time required to regain the target BIS at the end of induction. Performance during maintenance was defined as the percentage of case time with target BIS ± 10 from target and the amount of performance error (PE) between the observed and target BIS values and its derived median PE (MDPE) as a measure of control bias, median absolute PE (MDAPE) as a measure of control inaccuracy, divergence as a measure of the time-related trend of the measured BIS values relative to the target BIS values, and wobble as a measure of intrasubject variability in prediction error. The secondary end point was the hemodynamic stability of the patient during CL control.RESULTS:The applied CL system induced and maintained anesthesia within clinically accepted ranges. The percentage of case time [mean (standard deviation [SD]) across all study participants] with BIS ± 10 from the target was 82% (14%). The mean (SD) population MDPE and MDAPE were −6.6% (5.5%) and 11.2% (5.5%), respectively. A negative divergence [−0.001 (0.004)] and acceptable wobble [9.7% (4.0%)] were found. The correlation between the system PE and CeREMIwas low and only influenced by a CeREMI<2.8 ng/mL. Hemodynamic stability stayed within the clinically acceptable range.CONCLUSIONS:The applied CL system for propofol administration has an acceptable performance in the CeREMIrange of 2.8–7.5 ng/mL during the induction and maintenance of anesthesia. There was no evidence of a strong association between CeREMand the CL performance. This study also shows that when the CeREMIis <2.8 ng/mL, it might be more challenging to prevent arousal during propofol anesthesia.
Optimal Approach to Load Progressions during Strength Training in Older Adults
Authors: BUSKARD ANDREW N. L. , JACOBS KEVIN A. , ELTOUKHY MOATAZ M. , STRAND KERI L. , VILLANUEVA LAWRENCE , DESAI PARTH P. , SIGNORILE JOSEPH F. 
Published: May 2019

ABSTRACTProgressive resistance training (RT) is one of the most effective interventions for reducing age-related deficits in muscle mass and functional capacity.PurposeTo compare four approaches to load progressions in RT for older adults to determine if an optimal method exists.MethodsEighty-two healthy community-dwelling older adults (71.8 ± 6.2 yr) performed 11 wk of structured RT (2.5 d·wk−1) in treatment groups differing only by the method used to increase training loads. These included percent one repetition maximum (%1RM): standardized loads based on a percentage of the one repetition maximum (1RM); rating of perceived exertion (RPE): loads increased when perceived difficulty falls below 8/10 on the OMNI-Resistance Exercise Scale perceived exertion scale; repetition maximum (RM): loads increased when a target number of repetitions can be completed with a given load; repetitions in reserve (RiR): identical to RM except subjects must always maintain ≥1 “repetition in reserve,” thus avoiding the possibility of training to temporary muscular failure.ResultsMultiple analyses of covariance indicated no significant between-group differences on any strength (chest press 1RM; leg press 1RM) or functional performance outcome (usual walking speed, maximum walking speed, 8-ft timed up-and-go, gallon jug transfer test, 30 s sit-to-stand). The RPE group found the exercise to be significantly more tolerable and enjoyable than subjects in the RiR, RM, and %1RM groups.ConclusionGiven the RM, RPE, %1RM, and RiR methods appear equally effective at improving muscular strength and functional performance in an older population, we conclude that the RPE method is optimal because it is likely to be perceived as the most tolerable and enjoyable, which are two important factors determining older adults’ continued participation in RT.