bluuebunny/crossref_metadata_2025 huggingface dataset:
Breaking mean-motion resonances during Type I planet migration
Authors: Hands T O , Alexander R D
Published: October 2017

We present 2D hydrodynamical simulations of pairs of planets migrating simultaneously in the Type I regime in a protoplanetary disc. Convergent migration naturally leads to the trapping of these planets in mean-motion resonances. Once in resonance the planets’ eccentricity grows rapidly, and disc-planet torques cause the planets to escape resonance on a time-scale of a few hundred orbits. The effect is more pronounced in highly viscous discs, but operates efficiently even in inviscid discs. We attribute this resonance-breaking to overstable librations driven by moderate eccentricity damping, but find that this mechanism operates differently in hydrodynamic simulations than in previous analytic calculations. Planets escaping resonance in this manner can potentially explain the observed paucity of resonances in Kepler multitransiting systems, and we suggest that simultaneous disc-driven migration remains the most plausible means of assembling tightly packed planetary systems.
Recycling drug screen repurposes hydroxyurea as a sensitizer of glioblastomas to temozolomide targeting de novo DNA synthesis, irrespective of molecular subtype
Authors: Teng Jian , Hejazi Seyedali , Hiddingh Lotte , Carvalho Litia , de Gooijer Mark C , Wakimoto Hiroaki , Barazas Marco , Tannous Marie , Chi Andrew S , Noske David P , Wesseling Pieter , Wurdinger Thomas , Batchelor Tracy T , Tannous Bakhos A
Published: October 2017

Background

Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor. Standard-of-care treatment involves maximal surgical resection of the tumor followed by radiation and chemotherapy (temozolomide [TMZ]). The 5-year survival rate of patients with GBM is <10%, a colossal failure that has been partially attributed to intrinsic and/or acquired resistance to TMZ through O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status in the tumor.

Methods

A drug screening aimed at evaluating the potential recycling and repurposing of known drugs was conducted in TMZ-resistant GBM cell lines and primary cultures of newly diagnosed GBM with different MGMT promoter methylation status, phenotypic/genotypic background and subtype, and validated with sphere formation, cell migration assays, and quantitative invasive orthotopic in vivo models.

Results

We identified hydroxyurea (HU) to synergize with TMZ in GBM cells in culture and in vivo, irrespective of MGMT promoter methylation status, subtype, and/or stemness. HU acts specifically on the S-phase of the cell cycle by inhibiting the M2 unit of enzyme ribonucleotide reductase. Knockdown of this enzyme using RNA interference and other known chemical inhibitors exerted a similar effect to HU in combination with TMZ both in culture and in vivo.

Conclusions

We demonstrate preclinical efficacy of repurposing hydroxyurea in combination with TMZ for adjuvant GBM therapy. This combination benefit is of direct clinical interest given the extensive use of TMZ and the associated problems with TMZ-related resistance and treatment failure.
Prevalence of Aflatoxin Contamination in Maize and Groundnut in Ghana: Population Structure, Distribution, and Toxigenicity of the Causal Agents
Authors: Agbetiameh D. , Ortega-Beltran A. , Awuah R. T. , Atehnkeng J. , Cotty P. J. , Bandyopadhyay R.
Published: October 2017

Aflatoxin contamination in maize and groundnut is perennial in Ghana with substantial health and economic burden on the population. The present study examined for the first time the prevalence of aflatoxin contamination in maize and groundnut in major producing regions across three agroecological zones (AEZs) in Ghana. Furthermore, the distribution and aflatoxin-producing potential of Aspergillus species associated with both crops were studied. Out of 509 samples (326 of maize and 183 of groundnut), 35% had detectable levels of aflatoxins. Over 15% of maize and 11% of groundnut samples exceeded the aflatoxin threshold limits set by the Ghana Standards Authority of 15 and 20 ppb, respectively. Mycoflora analyses revealed various species and morphotypes within the Aspergillus section Flavi. A total of 5,083 isolates were recovered from both crops. The L morphotype of Aspergillus flavus dominated communities with 93.3% of the population, followed by Aspergillus spp. with S morphotype (6%), A. tamarii (0.4%), and A. parasiticus (0.3%). Within the L morphotype, the proportion of toxigenic members was significantly (P < 0.05) higher than that of atoxigenic members across AEZs. Observed and potential aflatoxin concentrations indicate that on-field aflatoxin management strategies need to be implemented throughout Ghana. The recovered atoxigenic L morphotype fungi are genetic resources that can be employed as biocontrol agents to limit aflatoxin contamination of maize and groundnut in Ghana.

[Formula: see text] Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Variable clinical presentations of babesiosis
Authors: Paparone Pamela , Paparone Philip W.
Published: October 2017

Human babesiosis continues to spread in multiple regions of the United States. It is transmitted by Ixodes species ticks, as are Lyme disease and anaplasmosis. Its variable clinical presentations, together with serologic detection limitations, require that a high index of clinical suspicion be present for prompt diagnosis. This article discusses case presentations showing the wide range of symptoms and presentations that are possible with babesiosis.
Failure of Isoflurane Cardiac Preconditioning in Obese Type 2 Diabetic Mice Involves Aberrant Regulation of MicroRNA-21, Endothelial Nitric-oxide Synthase, and Mitochondrial Complex I
Authors: Ge Zhi-Dong , Li Yingchuan , Qiao Shigang , Bai Xiaowen , Warltier David C. , Kersten Judy R. , Bosnjak Zeljko J. , Liang Mingyu
Published: October 2017

Background

Diabetes impairs the cardioprotective effect of volatile anesthetics, yet the mechanisms are still murky. We examined the regulatory effect of isoflurane on microRNA-21, endothelial nitric-oxide synthase, and mitochondrial respiratory complex I in type 2 diabetic mice.

Methods

Myocardial ischemia/reperfusion injury was produced in obese type 2 diabetic (db/db) and C57BL/6 control mice ex vivo in the presence or absence of isoflurane administered before ischemia. Cardiac microRNA-21 was quantified by real-time quantitative reverse transcriptional–polymerase chain reaction. The dimers and monomers of endothelial nitric-oxide synthase were measured by Western blot analysis. Mitochondrial nicotinamide adenine dinucleotide fluorescence was determined in Langendorff-perfused hearts.

Results

Body weight and fasting blood glucose were greater in db/db than C57BL/6 mice. Isoflurane decreased left ventricular end-diastolic pressure from 35 ± 8 mmHg in control to 23 ± 9 mmHg (P = 0.019, n = 8 mice/group, mean ± SD) and elevated ±dP/dt 2 h after post-ischemic reperfusion in C57BL/6 mice. These beneficial effects of isoflurane were lost in db/db mice. Isoflurane elevated microRNA-21 and the ratio of endothelial nitric-oxide synthase dimers/monomers and decreased mitochondrial nicotinamide adenine dinucleotide levels 5 min after ischemia in C57BL/6 but not db/db mice. MicroRNA-21 knockout blocked these favorable effects of isoflurane, whereas endothelial nitric-oxide synthase knockout had no effect on the expression of microRNA-21 but blocked the inhibitory effect of isoflurane preconditioning on nicotinamide adenine dinucleotide.

Conclusions

Failure of isoflurane cardiac preconditioning in obese type 2 diabetic db/db mice is associated with aberrant regulation of microRNA-21, endothelial nitric-oxide synthase, and mitochondrial respiratory complex I.
Development and use of biochemical markers in osteoarthritis: current update
Authors: Bay-Jensen Anne C. , Thudium Christian S. , Mobasheri Ali
Published: October 2017

Purpose of review

There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to review and comment on current availability of such biomarkers.

Recent findings

Many different biomarkers have been tested in the last 18 months. The main focus has been on testing whether the biomarkers, whether is reflect joint tissue turnover or inflammatory status, can differentiate osteoarthritis patients from healthy controls or whether the biomarkers are associated with progression. Less than a handful of studies, investigate the role of the biomarkers as response markers. Thus, there is still a great need for developing biomarkers that reflect disease activity and thereby can be used for treatment response or patient phenotyping.

Osteoarthritis is the most common form of joint disease. This presents the osteoarthritis research community and pharmaceutical companies developing disease-modifying osteoarthritis drugs (DMOADs) with great opportunities. There are different osteoarthritis subtypes, which complicates the traditional approaches for developing new treatments. If we can identify new markers that can distinguish different subtypes, this can greatly facilitate drug development from early discovery to late clinical development.
Preventing Wedge Deformities When Treating Intertrochanteric Femur Fractures With Intramedullary Devices: A Technical Tip
Authors: Butler Bennet A. , Selley Ryan S. , Summers Hobie D. , Stover Michael D.
Published: October 2017

Intertrochanteric femur fractures are common injuries associated with significant patient morbidity and mortality and high societal costs. Although intramedullary devices have shown promises for treating a wide range of intertrochanteric femur fractures, improper technique can lead to malalignment, fracture displacement, and/or iatrogenic fractures. In particular, a “wedge effect” has been described, in which the passage of conical reamers and the intramedullary nail itself results in the distraction of intertrochanteric fragments with lateralization of the shaft from the femoral neck and varus malalignment. Here, we describe the mechanism by which this deformity is generated and describe techniques for preventing it, including the use of a modified starting point and an alternative to the conical opening reamers.
Is the Best Plate a Nail? A Review of 3230 Unstable Intertrochanteric Fractures of the Proximal Femur
Authors: Tucker Adam , Donnelly Kevin J. , Rowan Clare , McDonald Sinead , Foster Andrew P.
Published: October 2017

Objectives:

To evaluate the functional outcomes, revision, and mortality rates of 3 implants used for unstable intertrochanteric hip fractures; the sliding hip screw (SHS), with or without a trochanteric stabilization plate (TSP); and a cephalomedullary nail (CMN).

Design:

Multicentre National Prospective Cohort Study.

Setting:

Northern Ireland.

Patient/Participants:

Patients were identified from a prospective database. Fractures were classified according to OTA/AO A31A2.2, A2.3, and A3. All patients had a minimum of 12 months of follow-up.

Intervention:

Patients received either an SHS, an SHS in combination with a TSP, or a CMN. Implant choice was at the discretion of the operating surgeon.

Outcome Measure:

Primary outcome was 12-month mortality analyzed by the Kaplan–Meier survival analysis. Secondary outcomes included 12-month functional status using a validated score and all time revision of implants for any reason.

Results:

In total, 3230 patients met the inclusion criteria (2474 SHS, 158 SHS + TSP, and 598 CMN). CMN use increased over time, with concomitant reduction in SHS use. There was no significant difference in functional outcomes at 12 months (analysis of variance, P = 0.177). Although men were significantly younger, they were at a higher risk of 12-month mortality. CMNs had statistically significantly lower 12-month mortality rates (P = 0.0148). The highest revision rate (4.04%) was seen in patients treated with SHS alone (P = 0.041).

Conclusions:

The use of a CMN in unstable intertrochanteric hip fractures conveys the best results in functional outcomes, 12-month mortality, and has lower revision rates compared with an SHS ± TSP.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Acetabular Fractures in Children and Adolescents: Comparison of Isolated Acetabular Fractures and Acetabular Fractures Associated With Pelvic Ring Injuries
Authors: Kruppa Christiane G. , Sietsema Debra L. , Khoriaty Justin D. , Dudda Marcel , Schildhauer Thomas A. , Jones Clifford B.
Published: October 2017

Objectives:

To compare mechanism of injury, fracture pattern, displacement, clinical, and radiographic outcome of isolated acetabular fractures (group 1) versus acetabular fractures associated with a pelvic ring injury (group 2).

Design:

Retrospective cohort comparative analysis.

Setting:

Private orthopaedic practice associated with a level one teaching trauma center.

Main Outcome Measurements:

Mechanism of injury, fracture pattern, displacement and treatment, Glasgow Coma Scale, Injury Severity Score, leg length discrepancy (LLD), and hip dysplasia.

Patients:

Thirty-two children (group 1: 12 fractures; group 2: 25) were classified as 9 A1, 21 A3, 3 B1, 3 B2, and 1 B3 OTA/AO types. Eighteen children (22 fractures) were included with average follow-up of 33.3 months (6–84). The average age was 12.8 years (4–16).

Results:

Main fracture pattern (75%) in group 1 was a posterior wall fracture (A1) caused by falls and sports in 50%. Six socket injuries had a hip dislocation, present only in group 1 (P < 0.001). The majority (84%) in group 2 had anterior wall/column (A3) fractures, caused by traffic accidents (88%). Fracture displacement in group 1 was higher than in group 2 (3.8 vs. 0.8 mm; P = 0.009). Group 2 had a lower Glasgow Coma Scale (P = 0.031) and a higher Injury Severity Score (P < 0.001). Nine (24%) fractures were treated operatively, significantly more were in group 1 (P < 0.001). Three (14%) children had complications including (LLD) (2) or hip dysplasia (2).

Conclusion:

Compared with isolated pediatric acetabular fractures, fractures associated with pelvic ring injuries have less displacement and are less likely to require operative treatment, but they show more associated injuries. Because of potential hip joint growth disturbance, LLD and hip dysplasia can occur.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Travel Distance as a Barrier to Receipt of Adjuvant Radiation Therapy After Radical Prostatectomy
Authors: Yang David D. , Muralidhar Vinayak , Mahal Brandon A. , Beard Clair J. , Mouw Kent W. , Martin Neil E. , Orio Peter F. , King Martin T. , Nguyen Paul L.
Published: October 2017

Objectives:

Following radical prostatectomy (RP), adjuvant radiation therapy (RT) decreases biochemical recurrence and potentially improves metastasis-free and overall survival for patients with high-risk pathologic features. Since adjuvant RT typically occurs daily over several weeks, the logistical challenges of extensive traveling may be a significant barrier to its use. We examined the association between distance to treatment facility and use of adjuvant RT.

Materials and Methods:

We identified 97,568 patients in the National Cancer Database diagnosed from 2004 through 2011 with cT1-4N0-xM0-x prostate cancer and found to have high-risk pathologic features (pT3-4 stage and/or positive surgical margins) at RP. Multivariable logistic regression adjusting for sociodemographic and clinicopathologic factors was used to examine the association between travel distance and receipt of adjuvant RT, defined as radiotherapy initiated within 12 months after RP.

Results:

Overall, 10.6% (10,346) of the study cohort received adjuvant RT. On multivariable analysis, increasing travel distance was significantly associated with decreased use of adjuvant RT, with adjusted odds ratios of 1.0 (reference), 0.67, 0.46, 0.39, and 0.32 (all P<0.001) and prevalence of use at 12.6%, 8.8%, 6.3%, 4.9%, and 3.7% for patients living ≤25.0, 25.1 to 50.0, 50.1 to 75.0, 75.1 to 100.0, and >100.0 miles away, respectively.

Conclusions:

Increasing travel distance was strongly associated with decreased use of adjuvant RT in this national cohort of postprostatectomy patients with high-risk pathologic features. These results strongly suggest that the logistical challenges of extensive travel are a significant barrier to the use of adjuvant RT. Efforts aimed at improving access to radiotherapy and reducing treatment time are urgently needed.
Dose Escalation Study of Concurrent Chemoradiotherapy With the Use of Involved-field Conformal Radiotherapy and Accelerated Hyperfractionation in Combination With Cisplatin and Vinorelbine Chemotherapy for Stage III Non–small Cell Lung Cancer
Authors: Yoshimura Naruo , Tada Takuhito , Matsumoto Yoshiya , Sawa Kenji , Yoshimoto Naoki , Suzumura Tomohiro , Tanaka Hidenori , Mitsuoka Shigeki , Kimura Tatsuo , Tamiya Tomohiro , Hirashima Tomonori , Kawaguchi Tomoya , Kudoh Shinzoh , Hosono Masako , Hirata Kazuto
Published: October 2017

Objectives:

A phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non–small cell lung cancer was conducted.

Materials and Methods:

We used chemotherapy of a cisplatin doublet and 2 dose levels of radiation with accelerated hyperfractionation. The radiation dose levels were: a total dose of 60 Gy in 40 fractions at level 1, and 66 Gy in 44 fractions at level 2. Eligible patients with unresectable stage III non–small cell lung cancer received cisplatin and vinorelbine. Radiation therapy started on day 2 of chemotherapy and was delivered twice daily for 5 days a week.

Results:

Total 12 patients were enrolled, with 6 patients each at dose levels 1 and 2. Dose-limiting toxicity was noted in 2 patients at level 1; one patient had grade 3 febrile neutropenia and the other patient had grade 3 esophagitis. No dose-limiting toxicity was noted in the 6 patients at level 2. Grade 3 to 4 leukopenia, neutropenia, and anemia were noted in 11 (92%), 9 (75%), and 8 (67%) of the total 12 patients, respectively. Grade 3 anorexia and infection were noted in 2 patients (17%) at each level. Grade 3 nausea, fatigue, esophagitis, and febrile neutropenia were noted in 1 patient (8%) at each level. The response rate in the total 12 patients was 83.3%. The median progression-free survival time and the median overall survival time were 10.7 and 24.2 months, respectively.

Conclusions:

Sixty-six gray in 44 fractions is the recommended dose for the following phase II study.
Association of Adverse Childhood Experiences with Co-occurring Health Conditions in Early Childhood
Authors: Bright Melissa A. , Thompson Lindsay A.
Published: October 2017

Objective:

To understand how adverse childhood experiences (ACEs) are associated with co-occurring physical, mental and developmental problems during early childhood.

Method:

A subsample of 19,957 children aged 2–5 years were selected from the 2011–2012 National Survey for Child Health. Outcomes included 18 health conditions organized in singular condition domains (physical, mental, and developmental), and combinations of condition domains (e.g., physical plus mental, mental plus developmental, etc.). Predictors included 8 ACEs (divorce of a parent, death of a parent, exposure to domestic violence, living with someone with a drug or alcohol abuse problem, household member with a mental illness, parent incarceration, neighborhood violence, discrimination). Multivariable logistic regression was performed controlling for demographic characteristics, having a personal doctor, health insurance coverage, and seeing a health care professional in the previous year.

Results:

Experiencing 3 or more ACEs before the age of 5 years was associated with increased likelihood of nearly every co-occurring condition combination across 3 domains of health. Most notably, experiencing 3 or more ACEs was also associated with a 2-fold increase in likelihood of having ≥1 physical condition and ≥1 developmental condition, a 9-fold increase in likelihood of having ≥1 mental and ≥1 developmental condition, and a 7-fold increase in likelihood of having ≥1 physical, ≥1 mental, and ≥1 developmental condition.

Conclusion:

This study demonstrates that we can identify the health effects of adversity quite early in development and that management should include communication between both health care and early childhood education providers.
Analytical Pitfalls of Therapeutic Drug Monitoring of Thiopurines in Patients With Inflammatory Bowel Disease
Authors: Simsek Melek , Meijer Berrie , Mulder Chris J. J. , van Bodegraven Adriaan A. , de Boer Nanne K. H.
Published: October 2017

The use of thiopurines in the treatment of inflammatory bowel disease (IBD) can be optimized by the application of therapeutic drug monitoring. In this procedure, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) metabolites are monitored and related to therapeutic response and adverse events, respectively. Therapeutic drug monitoring of thiopurines, however, is hampered by several analytical limitations resulting in an impaired translation of metabolite levels to clinical outcome in IBD. Thiopurine metabolism is cell specific and requires nucleated cells and particular enzymes for 6-TGN formation. In the current therapeutic drug monitoring, metabolite levels are assessed in erythrocytes, whereas leukocytes are considered the main target cells of these drugs. Furthermore, currently used methods do not distinguish between active nucleotides and their unwanted residual products. Last, there is a lack of a standardized laboratorial procedure for metabolite assessment regarding the substantial instability of erythrocyte 6-TGN. To improve thiopurine therapy in patients with IBD, it is necessary to understand these limitations and recognize the general misconceptions in this procedure.
Serum Concentrations of Paliperidone After Administration of the Long-Acting Injectable Formulation
Authors: Helland Arne , Spigset Olav
Published: October 2017

Background:

The pharmacokinetics of long-acting intramuscular paliperidone in a naturalistic setting is not well documented. The objective of this study was to investigate the relationship between dose and serum concentrations of paliperidone using data from a routine therapeutic drug monitoring service.

Methods:

Serum concentration measurements in 310 samples from 110 male and 75 female patients receiving depot injections of paliperidone were retrospectively retrieved from the therapeutic drug monitoring database.

Results:

The median dose was 100 mg every 28 days. The median concentration/dose (C/D) ratio of paliperidone was 16.1 (nmol/L)/(mg/d), with a 10–90 percentile range of 7.8–31.0 (nmol/L)/(mg/d). Dose-adjusted serum concentrations were 33% higher in patients 65 years or older and more than 50% lower in patients taking the p-glycoprotein inducer carbamazepine. There were no significant effects of sex or dose on the C/D ratio. The median serum concentrations of paliperidone at the end of the dose interval were 31 nmol/L at an intramuscular dose of 50 mg/28 d, 53 nmol/L after a dose of 75 mg/28 d, 59 nmol/L after a dose of 100 mg/28 d, and 93 nmol/L after a dose of 150 mg/28 d. Forty-five percent of the measurements were lower than the suggested therapeutic range of 20–60 ng/mL (47–140 nmol/L).

Conclusions:

The data show a 4-fold interindividual difference in dose-adjusted serum concentrations within the 10–90 percentile range and illustrate the significant effects of age and p-glycoprotein induction on the pharmacokinetics of paliperidone. The study also indicates that at least in some patients, it might take longer time than anticipated to reach steady state.
Development of a Liquid Chromatography–Tandem Mass Spectrometric Method for Quantification of Mycophenolic Acid and Its Glucuronides in Dried Blood Spot Samples
Authors: Iboshi Hiromasa , Yamaguchi Hiroaki , Suzuki Hiroyuki , Kikuchi Masafumi , Tanaka Masaki , Takasaki Shinya , Takahashi Akiko , Maekawa Masamitsu , Shimada Miki , Matsuda Yasushi , Okada Yoshinori , Mano Nariyasu
Published: October 2017

Background:

Personalized immunosuppressive therapy, including accurate drug dosing based on the drug blood level, leads to better clinical outcomes, specifically regarding avoidance of drug-induced adverse effects and maintenance of efficacy. Mycophenolic acid (MPA) is used as an immunosuppressant in transplantation of various solid organs. The aim of this study was to develop a method for quantification of MPA and its metabolites, mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl glucuronide, in dried blood spot (DBS) samples, using liquid chromatography/electrospray ionization/tandem mass spectrometry.

Methods:

For sample preparation, a microwave-drying approach was used to deactivate enzymes and reduce drying time. Blood volume was calculated in a DBS disk of 3 mm diameter. Concentrations of analytes in plasma from patients receiving mycophenolate mofetil were compared with DBS samples after hematocrit correction.

Results:

The method yielded good recoveries of all 3 analytes (90.3%–104.2%). Blood volume in the disk was calculated as 3.0 ± 0.2 μL. Linearity over concentration ranges of 0.1–30 mcg/mL MPA, 0.1–200 mcg/mL MPAG, and 0.125–10 mcg/mL mycophenolic acid acyl glucuronide was obtained with r2 ≥0.999. Intraday and interday variations were less than 14.6%, and accuracy was within ±11.9%. Passing–Bablok analysis showed no significant differences between plasma concentrations and DBS concentrations after hematocrit correction of MPA and MPAG.

Conclusions:

We developed and validated a liquid chromatography/electrospray ionization–tandem mass spectrometry method for analysis of MPA in DBS samples. The method is useful for monitoring the MPA blood level.
AUTOLOGOUS LENS CAPSULAR FLAP TRANSPLANTATION COMBINED WITH AUTOLOGOUS BLOOD APPLICATION IN THE MANAGEMENT OF REFRACTORY MACULAR HOLE
Authors: Peng Jie , Chen Chunli , Jin Haiying , Zhang Hongtao , Zhao Peiquan
Published: October 2017

Purpose:

To report results of lens capsular flap transplantation (LCFT) and autologous whole blood application in refractory macular hole (MH) treatment.

Methods:

Seven phakic and three aphakic eyes with persistent MH after standard surgery with internal limiting membrane peeling were studied. Lens capsule flap was acquired from the same eye in eight cases (seven phakic and one aphakic). The fellow eye was used in two aphakic eyes without sufficient lens capsule. The fellow eye underwent simultaneous phacoemulsification. All eyes underwent complete vitrectomy, LCFT into the MH, whole blood application, and 15% perfluoropropane (C3F8) tamponade. The patients were instructed to maintain a face-down or prone position for two weeks postoperatively. Structural and functional changes were evaluated.

Results:

The mean preoperative MH diameter was 1,472.78 ± 736.88 μm. The MH was completely closed in nine eyes: eight eyes receiving same-eye LCFT and one receiving fellow-eye LCFT. In the other fellow-eye LCFT recipient, the MH was partially closed. Visual acuity improved from 1.84 ± 0.49 logarithm of the minimum angle of resolution (median Snellen acuity: 20/1,750, range: 20/4,000–20/125) preoperatively to 1.34 ± 0.59 logarithm of the minimum angle of resolution (median Snellen acuity: 20/450, range: 20/4,000–20/63) postoperatively (P = 0.009).

Conclusion:

Lens capsular flap transplantation and autologous whole blood application may improve anatomical and visual outcomes in refractory MH cases. The lens equator and fellow eye may be promising sources of LCF.
Air Versus Sulfur Hexafluoride Gas Tamponade in Descemet Membrane Endothelial Keratoplasty: A Fellow Eye Comparison
Authors: von Marchtaler Philipp V. , Weller Julia M. , Kruse Friedrich E. , Tourtas Theofilos
Published: October 2017

Purpose:

To perform a fellow eye comparison of outcomes and complications when using air or sulfur hexafluoride (SF6) gas as a tamponade in Descemet membrane endothelial keratoplasty (DMEK).

Methods:

One hundred thirty-six eyes of 68 consecutive patients who underwent uneventful DMEK in both eyes for Fuchs endothelial corneal dystrophy were included in this retrospective study. Inclusion criteria were air tamponade (80% of the anterior chamber volume) in the first eye and 20% SF6 gas tamponade (80% of the anterior chamber volume) in the second eye; and same donor tissue culture condition in both eyes. All eyes received laser iridotomy on the day before DMEK. Main outcome measures included preoperative and postoperative best-corrected visual acuity, endothelial cell density, corneal volume, rebubbling rate, and rate of postoperative pupillary block caused by the air/gas bubble.

Results:

Thirteen of 68 eyes (19.1%) with an air tamponade needed rebubbling compared with 4 of 68 eyes (5.9%) with an SF6 gas tamponade (P = 0.036). Postoperative pupillary block necessitating partial release of air/gas occurred in 1 eye (1.5%) with an air tamponade and 3 eyes (4.4%) with an SF6 gas tamponade (P = 0.301). There were no significant differences in preoperative and postoperative best-corrected visual acuity, endothelial cell density, and corneal volume within 3-month follow-up.

Conclusions:

Our results confirm the previously reported better graft adhesion when using an SF6 gas tamponade in DMEK without increased endothelial cell toxicity. The rate of pupillary block in eyes with an SF6 gas tamponade was comparable to that with an air tamponade. As a consequence, we recommend using SF6 gas as the tamponade in DMEK.
Grade Assignment by Ki-67 Proliferative Index, Mitotic Count, and Phosphohistone H3 Count in Surgically Resected Gastrointestinal and Pancreatic Neuroendocrine Tumors
Authors: Murphy Claire E. , McCormick Kinsey A. , Shankaran Veena , Reddi Deepti M. , Swanson Paul E. , Upton Melissa P. , Papanicolau-Sengos Antonios , Khor Sara , Westerhoff Maria
Published: October 2017

Objectives

The aim of this study was to evaluate the concordance in grade assignment for gastroenteropancreatic neuroendocrine tumors using mitotic count (MC), Ki-67 proliferative index (KPI), and phosphohistone H3 count (PHH3C).

Methods

Resected gastroenteropancreatic neuroendocrine tumors were graded based on MC, KPI, and PHH3C. Concordance was determined using a weighted κ statistic. Median survival across each grade category was determined using Kaplan-Meier methods.

Results

Of the 110 patients, the majority had gastrointestinal primaries and grade 1 or 2 tumors. Rates of discordance in grade assignment were 29% of cases for KPI versus MC (κW = 0.26), 32% for PHH3C versus MC (κW = 0.34), and 32% for PHH3C versus KPI (κW = 0.37). There was fair agreement between grading by KPI and MC. Relative to grade by KPI and MC, PHH3C tended to upgrade tumors. The proportion alive at 3 and 5 years was not significantly different for patients with grade 1 versus grade 2 tumors.

Conclusions

The concordance between KPI and MC was fair. Phosphohistone H3 count tended to upgrade tumors using the cutoffs established by MC. Grade 1 and grade 2 tumors were associated with similar survival regardless of grading method. The overall relevance of the current cutoff values used in grading neuroendocrine tumors may need to be revisited.
Reduction of Recurrence Risk of Pancreatitis in Cystic Fibrosis With Ivacaftor
Authors: Carrion Andres , Borowitz Drucy S. , Freedman Steven D. , Siracusa Christopher M. , Goralski Jennifer L. , Hadjiliadis Denis , Srinivasan Saumini , Stokes Dennis C.
Published: October 2017

The effect of ivacaftor in patients with cystic fibrosis (CF) with recurrent pancreatitis is unknown. We conducted a multicenter retrospective study of patients with CF taking ivacaftor who had a history of recurrent pancreatitis. During the first 3 months of therapy, only 1 of the 6 patients had an episode of pancreatitis, which was managed on an outpatient basis. Between 3 and 12 months on ivacaftor therapy, none of the patients had recurrence of pancreatitis or required hospitalization. The use of ivacaftor was associated with a reduced frequency and recurrence rate of pancreatitis in patients with CF.
A Survey of Restraint Methods for the Safe Transport of Children in Ground Ambulances
Authors: Woods Rashida H. , Shah Manish , Doughty Cara , Gilchrest Anthony
Published: October 2017

Objectives

The National Highway Traffic Safety Administration (NHTSA) released draft recommendations in 2010 on the safe transport of children in ground ambulances. The purpose of this study was to assess awareness of these guidelines among emergency medical service (EMS) agencies and to identify implementation barriers.

Methods

We conducted a cross-sectional, anonymous online survey of 911-responding, ground transport EMS agencies in Texas. Demographics, modes of transport based on case scenarios, and barriers to implementation were assessed.

Results

Of 62 eligible EMS agencies that took the survey, 35.7% were aware of the NHTSA guidelines, 62.5% agreed they would improve safety, and 41.1% planned to implement them. Seventy-five percent of EMS agencies used the ideal or acceptable alternative to transport children requiring continuous monitoring, and 69.5% chose ideal or acceptable alternatives for children requiring spinal immobilization. The ideal or acceptable alternative was not chosen for children who were not injured or ill (93.2%), ill or injured but not requiring continuous monitoring (53.3%), and situations when multiple patients required transport (57.6%). The main requirements for implementation were provider education, ambulance interior modifications, new guidelines in the EMS agency, and purchase of new equipment.

Conclusions

Few EMS agencies are aware of the NHTSA guidelines on safe transport of children in ground ambulances. Although most agencies appropriately transport children who require monitoring, interventions, or spinal immobilization, they use inappropriate means to transport children in situations with multiple patients, lack of injury or illness, or lack of need for monitoring.
Code Team Training
Authors: Stewart Claire , Shoemaker Jamie , Keller-Smith Rachel , Edmunds Katherine , Davis Andrew , Tegtmeyer Ken
Published: October 2017

Objective

Pediatric code blue activations are infrequent events with a high mortality rate despite the best effort of code teams. The best method for training these code teams is debatable; however, it is clear that training is needed to assure adherence to American Heart Association (AHA) Resuscitation Guidelines and to prevent the decay that invariably occurs after Pediatric Advanced Life Support training. The objectives of this project were to train a multidisciplinary, multidepartmental code team and to measure this team's adherence to AHA guidelines during code simulation.

Methods

Multidisciplinary code team training sessions were held using high-fidelity, in situ simulation. Sessions were held several times per month. Each session was filmed and reviewed for adherence to 5 AHA guidelines: chest compression rate, ventilation rate, chest compression fraction, use of a backboard, and use of a team leader. After the first study period, modifications were made to the code team including implementation of just-in-time training and alteration of the compression team.

Results

Thirty-eight sessions were completed, with 31 eligible for video analysis. During the first study period, 1 session adhered to all AHA guidelines. During the second study period, after alteration of the code team and implementation of just-in-time training, no sessions adhered to all AHA guidelines; however, there was an improvement in percentage of sessions adhering to ventilation rate and chest compression rate and an improvement in median ventilation rate.

Conclusions

We present a method for training a large code team drawn from multiple hospital departments and a method of assessing code team performance. Despite subjective improvement in code team positioning, communication, and role completion and some improvement in ventilation rate and chest compression rate, we failed to consistently demonstrate improvement in adherence to all guidelines.
A Rare Case of Cecal Bascule in a Child With Normal Neurodevelopment
Authors: Loureiro Sandra Oliveira , Lynch Timothy , Medeiros Braeden John , Merritt Neil , Lim Rodrick
Published: October 2017

Cecal volvulus is a rare cause of bowel obstruction in adults and an extremely rare presentation in children. One form known as a cecal bascule has only previously been reported in children with neurodevelopmental issues or with severe chronic constipation. We present the case of a 10-year-old boy who presented with an acute history of left lower quadrant abdominal pain, who upon investigation was found to have a cecal bascule.
Dating Violence Against HIV-Infected Youth in South Africa: Associations With Sexual Risk Behavior, Medication Adherence, and Mental Health
Authors: Kidman Rachel , Violari Avy
Published: October 2017

Background:

As perinatal HIV-infected youth become sexually active, the potential for onward transmission becomes an increasing concern. In other populations, intimate partner violence (IPV) is a risk factor for HIV acquisition. We build on this critical work by studying the role of IPV in facilitating onward transmission among HIV-infected youth—an important step toward effective intervention.

Setting:

Soweto, South Africa.

Methods:

Self-report surveys were completed by 129 perinatal HIV-infected female youth (aged 13–24 years). We calculated the IPV prevalence and used logistic models to capture the association between IPV and health outcomes known to facilitate onward HIV transmission (eg, risky sex, poor medication adherence, depression, and substance abuse).

Results:

A fifth of perinatal HIV-infected participants reported physical and/or sexual IPV in the past year; one-third reported lifetime IPV. Childhood adversity was common and positively associated with IPV. Past-year physical and/or sexual IPV was positively correlated with high-risk sex [odds ratio (OR) = 8.96; 95% confidence interval (CI): 2.78 to 28.90], pregnancy (OR = 6.56; 95% CI: 1.91 to 22.54), poor medication adherence to antiretroviral therapy (OR = 5.37; 95% CI: 1.37 to 21.08), depression (OR = 4.25; 95% CI: 1.64 to 11.00), and substance abuse (OR = 4.11; 95% CI: 1.42 to 11.86). Neither past-year nor lifetime IPV was associated with viral load or HIV status disclosure to a partner.

Conclusions:

We find that IPV may increase risk for onward HIV transmission in perinatal HIV-infected youth by both increasing engagement in risky sexual behaviors and lowering medication adherence. HIV clinics should consider integrating primary IPV prevention interventions, instituting routine IPV screening, and collocating services for victims of violence.
Country of Birth of Children With Diagnosed HIV Infection in the United States, 2008–2014
Authors: Nesheim Steven R. , Linley Laurie , Gray Kristen M. , Zhang Tianchi , Shi Jing , Lampe Margaret A. , FitzHarris Lauren F.
Published: October 2017

Background:

Diagnoses of HIV infection among children in the United States have been declining; however, a notable percentage of diagnoses are among those born outside the United States. The impact of foreign birth among children with diagnosed infections has not been examined in the United States.

Methods:

Using the Centers for Disease Control and Prevention National HIV Surveillance System, we analyzed data for children aged <13 years with diagnosed HIV infection (“children”) in the United States (reported from 50 states and the District of Columbia) during 2008–2014, by place of birth and selected characteristics.

Results:

There were 1516 children [726 US born (47.9%) and 676 foreign born (44.6%)]. US-born children accounted for 70.0% in 2008, declining to 32.3% in 2013, and 40.9% in 2014. Foreign-born children have exceeded US-born children in number since 2011. Age at diagnosis was younger for US-born than foreign-born children (0–18 months: 72.6% vs. 9.8%; 5–12 years: 16.9% vs. 60.3%). HIV diagnoses in mothers of US-born children were made more often before pregnancy (49.7% vs. 21.4%), or during pregnancy (16.6% vs. 13.9%), and less often after birth (23.7% vs. 41%). Custodians of US-born children were more often biological parents (71.9% vs. 43.2%) and less likely to be foster or nonrelated adoptive parents (10.4% vs. 55.1%). Of 676 foreign-born children with known place of birth, 65.5% were born in sub-Saharan Africa and 14.3% in Eastern Europe. The top countries of birth were Ethiopia, Ukraine, Uganda, Haiti, and Russia.

Conclusions:

The increasing number of foreign-born children with diagnosed HIV infection in the United States requires specific considerations for care and treatment.
The Role of Preoperative Imaging in the Management of Nonsyndromic Lambdoid Craniosynostosis
Authors: Ranganathan Kavitha , Rampazzo Antonio , Hashmi Asra , Muraszko Karin , Strahle Jennifer , Vercler Christian J. , Buchman Steven R.
Published: October 2017

Background:

The necessity of imaging for patients with craniosynostosis is controversial. Lambdoid synostosis is known to be associated with additional anomalies, but the role of imaging in this setting has not been established. The purpose of this study was to evaluate the impact of preoperative imaging on intraoperative and postoperative management among patients undergoing operative intervention for lambdoid craniosynostosis.

Methods:

A retrospective review of patients undergoing cranial vault remodeling for lambdoid craniosynostosis between January 2006 and 2014 was conducted. Patient demographics, age at computed tomography scan, age at surgery, results of the radiologic evaluation, operative technique, and modification of the diagnosis following the radiologic studies were analyzed. A pediatric neuroradiology and the surgical team interpreted the radiographs. The primary outcome was change in intraoperative or postoperative management based on imaging results.

Results:

A total of 11 patients were diagnosed with lambdoid synostosis. Of these patients, 81.8% had abnormalities on imaging relevant to operative planning. The most common anomalies were Chiari I malformation (45%) and venous anomalies of the posterior fossa (36%). Preoperative imaging altered the management of 9 (81.8%) patients. Closer follow-up was required for 6 patients (54%). Suboccipital decompression was performed in 4 patients (36%). Venous anomalies were found in 4 patients (36%). The diagnosis was changed from positional plagiocephaly to lambdoid synostosis in 2 patients (18%).

Conclusions:

Given the frequency and significance of radiographic abnormalities in the setting of lamboid synostosis, preoperative imaging should be considered during the operative planning phase as it can affect postoperative and intraoperative management.
Perioperative glycemic control and postoperative complications in patients undergoing emergency general surgery: What is the role of Plasma Hemoglobin A1c?
Authors: Jehan Faisal , Khan Muhammad , Sakran Joseph V. , Khreiss Mohammad , O’Keeffe Terence , Chi Albert , Kulvatunyou Narong , Jain Arpana , Zakaria El Rasheid , Joseph Bellal
Published: October 2017

BACKGROUND

Plasma hemoglobin A1c (HbA1c) reflects quality of glucose control in diabetic patients. Literature reports that patients undergoing surgery with an elevated HbA1c level are associated with increased postoperative morbidity and mortality. The aim of our study was to evaluate the impact of HbA1c level on outcomes after emergency general surgery (EGS).

METHODS

We performed a 3-year analysis of our prospectively maintained EGS database. Patients who had HbA1c levels measured within 3 months before surgery were included. Patients were divided into two groups (HbA1c < 6 and HbA1c ≥ 6). Our primary outcome measures included in-hospital complications (major and minor complications), hospital and intensive care unit length of stay, and mortality. Secondary outcomes measures were 30-day complications, readmissions, and mortality. Multivariate and linear regressions were performed.

RESULTS

Of the 402 study patients, mean age was 61 ± 12 years, 53% were females, and 63.8% were diabetics. Overall, 49% had an HbA1c ≥ 6%; the mortality rate was 6%. Those with hypertension, history of coronary artery disease, and body mass index of 30 kg/m2 or greater were more likely to have HbA1c of 6.0% or greater. 7.9% patients experienced major complications. Patients with HbA1c of 6% or greater had a higher complication rate (36% vs 11%, p < 0.001) than those with HbA1c less than 6%. However there was no difference in mortality between two groups (p = 0.09). After controlling for confounders, HbA1c ≥ 6.0% (odds ratio [OR], 2.9; p < 0.01) and a postoperative random blood sugar (RBS) of 200 mg/dL or greater (OR, 2.3; p < 0.01) were independent predictors of major complications. Patients with both HbA1c of 6.0% or greater and postoperative RBS of 200 or greater had higher odds (OR, 4.2; p < 0.01) of developing major complication. After adjusting for confounders, a higher HbA1c was independently correlated with a higher postoperative RBS (b = 0.494, [19.7–28.4], p = 0.02), but there was no correlation with the preoperative RBS.

CONCLUSION

Patients with HbA1c of 6.0% or greater and a postoperative RBS of 200 mg/dL or greater have a four times higher risk of developing major complications after EGS. A preoperative HbA1c can stratify patients prone to develop postoperative hyperglycemia, regardless of their preoperative RBS.

LEVEL OF EVIDENCE

Prognostic, level III.
The temporal response and mechanism of action of tranexamic acid in endothelial glycocalyx degradation
Authors: Diebel Mark E. , Martin Jonathan V. , Liberati David M. , Diebel Lawrence N.
Published: October 2017

BACKGROUND

The endothelial glycocalyx (GCX) plays an important role in vascular barrier function. Damage to the GCX occurs due to a variety of causes including hypoxia, ischemia-reperfusion, stress-related sympathoadrenal activation, and inflammation. Tranexamic acid (TXA) may prevent GCX degradation. The therapeutic window for TXA administration and the mechanism of action has been under review. Membrane-anchored proteases (sheddases) are key components in endothelial cell biology including the regulation of vascular permeability. The effect of TXA administration on stress-related GCX damage, and the role of sheddases in this process was studied in a cell-based model.

METHODS

Confluent human umbilical vein endothelial cells (HUVEC) were exposed to hydrogen peroxide and/or epinephrine (EPI) to stimulate postshock reperfusion. TXA was added at various times after hydrogen peroxide (H2O2) and/or EPI exposure. GCX degradation was indexed by syndecan-1 and hyaluronic acid release. Activation of endothelial sheddases was indexed by A Disintegrin and Metalloproteinase-17 and matrix metalloproteinase-9 activity in culture supernatants.

RESULTS

Exposure of HUVEC to either/both EPI and H2O2 resulted in a cellular stress and GCX disruption demonstrated by increased levels of syndecan-1 shedding, hyaluronic acid release, tumor necrosis factor-α release. Shedding of these GCX components was associated with increased activity of both A Disintegrin and Metalloproteinase-17 and matrix metalloproteinase. Disruption of the GCX was further demonstrated via fluorescent imaging, which demonstrated disruption after exposure to either/both H2O2 and EPI. Early administration of either TXA or doxycycline resulted in preservation of the GCX. Late administration of TXA had no effect, whereas doxycycline had some residual protective effect.

CONCLUSION

Tranexamic acid as a serine protease inhibitor prevented GCX degradation via inhibition of endothelial sheddase activation. This effect was not apparent when TXA was administered greater than 60 minutes after “simulated” reperfusion. Our study supports the clinical practice of early TXA administration in the severely injured patient.