bluuebunny/crossref_metadata_2025 huggingface dataset:
Cecal Ligation and Puncture Alters Glucocorticoid Receptor Expression
Authors: Abraham Mabel N. , Jimenez Daniela M. , Fernandes Tiago D. , Deutschman Clifford S.
Published: May 2018

Objectives:

Interventional trials on glucocorticoids in sepsis have yielded capricious results. Recent studies have identified multiple glucocorticoid receptor isoforms. The relative abundance of these isoforms in septic patients and following murine cecal ligation and puncture is unknown. The objective of this study is to determine the effects of cecal ligation and puncture on glucocorticoid receptor isoform abundance.

Design:

Determination of effects of cecal ligation and puncture on glucocorticoid receptor isoform subtype abundance in C57BL/6 mice. Examination of glucocorticoid receptor isoform abundance in tissues harvested from patients immediately after death from sepsis or nonseptic critical illness.

Setting:

Research laboratory.

Subjects:

C57BL/6 mice and human tissue sections from recently deceased critically ill patients.

Interventions:

C57BL/6 mice were subjected to cecal ligation and puncture or sham operation. Abundance of the activating glucocorticoid receptor α and the inactivating glucocorticoid receptor β isoforms was determined in mouse and human tissue using immunoblotting. Cardiac output with or without stimulation with dexamethasone was assessed using echocardiography. The expression of the gene encoding the glucocorticoid-dependent enzyme glucose-6-phosphatase was identified using polymerase chain reaction. Statistical significance (p < 0.05) was determined using analysis of variance.

Measurements and Main Results:

Results in baseline and sham operation mice were identical. At baseline, glucocorticoid receptor αA predominated in heart, lung, and skeletal muscle; abundance was decreased post cecal ligation and puncture. All glucocorticoid receptor α subtypes were identified in liver. Cecal ligation and puncture decreased the summed abundance of hepatic glucocorticoid receptor α subtypes and those of glucocorticoid receptors αA, B, and D. However, glucocorticoid receptor αC abundance was unchanged. Cecal ligation and puncture increased glucocorticoid receptor β protein abundance in the heart and lung. Relative to T0, cecal ligation and puncture decreased cardiac output and attenuated the cardiac output response to dexamethasone. Cecal ligation and puncture also decreased expression of glucose-6-phosphatase. Compared with nonseptic patients, human sepsis decreased the abundance of glucocorticoid receptor α and increased the abundance of glucocorticoid receptor β in heart and liver biopsies.

Conclusions:

Cecal ligation and puncture altered glucocorticoid receptor α and glucocorticoid receptor β isoform expression in tissues and decreased functional responses in heart and liver. Decreases in glucocorticoid receptor α and increases in glucocorticoid receptor β might explain the diminished glucocorticoid responsiveness observed in sepsis.
Autoimmune Granulomatous Inflammation of Lacrimal Glands and Axonal Neuritis Following Treatment With Ipilimumab and Radiation Therapy
Authors: Ileana Dumbrava Ecaterina , Smith Veronica , Alfattal Rasha , El-Naggar Adel K. , Penas-Prado Marta , Tsimberidou Apostolia M.
Published: May 2018

Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte–associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response. The use of immune checkpoint inhibitors exhibit an unique toxicity profile, the immune-related adverse events (irAEs). The most notable immune reactions are noted in skin (rash), gastrointestinal track (colitis, hepatitis, pancreatitis), lung (pneumonitis), heart (myocarditis), and endocrine system (thyroiditis, hypophysitis). We present a patient with metastatic adenoid cystic carcinoma of the left submandibular gland with granulomatous inflammation of the lacrimal glands and axonal neuritis of the cervical and paraspinal nerves following treatment with ipilimumab and radiation therapy.
Melatonin Receptor Agonist Ramelteon Reduces Ischemia-Reperfusion Injury Through Activation of Mitochondrial Potassium Channels
Authors: Stroethoff Martin , Christoph Iris , Behmenburg Friederike , Raupach Annika , Bunte Sebastian , Senpolat Semra , Heinen André , Hollmann Markus W. , Mathes Alexander , Huhn Ragnar
Published: May 2018

Activation of melatonin receptors induces cardioprotection. Mitochondrial potassium channels (mKCa and mKATP) are involved in the signaling cascade of preconditioning. The melatonin receptor agonist ramelteon is an approved oral medication for treatment of insomnia, but nothing is known about possible cardioprotective properties. We investigated whether (1) ramelteon induces cardioprotection mediated by the melatonin receptor; (2) this effect is concentration-dependent; and (3) mKCa and/or mKATP channels are critically involved in ramelteon-induced cardioprotection. Hearts of male Wistar rats were randomized and placed on a Langendorff system, perfused with Krebs–Henseleit buffer at a constant pressure of 80 mm Hg. All hearts were subjected to 33 minutes of global ischemia and 60 minutes of reperfusion. Before, ischemic hearts were perfused with different concentrations of ramelteon (0.01–5 μM) for determination of a concentration–effect curve. In subsequent experiments, the lowest protective concentration of ramelteon was administered together with paxilline (mKCa channel inhibitor) and 5-hydroxydecanoate (mKATP channel inhibitor). To determine whether the reduction of ischemia and reperfusion injury by ramelteon is mediated by melatonin receptor, we combined ramelteon with luzindole, a melatonin receptor antagonist. Infarct size was determined by triphenyltetrazolium chloride staining. In control animals, infarct size was 58% ± 6%. Ramelteon in a concentration of 0.03 µM reduced infarct size to 28% ± 4% (P < 0.0001 vs. Con). A lower concentration of ramelteon did not initiate cardioprotection, and higher concentrations did not further decrease infarct size. Paxilline, 5-hydroxydecanoate, and luzindole completely blocked the ramelteon-induced cardioprotection. This study shows for the first time that (1) ramelteon induces cardioprotection through melatonin receptor; (2) the effect is not concentration-dependent; and (3) activation of mKCa and mKATP channels is involved.
Effect of a 1-year elastic band resistance exercise program on cardiovascular risk profile in postmenopausal women
Authors: Gómez-Tomás Cinta , Chulvi-Medrano Iván , Carrasco Juan José , Alakhdar Yasser
Published: May 2018

Objective:

The aim of this study was to investigate the effects of a 1-year progressive resistance training program using elastic bands on cardiovascular profile parameters in sedentary postmenopausal (>12 months’ amenorrhea) women.

Methods:

This longitudinal prospective experimental study included 38 menopausal women who were randomly divided into two groups: an intervention group (IG, n = 18), who completed a progressive resistance training program with elastic bands over the course of 12 months (six exercises for whole body training, three sets × 10 repetitions), and a control group (CG, n = 20) that did not perform any training. Blood analysis and body composition were determined at baseline and 1 year after intervention.

Results:

After the 1-year training program, weight, waist circumference, total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein showed a decrease compared with baseline values in the IG, showing a significant (P < 0.05) improvement in cardiovascular profile. Very-low-density lipoprotein, high-density lipoprotein, and triglycerides showed a nonsignificant (P > 0.05) improvement. The CG increased significantly in weight and waist circumference, whereas the rest of the variables remained unchanged.

Conclusion:

One year of progressive resistance training with elastic bands has beneficial effects on anti-inflammatory and anthropometric cardiovascular risk factors in menopausal women, including changes in lipid profile.
Metabolic syndrome and its components in premenopausal and postmenopausal women: a comprehensive systematic review and meta-analysis on observational studies
Authors: Hallajzadeh Jamal , Khoramdad Maliheh , Izadi Neda , Karamzad Nahid , Almasi-Hashiani Amir , Ayubi Erfan , Qorbani Mostafa , Pakzad Reza , Hasanzadeh Amir , Sullman Mark J.M. , Safiri Saeid
Published: May 2018

Objectives:

To perform a meta-analysis on the global prevalence of metabolic syndrome (MetS) in postmenopausal women. The meta-analysis also sought to measure the relationship menopause status has with MetS and its components.

Methods:

The Web of Science, Medline, PubMed, Scopus, Embase, CINAHL, DOAJ, and Google Scholar were all searched using the relevant keywords. Articles published during the period 2004 to 2017 that met our inclusion criteria and reported the prevalence of MetS among premenopausal and postmenopausal women were included. In the presence of heterogeneity, random-effects models were used to pool the prevalence and odds ratios (ORs), as measures of association in cross-sectional and comparative cross-sectional studies, respectively.

Results:

The prevalence of MetS among postmenopausal women (119 studies [n = 95,115]) and the OR comparing the prevalence of MetS among postmenopausal and premenopausal women (23 studies [n = 66,801]) were pooled separately. The pooled prevalence of MetS among postmenopausal women was found to be 37.17% (95% confidence interval [CI] 35.00%–39.31%), but varied from 13.60% (95% CI 13.55%–13.64%) to 46.00% (95% CI 1.90%–90.09%), depending upon the diagnostic criteria used. The overall pooled OR for MetS in postmenopausal women, compared with premenopausal women, was OR 3.54 (95% CI 2.92-4.30), but this ranged from OR 2.74 (95% CI 1.32-5.66) to OR 5.03 (95% CI 2.25-11.22), depending upon the criteria used. Furthermore, the odds of high fasting blood sugar (OR 3.51, 95% CI 2.11-5.83), low high-density lipoprotein cholesterol (OR 1.45, 95% CI 1.03-2.03), high blood pressure (OR 3.95, 95% CI 2.01-7.78), high triglycerides (OR 3.2, 95% CI 2.37-4.31), and high waist circumference (OR 2.75, 95% CI 1.80-4.21) were all found to be higher in postmenopausal women than in premenopausal women.

Conclusions:

The prevalence of MetS is relatively high in postmenopausal women and was more prevalent among postmenopausal than premenopausal women. Menopausal hormone therapy should be used with caution in patients with MetS, as its safety has not yet been evaluated among MetS patients and meticulous evaluation of each individual patient before starting MHT is needed.
Neuroma Implantation into Long Bones: Clinical Foundation for a Novel Osseointegrated Peripheral Nerve Interface
Authors: Israel Jacqueline S. , Dingle Aaron M. , Sanchez Ruston J. , Kapur Sahil K. , Brodnick Sarah , Richner Thomas J. , Ness Jared P. , Novello Joseph , Williams Justin C. , Poore Samuel O.
Published: May 2018

Symptomatic neuroma after major extremity amputation is a challenging clinical problem for which there are many described treatment options. Neuroma excision and implantation into the medullary canal of long bones offers durability and insulation, and minimizes chronic pain. Another challenge in amputees is impaired function and an ongoing need for accessible and functional prostheses that are “bidirectional,” in that they provide both fine motor control and sensory feedback. Drawing on clinical experience with neuroma implantation into the medullary canal of long bones, the authors propose a novel neural interface whereby a terminal nerve end is redirected into the medullary canal of a nearby long bone and interfaced with an electrode array. The osseointegrated neural interface aims to exploit electrical signals from peripheral nerves to control advanced prosthetic devices for amputees. The purpose of this article is to present 2 clinical cases of nerve translocation into bone that serve as the clinical foundation of the osseointegrated neural interface as an innovative interface for prosthetic control.
Actinide-contaminated Skin: Comparing Decontamination Efficacy of Water, Cleansing Gels, and DTPA Gels
Authors: Tazrart A. , Bolzinger M.A. , Lamart S. , Coudert S. , Angulo J.F. , Jandard V. , Briançon S. , Griffiths N.M.
Published: May 2018

Skin contamination by alpha-emitting actinides is a risk to workers during nuclear fuel production and reactor decommissioning. Also, the list of items for potential use in radiological dispersal devices includes plutonium and americium. The actinide chemical form is important and solvents such as tributyl phosphate, used to extract plutonium, can influence plutonium behavior. This study investigated skin fixation and efficacy of decontamination products for these actinide forms using viable pig skin in the Franz cell diffusion system. Commonly used or recommended decontamination products such as water, cleansing gel, diethylenetriamine pentaacetic acid, or octadentate hydroxypyridinone compound 3,4,3‐LI(1,2‐HOPO), as well as diethylenetriamine pentaacetic acid hydrogel formulations, were tested after a 2‐h contact time with the contaminant. Analysis of skin samples demonstrated that more plutonium nitrate is bound to skin as compared to plutonium-tributyl phosphate, and fixation of americium to skin was also significant. The data show that for plutonium-tributyl phosphate all the products are effective ranging from 80 to 90% removal of this contaminant. This may be associated with damage to the skin by this complex and suggests a mechanical/wash-out action rather than chelation. For removal of americium and plutonium, both Trait Rouge cleansing gel and diethylenetriamine pentaacetic acid are better than water, and diethylenetriamine pentaacetic acid hydrogel is better than Osmogel. The different treatments, however, did not significantly affect the activity in deeper skin layers, which suggests a need for further improvement of decontamination procedures. The new diethylenetriamine pentaacetic acid hydrogel preparation was effective in removing americium, plutonium, and plutonium-tributyl phosphate from skin; such a formulation offers advantages and thus merits further assessment.
Impact of Ionizing Radiation on Electrophysiological Behavior of Human-induced Ipsc-derived Cardiomyocytes on Multielectrode Arrays
Authors: Becker Benjamin V. , Seeger Thomas , Beiert Thomas , Antwerpen Markus , Palnek Andreas , Port Matthias , Ullmann Reinhard
Published: May 2018

Cardiac arrhythmia presumably induced through cardiac fibrosis is a recurrent long-term consequence of exposure to ionizing radiation. However, there is also evidence that cardiac arrhythmia can occur in patients shortly after irradiation. In this study, the authors employed multielectrode arrays to investigate the short-term effects of x-ray radiation on the electrophysiological behavior of cardiomyocytes derived from human-induced pluripotent stem cells. These cardiomyocytes with spontaneous pacemaker activity were cultured on single-well multielectrode arrays. After exposure to 0, 0.5, 1, 2, 5, 10 Gy x-ray radiation, electrical activity was measured at time points ranging from 10 min to 96 h. RNA sequencing was employed to verify the expression of genes specifically involved in cardiomyocyte differentiation and function. A decrease in beating rate was observed after irradiation with 5 and 10 Gy starting 48 h after exposure. Cells exposed to higher doses of radiation were more prone to show changes in electrophysiological spatial distribution. No radiation-induced effects with respect to the corrected QT interval were detectable. Gene expression analysis showed up regulation of typical cardiac features like ACTC1 or HCN4. In this study, early dose-dependent changes in electrophysiological behavior were determined after x-ray irradiation. Results point towards a dose-dependent effect on pacemaker function of cardiomyocytes and indicate a possible connection between irradiation and short-term changes in electrophysiological cardiac function. Cardiomyocytes derived from human-induced pluripotent stem cells on multielectrode arrays represent a promising in vitro cardiac-modeling system for preclinical studies.
French Policies for Victim Management During Mass Radiological Accidents/Attacks
Authors: Riccobono Diane , Valente Marco , Drouet Michel , Calamai Franck , Abriat Amandine
Published: May 2018

In the current international context, emergency medical services have to be prepared for chemical, biological, radiological, and nuclear events. Emergency response to radiological or nuclear events requires coordination between many components: the fire brigade, emergency medical services (including nurses and physicians), police, hospitals, etc. To optimize efficiency, victim management in France is governed by specific policies and planned responses. This plan for radiological/nuclear event response is inspired by military chemical, biological, radiological, and nuclear victim management in the operational theatre and is based on extraction (removal to a safe environment), first triage, decontamination, second triage, treatment, substance identification, and training. It is also supported by specific equipment. Prehospital victim management in case of nuclear and radiological accident or attack will be described, as well as French-specific supplies. This response plan is constantly evolving due to the complexity of radiological and nuclear events.
PEGylated IL‐11 (BBT‐059): A Novel Radiation Countermeasure for Hematopoietic Acute Radiation Syndrome
Authors: Kumar Vidya P. , Biswas Shukla , Sharma Neel K. , Stone Sasha , Fam Christine M. , Cox George N. , Ghosh Sanchita P.
Published: May 2018

Interleukin-11 was developed to reduce chemotherapy-induced thrombocytopenia; however, its clinical use was limited by severe adverse effects in humans. PEGylated interleukin‐11 (BBT‐059), developed by Bolder Biotechnology, Inc., exhibited a longer half-life in rodents and induced longer-lasting increases in hematopoietic cells than interleukin‐11. A single dose of 1.2 mg kg−1 of BBT‐059, administered subcutaneously to CD2F1 mice (12–14 wk, male) was found to be safe in a 14 d toxicity study. The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to 60Co gamma total-body irradiation. A single dose of 0.3 mg kg−1, administered either 24 h pre-, 4 h post-, or 24 h postirradiation increased the survival of mice to 70–100% from lethal doses of radiation. Preadministration (−24 h) of the drug conferred a significantly (p < 0.05) higher survival compared to 24 h post-total-body irradiation. There was significantly accelerated recovery from radiation-induced peripheral blood neutropenia and thrombocytopenia in animals pretreated with BBT‐059. The drug also increased bone marrow cellularity and megakaryocytes and accelerated multilineage hematopoietic recovery. In addition, BBT‐059 inhibited the induction of radiation-induced hematopoietic biomarkers, thrombopoietin, erythropoietin, and Flt‐3 ligand. These results indicate that BBT‐059 is a promising radiation countermeasure, demonstrating its potential to be used both pre- and postirradiation for hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.
NHEJ Contributes to the Fast Repair of Radiation-induced DNA Double-strand Breaks at Late Prophase I Telomeres
Authors: Ahmed Emad A. , Rosemann Michael , Scherthan Harry
Published: May 2018

Exposure of cells to ionizing radiation induces DNA double-strand breaks. To repair double-strand breaks correctly, cells must distinguish between the ends of chromosomes (telomeres) and DNA double-strand breaks within chromosomes. Double-strand breaks in telomeric DNA may lead to telomere shortening and mutagenesis. Eukaryotic cells repair double-strand breaks primarily by two mechanisms: error-free homologous recombination and error-prone nonhomologous end joining, of which homologous recombination is used in early meiotic prophase I to create recombined haploid gametes by two meiotic cell divisions lacking an intervening S-phase. Genotoxic exposures put meiosis at risk to transmit mutations, and ionizing radiation is known to induce large double-strand break-marking phospho (gamma)-H2AX foci along the cores and ends of mouse meiotic chromosomes. However, it remained unclear through which repair pathway the ionizing radiation-induced telomeric double-strand breaks are repaired in late prophase I spermatocytes. Using male wild-type and nonhomologous end joining-deficient (severe combined immunodeficient) mice, this study investigated the kinetics of in vivo double-strand break formation and repair at telomeres of late prophase I chromosomes up to 12 h after 0.5 Gy of whole-body gamma irradiation. Late pachytene and diplotene spermatocytes revealed overlapping gamma-H2AX and telomere repeat signal foci, indicating telomeric DNA damage. The comparison of double-strand break repair rates at telomeres and internal prophase chromosome sites revealed a more rapid double-strand break repair at wild-type telomeres during the first hour after irradiation. Increased double-strand break foci numbers at nonhomologous end joining-deficient telomeres and chromosomes and a slowed repair rate in this DNA-dependent protein kinase catalytic subunit mutant suggest that the fast repair of double-strand breaks in telomeric DNA repeats during late prophase I is largely mediated by canonical nonhomologous end joining.
Deployment of the DosiKit System Under Operational Conditions: Experience From a French Defense National Nuclear Exercise
Authors: Entine F. , Bensimon Etzol J. , Bettencourt C. , Dondey M. , Michel X. , Gagna G. , Gellie G. , Corre Y. , Ugolin N. , Chevillard S. , Amabile J.-C.
Published: May 2018

Estimation of the dose received by accidentally irradiated victims is based on a tripod: clinical, biological, and physical dosimetry. The DosiKit system is an operational and mobile biodosimetry device allowing the measurement of external irradiation directly on the site of a radiological accident. This tool is based on capillary blood sample and hair follicle collection. The aim is to obtain a whole-body and local-surface dose assessment. This paper is about the technical evaluation of the DosiKit; the analytical process and scientific validation are briefly described. The Toulon exercise scenario was based on a major accident involving the reactor of a nuclear attack submarine. The design of the scenario made it impossible for several players (firefighters, medical team) to leave the area for a long time, and they were potentially exposed to high dose rates. The DosiKit system was fully integrated into a deployable radiological emergency laboratory, and the response to operational needs was very satisfactory.
Liquid Biopsy Using Whole Blood from Testis Tumor and Colon Cancer Patients—A New and Simple Way?
Authors: Majewski Matthäus , Nestler Tim , Kägler Sebastian , Richardsen Ines , Ruf Christian G. , Matthies Cord , Willms Arnulf , Schmelz Hans-Ulrich , Wagner Walter , Schwab Robert , Abend Michael
Published: May 2018

Tumor cells shed exosomes, which are released to the blood. Detecting tumor-derived exosomes containing RNA in plasma (liquid biopsy) is currently being investigated for early identification of occult metastases or relapses. Isolation of exosomes is laborious, resulting in low RNA yields. As a more robust (but less sensitive) alternative, the authors examined whether whole blood can be used as well. Tumor samples from nonmetastasized seminoma (n = 5) and colon cancer patients (n = 6) were taken during surgery. Whole-blood samples were taken before and 5–7 d after surgery. A whole genome mRNA microarray screening was performed. Candidate genes were selected based on two criteria: (1) gene expression in the presurgical whole-blood sample/tumor biopsy; and (2) a two-fold decrease in the copy number of candidate genes was expected in the postsurgical whole-blood sample 5–7 d after intervention, relative to the presurgical blood sample. The rationale behind this is the loss of tumor material in the body and the decline in the release of tumor-derived RNA in exosomes. For both tumor entities and for each patient, several hundred candidate genes could be identified. In a group-wise comparison, 20 candidate genes could be identified in the seminoma and 32 in the colon cancer group. These findings indicate that whole blood might be suitable for a liquid biopsy. However, this study identified the short period after surgery (5–7 d) as a possible confounder. The authors plan to add an additional time point several weeks after the operation to discriminate tumor candidate genes from genes induced by the surgery.
Developments in Biodosimetry Methods for Triage With a Focus on X-band Electron Paramagnetic Resonance In Vivo Fingernail Dosimetry
Authors: Swarts Steven G. , Sidabras Jason W. , Grinberg Oleg , Tipikin Dmitriy S. , Kmiec Maciej M. , Petryakov Sergey V. , Schreiber Wilson , Wood Victoria A. , Williams Benjamin B. , Flood Ann Barry , Swartz Harold M.
Published: May 2018

Instrumentation and application methodologies for rapidly and accurately estimating individual ionizing radiation dose are needed for on-site triage in a radiological/nuclear event. One such methodology is an in vivo X-band, electron paramagnetic resonance, physically based dosimetry method to directly measure the radiation-induced signal in fingernails. The primary components under development are key instrument features, such as resonators with unique geometries that allow for large sampling volumes but limit radiation-induced signal measurements to the nail plate, and methodological approaches for addressing interfering signals in the nail and for calibrating dose from radiation-induced signal measurements. One resonator development highlighted here is a surface resonator array designed to reduce signal detection losses due to the soft tissues underlying the nail plate. Several surface resonator array geometries, along with ergonomic features to stabilize fingernail placement, have been tested in tissue-equivalent nail models and in vivo nail measurements of healthy volunteers using simulated radiation-induced signals in their fingernails. These studies demonstrated radiation-induced signal detection sensitivities and quantitation limits approaching the clinically relevant range of ≤ 10 Gy. Studies of the capabilities of the current instrument suggest that a reduction in the variability in radiation-induced signal measurements can be obtained with refinements to the surface resonator array and ergonomic features of the human interface to the instrument. Additional studies are required before the quantitative limits of the assay can be determined for triage decisions in a field application of dosimetry. These include expanded in vivo nail studies and associated ex vivo nail studies to provide informed approaches to accommodate for a potential interfering native signal in the nails when calculating the radiation-induced signal from the nail plate spectral measurements and to provide a method for calibrating dose estimates from the radiation-induced signal measurements based on quantifying experiments in patients undergoing total-body irradiation or total-skin electron therapy.
Clinical Performance of a New Bitangential Mini-scleral Lens
Authors: Otten Henny M. , van der Linden Bart J. J. J. , Visser Esther-Simone
Published: May 2018

SIGNIFICANCE

New bitangential mini-scleral lens designs provide a highly precise fit, follow the scleral shape, are comfortable to wear, and can correct residual astigmatism. This new scleral lens design complements the arsenal of medical contact lenses available to eye care practitioners.

PURPOSE

The aim of this study was to evaluate the subjective and objective performance of a new mini-scleral lens design with a bitangential periphery.

METHODS

In this observational study, data were collected for up to 15 months (median, 84 days; interquartile range, 76 days) from the left eyes of 133 patients fitted with this newly designed lens. Data were recorded during regular visits at Visser Contact Lens Practice's scleral lens clinics: diagnosis, clinical indication for scleral lenses, previous contact lens type, subjective performance, horizontal visible iris diameter, corrected distance visual acuity, and scleral lens fitting characteristics.

RESULTS

The most common indication was keratoconus (45%), followed by irregular astigmatism (22%), keratoplasty (16.5%), ocular surface disease (13.5%), and other forms of irregular astigmatism (3%). The majority of patients (79%) scored comfort as either a 4 or 5 (out of 5), and 82% wore their lenses 12 hours or longer a day. Most lenses (81%) had a diameter of 16 mm (median, 16 mm; range, 15.5 to 17 mm) and were composed of Boston XO2 (46%), Menicon Z (44%), Boston XO (9%), or Boston Equalens II (1%). The median corrected distance visual acuity was 0.022 logarithm of the minimal angle of resolution (interquartile range, 0.155). The fitting characteristics revealed optimal values for centration and movement in 91% and 83%, respectively. Finally, the median stabilization axis was 50 degrees.

CONCLUSIONS

New mini-scleral lenses with bitangential peripheral geometry yield satisfactory clinical results and good subjective performance and are therefore an effective option for managing patients who have irregular astigmatism or other corneal pathology.
Closing Knowledge Gaps to Optimize Patient Outcomes and Advance Precision Medicine
Authors: Giusti Kathy , Young Anne Quinn , Lehrhaupt Kerri
Published: May 2018

Realizing the promise of precision medicine requires patient engagement at the key decision points throughout the cancer journey. Previous research has shown that patients who make the “right” decisions, such as being treated at a high-volume academic medical center, for example, have better outcomes. An online survey was conducted to understand awareness of and barriers to these decision points among patients with multiple myeloma and pancreatic, lung, prostate, and metastatic breast cancers. Survey respondents were identified by 5 participating foundations (multiple myeloma: n = 86, pancreatic: n = 108, lung: n = 56, prostate: n = 50, metastatic breast: n = 86) and recruited by an e-mail or social media invitation. Descriptive analyses were calculated, and the proportion of patients from each of the 5 groups was compared for each response category for each survey item. Consistent gaps in knowledge and actions were identified across all cancers evaluated in terms of finding the right doctors/team at the right center; getting the right diagnostic testing done before beginning treatment; engaging in the right course of treatment, including clinical trials; and in sharing data. Improving awareness of and changing behavior around these 4 decision points will allow patients to receive better care and contribute to the advancement of precision medicine.
Real-Time Ultrasound–Assisted Gluteal Fat Grafting
Authors: Cansancao Alvaro Luiz , Condé-Green Alexandra , Vidigal Rafael A. , Rodriguez Ricardo Luis , D’Amico Richard A.
Published: May 2018

Background:

The number of gluteal fat augmentation procedures has increased recently and so has the number of complications. Because of the increased risk of morbidity and mortality when fat is injected intramuscularly, not knowing where fat is injected is concerning. We sought to identify the planes in which fat is injected during the procedure.

Methods:

We selected 15 consecutive female patients who desired gluteal fat augmentation. All patients had epidural anesthesia and the gluteal region was infiltrated with a vasoconstrictive solution. With the patient in prone position, an ultrasound probe placed on the buttocks was used to identify the fascial layers. While decanted fat was being injected with a blunt cannula, the images were projected wirelessly to a screen, so that the surgeon and assistant could follow the planes in which the cannula was being introduced and the fat injected.

Results:

The mean volume of harvested fat was 3533 ml and the mean volume of fat injected per gluteal region was 528 ml. The evaluation of the depth and location of the cannula was performed in real time with the ultrasound, accurately and reliably identifying the planes of fat injection. All injections were subcutaneous. The downsides of this technique were the purchase cost of the ultrasound device, increased surgical time, the need for an assistant to follow the cannula and the probe constantly, and the learning curve.

Conclusion:

Real–time ultrasound–assisted gluteal fat grafting is reliable and may avoid injuring the deep vessels, further decreasing the risks of major complications.
Cortical Thickness Alterations in Chronic Pain Disorder: An Exploratory MRI Study
Authors: Magon Stefano , Sprenger Till , Otti Alexander , Papadopoulou Athina , Gündel Harald , Noll-Hussong Michael
Published: May 2018

Objective

Chronic pain disorder (CPD) has been associated with brain changes, especially in limbic circuits. However, in most patients with chronic pain, depression or anxiety is a common comorbidity. In this exploratory and naturalistic study, we investigated brain cortical thickness (CTh) differences between patients with CPD and healthy controls, with consideration of concurrent psychiatric symptoms.

Methods

Twenty-three patients with CPD and 23 age- and sex-matched healthy volunteers were included in this study. CTh was estimated using Freesurfer on high-resolution three-dimensional T1-weighted images acquired with a 3T scanner. Group differences were investigated using an analysis of covariance model that included age, sex, and Beck Depression Inventory I and Trait Anxiety Inventory scores as covariates. The relationship between CTh and Toronto Alexithymia Scale (TAS-20) scores was also investigated in patients. Data were corrected for multiplicity using the False Discovery Rate approach (q < .05).

Results

The comparison between groups using demographics and Beck Depression Inventory I scores as covariates showed thinner cortex in patients compared with controls, after correction for multiplicity in the left precentral (F(1,42) = 21.9, p < .05) and postcentral gyri (F(1,42) = 26.9, p < .05) and in the left inferior temporal sulcus (F(1,42) = 19.6, p < .05). Moreover, using the Trait Anxiety Inventory as covariate, a trend toward significance (p < .001 uncorrected) was seen for the left precentral gyrus (F(1,42) = 13.8), right middle frontal (F(1,42) = 14.3) and inferior parietal gyri (F(1,42) = 13.4), and right anterior temporal pole (F(1,42) = 15.9).

Conclusions

The results indicate that brain morphological differences between patients with chronic pain disorder and healthy controls are localized to regions that correspond to sensory as well as affective dimensions of pain processing.
“Barbell Sign”: A Diagnostic Imaging Finding in Progressive Multifocal Leukoencephalopathy
Authors: Bezuidenhout A. Fourie , Andronikou Savvas , Ackermann Christelle , Du Plessis Anne-Marie , Basson Derik , Bhadelia Rafeeque A.
Published: May 2018

The recently proposed diagnostic algorithm for progressive multifocal leukoencephalopathy underscores the importance of imaging and emphasizes the role of the radiologist in the diagnostic workup. We describe a case series of patients with visual symptoms and a typical pattern of brain involvement in definite progressive multifocal leukoencephalopathy, for which we have coined the term barbell sign.
Magnetic Resonance Imaging Features of Breast Encapsulated Papillary Carcinoma
Authors: Jiang Tingting , Tang Wei , Gu Yajia , Xu Midie , Yang Wentao , Peng Weijun
Published: May 2018

Objective

This study aimed to describe the magnetic resonance imaging (MRI) features of pure breast encapsulated papillary carcinoma (EPC).

Materials and Methods

Ten patients with histopathologically confirmed breast pure EPC were reviewed. Two radiologists evaluated lesion MRI characteristics.

Results

The EPC presented oval or round mass with circumscribed margin on MRI. In addition, 4 cases exhibited a cystic-solid mixed mass with mural nodules, and 4 cases exhibited a liquid level that indicated the possibility of hemorrhage.

Conclusions

A well-defined cystic-solid mixed mass with mural nodules, or a circumscribed mass exhibiting the possibility of hemorrhage, may suggest the diagnosis of EPC.
Lithium batteries: A technological advance with unintended injury consequences
Authors: Palmieri Tina L. , Yelon Jay , Shapiro David , Duncan Thomas , Kuhls Deborah
Published: May 2018

Lithium-ion (Li-ion) batteries have been powering portable electronic equipment since the mid-1990s. Today, they are ubiquitous in portable electronics, with more than four billion manufactured each year. However, Li-ion batteries are also associated with a spectrum of injuries related to the type of device as well as the person using the device. These injuries range from cutaneous injuries due to flame burns and explosions to corrosion injuries from ingestion. This article describes how the composition of Li-ion batteries can cause injury, the types and extent of Li-ion battery–related injuries, and suggests strategies for prevention.
A concomitant bone fracture delays cognitive recovery from traumatic brain injury
Authors: Suto Yujin , Nagata Katsuhiro , Ahmed Syed M. , Jacovides Christina , Browne Kevin D. , Cognetti John , Weber Maura T. , Johnson Victoria E. , Leone Ryan , Kaplan Lewis J. , Smith Douglas H. , Pascual Jose L.
Published: May 2018

BACKGROUND

Brain injury progression after severe traumatic brain injury (TBI) is associated with worsening cerebral inflammation but it is unknown how a concomitant bone fracture (BF) affects this progression. Enoxaparin (ENX) decreases penumbral leukocyte mobilization after TBI and improves neurologic recovery. We hypothesized that a concomitant BF worsens learning/memory recovery weeks after TBI and that ENX improves this recovery.

METHODS

CD1 male mice underwent controlled cortical impact or sham craniotomy with or without tibial fracture, receiving either daily ENX (0.8 mg/kg) or saline for 14 days after injury. Randomization defined four groups (Sham, TBI only, TBI + Fx, TBI + Fx + ENX, n = 5/each). Body weight loss and neurologic recovery (Garcia Neurologic Test, max score = 18) were assessed each day. Mouse learning (swimming time [s] and total distance [m] to reach the submerged platform Days 14 to 17 after TBI) and memory (swimming time [s] in platform quadrant after platform removed [probe]) was assessed by the Morris water maze. Ly-6G (cerebral neutrophil sequestration) and glial fibrillary acidic protein were evaluated by immunohistochemistry in brain tissue post mortem. Analysis of variance with Tukey's post hoc test determined significance (p< 0.05).

RESULTS

A concurrent BF worsened Garcia Neurologic Test scores post-TBI Days 2 to 4 (p< 0.01) as compared with TBI only, and ENX reversed this worsening on Day 4 (p< 0.01). Learning was significantly slower (greater swimming time and distance) in TBI + Fx versus TBI only on Day 17 (p< 0.01). This was despite similar swimming velocities in both groups, indicating intact extremity motor function. Memory was similar in isolated TBI and Sham which was significantly better than in TBI + Fx animals (p< 0.05). Glial fibrillary acidic protein–positive cells in penumbral cortex were most prevalent in TBI + Fx animals, significantly greater than in Sham (p< 0.05).

CONCLUSION

A long BF accompanying TBI worsens early neurologic recovery and subsequent learning/memory. Enoxaparin may partially counter this and improve neurologic recovery.
Timing of surgery and the risk of complications in patients with acute appendicitis: A population-level case-crossover study
Authors: Patel Sunil V. , Groome Patti A. , J. Merchant Shaila , Lajkosz Katherine , Nanji Sulaiman , Brogly Susan B.
Published: May 2018

BACKGROUND

Delays in surgery for patients with acute appendicitis may increase the risk of perforation and complications. These risks must be balanced with the theoretical risk of nighttime operations.

OBJECTIVE

To determine the effect of (i) time of day of surgery and (ii) time between triage presentation and surgery, on surgical complications in patient undergoing appendectomy for appendicitis.

METHODS

Population level data from Ontario from 2009 to 2015 was used to conduct this retrospective cohort study. The primary exposure was (i) time of day of surgery and (ii) time between triage and surgery. The primary outcome was a composite outcome of perioperative complications. Conditional logistic regression adjusted for patient factors was used to estimate adjusted odds ratios (OR) between the exposure and complications.

RESULTS

Twelve thousand nine hundred thirty-seven matched pairs (N = 25,874) of adult patients were included. Compared to day operations, the odds of complications were lower during the evening (OR, 0.90; 95% confidence interval [CI], 0.84–0.96) and no different at night (OR, 0.90; 95% CI, 0.77–1.04). The odds of complications were higher in patients who waited longer than 24 hours for surgery compared with those who waited less than 6 hours (OR, 1.27; 95% CI, 1.14–1.43) with no increased risk in those who waited 6 hours to 12 hours or 12 hours to 24 hours.

CONCLUSION

This large population study is the first to assess surgical risks using a case-crossover design to account for the surgeon as a potential confounder. Nighttime surgery and delaying surgery up to 24 hours were not associated increased risks of complications.

LEVEL OF EVIDENCE

Therapeutic, level III.
Using clinical analysis to classify 30-day trauma readmissions
Authors: West Sarah K. , O'Mara Michael “Shay” , Spalding M. Chance
Published: May 2018

BACKGROUND

Unplanned hospital readmissions are common across specialties. Descriptive readmission studies commonly query large administrative databases, which some speculate lack clinical granularity. This article provides the framework for a process improvement initiative aimed at identifying clinically meaningful reasons for trauma readmission. Our study hypothesizes an expected difference between the clinically abstracted reasons for readmission and those documented by the data processing staff in the trauma registry and that those differences will be the starting point to target performance improvement.

METHODS

This is a retrospective, cohort study from 2014 to 2016 involving 18,998 trauma evaluations at a Level I trauma center. The systematic categorization of trauma readmissions was completed via clinical chart review. Readmissions were categorized following an organizational flowchart. The chart reviews ultimately resulted in two readmission categories: primary and secondary reasons for 30-day trauma readmission.

RESULTS

There were 413 readmissions, an overall readmission rate of 2.7%. The highest rate of readmission, by mechanism of injury, was gunshot wounds (11%). Secondary reasons for readmission predominated (76.1%). Complications led (41%), followed by observation (8.8%) and pain (8.6%). Following readmission chart review and categorization, the trauma registry data were queried and categorized via the same method. When the two methods of data collection were compared, there was a significant difference (p < 0.0001).

CONCLUSIONS

The granular dissection of readmission charts proved to assist in isolating clinically significant readmission variables, providing clarity into the reasons behind trauma readmission. If determined solely by the trauma registry data, our performance and quality improvement initiatives would be misguided. We recommend clinical oversight of databases, with clinical review of key areas in order to guide performance improvement.
The effect of verified pediatric trauma centers, state laws, and crash characteristics on time trends in adolescent motor vehicle fatalities, 1999-2015
Authors: Notrica David M. , Sayrs Lois W. , Krishna Nidhi
Published: May 2018

BACKGROUND

Motor vehicle crashes are a leading cause of adolescent death from trauma. A recent study found American College of Surgeons–verified pediatric trauma centers (vPTC) were inversely correlated with pediatric mortality, but the analysis was limited to a single year. This study assesses the contribution of vPTCs, crash characteristics, and state driver laws on 15- to 17-year-old motor vehicle crash mortality for all 50 states from 1999 to 2015.

METHODS

Prospective data on motor vehicle fatalities, crash characteristics, state driving laws, and American College of Surgeons–verified trauma centers were collected from publicly available sources for 50 US states from 1999 to 2015. A mixed fixed/random effects multivariate regression model was fitted to assess the relative contribution of crash characteristics, state laws, and vPTCs while controlling for state variation and time trends.

RESULTS

The final regression model included driver and crash characteristics, verified trauma centers, and state laws. Camera laws ([B= −0.57 [p< 0.001]) were associated with a 57% decrease in the rate of change in adolescent crude fatalities. The lagged Level 1 vPTC crude rate (B= −0.12 [p< .001]) was protective and contributed independently to a 12% decline in the rate of change in teen fatalities over the time period. Seat belt laws (B= −0.15 [p< 0.001]), graduated driver’s license passenger restrictions (B= −0.07[p< 0.001]), graduated driver’s license learner permit period (B= −0.04 [p< 0.002]), nondeployed airbag (B= −0.003 [p< 0.001]), and Hispanic heritage (B= −0.003 [p< 0.05]) were protective. Increased risk of fatality was associated with minivan (B= 0.01 [p< 0.001]), speed > 90 mph (B= 0.004 [p< 0.001]), rural roads (B= 0.002 [p< 0.002], unknown seat belt compliance (B= 0.004 [p< 0.001]), and dry road surface (B= 0.005 [p< 0.001]).

CONCLUSIONS

State camera laws during the study time frame are associated with a 57% decrease in the rate of change in adolescent crude fatalities; vPTCs during the study time period reduced overall rate of change in the crude fatality rate by 12%. State laws, restrictions on teenage passengers and longer learner’s permit periods, and seat belt laws are associated with significant decreases in the crude teen mortality rate.

LEVEL OF EVIDENCE

Prospective study and prevention, level III.