bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of material flexibility on the thermodynamics and kinetics of hydrophobically induced evaporation of water
Authors: Altabet Y. Elia , Haji-Akbari Amir , Debenedetti Pablo G.
Published: March 2017

Significance

The evaporation of water in hydrophobic confinement is important for the formation and function of both natural and synthetic hydrophobic self-assemblies. Using advanced computational techniques, we find that the thermodynamic and kinetic stability of water in hydrophobic confinement is extremely sensitive to the flexibility of the confining material. In the context of engineered systems, this work suggests that the mechanical properties of the building blocks in a self-assembled system are a crucial design consideration. With respect to biophysical phenomena, it suggests that small changes in flexibility can induce switch-like responses such as the opening and closing of membrane channels and the conversion between active and inactive states in receptors, both of which are common drug targets.
Phosphorylation-induced conformational dynamics in an intrinsically disordered protein and potential role in phenotypic heterogeneity
Authors: Kulkarni Prakash , Jolly Mohit Kumar , Jia Dongya , Mooney Steven M. , Bhargava Ajay , Kagohara Luciane T. , Chen Yihong , Hao Pengyu , He Yanan , Veltri Robert W. , Grishaev Alexander , Weninger Keith , Levine Herbert , Orban John
Published: March 2017

Significance

The onset of androgen resistance is a major impediment in treating prostate cancer (PCa). However, the underlying molecular mechanisms are not fully understood. Here, we integrate multiple biophysical approaches that report conformational preferences of the intrinsically disordered protein (IDP) Prostate-Associated Gene 4 (PAGE4) with human cancer biology and nonlinear dynamics. Based on our biophysical, biochemical, and cellular data, a mathematical model is presented that suggests a mechanism by which phosphorylation-induced conformational changes in PAGE4 can switch from an androgen-dependent phenotype to an androgen-independent phenotype in PCa cells. The study underscores how IDPs that engage in multiple “promiscuous” interactions due to their conformational dynamics when overexpressed or aberrantly expressed can stochastically orchestrate phenotypic heterogeneity in PCa.
Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum
Authors: Kitamura Takuya , Seki Naoya , Kihara Akio
Published: March 2017

Significance

Although the synthetic pathway of phytosphingosine is already known, its degradation pathway has remained unclear. In the present study, we reveal the entire phytosphingosine degradation pathway, where fatty acid α-oxidation is involved. We show that the Sjögren–Larsson syndrome-causative gene
ALDH3A2
and
HACL2
(2-hydroxyacyl-CoA lyase 2) are involved in the fatty acid α-oxidation reactions as an aldehyde dehydrogenase and a 2-hydroxy acyl-CoA lyase, respectively. Our findings are important for understanding the molecular mechanism of phytosphingosine/sphingolipid homeostasis. HACL2 is localized in the endoplasmic reticulum, indicating that fatty acid α-oxidation occurs in the endoplasmic reticulum in mammals, in addition to the α-oxidation already known to occur in peroxisomes.
Modulating IgG effector function by Fc glycan engineering
Authors: Li Tiezheng , DiLillo David J. , Bournazos Stylianos , Giddens John P. , Ravetch Jeffrey V. , Wang Lai-Xi
Published: March 2017

Significance

The
N
-glycan composition of the constant (Fc) domain of IgG can modulate antibody effector functions by affecting the ability of the Fc to bind various Fc receptors (FcγRs). Most therapeutic IgG antibodies carry heterogeneous
N
-glycans, which might not be optimal for their therapeutic purpose. To understand the contribution of each
N
-glycan component on antibody effector function, we generated homogeneous IgG1 glycoforms using a chemoenzymatic approach and performed side-by-side in vitro binding, antibody-dependent cell-mediated cytotoxicity (ADCC), and in vivo IgG-mediated cell depletion assays. Our results confirm the dominant positive effect of removing the core fucose on FcγRIIIA binding and ADCC. Our study further reveals that sialylation adversely impacts ADCC in the context of core fucosylation but not in its absence.
Phenopolis: an open platform for harmonization and analysis of genetic and phenotypic data
Authors: Pontikos Nikolas , Yu Jing , Moghul Ismail , Withington Lucy , Blanco-Kelly Fiona , Vulliamy Tom , Wong Tsz Lun Ernest , Murphy Cian , Cipriani Valentina , Fiorentino Alessia , Arno Gavin , Greene Daniel , Jacobsen Julius OB , Clark Tristan , Gregory David S , Nemeth Andrea M , Halford Stephanie , Inglehearn Chris F , Downes Susan , Black Graeme C , Webster Andrew R , Hardcastle Alison J ,   UKIRDC, Plagnol Vincent
Published: March 2017

Phenopolis is an open-source web server providing an intuitive interface to genetic and phenotypic databases. It integrates analysis tools such as variant filtering and gene prioritization based on phenotype. The Phenopolis platform will accelerate clinical diagnosis, gene discovery and encourage wider adoption of the Human Phenotype Ontology in the study of rare genetic diseases.

Availability and Implementation

A demo of the website is available at https://phenopolis.github.io. If you wish to install a local copy, source code and installation instruction are available at https://github.com/phenopolis. The software is implemented using Python, MongoDB, HTML/Javascript and various bash shell scripts.

Supplementary information

Supplementary data are available at Bioinformatics online.
Prediction of sudden and non-sudden cardiac death in post-infarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy
Authors: Rizas Konstantinos D. , McNitt Scott , Hamm Wolfgang , Massberg Steffen , Kääb Stefan , Zareba Wojciech , Couderc Jean-Philippe , Bauer Axel
Published: March 2017

Aims

To test the value of Periodic Repolarization Dynamics (PRD), a recently validated electrocardiographic marker of sympathetic activity, as a novel approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N-SCD) and to improve identification of patients that profit from ICD-implantation.

Methods and results

We included 856 post-infarction patients with left-ventricular ejection fraction (LVEF) ≤30% of the MADIT-II trial in sinus rhythm. Of these, 507 and 348 patients were randomized to ICD or conventional treatment. PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary endpoints were total mortality, SCD and N-SCD. Multivariable analyses included treatment group, QRS-duration, New York Heart Association classification, blood-urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable analyses, increased PRD was a significant predictor of mortality (standardized coefficient 1.37[1.19–1.59]; P < 0.001) and SCD (1.40 [1.13–1.75]; P = 0.003) but also predicted N-SCD (1.41[1.10–1.81]; P = 0.006). While increased PRD predicted SCD in conventionally treated patients (1.61[1.23–2.11]; P < 0.001), it was predictive of N-SCD (1.63[1.28–2.09]; P < 0.001) and adequate ICD-therapies (1.20[1.03–1.39]; P = 0.017) in ICD-treated patients. ICD-treatment substantially reduced mortality in the lowest three PRD-quartiles by 53% (P = 0.001). However, there was no effect in the highest PRD-quartile (mortality increase by 29%; P = 0.412; P < 0.001 for difference) as the reduction of SCD was compensated by an increase of N-SCD.

Conclusion

In post-infarction patients with impaired LVEF, PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising tool to identify post-MI patients with reduced LVEF who might benefit from intensified treatment.
The influence of physique on dose conversion coefficients for idealised external photon exposures: a comparison of doses for Chinese male phantoms with 10th, 50th and 90th percentile anthropometric parameters
Authors: Lv Wei , He Hengda , Liu Qian
Published: March 2017

For evaluating radiation risk, the construction of anthropomorphic computational phantoms with a variety of physiques can help reduce the uncertainty that is due to anatomical variation. In our previous work, three deformable Chinese reference male phantoms with 10th, 50th and 90th percentile body mass indexes and body circumference physiques (DCRM-10, DCRM-50 and DCRM-90) were constructed to represent underweight, normal weight and overweight Chinese adult males, respectively. In the present study, the phantoms were updated by correcting the fat percentage to improve the precision of radiological dosimetry evaluations. The organ dose conversion coefficients for each phantom were calculated and compared for four idealized external photon exposures from 15 keV to 10 MeV, using the Monte Carlo method. The dosimetric results for the three deformable Chinese reference male phantom (DCRM) phantoms indicated that variations in physique can cause as much as a 20% difference in the organ dose conversion coefficients. When the photon energy was <50 keV, the discrepancy was greater. The irradiation geometry and organ position can also affect the difference in radiological dosimetry between individuals with different physiques. Hence, it is difficult to predict the conversion coefficients of the phantoms from the anthropometric parameters alone. Nevertheless, the complex organ conversion coefficients presented in this report will be helpful for evaluating the radiation risk for large groups of people with various physiques.
PARP inhibitors as precision medicine for cancer treatment
Authors: Du Yi , Yamaguchi Hirohito , Hsu Jennifer L. , Hung Mien-Chie
Published: March 2017

Personalized or precision medicine is an emerging treatment approach tailored to individuals or certain groups of patients based on their unique characteristics. These types of therapies guided by biomarkers tend to be more effective than traditional approaches, especially in cancer. The inhibitor against poly (ADP-ribose) polymerase (PARP), olaparib (Lynparza, AstraZeneca), which was approved by the US Food and Drug Administration (FDA) in 2014, demonstrated efficacy specifically for ovarian cancer patients harboring mutations in BRCA genes, which encode proteins in DNA double-strand break repairs. However, the response to PARP inhibitors has been less encouraging in other cancer types that also carry defects in the BRCA genes. Thus, furthering our understanding of the underlying mechanism of PARP inhibitors and resistance is critical to improve their efficacy. In this review, we summarize the results of preclinical studies and the clinical application of PARP inhibitors, and discuss the future direction of PARP inhibitors as a potential marker-guided personalized medicine for cancer treatment.
The gravitational-wave physics
Authors: Cai Rong-Gen , Cao Zhoujian , Guo Zong-Kuan , Wang Shao-Jiang , Yang Tao
Published: March 2017

The direct detection of gravitational wave by Laser Interferometer Gravitational-Wave Observatory indicates the coming of the era of gravitational-wave astronomy and gravitational-wave cosmology. It is expected that more and more gravitational-wave events will be detected by currently existing and planned gravitational-wave detectors. The gravitational waves open a new window to explore the Universe and various mysteries will be disclosed through the gravitational-wave detection, combined with other cosmological probes. The gravitational-wave physics is not only related to gravitation theory, but also is closely tied to fundamental physics, cosmology and astrophysics. In this review article, three kinds of sources of gravitational waves and relevant physics will be discussed, namely gravitational waves produced during the inflation and preheating phases of the Universe, the gravitational waves produced during the first-order phase transition as the Universe cools down and the gravitational waves from the three phases: inspiral, merger and ringdown of a compact binary system, respectively. We will also discuss the gravitational waves as a standard siren to explore the evolution of the Universe.
Implementation of a Quality Improvement Initiative: Improved Congenital Muscular Torticollis Outcomes in a Large Hospital Setting
Authors: Strenk Mariann L. , Kiger Michelle , Hawke Jesse L. , Mischnick Amy , Quatman-Yates Catherine
Published: March 2017

Background. The American Physical Therapy Association (APTA) published a guideline for congenital muscular torticollis (CMT) in 2013. Our division adopted the guideline as the institutional practice standard and engaged in a quality improvement (QI) initiative to increase the percentage of patients who achieved resolution of CMT within 6 months of evaluation.

Objective. The aims of this report are to describe the QI activities conducted to improve patient outcomes and discuss the results and implications for other institutions and patient populations.

Design. This was a quality improvement study.

Methods. In alignment with the Chronic Care Model and Model of Improvement, an aim and operationally defined key outcome and process measures were established. Interventions were tested using Plan-Do-Study-Act cycles. A CMT registry was established to store and manage data extracted from the electronic record over the course of testing. Statistical process control charts were used to monitor progress over time.

Results. The QI initiative resulted in an increase in the percentage of patients who achieved full resolution of CMT within a 6-month episode of care from 42% to 61% over an 18-month period. Themes that emerged as key drivers of improvement included: (1) timely, optimal access to care, (2) effective audit and clinician feedback, and (3) accurate, timely documentation.

Limitations. The initiative took place at a single institution with a supportive culture and strong QI resources, which may limit direct translation of interventions and findings to other institutions and patient populations.

Conclusions. Improvement science methodologies provided the tools and structure to improve division-wide workflow and increase consistency in the implementation of the APTA CMT guideline. In doing so, significant CMT population outcome improvements were achieved.
Development and Application of qPCR and RPA Genus- and Species-Specific Detection of Phytophthora sojae and P. sansomeana Root Rot Pathogens of Soybean
Authors: Rojas J. Alejandro , Miles Timothy D. , Coffey Michael D. , Martin Frank N. , Chilvers Martin I.
Published: March 2017

Phytophthora root rot of soybean, caused by Phytophthora sojae, is one of the most important diseases in the Midwestern United States, and is estimated to cause losses of up to 1.2 million metric tons per year. Disease may also be caused by P. sansomeana; however, the prevalence and damage caused by this species is not well known, partly due to limitations of current diagnostic tools. Efficient, accurate, and sensitive detection of pathogens is crucial for management. Thus, multiplex qPCR and isothermal RPA (recombinase polymerase amplification) assays were developed using a hierarchical approach to detect these Phytophthora spp. The assays consist of a genus-specific probe and two species-specific probes that target the atp9-nad9 region of the mitochondrial genome that is highly specific for the genus Phytophthora. The qPCR approach multiplexes the three probes and a plant internal control. The RPA assays run each probe independently with a plant internal control multiplexed in one amplification, obtaining a result in as little as 20 mins. The multicopy mitochondrial genome provides sensitivity with sufficient variability to discern among different Phytophthora spp. The assays were highly specific when tested against a panel of 100 Phytophthora taxa and range of Pythium spp. The consistent detection level of the assay was 100 fg for the qPCR assay and 10 pg for the RPA assay. The assays were validated on symptomatic plants collected from Michigan (U.S.) and Ontario (Canada) during the 2013 field season, showing correlation with isolation. In 2014, the assays were validated with samples from nine soybean producing states in the U.S. The assays are valuable diagnostic tools for detection of Phytophthora spp. affecting soybean.
Phytophthora pluvialis Studies on Douglas-fir Require Swiss Needle Cast Suppression
Authors: Gómez-Gallego Mireia , Bader Martin Karl-Friedrich , Scott Peter Matthew , Leuzinger Sebastian , Williams Nari Michelle
Published: March 2017

Phytophthora pluvialis is associated with early defoliation and shoot dieback in Douglas-fir in Oregon and New Zealand. In 2013, P. pluvialis was described from mixed tanoak-Douglas-fir forests in the Pacific Northwest and concurrently recognized as the main causal agent of red needle cast (RNC) in New Zealand radiata pine plantations. Little is known about its infection cycle and impact on host physiology. P. pluvialis studies in Douglas-fir are challenging due to the ubiquitous presence of the endophyte Phaeocryptopus gaeumannii, which produces similar symptoms and premature defoliation with persistent needle wetness, known as Swiss needle cast (SNC). Nonetheless, our study showed P. pluvialis infection in the presence of SNC. Exclusive expression of P. pluvialis is difficult to achieve as both diseases are promoted by high humidity. Here we established a ‘dry leaf’ strategy to suppress SNC when inoculating Douglas-fir needles for RNC studies. Sheltering plants along with drip irrigation to avoid needle wetness during the P. gaeumannii sporulation period suppressed its development in the new season flush. The diminished endophyte inoculum enabled bias-reduced studies of P. pluvialis impacts on Douglas-fir without the confounding effects of stomatal blockage and premature defoliation caused by P. gaeumannii.
Pedicled Vascularized Clavicular Graft for Anterior Cervical Arthrodesis
Authors: Bohl Michael A. , Mooney Michael A. , Catapano Joshua S. , Almefty Kaith K. , Preul Mark C. , Chang Steve W. , Kakarla U. Kumar , Reece Edward M. , Turner Jay D. , Porter Randall W.
Published: March 2017

Study Design.

Cadaveric feasibility study.

Objective.

To assess the anatomic and technical feasibility of rotating a clavicular segment on a sternocleidomastoid muscle (SCM) pedicle into the ventral cervical spine using a cadaveric model and to provide the first clinical case description of performing this procedure.

Summary of Background Data.

Reconstruction of the anterior cervical spine in patients with a high risk of pseudoarthrosis may require the use of a vascularized bone graft (VBG). A vascularized clavicular graft rotated on an SCM pedicle would afford all the benefits of a VBG without the added morbidity of free-tissue transfer; however, this technique has not been described.

Methods.

A multidisciplinary team hypothesized that it would be anatomically and technically feasible to rotate a pedicled clavicular bone graft from the bottom of C2 to the top of T2 via an anterior approach. Five cadavers underwent bilateral anterior neck dissections for a total of 10 clavicular graft assessments. A case report describes the use of a clavicular VBG in a patient with a 3-level corpectomy defect and a history of failed fusion.

Results.

Ten clavicles were rotated on an SCM pedicle. The grafts were either harvested as an entire segment or as the superior two-thirds of clavicle, leaving the inferior one-third in situ with pectoralis attachments intact. All grafts reached from the bottom of C2 to the top of T2. When the entire length of exposed clavicle was mobilized, it could cover five to six levels. The case report highlights technical challenges of this procedure in a living patient and provides the clinical context for its potential utility in the reconstruction of the ventral cervical spine.

Conclusion.

This surgical technique is best suited for patients with long-segment cervical defects and an increased risk of pseudarthrosis. Further clinical experience with this technique is required before definitive conclusions can be made.

Level of Evidence: 5
Papillomas of the breast: factors associated with underestimation
Authors: Boufelli Gabriela , Giannotti Marcelo A. , Ruiz Carlos A. , Barros Nestor de , Chala Luciano F. , Maesaka Jonathan Y. , Goncalves Rodrigo , Bresciani Bárbara H. , Vianna Paula , Soares José M. , Baracat Edmund C. , Filassi José R.
Published: March 2017

The distinction between benign and malignant papilloma of the breast through percutaneous needle biopsy can be difficult because of limited samples; the underestimation rate can be up to 25%. The aim of this study is to identify clinical and histological factors associated with underestimation, invasive ductal carcinoma, or ductal in-situ carcinoma (DCIS) of the breast found in surgical specimens from papillary lesions. This may contribute toward selection of patients for a follow-up strategy without the need for surgical excision. From a database of 3563 patients, we identified 85 with intraductal papilloma between 2007 and 2013 who had undergone breast-imaging studies, percutaneous needle biopsy, and surgical resection of the lesion. Central papillomas normally present with a palpable mass, whereas peripheral papillomas generally do not have clinical manifestations (microcalcifications); both central and peripheral papillomas were related to atypical lesions, 13.5 and 15.4%, respectively. Among the 59 cases of central papillomas, there were four cases of underestimation, three DCIS and one invasive ductal carcinoma (6.8%). Among the 26 cases of peripheral papillomas, there was one case of DCIS (3.8%), with a total underestimation rate of 5.8%; all underestimated lesions measured more than 1 cm. The median size was 11 mm at mammography and 19 mm at ultrasound. Our data suggest that lesions less than 1 cm in size, without atypia and concordant imaging and clinical findings, may not require surgical resection.
Depletion of Epidermal Langerhans Cells in the Skin Lesions of Pellagra Patients
Authors: Yamaguchi Sayaka , Miyagi Takuya , Sogabe Yoko , Yasuda Masahito , Kanazawa Nobuo , Utani Atsushi , Izaki Seiichi , Uezato Hiroshi , Takahashi Kenzo
Published: March 2017

Pellagra is a nutrient deficiency disease caused by insufficient niacin levels. Recent studies have shown that numbers of epidermal Langerhans cells decreased in other diseases caused by nutritional deficiencies, including necrolytic migratory erythema and acrodermatitis enteropathica. Epidermal Langerhans cells are capable of modulating or even halting the inflammatory reaction. The aim of this study was to examine changes in the number of Langerhans cells and other dendritic cells, and maturation of epidermal Langerhans cells in the lesional and adjacent non-lesional skin in pellagra patients. Seven pellagra patients and 10 healthy individuals who served as controls were included. The number and distribution of dendritic cells and other cutaneous cells were examined by immunohistochemistry. Epidermal Langerhans cells decreased considerably in the skin lesions of pellagra patients, whereas other dendritic cells did not change. The decrease in the number of Langerhans cells was positively correlated with the histological severity of skin lesions. As the number of Langerhans cells was not reduced in the undisturbed neighboring skin, the depletion of epidermal Langerhans cells did not precede skin damage but was a cause of prolonged severe inflammation.
Pulsed CO2 Laser Ablation of Superficial Basal Cell of Limbs and Trunk: A Comparative Randomized Clinical Trial With Cryotherapy and Surgical Ablation
Authors: Zane Cristina , Facchinetti Elena , Arisi Mariachiara , Ortel Bernhard , Calzavara-Pinton Piergiacomo
Published: March 2017

BACKGROUND

Pulsed CO2 laser is a treatment of superficial basal cell carcinoma (sBCC) although robust clinical evidence has not been reported so far.

OBJECTIVE

The authors investigated efficacy, safety, time to wound healing, cosmetic outcome, patient satisfaction, and cost-effectiveness ratio of pulsed CO2 laser in comparison to cryotherapy and surgery.

MATERIALS AND METHODS

BCCs of the trunk and extremities were randomized to one of the treatments. After 90 days, efficacy and cosmetic outcome were assessed. Patients recorded the time to complete healing of the wound and scored their overall satisfaction.

RESULTS

Two hundred forty patients were randomized. After 3 months, complete remission (CR) rate with pulsed CO2 laser was 78.8%. This was significantly lower than surgery, whereas the CR rate with cryotherapy was not significantly different. Cosmetic result was better with surgery. High satisfaction was reported by 65.0% of patients treated with CO2 ablation. Time of wound healing was significantly shorter with CO2 laser.

CONCLUSION

In comparison to cryotherapy, pulsed CO2 laser showed no statistically significant difference in efficacy, cosmetic outcome, and patient satisfaction. Time to healing was shorter; the cost and cost-effectiveness ratio were similar. Surgery had the greatest efficacy rate. The main limitation of this study was the short duration of follow-up (3 months).
ASSESSMENT OF DRUSEN AND OTHER RETINAL DEGENERATIVE CHANGES IN PATIENTS WITH HEREDITARY HEMOCHROMATOSIS
Authors: Menghini Moreno , Prünte Christian , Krayenbuehl Pierre A. , Nowak Albina
Published: March 2017

Purpose:

Iron can exert oxidative damage, and increased accumulation is believed to play a role in age-related macular degeneration. Hereditary hemochromatosis leads to an increase in total body iron. Patients with HH were assessed for drusen and other retinal changes.

Methods:

Descriptive uncontrolled study of spectral-domain optical coherence tomography, short-wavelength autofluorescence, and color fundus images from patients with HH were used. Diagnosis of HH was established by measuring ferritin and transferrin saturation, and confirmed by genetic testing. Classification of the patients according to initial ferritin level was: Group A >1,032 μg/L; Group B below.

Results:

Twenty-five percent of the invited participants were enrolled. Mean age at diagnosis was 46 ± 15 years in Group A, and 38 ± 13 years in Group B, P = 0.07, whereas mean age at imaging was 60 ± 13 years in Group A, and 48 ± 15 years in Group B (P = 0.003). The median of the initial ferritin level was 1,869 (1,262–3,256) ng/mL in Group A, and 534 (439–679) ng/mL in Group B. No subject in either group revealed multiple drusen, unambiguous changes of the retinal pigment epithelium, or increased lipofuscin in any of the images.

Conclusion:

The study results did not show an increased prevalence of drusen or other retinal degenerative changes in patients with HH. Thus, it was concluded that increased intestinal iron absorption as well as increased blood iron concentration are not risk factors for the early development of retinal degenerative changes in this study population.
PPI Trial for Eosinophilic Esophagitis
Authors: Lipka Seth , Kumar Ambuj , Richter Joel E.
Published: March 2017

Introduction:

Despite consensus eosinophilic esophagitis (EoE) statement published in 2011 calling for a 2-month trial of protons pump inhibitor (PPI), the guidelines are not followed by many. We studied the practice patterns in our community and response to a PPI retrial in patients previously diagnosed with “idiopathic EoE.”

Methods:

All patients presenting to the senior author’s practice with suspected EoE from 2011 to 2015. Two cohorts were studied: (1) patients diagnosed in the community as “idiopathic EoE”; (2) treatment naïve patients given a PPI trial at University of South Florida. PPI responsive eosinophilia was defined after 2 months of high dose PPIs after initial diagnosis of mucosal eosinophilia and histologic response of <15 eosinophils per HPF. SPSS v19.0 was used to calculate mean difference and odds ratios (OR) and 95% confidence intervals.

Results:

In total, 78 patients met inclusion criteria, 46 patients had outside diagnosis of “idiopathic EoE,” and 41 patients received a PPI trial at University of South Florida. In total, 34/46 (73.9%) community patients were placed on a PPI, 3/46 (6.5%) were placed on elimination diets, 31/46 (67.4%) steroids, and 21/46 (45.7%) were treated with both steroids/PPIs. Fewer patients received PPI trials in the community 3/46 (6.5%) versus 26/34 (76.5%) at our center [OR, 46.6 (95% CI, 11.3-191.5); P<0.0001]. In total, 12/26 (46.2%) were PPI responders on our retrial despite previously being diagnosed with idiopathic EoE. The group initially diagnosed at our center had a higher PPI response rate 12/15 (80%) versus 12/26 (46.2%) in the community group [OR, 7.58 (1.42, 40.55; P=0.018)].

Conclusions:

The importance of a PPI trial is misunderstood and may be confused with the more traditional PPI trial for gastroesophageal reflux disease. This algorithm is critical and should be done before empiric steroids/diet therapies.
Perspectives on Low-grade Sarcomas: The Extraordinary Contributions of Sharon W. Weiss, MD
Authors: Hastings Hope , Goldblum John R.
Published: March 2017

Soft-tissue pathology encompasses a wide spectrum of neoplasms that represent some of the most challenging and problematic tumors in surgical pathology. Owing to the intensive work of dedicated pathologists, this once esoteric field has become increasingly well defined. In this review, Dr Sharon Weiss’ monumental contributions to low-grade sarcomas, including low-grade fibromyxoid sarcoma/so-called hyalinizing spindle cell tumor, atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma, epithelioid hemangioendothelioma, and dermatofibrosarcoma protuberans with fibrosarcomatous transformation will be discussed.
Primary Cystic Trophoblastic Tumor of the Testis
Authors: Gondim Dibson D. , Ulbright Thomas M. , Cheng Liang , Idrees Muhammad T.
Published: March 2017

Cystic trophoblastic tumor (CTT) has been described in postchemotherapy retroperitoneal lymph node dissections of patients with testicular germ cell tumors. Prognostically, this lesion is similar to teratoma and no further treatment is required after surgery in the absence of other components. CTT has not, however, been reported in the testis. We identified 14 CTTs in the treated (4) and untreated (9; no information for 1 patient) testes of patients 15 to 43 years old (median, 25) with mixed germ cell tumors. The CTT was a minor component (<1% to 10%) and associated with teratoma (14), embryonal carcinoma (7), yolk sac tumor (7), seminoma (1), and choriocarcinoma (1). At follow-up, CTT and teratoma were also found in 2 subsequent resections (spermatic cord and pelvis mass) in 2 patients. The CTTs were not grossly distinct but on microscopic examination were cystic to partly solid, with cysts often containing fibrinoid material and lined by mononucleated squamoid cells with eosinophilic to pale, frequently vacuolated cytoplasm and having pleomorphic nuclei with dense, often smudged chromatin. Mitotic activity was inconspicuous. Immunostains for hCG (6/6), inhibin (6/6), and p63 (2/6) were focally positive. The pathogenesis of CTT is not completely understood. As untreated patients without choriocarcinoma may have CTT in the testis, it is suggested that testicular CTT represents a form of regressed choriocarcinoma or a late morphologic phase in the transformation of choriocarcinoma to teratoma.
Adenovirus Hepatitis
Authors: Schaberg Kurt B. , Kambham Neeraja , Sibley Richard K. , Higgins John P.T.
Published: March 2017

Adenoviruses are common pathogens that usually cause self-limited infections. However, in the immunocompromised host they can cause severe infections involving multiple organs including the liver. A search of the pathology database at Stanford University Medical Center (1995 to 2016) identified 12 cases of adenovirus hepatitis including biopsy and autopsy specimens. There were 8 pediatric patients, 7 of which had received orthotropic liver transplants and 1 of which was receiving chemotherapy for lymphoblastic leukemia. There were 4 adult patients, of which 1 was actively receiving chemotherapy for chronic lymphocytic leukemia and 2 had undergone hematopoietic stem cell transplantation for hematologic malignancies. One patient had lymphoplasmacytic lymphoma and had received chemotherapy over a year prior but was not receiving therapy at the time he contracted adenovirus hepatitis. In all cases, histologic sections showed nonzonal coagulative hepatocyte necrosis and characteristic intranuclear inclusions. Hepatocyte necrosis ranged from spotty to massive. The majority of cases (7/12; 58%) had no associated inflammation. If present, inflammation was focal and lymphohistiocytic. In 1 case, findings were focal within the liver, requiring an image-guided biopsy. This patient underwent a simultaneous nontargeted liver biopsy that lacked histologic evidence of adenovirus. Among the pediatric patients, 63% (5/8) died secondary to organ failure, while there was 100% (4/4) mortality in the adult population.
RBM10-TFE3 Renal Cell Carcinoma
Authors: Argani Pedram , Zhang Lei , Reuter Victor E. , Tickoo Satish K. , Antonescu Cristina R.
Published: March 2017

Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion. TFE3 rearrangement was not detected by conventional TFE3 break-apart FISH, but was suggested by strong diffuse TFE3 immunoreactivity in a clean background. We then developed novel fosmid probes to detect the RBM10-TFE3 gene fusion in archival material. These cases validate RBM10-TFE3 as a recurrent gene fusion in Xp11 translocation RCC, illustrate a source of false-negative TFE3 break-apart FISH, and highlight the complementary role of TFE3 IHC and TFE3 FISH.
Medical Student Documentation in the Emergency Department in the Electronic Health Record Era—A National Survey
Authors: Virden Ryan A. , Sonnett F. Meridith , Khan Abu N.G.A.
Published: March 2017

Objectives

Implementation of electronic health record (EHR) has generated a new challenge in the practice of medical student documentation in the emergency department (ED). This study discerns both the current practices and consensus opinions of pediatric ED directors and Association of American Medical Colleges (AAMC) student representatives regarding best practices for documentation by medical students in the ED EHR nationwide.

Methods

The authors conducted a cross-sectional Web-based survey of the directors of academic pediatric EDs and AAMC student representatives using Qualtric survey engine. The survey asked participants to describe their current practices and their opinion regarding the utility of and best practices for medical student documentation in the ED.

Results

Approximately 47% (35/74) of pediatric ED directors and 54% (70/129) of AAMC medical schools’ student representatives responded to the survey. Both groups demonstrated similar opinions of the critical importance and advantage of medical students’ documentation in the ED (P ≥ 0.99). However, these 2 groups differed in opinion on the impact of medical student documentation on clinical care of the ED patients (P = 0.008). The survey found that 83% of medical students and 74% of ED directors believe that medical students should be documenting in the EHR. The majority of both groups (51% of medical students and 65% of ED directors) preferred a single, combined attending physician–medical student note for clinical documentation.

Conclusions

This study presents data describing the current practice of medical student documentation in academic pediatric EDs in the United States. There is a strong consensus among educators and students on the usefulness of medical student documenting patient encounters in the ED.
Binky Bites and Other Oronasal Pressure Injuries
Authors: Mook Louisa B. , Metz James B. , Boos Stephen C. , Feldman Kenneth W.
Published: March 2017

Initial examination and exploration of childhood injuries may not lead to an obvious explanation of abuse. Although abusive oronasal injuries have been described, ones including nasal destruction are rare. We describe 4 children abused using implements that ultimately were thought to have caused significant nasal tissue destruction. In 2 of the cases, a forced pacifier placement was implicated in causing pressure injuries. In the other 2 cases, gags were part of the children's injuries. All 4 children had other findings of abuse and neglect.
Treatment of a Patient With Depersonalization Disorder With Low Frequency Repetitive Transcranial Magnetic Stimulation of the Right Temporo-Parietal Junction in a Private Practice Setting
Authors: RACHID FADY
Published: March 2017

Depersonalization disorder (DPD) is a debilitating dissociative condition with no proven treatments. Although the pathophysiology of DPD is poorly understood, there are reports of increased excitability of the prefrontal cortex in patients with this condition. The temporo-parietal junction may also play a major role in the conscious experience of the spatial unity of the normal self and body. Repetitive transcranial magnetic stimulation has been shown in some case studies to effectively treat this condition. This report describes an additional such case, a 26-year-old man with a 6-month history of DPD who responded safely and significantly to repetitive transcranial magnetic stimulation to the right temporo-parietal junction.
Commentary. Transcranial Magnetic Stimulation: Does It Matter Where or What or Whom You Target?
Authors: BERMAN JOSHUA
Published: March 2017

Repetitive transcranial magnetic stimulation is a promising treatment for depression and possibly for other psychiatric disorders. Clinical trials show a small but significant benefit compared with sham treatment. Occasional patients respond dramatically, as witnessed in the 2 cases presented here of patients with depersonalization symptoms. The guest discussant, Dr Joshua Berman, analyzes the challenges of finding individualized treatment parameters that could make repetitive transcranial magnetic stimulation more predictably effective.
First-Line Antiretroviral Treatment Outcomes and Durability in HIV-Infected Children Treated Through the Universal Coverage Health Program in Thailand
Authors: Teeraananchai Sirinya , Bunupuradah Torsak , Puthanakit Thanyawee , Kerr Stephen J. , Ruxrungtham Kiat , Chaivooth Suchada , Bhakeecheep Sorakij , Law Matthew G. , Chokephaibulkit Kulkanya
Published: March 2017

Background:

We assessed the treatment outcomes on first-line antiretroviral therapy (ART), and factors associated with switching regimen in HIV-infected children treated through the universal coverage health program (UC) in Thailand.

Methods:

Children aged <15 years at ART initiation who had been receiving ART for at least 6 months between 2008 and 2014 through UC were included in the analysis. The Kaplan–Meier method was used to estimate immunological recovery (IMR), immunological failure, and virological failure (VF). Cox models were used to assess predictors of IMR and VF. Competing risk models were used to assess factors associated with switching to a second-line regimen, with death considered as a competing risk.

Results:

A total of 4120 children initiated ART at a median (interquartile range) age of 9.3 (5.8–12.0) years. The median duration of ART was 3.7 years with 17,950 person-years of follow-up. Two thousand eight hundred five children achieved IMR, and the probability of IMR increased to 76% by 3 years after ART initiation. Among 1054 children switched to second-line regimens, 84% had VF and 19% had immunological failure. The cumulative rate of switching regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged ≥12 years at ART initiation, starting with nonnucleoside reverse-transcriptase inhibitors, and baseline CD4% <10% had an increased risk of switching to second-line regimens.

Conclusions:

Children receiving ART through UC had good treatment outcomes, although a fifth required switching regimen by 3 years. Earlier treatment initiation and avoiding nonnucleoside reverse-transcriptase inhibitor first-line regimens in high-risk children may prevent treatment failure.
Thirty-day Readmission Rates in an HIV-infected Cohort From Rio de Janeiro, Brazil
Authors: Coelho Lara E. , Ribeiro Sayonara R. , Japiassu Andre M. , Moreira Ronaldo I. , Lara Priscila C. , Veloso Valdilea G. , Grinsztejn Beatriz , Luz Paula M.
Published: March 2017

Background:

The 30-day readmission rate is an indicator of the quality of hospital care and transition to the outpatient setting. Recent studies suggest HIV infection might increase the risk of readmission although estimates of 30-day readmission rates are unavailable among HIV-infected individuals living in middle/low-income settings. Additionally, factors that may increase readmission risk in HIV-infected populations are poorly understood.

Methods:

Thirty-day readmission rates were estimated for HIV-infected adults from the Instituto Nacional de Infectologia Evandro Chagas/Fiocruz cohort in Rio de Janeiro, Brazil, from January 2007 to December 2013. Cox regression models were used to evaluate factors associated with the risk of 30-day readmission.

Results:

Between January 2007 and December 2013, 3991 patients were followed and 1861 hospitalizations were observed. The estimated 30-day readmission rate was 14% (95% confidence interval: 12.3 to 15.9). Attending a medical visit within 30 days after discharge (adjusted hazard ratio [aHR] = 0.73, P = 0.048) and being hospitalized in more recent calendar years (aHR = 0.89, P = 0.002) reduced the risk of 30-day readmission. In contrast, low CD4 counts (51–200 cells/mm³: aHR = 1.70, P = 0.024 and ≤ 50 cells/mm³: aHR = 2.05, P = 0.003), time since HIV infection diagnosis ≥10 years (aHR = 1.58, P = 0.058), and leaving hospital against medical advice (aHR = 2.67, P = 0.004) increased the risk of 30-day readmission.

Conclusions:

Patients with advanced HIV/AIDS are most at risk of readmission and should be targeted with prevention strategies to reduce this risk. Efforts to reduce discharge against medical advice and to promote early postdischarge medical visit would likely reduce 30-day readmission rates in our population.
Brief Report: Antibody Responses to Quadrivalent HPV Vaccination in HIV-Infected Young Women as Measured by Total IgG and Competitive Luminex Immunoassay
Authors: Kahn Jessica A. , Xu Jiahong , Kapogiannis Bill G. , Sleasman John W.
Published: March 2017

We compared antibody responses of HIV-infected young women to the human papillomavirus (HPV) 6, 11, 16, and 18 vaccine using total immunoglobulin (Ig) G Luminex immunoassay (LIA) and competitive Luminex immunoassay (cLIA) assays. HPV18 seropositivity after HPV vaccination as measured with IgG LIA remained high (98%) 48 weeks after vaccination, in contrast with seropositivity as measured with cLIA (73%). Seropositivity rates at week 48 as measured by both IgG LIA and cLIA remained high for HPV6, 11, and 16 (93.5%–100%). These results suggest that the lower rate of seropositivity to HPV18 when cLIA vs. IgG LIA is used is a function of the assay and does not imply lower vaccine immunogenicity.
Brief Report: Medication Sharing Is Rare Among African HIV-1 Serodiscordant Couples Enrolled in an Efficacy Trial of Oral Pre-exposure Prophylaxis (PrEP) for HIV-1 Prevention
Authors: Thomson Kerry A. , Haberer Jessica E. , Marzinke Mark A. , Mujugira Andrew , Hendrix Craig W. , Celum Connie , Ndase Patrick , Ronald Allan , Bangsberg David R. , Baeten Jared M. ,   for the Partners PrEP Study Team
Published: March 2017

Sharing of pre-exposure prophylaxis (PrEP) medications is a concern for PrEP implementation. For HIV-1 serodiscordant couples, sharing may undermine the HIV-1 prevention benefit and also cause antiretroviral resistance if taken by HIV-1 infected partners. Within a PrEP efficacy trial among HIV-1 serodiscordant couples, we assessed the occurrence of PrEP sharing by self-report and plasma tenofovir concentrations in HIV-1 infected partners. PrEP sharing was self-reported at <0.01% of visits, and 0%–1.6% of randomly selected and 0% of purposively selected specimens from HIV-1 infected participants had detectable tenofovir concentrations (median: 66.5 ng/mL, range: 1.3–292 ng/mL). PrEP sharing within HIV-1 serodiscordant couples was extremely rare.
Safety of Tenofovir Disoproxil Fumarate–Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis
Authors: Nachega Jean B. , Uthman Olalekan A. , Mofenson Lynne M. , Anderson Jean R. , Kanters Steve , Renaud Francoise , Ford Nathan , Essajee Shaffiq , Doherty Meg C. , Mills Edward J.
Published: March 2017

Background:

There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants.

Methods:

We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non–TDF-based ART during pregnancy. The risk ratio (RR) for associations was pooled using a fixed-effects model.

Results:

Seventeen studies met the study inclusion criteria. We found that the rate of preterm (<37 weeks gestation) delivery (RR = 0.90, 95% confidence interval [CI]: 0.81 to 0.99, I2 = 59%) and stillbirth (RR = 0.60, 95% CI: 0.43 to 0.84, I2 = 72.0%) were significantly lower in women exposed (vs. not) to TDF-based ART regimen. We found no increased risk in maternal severe (grade 3) or potentially life-threatening (grade 4) adverse events (RR = 0.62; 95% CI: 0.30 to 1.29), miscarriage (RR = 1.09; 95% CI: 0.80 to 1.48), very preterm (<34 weeks gestation) delivery (RR = 1.08, 95% CI: 0.72 to 1.62), small for gestational age (RR = 0.87, 95% CI: 0.67 to 1.13), low birth weight (RR = 0.91; 95% CI: 0.80 to 1.04), very low birth weight (RR = 3.18; 95% CI: 0.65 to 15.63), congenital anomalies (RR = 1.03; 95% CI: 0.83 to 1.28), infant adverse outcomes or infant mortality (age >14 days) (RR = 0.65; 95% CI: 0.23 to 1.85), but increased neonatal mortality (age <14 days) risk (RR = 5.64, 95% CI: 1.70 to 18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age 1 year.

Conclusions:

TDF-based ART in pregnancy seems generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.
Correlation of Bowel Wall Thickening Seen Using Computerized Tomography With Colonoscopies: A Preliminary Study
Authors: Isik Arda , Soyturk Mehmet , Süleyman Sakir , Firat Deniz , Peker Kemal , Yilmaz İsmayil , Celebi Fehmi
Published: March 2017

Purpose:

Bowel wall thickening (BWT) is a common finding in abdominal computerized tomography imaging (CTi). The purpose of the present study was a prospective assessment and management of patients who have BWT in abdominal CTi.

Materials and Methods:

This study was conducted between January 2012 and July 2014 at Erzincan University Hospital, Turkey, with 64 patients who were admitted to the emergency and general surgery department. All of the patients had received colonoscopies due to BWT seen in abdominal CTi.

Results:

Twenty-three (36%) female and 41 (64%) male patients were included in the study. The mean age was 56.2 years (range, 14 to 84 y). The positive predictive value of CTi for BWT was 87.5%. The positive predictive value of a CTi diagnosis of the disease according to a radiologist’s report was 78.1%. Common pathologies detected by colonoscopy included neoplasia and inflammatory bowel disease.

Conclusions:

Diagnosis of BWT by abdominal CTi reveals pathologies in many cases. Colonoscopies will be helpful in the differential diagnosis.