bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratumoral Heterogeneity of Glioblastoma Infiltration Revealed by Joint Histogram Analysis of Diffusion Tensor Imaging
Authors: Li Chao , Wang Shuo , Yan Jiun-Lin , Piper Rory J , Liu Hongxiang , Torheim Turid , Kim Hyunjin , Zou Jingjing , Boonzaier Natalie R , Sinha Rohitashwa , Matys Tomasz , Markowetz Florian , Price Stephen J
Published: August 2018

Background

Glioblastoma is a heterogeneous disease characterized by its infiltrative growth, rendering complete resection impossible. Diffusion tensor imaging (DTI) shows potential in detecting tumor infiltration by reflecting microstructure disruption.

OBJECTIVE

To explore the heterogeneity of glioblastoma infiltration using joint histogram analysis of DTI, to investigate the incremental prognostic value of infiltrative patterns over clinical factors, and to identify specific subregions for targeted therapy.

Methods

A total of 115 primary glioblastoma patients were prospectively recruited for surgery and preoperative magnetic resonance imaging. The joint histograms of decomposed anisotropic and isotropic components of DTI were constructed in both contrast-enhancing and nonenhancing tumor regions. Patient survival was analyzed with joint histogram features and relevant clinical factors. The incremental prognostic values of histogram features were assessed using receiver operating characteristic curve analysis. The correlation between the proportion of diffusion patterns and tumor progression rate was tested using Pearson correlation.

Results

We found that joint histogram features were associated with patient survival and improved survival model performance. Specifically, the proportion of nonenhancing tumor subregion with decreased isotropic diffusion and increased anisotropic diffusion was correlated with tumor progression rate (P = .010, r = 0.35), affected progression-free survival (hazard ratio = 1.08, P < .001), and overall survival (hazard ratio = 1.36, P < .001) in multivariate models.

Conclusion

Joint histogram features of DTI showed incremental prognostic values over clinical factors for glioblastoma patients. The nonenhancing tumor subregion with decreased isotropic diffusion and increased anisotropic diffusion may indicate a more infiltrative habitat and potential treatment target.
The Effects of Tobacco Smoking, and Prenatal Tobacco Smoke Exposure, on Risk of Schizophrenia: A Systematic Review and Meta-Analysis
Authors: Hunter Abby , Murray Rachael , Asher Laura , Leonardi-Bee Jo
Published: August 2018

Background

The association between cigarette smoking and schizophrenia is well established. However, up to 90% of people with schizophrenia begin smoking before the onset of their illness; thus, smoking could be an independent risk factor for schizophrenia. Prenatal exposure to maternal cigarette smoke is also associated with psychiatric problems in adolescence. Therefore, our aim was to undertake a systematic review and meta-analysis to explore the effect of smoking, and prenatal smoke exposure, on risk of schizophrenia.

Method

We systematically searched Medline, EMBASE, PsychInfo, Maternity and Infant Care, and Web of Science (from inception to February 2018) to identify comparative observational studies of the risk of schizophrenia in relation to smoking status. Measures of relative risk (RR) were pooled in a meta-analysis with 95% confidence intervals (CI), using random effects model.

Results

Twelve studies (9 cohort, 3 case-control) were included. Odds ratios (OR) and hazard ratios (HR) were pooled together to estimate pooled relative risks and estimates combined in a meta-analysis on an assumption of constant risk over time. Smokers had a significantly increased risk of schizophrenia compared with nonsmokers (RR = 1.99, 95% CI = 1.10% to 3.61%, I2 = 97%, 5 studies). Exposure to prenatal smoke increased the risk of schizophrenia by 29% (95% CI = 1.10% to 1.51%, I2 = 71%, 7 studies). Sensitivity analyses identified no significant differences between the results from studies reporting OR and hazard ratio.

Conclusions

Our findings suggest smoking, and prenatal smoke exposure, may be an independent risk factor for schizophrenia. Care should be taken when inferring causation, given the observational nature of the studies.

Implications

In this meta-analysis of 12 studies, smokers had a significantly increased risk of schizophrenia compared with nonsmokers. Exposure to prenatal tobacco smoke also increased the risk of schizophrenia by 29% compared with those with no exposure to prenatal tobacco smoke. Our findings suggest that smoking, and prenatal tobacco smoke exposure, may be independent risk factors for schizophrenia. These results may have important public health implications for decreasing the incidence of schizophrenia. The possibility of a causal link between smoking and schizophrenia warrants further investigation.
Missing Children: On the Extent, Patterns, and Correlates of Repeat Disappearances by Young People
Authors: Babuta Alexander , Sidebottom Aiden
Published: August 2018

Missing persons investigations are arguably the most common and costly non-crime problem the police are expected to handle, with a large proportion of all cases attributable to young people. This article investigates the prevalence, time course, distance, and correlates of repeat disappearances by children (under the age of 18 years). Using data from one UK police force for the period January 2011 to May 2013 (n = 1,885), we find that (1) nearly two-thirds of all missing child reports are repeat disappearances, (2) a small proportion of children who go missing repeatedly (15%) account for over half of all missing persons incidents, (3) children who go missing repeatedly tend to travel shorter distances than children reported missing once, and (4) the likelihood of a child going missing on multiple occasions is associated with age, being in care, a history of family conflict, and if going missing was judged to be ‘out of character’. The implications of our findings for the prevention of repeat disappearances by young people are discussed.
Different and Not Equal:The Uneven Association of Race, Poverty, and Abortion Laws on Abortion Timing
Authors: Solazzo Alexa L
Published: August 2018

The number of regulations surrounding abortion has increased drastically in recent years. It is important to assess how these laws relate to abortion timing, since the cost, safety, and accessibility of abortion varies by how many weeks pregnant a woman is when the procedure occurs. Research examining how state laws relate to abortion timing generally use rates or data from vital statistics; while informative, such methods do not allow researchers to examine how these laws may be disproportionately associated with abortion timing among select groups of women, including poor and nonwhite women. To fill this research gap, I analyze data from the nationally representative 2008 Abortion Patient Survey, with appended information on state laws regarding abortion in 2008. I find that laws requiring second trimester abortions be performed in a hospital and both in-person counselling and waiting periods have different associations with abortion timing based on race and income-to-poverty status. Predicted abortion timing for black and Hispanic women differs based on state laws and their income-to-poverty status, while for white women, models show that the association between state laws and abortion timing is not dependent on their income-to-poverty status. Overall, this research illustrates the relevance of state-level abortion laws for shaping abortion timing among women, highlighting how these relationships differ across racial and socioeconomic groups in the United States.
Congenital heart block in neonatal lupus erythematosus
Authors: Pullen Richard L. , Branson Marietta
Published: August 2018

NLE occurs in 1 out of every 15,000 live births annually and accounts for 85% of all cases of congenital heart block in the absence of cardiac structural abnormalities. Here's what you need to know.
Teen issues, part 1
Authors: Perkins Amanda
Published: August 2018

The teenage years can be a confusing time in which myriad social and emotional factors come into play. We take a look at some of the challenges our adolescent patients may face.
Stereoselective Ketamine Metabolism by Genetic Variants of Cytochrome P450 CYP2B6 and Cytochrome P450 Oxidoreductase
Authors: Wang Pan-Fen , Neiner Alicia , Kharasch Evan D.
Published: August 2018

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Human ketamine N-demethylation to norketamine in vitro at therapeutic concentrations is catalyzed predominantly by the cytochrome P4502B6 isoform (CYP2B6). The CYP2B6 gene is highly polymorphic. CYP2B6.6, the protein encoded by the common variant allele CYP2B6*6, exhibits diminished ketamine metabolism in vitro compared with wild-type CYP2B6.1. The gene for cytochrome P450 oxidoreductase (POR), an obligatory P450 coenzyme, is also polymorphic. This investigation evaluated ketamine metabolism by genetic variants of human CYP2B6 and POR.

Methods

CYP2B6 (and variants), POR (and variants), and cytochrome b
5 (wild-type) were coexpressed in a cell system. All CYP2B6 variants were expressed with wild-type POR and b
5. All POR variants were expressed with wild-type CYP2B6.1 and b
5. Metabolism of R- and S-ketamine enantiomers, and racemic RS-ketamine to norketamine enantiomers, was determined using stereoselective high-pressure liquid chromatography–mass spectrometry. Michaelis–Menten kinetic parameters were determined.

Results

For ketamine enantiomers and racemate, metabolism (intrinsic clearance) was generally wild-type CYP2B6.1 > CYP2B6.4 > CYP2B6.26, CYP2B6.19, CYP2B6.17, CYP2B6.6 > CYP2B6.5, CYP2B6.7 > CYP2B6.9. CYP2B6.16 and CYP2B6.18 were essentially inactive. Activity of several CYP2B6 variants was less than half that of CYP2B6.1. CYP2B6.9 was 15 to 35% that of CYP2B6.1. The order of metabolism was wild-type POR.1 > POR.28, P228L > POR.5. CYP2B6 variants had more influence than POR variants on ketamine metabolism. Neither CYP2B6 nor POR variants affected the stereoselectivity of ketamine metabolism (S > R).

Conclusions

Genetic variants of CYP2B6 and P450 oxidoreductase have diminished ketamine N-demethylation activity, without affecting the stereoselectivity of metabolism. These results suggest candidate genetic polymorphisms of CYP2B6 and P450 oxidoreductase for clinical evaluation to assess consequences for ketamine pharmacokinetics, elimination, bioactivation, and therapeutic effects.
The Rise and Fall of Mesh in Pelvic Surgery and the Shortcomings of Medical Device Regulation
Authors: Trabuco Emanuel C. , Montori Victor M.
Published: August 2018

Two U.S. Food and Drug Administration public health warnings regarding the use of mesh in stress incontinence and prolapse repairs have had far-reaching clinical and legal consequences. In this commentary, we explore the drastically distinct results from these mesh-based procedures, which revealed systemic flaws with the medical device approval process across specialties and affected thousands of patients.
Provision of Moderately and Highly Effective Reversible Contraception to Insured Women With Intellectual and Developmental Disabilities
Authors: Wu Justine , Zhang Jianying , Mitra Monika , Parish Susan L. , Minama Reddy Geeth Kavya
Published: August 2018

OBJECTIVE:

To estimate provision of moderately and highly effective reversible contraceptives to women with intellectual and developmental disabilities.

METHODS:

We used data from the Massachusetts All-Payer Claims Database to identify women aged 15–44 years with and without intellectual and developmental disabilities who were continuously enrolled in a private commercial insurance plan, Medicaid, or Medicare in 2012. We calculated the percentage of women aged 15–44 years who were not medically or surgically sterile and were provided 1) highly effective, long-acting reversible contraception (LARC, the intrauterine device or subdermal implant); or 2) prescriptions for moderately effective methods (pill, patch, ring, shot, or diaphragm). Logistic regression models estimated the odds of LARC and moderately effective method provision by disability status, adjusted for age, income, and Medicaid receipt.

RESULTS:

Among 915,561 women who were not medically or surgically sterile, 13,059 women (1.4%) had at least one intellectual and developmental disability. Women with intellectual and developmental disabilities were less likely to be provided LARC (2.1% vs 4.2%, P<.001, adjusted odds ratio [OR] 0.43, 95% CI 0.38–0.48, P<.001) and moderately effective methods (21.1% vs 29.9%, P<.001, adjusted OR 0.68, 95% CI 0.65–0.71, P<.001) than women without intellectual and developmental disabilities. The one exception was the progestin shot, which was provided more often to women with intellectual and developmental disabilities than women without these disabilities (14.7% vs 4.3%, P<.001). Among a subset of women who only received moderately effective methods or LARC (n=310,344), women with intellectual and developmental disability had lower odds of receiving LARC than moderately effective methods (adjusted OR 0.59, 95% CI 0.52–0.67).

CONCLUSION:

The study findings raise concerns that the provision of LARC and moderately effective methods differs based on the presence of intellectual and developmental disabilities. Greater understanding is needed regarding factors that underlie lower provision of LARC in comparison with moderately effective methods, especially the progestin shot, among women with intellectual and developmental disabilities.
An Original Suprapannicular Incision Technique for Cesarean Delivery in the Morbidly Obese Parturient
Authors: Lakhi Nisha A. , Williamson Katherine , Moretti Michael L.
Published: August 2018

BACKGROUND:

Obese patients are at an increased risk of cesarean delivery and its associated wound complications. We present an alternative incision technique for obese parturients that avoids making a Pfannenstiel incision under the panniculus while still providing access to the lower uterine segment.

TECHNIQUE:

For our technique, an assistant uses Allis clamps to exert caudal traction on the patient's panniculus and a transverse skin incision is made under the umbilicus, 3 cm below the line joining the anterosuperior iliac crests. On entry to the abdominal cavity, a wound retractor is placed to optimize access to the lower uterine segment so that a low transverse uterine incision can be made.

EXPERIENCE:

We have used this incision technique on 17 obese patients with no incidence of intraoperative complications, no requirement to perform a vertical hysterotomy incision, and no postoperative wound infections.

CONCLUSION:

Our technique is a feasible alternative incision for obese parturients that avoids making a subpannicular Pfannenstiel incision and still allows for good access to the lower uterine segment.
Risk of Cervical Intraepithelial Neoplasia 2 or Worse by Cytology, Human Papillomavirus 16/18, and Colposcopy Impression
Authors: Silver Michelle I. , Andrews Jeff , Cooper Charles K. , Gage Julia C. , Gold Michael A. , Khan Michelle J. , Massad L. Stewart , Parvu Valentin , Perkins Rebecca B. , Schiffman Mark , Smith Katie M. , Wentzensen Nicolas
Published: August 2018

OBJECTIVE:

To calculate pooled risk estimates for combinations of cytology result, human papillomavirus (HPV) 16/18 genotype and colposcopy impression to provide a basis for risk-stratified colposcopy and biopsy practice.

DATA SOURCE:

A PubMed search was conducted on June 1, 2016, and a ClinicalTrials.gov search was conducted on June 9, 2018, using key words such as “uterine cervical neoplasms,” “cervical cancer,” “mass screening,” “early detection of cancer,” and “colposcopy.”

METHODS OF STUDY SELECTION:

Eligible studies must have included colposcopic impression and either cytology results or HPV 16/18 partial genotype results as well as a histologic biopsy diagnosis from adult women. Manuscripts were reviewed for the following: cytology, HPV status, and colposcopy impression as well as age, number of women, and number of cervical intraepithelial neoplasia (CIN) 2, CIN 3, and cancer cases. Strata were defined by the various combinations of cytology, genotype, and colposcopic impression.

TABULATION, INTEGRATION, AND RESULTS:

Of 340 abstracts identified, nine were eligible for inclusion. Data were also obtained from three unpublished studies, two of which have since been published. We calculated the risk of CIN 2 or worse and CIN 3 or worse based on cytology, colposcopy, and HPV 16/18 test results. We found similar risk patterns across studies in the lowest risk groups such that risk estimates were similar despite different referral populations and study designs. Women with a normal colposcopy impression (no acetowhitening), less than high-grade squamous intraepithelial lesion cytology, and HPV 16/18-negative were at low risk of prevalent precancer. Women with at least two of the following: high-grade squamous intraepithelial lesion cytology, HPV16- or HPV18-positive, and high-grade colposcopic impression were at highest risk of prevalent precancer.

CONCLUSION:

Our results support a risk-based approach to colposcopy and biopsy with modifications of practice at the lowest and highest risk levels.
Alternatives to spinal fusion surgery in pediatric deformity
Authors: Betz Randal R. , Antonacci M. Darryl , Cuddihy Laury A.
Published: August 2018

The standard of care for skeletally immature patients with idiopathic scoliosis is bracing for moderate curves. The standard of care for both skeletally immature and mature patients who have more severe or progressive curves is spinal fusion. We present a summary of four currently used non-fusion surgical techniques as alternatives to bracing and spinal fusion. Vertebral body stapling (VBS) is suggested for patients between the ages of 8 and 13 yr for girls and younger than 15 yr for boys with at least one year of growth remaining (Risser 0-1, Sanders digital stage ≤4). Thoracic curves should measure 25-35 degrees and lumbar curves 25-45 degrees. For best results, the curves should be flexible, bending to < 20 degrees. Correction with a cord/screw construct includes vertebral body tethering (VBT) and anterior scoliosis correction (ASC), which are most commonly being performed for skeletally immature patients (Risser 0-2, Sanders digital stage ≤4) with thoracic and lumbar curves between 30-70 degrees that bend to < 30 degrees. The authors of this article have expanded the indications for treating adolescents with idiopathic scoliosis who are more mature (Risser > 2) with ASC. One commercial product has received CE mark approval in Europe for ASC treatment in both skeletally immature and mature patients. A second product utilizing posterior dynamic concave distraction, also with CE mark approval in Europe, is indicated for patients who are 10-17 yr old with primary single main thoracic or thoracolumbar curves between 30-60 degrees that correct to ≤35 degrees on bending films.
Anterior Subcutaneous Internal Pelvic Fixation/INFIX: A Systemic Review
Authors: Vaidya Rahul , Woodbury Derrek , Nasr Kerrelos
Published: August 2018

Introduction:

The purpose of this article is to review the available literature on anterior subcutaneous internal pelvic fixation (ASIPF) to identify indications, clinical and radiographic outcomes, and compare these with alternative fixation methods.

Methods:

Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search on PubMed and Google Scholar was performed. Articles included were in the English language or English translations and published between 2007 and 2018. Studies included were appraised with narrative data synthesis.

Results:

Twenty-five articles with 496 patients were included. These included 17 case series, with 3 case reports reporting adverse events.

Conclusions:

ASIPF and the appropriate posterior fixation resulted in healing of pelvic ring injuries in 99.5% of cases. Indications include unstable pelvic ring injuries with the appropriate posterior fixation. Radiographic parameters and outcome measures were infrequently reported. ASIPF is a valuable tool for reduction and fixation in unstable pelvic ring injuries. Complications include lateral femoral cutaneous nerve irritation (26.3%); heterotopic ossification (36%); infection (3%); and femoral nerve palsy (1%), which is likely related to placing the bar and screws too deep.
Sleep Disturbance in Orthopaedic Trauma Patients
Authors: Swann Matthew C. , Batty Miles , Hu Gene , Mitchell Thomas , Box Hayden , Starr Adam
Published: August 2018

Objective:

To evaluate the prevalence and severity of sleep disturbance experienced by patients who have sustained a traumatic orthopaedic injury, how sleep disturbance affects the patient's perceived health quality, and identify factors associated with sleep disturbance.

Design:

Cross-sectional cohort study.

Setting:

Urban Level I trauma center.

Patients/Participants:

Three hundred thirty-five nonconsecutive patients who presented to clinic at various stages of treatment for their traumatic orthopaedic injuries.

Main Outcome Measurements:

Pittsburgh sleep quality index (PSQI) and 36-item short form-36 (SF-36) survey questionnaires; injury severity score (ISS).

Results:

The average PSQI score was 10.3 (±4.8). Two hundred eighty-eight (86.0%) patients had a PSQI score ≥5, indicating the presence of sleep disturbance. The PSQI score was ≥10 in 183 (54.6%) patients, which is sleep disturbance similar to the level seen in clinical depression. Patients reported an average sleep latency of 38.9 (±37.5) minutes, with a total nightly sleep time of 6.3 (±1.9) hours. Univariate statistical analysis demonstrated that age, time since injury, and all components of the SF-36 were significantly associated with increased PSQI scores. When these variables were assessed with multivariate analysis to control for confounding variables, the bodily pain, vitality, and mental health components of the SF-36 remained independently associated with PSQI (P ≤ 0.001, 0.002, and 0.001, respectively). ISS measurements at the time of presentation were not associated with PSQI scores.

Conclusions:

Our findings suggest that sleep disturbance is both highly prevalent (86% PSQI ≥5) and severe (54.6% PSQI ≥10) in patients recovering from a traumatic orthopaedic injury. The bodily pain, vitality, and mental health components of the SF-36 were independently associated with worse sleep quality. The average orthopaedic trauma patient presents with a sleep score similar to that seen in clinical sleep disorders and clinical depression. Interestingly, in our study, the severity of the overall injury burden as measured by ISS and time since injury were not independently associated with the severity of sleep disturbance, as one might expect.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Biomechanical Assessment of Locking Plate Fixation of Comminuted Proximal Olecranon Fractures
Authors: Fantry Amanda , Sobel Andrew , Capito Nicholas , Hodax Jonathan D. , Pidgeon Tyler , Koruprolu Sarath , Rich Ryan , Fava Joseph L. , Green Andrew , Paxton Scott
Published: August 2018

Objectives:

To determine if mean ultimate strength or failure mechanism differed between comminuted olecranon fractures created at the proximal 25% or 50% of the trochlear notch and fixed with precontoured posterior locking plates (PLPs).

Methods:

Comminuted osteotomies were created in 10 matched pairs of cadaveric upper extremities at either the proximal 25% or 50% of the trochlear notch after quantitative computed tomography scans were performed to evaluate bone mineral density. Variable-angle olecranon PLPs were fixed to the specimens. The triceps tendon of each specimen was loaded cyclically and then to failure. Comparison of mean force at failure (displacement >2 mm) was performed using the 2-tailed t test.

Results:

There were no significant differences in specimen bone mineral density within matched pairs. Nineteen specimens failed by olecranon bisection fracture in the sagittal plane. Specimens in the 25% osteotomy group failed at lower ultimate forces of 808 N (SD ± 474 N) versus 1058 N (SD ± 480 N) in the 50% osteotomy group (P = 0.044).

Conclusions:

The ultimate strength of comminuted olecranon fracture fixation with a PLP decreases significantly if the fracture is proximal to the midpoint of the trochlear notch. Fractures proximal to the midpoint of the trochlear notch may benefit from supplemental fixation or suture augmentation to prevent failure, particularly at force ranges higher than those experienced during active elbow range of motion.
Molecular profiling of Spitz nevi identified by digital RNA counting
Authors: Hillen Lisa M. , Geybels Milan S. , Rennspiess Dorit , Spassova Ivelina , Ritter Cathrin , Becker Jürgen C. , Garmyn Marjan , zur Hausen Axel , Van den Oord Joost , Winnepenninckx Véronique
Published: August 2018

The molecular properties of benign melanocytic lesions are poorly understood. Only a few studies have been carried out on specific nevi subtypes, including common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in melanoma-associated oncogenes are typically absent in SN. In the present study, mRNA expressions of 25 SN and 15 NCN were analyzed. Molecular profiling was performed using the RNA NanoString nCounter Gene Expression Platform (number of genes=770). Marker discovery was performed with a training set consisting of seven SN and seven NCN samples from the same patients, and validation was performed using a second set consisting of 18 SN and eight NCN samples. Using the training set, 197 differentially expressed genes were identified in SN versus NCN. Of these, 74 genes were validated in the validation set (false discovery rate q≤0.13). In addition, using random forest and least absolute shrinkage and selection operator feature selection, a molecular signature of SN versus NCN was identified including 15 top-ranked genes. The present study identified a distinct molecular expression profile in SN compared with NCN, even when lesions were obtained from the same patients. Gene set analysis showed upregulation of gene pathways with increased expression of transcripts related to immunomodulatory, inflammatory, and extracellular matrix interactions as well as angiogenesis-associated processes in SN. These findings strongly indicate that SN represent a distinct group of melanocytic neoplasms and evolve differentially and not sequentially from NCN.
Atypical Histiocytic Lesion Preceding a Peripheral T-Cell Lymphoma Involving the Skin Exhibiting the Same Molecular Alterations
Authors: Machan Salma , Córdoba Raúl , Carvajal Nerea , Requena Luis , Piris Miguel Ángel , Facchetti Fabio , Rodríguez-Pinilla Socorro María
Published: August 2018

Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) is a diagnosis of exclusion, showing extreme cytological and phenotypic heterogeneity. Skin involvement of PTCL may be primary or secondary. Diagnosis of histiocytosis may be difficult, requiring clinical–pathological correlation. We describe a laryngeal atypical histiocytic lesion (AHL) and a nasal PTCL, NOS with cutaneous involvement in the same patient presenting with peculiar histopathologic and immunophenotypic features. The laryngeal neoplasm showed morphological and immunophenotypic evidence of histiocytic differentiation and does not fit any other category of the WHO classification nor the revised classification of histiocytosis. The nasal and cutaneous lesions presented features close to natural killer/T-cell lymphoma and gamma–delta T-cell lymphoma but did not meet accurately the WHO criteria. A somatic activating Q61K mutation was found on exon 3 of the NRAS gene in both AHL and PTCL, NOS. The mutation on NRAS gene in both AHL and PTCL, NOS may suggest a common origin from a precursor cell.
Simple LC-MS/MS Methods Using Core–Shell Octadecylsilyl Microparticulate for the Quantitation of Total and Free Daptomycin in Human Plasma
Authors: Miyadera Yukari , Naito Takafumi , Yamada Takahiro , Kawakami Junichi
Published: August 2018

Background:

Daptomycin, a cyclic lipopeptide antibiotic, displays high plasma protein binding. This study developed the simple method of liquid chromatographic separation using a core–shell octadecylsilyl microparticulate coupled to tandem mass spectrometry for the quantitation of total and free daptomycin in human plasma.

Methods:

Free daptomycin in plasma was obtained by centrifugal ultrafiltration. Deproteinized plasma specimens were directly separated using a core–shell octadecylsilyl microparticulate with isocratic elution. The mass spectrometer was run in positive-ion electrospray ionization mode. This method was applied to the quantitation of plasma samples in patients treated with intravenous daptomycin.

Results:

Daptomycin and diazepam as an internal standard were eluted with a total run time of 10 minutes. The calibration curves of total and free daptomycin in human plasma were linear over the concentration ranges of 1–100 and 0.1–10 mcg/mL, respectively. The lower limits of quantitation of the total and free daptomycin in human plasma were 1.0 and 0.1 mcg/mL, respectively. Their extraction recovery rates in nonfiltrated and ultrafiltrated plasma samples were 106.1% and 98.2%, respectively. Total and free daptomycin did not exhibit any matrix effects in human plasma. The intraday and interday accuracies and imprecisions of total daptomycin were 88.7%–106.0% and 98.7%–105.9%, and within 4.1% and 10.4%, whereas those of free daptomycin were 86.8%–101.6% and 103.0%–107.8%, and within 14.6% and 14.6%, respectively. The plasma concentration ranges of total and free daptomycin in 15 infected patients were 3.01–34.1 and 0.39–3.64 mcg/mL, respectively. The plasma protein binding rate of daptomycin ranged from 80.8% to 94.9%.

Conclusions:

The present simple method with an acceptable analytical performance can be helpful for monitoring the pharmacokinetics of daptomycin in infected patients observed in clinical settings.
Volume Retention, Metabolism, and Cellular Composition of Human Fat Xenografts
Authors: Merrifield Brittany A. , Chang Anthony , Hostetter Galen , Komorowska-Timek Ewa
Published: August 2018

Background:

To optimize the take of transferred fat, better understanding of fat graft morphology and growth properties in vivo is critical. We aim to evaluate survival, volume retention, metabolism, and cellular composition of various aliquots of human fat xenografts.

Methods:

Twenty athymic nude mice were injected subcutaneously in opposing flanks with 0.1 ml (small) and 1.0 ml (large) aliquots of human fat graft. Volume (ultrasound) of fat aliquots was measured at baseline, 1, 3, and 12 weeks after implantation. Tissue metabolism (18F-FDG), Hematoxylin and Eosin, special stains, and immunohistochemical analysis were performed at 3 and 12 weeks to determine graft viability, cell origin, and proliferative activity.

Results:

Only 1 of 10 small grafts were detected after 12 weeks by ultrasound and 5 of 10 were found at necropsy. Volume of large grafts decreased significantly from baseline at 3 (827 ± 195 mm3 versus 953 ± 122 mm3; P = 0.004) and 12 weeks (515 ± 163 mm3 versus 953 ± 122 mm3; P = 0.0001). Metabolism increased with time in small (0.6 ± 0.4%ID/g versus 2.0 ± 1.1%ID/g, P = 0.01) and large grafts (0.4 ± 0.3%ID/g versus 1.4 ± 0.9 %ID/g; P = 0.005). Large grafts viability decreased between 3 and 12 weeks (72 ± 20% versus 31 ± 30%; P = 0.012) although small graft viability remained unchanged. Viable and proliferating human and mouse adipocytes and chimeric blood vessels were seen within grafts at both time points.

Conclusions:

Larger graft aliquot was associated with better volume retention by ultrasound but lower viability by histology. Graft metabolism increased with time irrespective of aliquot size potentially due to regenerative processes of both donor and recipient origin.
A Novel Tube-Drainage Technique of Negative Pressure Wound Therapy for Fistulae after Reconstructive Surgery
Authors: Umezawa Hiroki , Matsutani Takeshi , Yokoshima Kazuhiko , Nakamizo Munenaga , Ogawa Rei
Published: August 2018

Background:

Patients with head and neck or esophageal cancer who undergo resection and reconstructive surgery sometimes develop fistulae that exhibit delayed wound healing. We developed a novel negative pressure wound therapy (NPWT) that employs a Penrose drain. This case series report describes its effect on the wound healing and treatment duration of cancer patients with postoperative fistulae.

Methods:

This consecutive case series consisted of all patients from February 2014 to February 2017 who underwent resection and reconstruction for head and neck or esophageal cancer and who then developed a fistula that was treated with either NPWT or a second flap that did not resolve the fistula or led to fistula recurrence and was then treated with NPWT. A Penrose drainage tube was inserted into the fistula, and a NPWT device was applied.

Results:

Eleven patients (10 males, 1 female; mean age, 67.4 years) underwent NPWT for fistulae that arose after tumor resection and reconstruction (n = 6) or after fistula reconstruction (n = 5). The resection was for esophageal (n = 4), laryngeal (n = 3), oral (n = 2), and hypopharyngeal (n = 2) cancer. In 9 cases, 1 week of NPWT led to rapid and complete wound healing. In 2 cases, complete healing occurred after 3–4 weeks of NPWT.

Conclusions:

Our NPWT applies continuous negative pressure inside the fistula only and dramatically promoted fistula healing. This approach may work by cleaning the fistula and promoting mucosal surface adhesion. It is particularly effective when the tissue surrounding the fistula is soft due to fresh tissue transfer.
Evaluating Medical Spanish Proficiency: A Comparison of Physician Assistant Student Self-Assessment to Standardized Patient and Expert Faculty Member Ratings
Authors: Lie Désirée A. , Forest Christopher P. , Richter-Lagha Regina
Published: August 2018

Purpose

Whether physician assistant (PA) students' self-assessment or standardized patient (SP) evaluations of students' medical Spanish proficiency accurately reflect their language proficiency is unclear. This study compares PA student and SP ratings with an expert faculty member's rating to determine whether student or SP ratings can be used to evaluate language proficiency.

Methods

Fifty-eight students participated in a single-station Spanish Objective Structured Clinical Examination (OSCE) at the midpoint of a medical Spanish curriculum. Using the Interagency Language Roundtable (ILR)—a 6-point, single-item language proficiency scale previously validated among physicians—PA students and SPs evaluated students' medical Spanish proficiency. Their scores were then compared with the scores derived by an expert faculty rater who had viewed a video of each student–SP encounter. The faculty's score was considered the gold standard. Correlation between scores was calculated using Spearman's rank correlation coefficient.

Results

Mean student scores were highest when rated by SPs (M = 3.8, SD = 0.9), followed by self (M = 3.0, SD = 0.9), and then faculty (M = 2.5, SD = 1.2). Spearman's rank correlation coefficient showed a strong positive correlation between students and the expert faculty rater (r

s
= 0.67, P < .001) and between SPs and the expert faculty rater (r

s
= 0.72, P < .001). The correlation was stronger for high- than for low-proficiency students. Students' self-rated scores showed significant improvement from baseline to the OSCE.

Conclusions

PA students participating in a medical Spanish curriculum and SPs show good correlation with an expert faculty rater in assessing Spanish proficiency during an OSCE. Standardized patients demonstrate scoring leniency. The ILR has potential for tracking aggregate student progress and curriculum effectiveness. With training, student self-rating could be used for interval assessment of medical Spanish communication.
Assessing the Impact of a Professional Development Program for Physician Assistant Program Directors
Authors: Alexander Lisa Mustone , Auth Patrick , Carlson Rachel , Davison Meredith
Published: August 2018

Purpose

The growth of physician assistant (PA) programs nationally has stretched the available capacity of experienced PA program directors. To address this need, a professional developmental program was designed to provide new program directors with the knowledge, skills, and resources necessary to succeed in the role. This study sought to characterize the impact of program attendance over time. Data were collected from individuals representing 5 cohorts that participated in the annual Physician Assistant Education Association New Program Directors Retreat between 2011 and 2015.

Methods

An electronic survey was developed and sent to all 5 cohorts (n = 139). Anonymous responses were collected and quantitative data were analyzed in the aggregate and also by year of participation. Qualitative data were analyzed, and a thematic analysis was conducted. Results were compared with baseline data collected during the program registration process and with published national data on program director characteristics.

Results

Seventy-five program participants completed the survey, for a response rate of 57%. Program director stability, educational achievement, and involvement in leadership and service activities were found to be positive outcomes for individuals who had participated in the professional development program.

Conclusion

Survey respondents reported positive outcomes after attending a professional development program; these outcomes are consistent with research on similar programs published in the literature. Our findings suggest that new program directors who participated in this professional development program not only derived career-stabilizing benefits but also succeeded in creating supportive peer networks while gaining greater confidence in their new academic role.
Aim high, shoot often
Authors: Adcock Gale
Published: August 2018

The first nurse practitioner serving in the North Carolina legislature reflects on decades of advocacy that helped prepare her for election.
Gender dysphoria in youth: An overview for primary care providers
Authors: Kameg Brayden N. , Nativio Donna G.
Published: August 2018

Background and purpose:

Primary care providers who encounter children are often the first line of contact for individuals with gender dysphoria, which occurs when sex assigned at birth is incongruent with one's true, expressed sexual identity. Because those with untreated gender dysphoria are at risk of a variety of negative outcomes, including mood symptomatology, suicidality, substance use disorders, and other psychosocial risk factors, it is critical that health care providers are adept in the provision of holistic, patient-centered care. The purpose of this report is to provide an updated review of the current evidence from the literature pertaining to the identification, treatment, and coordination of care among children with gender dysphoria within the primary care setting or medical home.

Methods:

Using PubMed and CINAHL, a literature review spanning from 2012 to the present was conducted using the following key words: gender dysphoria, transgender health, LGBT health, and hormone therapy. Reference lists of identified articles were also explored for relevance.

Conclusions:

Treatment may include a social transition, hormone antagonist therapy, or the administration of cross-sex hormone therapy, with a medical home needed to facilitate coordination of care. Best practice guidelines vary across pediatric and developmental groups and include both reversible and nonreversible modalities. Screening for negative psychosocial sequelae must be completed to include mood symptomatology, suicidality, substance use disorders, and risky sexual behavior, so that appropriate screening, identification, and treatment interventions can be implemented.

Implications for practice:

The primary care medical home must act as a foundation for the identification of gender dysphoria and/or associated comorbidities and must treat, when able, or refer, when indicated. In addition, because of structural barriers and stigmatization, public policy often fails the transgender community and can exacerbate the aforementioned psychosocial comorbidities faced by the transgender youth community. Health care providers, particularly nurse practitioners, are in a unique position to expand on the face-to-face care provided to the community and engage in advocacy efforts to dismantle structural barriers impeding transgender individuals and communities while also providing primary health care, anticipatory guidance, and care coordination.
What Do Breast Cancer Survivors Expect From Exercise?
Authors: Hirschey Rachel , Pan Wei , Hockenberry Marilyn , Kimmick Gretchen , Shaw Ryan , Lipkus Isaac
Published: August 2018

Background

Exercise outcome expectations (OEs) (ie, what one expects to obtain or avoid by exercising) are influential to increase exercise among cancer survivors.

Objective

The aim of this study was to measure the accessibility (ie, frequency one thinks about exercise resulting in an outcome) and importance (ie, one’s value of the outcome) of OEs among breast cancer survivors.

Methods

Stage IA to IIB breast cancer survivors who were 1 to 5 years posttreatment completed OE questionnaires. Descriptive statistics were used to examine OE accessibility and importance.

Results

The sample (n = 73) was 91.8% white, 5.4% African American, 1.4% Asian or Pacific Islander, and 1.4% other. The mean age was 58 (SD, 9.6) years. Outcome expectation importance mean was 6.1 (SD, 0.4), indicating OEs are overall “important.” Accessibility mean was 4.8 (SD, 0.6), demonstrating breast cancer survivors think about exercise OEs “sometimes/50% of the time.” There was a moderate (r
s = 0.48) relationship between OE importance and accessibility, indicating they are related, yet distinct.

Conclusions

Outcome expectations are generally important to breast cancer survivors. Thus, OEs may motivate increased exercise among this population.

Implications for Practice

Oncology providers should encourage patients to think about OEs more often to increase exercise. Compared with traditional approaches of informing patients about exercise benefits, this may be a more comprehensive and powerful approach to motivate exercise among breast cancer survivors.
Using Continuous Vital Sign Monitoring to Detect Early Deterioration in Adult Postoperative Inpatients
Authors: Verrillo Sue Carol , Cvach Maria , Hudson Krysia Warren , Winters Bradford D.
Published: August 2018

Background:

Episodic vital sign collection (eVSC), as single data points, gives an incomplete picture of adult patients' postoperative physiologic status.

Local Problem:

Late detection of patient deterioration resulted in poor patient outcomes on a postsurgical unit.

Methods:

Baseline demographic and outcome data were collected through retrospective chart review of all patients admitted to the surgical unit for 12 weeks prior to this quality improvement project. Data on the same outcomes were collected during the 12-week project.

Intervention:

This project compared outcomes between the current standard of eVSC and the proposed standard of continuous vital sign monitoring (cVSM).

Results:

Using cVSM demonstrated a statistically significant 27% decrease in the complication rate, and a clinically significant decrease in transfers to an intensive care unit and failure-to-rescue (FTR) events rate.

Conclusions:

cVSM demonstrated detection of early signs of patient deterioration to prevent FTR.
Pericytoma With t(7;12): The First Ovarian Case Reported and a Review of the Literature
Authors: Koh Nicholas Wee Chong , Seow Wan Yi , Lee York Tien , Lam Joyce Ching Mei , Lian Derrick Wen Quan
Published: August 2018

We report the first case of an ovarian pericytoma with t(7;12). An 11-year-old child presented with abdominal pain and distension. A suprapubic mass was detected on examination and radiological investigations revealed a 16.5 cm solid-cystic ovarian mass. Histologically, the tumor was composed of spindle cells with S100-protein, Bcl-2, and CD10 reactivity on immunohistochemistry. Alpha fetoprotein, calretinin, alpha-inhibin, WT1, smooth muscle actin, caldesmon, desmin, cytokeratins, chromogranin, synaptophysin, EMA, Sox10, CD117, CD31, CD34, and CD68 were all negative. Molecular tests showed t(7;12)(p22;q13), resulting in the fusion of the ACTB with GLI1 genes and a diagnosis of pericytoma with t(7;12) of the ovary was made. We discuss the difficulties in diagnosing this lesion in the ovary and highlight the importance on molecular tests in characterizing challenging cases, especially primary ovarian spindle cell mesenchymal tumors.
SATB2 is Consistently Expressed in Squamous Morules Associated With Endometrioid Proliferative Lesions and in the Stroma of Atypical Polypoid Adenomyoma
Authors: McCluggage W. Glenn , Van de Vijver Koen
Published: August 2018

So-called squamous morules are closely associated with endometrioid proliferative lesions, in the endometrium and the ovary. Morules have an unusual immunophenoptype, typically exhibiting nuclear staining with β-catenin, positivity with CDX2, CD10, and p16 and are negative with hormone receptors and p63. We report the previously undescribed occurrence of consistent SATB2 nuclear positivity within morules. Nuclear positivity was present in 38/43 (88%) cases of morules (24 focal; 14 diffuse) while all cases of nonmorular squamous metaplasia in endometrioid proliferative lesions (n=13) were SATB2 negative, except for occasional positive nuclei in 1 case. We also observed that the stromal cells of atypical polypoid adenomyoma typically exhibited diffuse nuclear immunoreactivity with SATB2 while the stromal cells of other endometrial polypoid lesions (endometrial polyp, adenomyoma, adenosarcoma) were usually negative, although there was focal weak staining in occasional cases. Pathologists should be aware of this previously undescribed phenomenon which represents a further example of the unusual immunophenotype of so-called squamous morules. The reasons underlying SATB2 nuclear positivity in squamous morules and the stroma of atypical polypoid adenomyoma are unknown.
Understanding Anosognosia for Hemiplegia After Stroke
Authors: Byrd Elizabeth M. , Jablonski Rita J. , Vance David E.
Published: August 2018

Background

Anosognosia for hemiplegia (AHP) after stroke is a complex cognitive behavioral disorder that removes awareness of one-sided paralysis (hemiplegia). As a result, stroke survivors afflicted with AHP may be more likely to have unrealistic expectations for stroke rehabilitation, display unsafe behaviors and experience falls, and ultimately suffer the physical and psychological consequences of frequent falling.

Objective

The purpose of this article is to describe AHP by discussing anosognosia within the context of contemporary theoretical understandings, examining current imaging evidence of the disorder, and summarizing emerging interventions designed to reinstate self-awareness in anosognosic patients.

Method

Systematic review with a focus on defining and describing AHP based on human experimental studies was conducted within a 10-year period.

Results

Eleven studies were identified. The content and foci of the 11 studies fell into one of three categories: theory testing, imaging evidence, and interventions for individuals with AHP.