bluuebunny/crossref_metadata_2025 huggingface dataset:
LAG3 in Solid Tumors as a Potential Novel Immunotherapy Target
Authors: Lee Su Jin , Byeon Sun-Ju , Lee Jeeyun , Park Se Hoon , Park Joon Oh , Park Young Suk , Kang Won Ki , Lim Ho Yeong , Kim Kyoung-Mee , Kim Seung Tae
Published: June 2019

We performed a prospective immunohistochemical analysis of lymphocyte activation gene 3 (LAG3) for 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Most patients (428/430, 99.5%) were evaluable for LAG3 expression by immunohistochemistry. In total, 18.5% (79/428) of the evaluated cancers expressed LAG3, including pancreatic cancer (33.3%, 2/6), gastric cancer (24.7%, 21/85), colorectal cancer (23.6%, 48/203), melanoma (12.5%, 1/8), genitourinary cancer (9.5%, 4/46), biliary tract cancer (6.3%, 1/16), and sarcoma (5.4%, 2/37), but not miscellaneous (0.0%, 0/14) or hepatocellular (0.0%, 0/15) cancer. Among 149 metastatic colorectal cancer patients, there was no statistically significant difference in sex, age, primary tumor site, pathologic differentiation, KRAS and NRAS status, BRAF status, and microsatellite instability according to LAG3 status (expressed vs. nonexpressed). Among 53 metastatic gastric cancer patients, LAG3 was only significantly associated with Epstein Barr virus status (P=0.042). Our results add to the emerging literature on LAG3 expression in various cancer types and support the need for extended clinical exploration of this target for immunotherapy.
Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden
Authors: Qu Changju , Ping Nana , Kang Liqing , Liu Hailing , Qin Songbin , Wu Qian , Chen Xiaochen , Zhou Meng , Xia Fan , Ye Aihua , Kong Danqing , Li Caixia , Yu Lei , Wu Depei , Jin Zhengming
Published: June 2019

Chimeric antigen receptor T-cell (CAR-T) therapy demonstrates impressive efficacy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T therapy–related severe cytokine release syndrome and neurological toxicity limit its clinical application in R/R DLBCL patients with high tumor burden. Here, we conducted a phase II clinical trial testing the efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin lymphoma patients (NCT03196830). Among the enrolled patients, 10 R/R DLBCL patients with high tumor burden were analyzed. Before CAR-T therapy, 4 were treated with intensive combined chemotherapy (C-CAR-cohort), and 6 were exposed to radiotherapy (R-CAR-cohort). Patients in the R-CAR-T-cohort showed a higher overall response rate (100% vs. 25%, P=0.033) and less severe cytokine release syndrome (0% vs. 100%, P=0.0048) and neurotoxicity (0% vs. 75%, P=0.033) incidences than patients in the C-CAR-T-cohort. Furthermore, one case who responded to CAR-T therapy initially and who suffered a relapse shortly was exposed to radiation and achieved complete remission, with an increase in the number of CAR-T copies detected. This study demonstrates that radiotherapy is an optimal debulking regimen to managing R/R DLBCL patients before CAR-T therapy and a promising alternative salvage therapy for patients who suffer a relapse after CAR-T therapy by fuelling CAR-T copies.
Change in PM2.5 exposure and mortality among Medicare recipients
Authors: Awad Yara Abu , Di Qian , Wang Yan , Choirat Christine , Coull Brent A. , Zanobetti Antonella , Schwartz Joel
Published: June 2019

The association between PM2.5 and mortality is well established; however, confounding by unmeasured factors is always an issue. In addition, prior studies do not tell us what the effect of a sudden change in exposure on mortality is. We consider the sub-population of Medicare enrollees who moved residence from one ZIP Code to another from 2000 to 2012. Because the choice of new ZIP Code is unlikely to be related with any confounders, restricting to the population of movers allows us to have a study design that incorporates randomization of exposure. Over 10 million Medicare participants moved. We calculated change in exposure by subtracting the annual exposure at original ZIP Code from exposure at the new ZIP Code using a validated model. We used Cox proportional hazards models stratified on original ZIP Code with inverse probability weights (IPW) to control for individual and ecological confounders at the new ZIP Code. The distribution of covariates appeared to be randomized by change in exposure at the new locations as standardized differences were mostly near zero. Randomization of measured covariates suggests unmeasured covariates may be randomized also. Using IPW, per 10 µg/m3 increase in PM2.5, the hazard ratio was 1.21 (95% confidence interval [CI] = 1.20, 1.22] among whites and 1.12 (95% CI = 1.08, 1.15) among blacks. Hazard ratios increased for whites and decreased for blacks when restricting to exposure levels below the current standard of 12 µg/m3. This study provides evidence of likely causal effects at concentrations below current limits of PM2.5.
Complications of Cosmetic Surgery Abroad – Cost Analysis and Patient Perception
Authors: Farid Mohammed , Nikkhah Dariush , Little Max , Edwards Daren , Needham Wendy , Shibu Mohamed
Published: June 2019

Background:

Cosmetic surgery tourism is rapidly becoming more prevalent in the United Kingdom. We aim to identify the motivational factors underlying patients’ decisions to go abroad for their treatment and gather information about the ensuing complications.

Methods:

A retrospective review (January 2013–August 2017) was conducted of patients seen at a single major trauma center for complications from cosmetic surgery performed overseas. Cost analysis was performed based on national tariffs. Complications were grouped based on Clavien-Dindo classification and the Clinical Commissioning Group cost. A telephone survey was conducted to evaluate reasons for travel, details of complications, and impression of healthcare at home and abroad.

Results:

A total of 20 patients (one male, 19 females) with a mean age 36 years (23–59 years) were included. Lower cost was the most popular reason for travel, followed by lack of expertise and friend’s recommendation. Abdominoplasty (n = 9) had the highest number of complications followed by gluteal augmentation (n = 7). All major complications were due to gluteal augmentation (n = 4). The cost was for minor (n = 8, £3,448), intermediate (n = 8, £18,271), and major (n = 4, £42,083.59) complications.

Conclusions:

We raise serious concerns about the lack of regulation in cosmetic tourism and the absence of patient follow-up abroad. A particular concern was all gluteal augmentation cases had major complications. An international consensus to regulate surgical practice abroad is crucial to protect patients’ interests and promote safe cosmetic surgery.
Mastectomy in Transgender and Cisgender Patients: A Comparative Analysis of Epidemiology and Postoperative Outcomes
Authors: Cuccolo Nicholas G. , Kang Christine O. , Boskey Elizabeth R. , Ibrahim Ahmed M.S. , Blankensteijn Louise L. , Taghinia Amir , Lee Bernard T. , Lin Samuel J. , Ganor Oren
Published: June 2019

Background:

Mastectomy is a commonly requested procedure in the transmasculine population and has been shown to improve quality of life, although there is limited research on safety. The aim of this study was to provide a nationwide assessment of epidemiology and postoperative outcomes following masculinizing mastectomy and compare them with outcomes following mastectomy for cancer prophylaxis and gynecomastia correction in cisgender patients.

Methods:

The American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2017 was queried using International Classification of Diseases and Current Procedural Terminology codes to create cohorts of mastectomies for 3 indications: transmasculine chest reconstruction, cancer risk-reduction (CRRM), and gynecomastia treatment (GM). Demographic characteristics, comorbidities, and postoperative complications were compared between the 3 cohorts. Multivariable regression analysis was used to control for confounders.

Results:

A total of 4,170 mastectomies were identified, of which 14.8% (n = 591) were transmasculine, 17.6% (n = 701) were CRRM, and 67.6% (n = 2,692) were GM. Plastic surgeons performed the majority of transmasculine cases (85.3%), compared with the general surgeons in the CRRM (97.9%) and GM (73.7%) cohorts. All-cause complication rates in the transmasculine, CRRM, and GM cohorts were 4.7%, 10.4%, and 3.7%, respectively. After controlling for confounding variables, transgender males were not at an increased risk for all-cause or wound complications. Multivariable regression identified BMI as a predictor of all-cause and wound complications.

Conclusion:

Mastectomy is a safe and efficacious procedure for treating gender dysphoria in the transgender male, with an acceptable and reassuring complication profile similar to that seen in cisgender patients who approximate either the natal sex characteristics or the new hormonal environment.
The impact of interpersonal support, supervisory support, and employee engagement on employee turnover intentions: Differences between financially distressed and highly financially distressed hospitals
Authors: Boakye Kwabena G. , Apenteng Bettye A. , Hanna Mark D. , Kimsey Linda , Mase William A. , Opoku Samuel T. , Owens Charles , Peden Angela
Published: June 2019

Background

Critical access hospitals (CAHs) are small hospitals in rural communities in the United States. Because of changes in rural population demographics, legacy financial obligations, and/or structural issues in the U.S. health care system, many of these institutions are financially distressed. Indeed, many have closed due to their inability to maintain financial viability, resulting in a health care and economic crisis for their communities. Employee recruitment, retention, and turnover are critical to the performance of these hospitals. There is limited empirical study of the factors that influence turnover in such institutions.

Purpose

The primary purpose of the study was to study relationships between interpersonal support, supervisory support, employee engagement, and employee turnover intentions in CAHs. A secondary purpose was to study how financial distress affects these relationships.

Methodology

Based on a survey of CAH employees (n = 218), the article utilizes mediated moderation analysis of a structural equation model.

Results

Interpersonal support and supervisory support are positively associated with employee engagement, whereas employee engagement mediates the relationships between both interpersonal support and supervisory support and employee turnover intentions. Statistically significant differences are found between these relationships in financially distressed and highly financially distressed institutions.

Conclusions

Our results are consistent with the social exchange theory upon which our hypotheses and model are built and demonstrate the value of using the degree of organizational financial distress as a contextual variable when studying motivational factors influencing employee turnover intentions.

Practical Implications

In addition to advancing management theory as applied in the CAH context, our study presents the practical insight that employee perceptions of their employer’s financial condition should be considered when organizations develop employee retention strategies. Specifically, employee engagement strategies appear to be of greater value in the case of highly financially distressed organizations, whereas supervisory support seems more effective in financially distressed organizations.
Are community health centers’ chief executive officers’ compensation related to clinical performance?
Authors: Davlyatov Ganisher , Borkowski Nancy , Qu Haiyan , Burke Darrell , Bronstein Janet , Brickman Andrew
Published: June 2019

Background

Most research of chief executive officer (CEO) compensation in the health care industry has been limited to hospitals. This study expands our knowledge of CEO compensation into the nonhospital areas of the industry, specifically community health centers (CHCs). CHCs are safety-net providers that are an integral part of the U.S. health delivery system for medically underserved populations. Since the passage of the Patient Protection and Affordable Care Act, the federal government has created financial incentives for CHCs to improve care through access and quality performance criteria. To promote quality improvement, CEOs need to set their organization’s priorities. One method used to achieve this goal is to tie the CEO’s compensation to the organization’s quality performance. However, there is a gap in our knowledge if CHCs’ CEOs compensation is associated with quality performance outcomes.

Purpose

The primary aim of this study was to examine the relationship between clinical performance and CEO compensation in CHCs.

Methods/Approach

Agency, social comparison, and managerial power theories guided this research, which examines the relationship of clinical performance and CEO compensation. Secondary data on Uniform Data System’s CHC clinical performance combined with CEO compensation from Internal Revenue Service Form 990 were analyzed using generalized estimating equations with state and year fixed effects on a national sample of section 330 grant-funded CHCs (N = 984) for the period 2011–2016.

Results

We found no evidence that clinical performance was associated with CHCs’ CEO compensation. Except for race, all other CEO characteristics were positively associated with CEO compensation and in line with previous research. We found that non-White CEOs were compensated more than White CEOs. In addition, further subanalyses revealed that an increase in the highest paid employees’ compensation was associated with an increase in CEO compensation.

Practice Implications

The findings of this study can assist Health Resources and Services Administration improve its assessment policies in funding allocation to CHCs, as well as help board members make informed decisions regarding tying CEO compensation to predetermined performance metrics.
Successful Migration from Radioactive Irradiators to X-ray Irradiators in One of the Largest Medical Centers in the US
Authors: Kamen Jacob , Hsu Wen-Ya , Boswell Brandon , Hill Colin
Published: June 2019

This paper summarizes about 9 years of effort by Mount Sinai to successfully migrate completely from radioactive irradiators to x-ray irradiators without compromising patient care or research studies. All the effort by Mount Sinai to permanently remove the risk of malicious use of radioactive materials as Radiological Dispersal Device or dirty bomb is reviewed. Due to the unique characteristics of the cesium chloride (137CsCl) used in irradiators, it is especially susceptible to be used as a dirty bombs. Mount Sinai originally had four of such irradiators. To reduce and eventually remove the risk of malicious use of radioactive materials, Mount Sinai in New York City has taken several steps. One of such measures was to harden the radioactive irradiators to make the radioactive materials harder to be stolen for malicious purposes. By increasing the delay time, the local law enforcement agency (LLEA) will have more time to stop the intruder. Another measure taken was to implement enhanced security in facilities having radioactive materials. We collaborated with the National Nuclear Security Administration and used state-of-the-art security equipment such as Biometric Access Control and 24/7 video monitoring. In addition, a remote monitoring system with alarms was installed and connected to LLEA for constant monitoring and possible intervention, if necessary, in a timely manner. The other measure taken was to limit the number of people who have access to such radioactive materials. We adopted a single person operator method and reduced the number of people having access from 145 people to only a few people. The adoption of such measures has reduced the risk significantly; however, the best way to remove the permanent risk of these radioactive materials that may be used for a dirty bomb is to use alternative technology to replace these high-activity radioactive sources. In 2013, Mount Sinai purchased its first x-ray irradiator to investigate the feasibility of using x-ray irradiators instead of cesium irradiators for research purposes for cells and small mice. The results from comparison studies were promising, which led to the decision of permanent migration of all cesium irradiators to x-ray irradiators. As of January 2018, Mount Sinai successfully disposed all its 137Cs irradiators. At this time, Mount Sinai, as one of the largest health care institutions in NY with about 50,000 employees, has migrated completely to alternative technology and removed the risk of malicious use of radioactive materials permanently.
C-Press Technique to Facilitate Descemet Membrane Endothelial Keratoplasty Surgery in Vitrectomized Patients: A Case Series
Authors: Saad Alain , Awwad Shady T. , El Salloukh Nasrine Anais , Panthier Christophe , Bashur Ziad , Gatinel Damien
Published: June 2019

Purpose:

To describe an original technique to unfold the graft in vitrectomized eyes undergoing Descemet membrane endothelial keratoplasty (DMEK).

Methods:

We performed a retrospective chart and video review of successive cases presenting with corneal decompensation in vitrectomized eyes or aphakic eyes in which DMEK or combined DMEK/scleral-fixated intraocular lens implantation was indicated and in which a specific technique [Cornea-Press (C-Press)] was used to unfold the graft. C-Press is characterized by corneal indentation intended to artificially shallow the anterior chamber and allow the graft to unroll. Best spectacle-corrected visual acuity, central corneal thickness, the time of graft unfolding, endothelial cell count, and the incidence of intraoperative/postoperative complications were analyzed.

Results:

Eleven eyes of 11 patients (8 men, mean age: 73 ± 12 years) were included. Corrected distance visual acuity (logarithm of the minimum angle of resolution) improved from 1.44 ± 0.23 preoperatively to 0.77 ± 0.36 6 months postoperatively (P < 0.001). Central corneal thickness (CCT) decreased from 644 ± 79 preoperatively to 516 ± 49 μm 6 months postoperatively. The graft unfolding time was 4.4 ± 2.5 minutes. Mean endothelial cell density was 2762 ± 192 preoperatively and 1872 ± 324 cells/mm2 6 months postoperatively. No eye showed intraoperative complications. Rebubbling for partial detachment was needed in 2 cases (18%).

Conclusions:

The C-Press technique enables likely safe and reproducible DMEK surgery in vitrectomized eyes. Further clinical studies with a large number of patients and longer follow-up are required to confirm our preliminary results.
Corneal and Scleral Problems Caused by Skin-Lightening Creams
Authors: Hollick Emma J. , Igwe Chinedu , Papamichael Esther , Gore Daniel M. , Angunawela Romesh I. , Philippidou Marianne , Jones Sophie M.
Published: June 2019

Purpose:

To present a case series of patients with corneal and scleral changes associated with the use of skin-lightening creams. This is the first report of corneal changes with these widely available creams.

Methods:

Three patients of West African origin presented with strikingly similar skin, corneal, and scleral changes and were found to have all been using skin-lightening creams containing hydroquinone. Histopathology was obtained for 1 patient.

Results:

Three patients were referred to the corneal clinics of 2 hospitals with corneal changes and a history of blurred vision for 1 to 3 years. There was a 60-year-old woman from Nigeria and a 68-year-old woman and a 73-year-old man both from Ghana. All 3 had been using skin-lightening lotions containing hydroquinone on their faces for between 3 and 15 years and had black-blue facial pigmentation of exogenous ochronosis, a recognized complication of these creams. Their corneas all had horizontal striae radiating across the posterior corneas with scleral thinning and plaques. Linear brown epithelial pigmentation was observed within the lower third of the corneas. Biopsy of the sclera in 1 patient showed ochronosis.

Conclusions:

We present previously unreported eye changes associated with the use of skin-lightening creams containing hydroquinone, with a triad of signs: posterior corneal striae radiating from 3 o'clock to 9 o'clock, thinning and plaques in the sclera, and a normal endothelial cell count. Similar pathological changes are seen in exogenous ochronosis, a recognized skin complication of hydroquinone, are seen in the sclera.
Sensory Adaptation to Silicone Hydrogel Contact Lens Wear Is Not Associated With Alterations in the Corneal Subbasal Nerve Plexus
Authors: Kocabeyoglu Sibel , Colak Dilan , Mocan Mehmet C. , Irkec Murat
Published: June 2019

Purpose:

To evaluate corneal subbasal nerve alterations in contact lens (CL)-naive silicone hydrogel CL wearers and to investigate the relationship between structural subbasal nerve changes with corneal sensitivity.

Methods:

Twenty eyes of 20 neophyte daily silicone hydrogel CL wearers and 20 eyes of age-matched control subjects were recruited for this prospective longitudinal study. Corneal subbasal nerve densities were evaluated using in vivo confocal microscopy. Central corneal tactile sensitivity was measured using Cochet–Bonnet esthesiometers. In vivo confocal microscopy and Cochet–Bonnet esthesiometry were performed before and at the 6-month time point after the initiation of CL wear. Two-way repeated measures analysis of variance, χ2, and Wilcoxon signed-rank tests were used for statistical analyses.

Results:

The mean ages of CL users and control subjects were 21.8 ± 1.8 years (range = 19–24 years) and 21.5 ± 2.3 years (range = 20–24 years), respectively (P = 0.579). Compared with their baseline values, there were no significant changes at the 6-month follow-up period in the mean total subbasal nerve fiber length (2266.6 ± 414.6 vs. 2277.9 ± 405.0 μm/frame; P = 0.432), mean total subbasal nerve branch density (10.4 ± 1.5 vs. 10.5 ± 1.3 nerves/frame; P = 0.655), or the mean long nerve fiber density (4.7 ± 0.7 vs. 4.8 ± 0.7 nerves/frame; P = 0.564) of CL users. Mechanical corneal sensitivity remained unaltered during the 6-month period in CL users (11.2 ± 0.5 vs. 11.2 ± 0.5; P = 1.000). No significant changes were observed in the subbasal nerve plexus or corneal tactile sensitivity of the control subjects during the study interval.

Conclusions:

Sensory adaptation to CL wear is not mediated through attenuation of the subbasal nerve or reduction of corneal tactile sensitivity in CL-naive users.
Evaluating Immunopathogenic Biomarkers During Severe Malaria Illness as Modifiers of the Neuropsychologic Benefits of Computer Cognitive Games Rehabilitation in Ugandan Children
Authors: Boivin Michael J. , Sikorskii Alla , Nakasujja Noeline , Ruiseñor-Escudero Horacio , Familiar-Lopez Itziar , Opoka Robert O. , Giordani Bruno
Published: June 2019

Background:

We explored 3 immunopathogenic biomarkers collected during acute malaria illness as potential moderators of gains from a computerized cognitive rehabilitation training (CCRT) intervention.

Method:

Von Willebrand Factor (vWF), tumor necrosis factor (TNF) and Regulated on Activation, Normal T Expressed and Secreted (RANTES) were assayed from plasma and cerebral spinal fluid (CSF) of children during acute severe malaria anemia or cerebral malaria. Two years after acute malaria illness, 150 surviving children and 150 nonmalaria community controls (CCs) from their households 6–12 years old entered a 3-arm randomized controlled trial of titrating and nontitrating CCRT against no CCRT. Tests of cognition [Kaufman Assessment Battery for Children (KABC)], Tests of Variables of Attention and Achenbach Child Behavior Checklist (CBCL) were administered before and after 24 CCRT sessions over a 3-month period, and at 1-year follow-up. Differences in outcomes by trial arms and biomarker levels were evaluated using linear mixed effects models.

Results:

Severe malaria survivors with lower levels of vWF, lower CSF levels of TNF and higher levels of plasma and CSF RANTES had better KABC cognitive performance after both titrating and nontitrating CCRT compared with no CCRT. For the CBCL, high plasma RANTES was associated with no benefit from either the titrating and nontitrating CCRT, whereas high TNF plasma was predictive of the benefit for both interventions. These biomarker moderating effects were not evident for CC children.

Conclusions:

Severe malaria immunopathogenic biomarkers may be related to poorer long-term brain/behavior function as evidenced by diminished benefit from a computerized cognitive rehabilitation intervention.
Vancomycin-associated Nephrotoxicity and Risk Factors in Critically Ill Children Without Preexisting Renal Injury
Authors: Feiten Helen dos Santos , Okumura Lucas Miyake , Martinbiancho Jacqueline Kohut , Andreolio Cinara , da Rocha Taís Sica , Antonacci Carvalho Paulo Roberto , Pedro Piva Jefferson
Published: June 2019

Background:

A recent systematic review concluded that critically ill pediatric patients have higher odds of vancomycin-related nephrotoxicity [odds ratio (OR): 3.61, 95% CI: 1.21–10.74]. We aimed to assess the incidence and risk factors for vancomycin-associated nephrotoxicity in critically ill children without preexisting renal injury.

Methods:

A cohort of children admitted to a pediatric intensive care unit, from 2011 to 2016 treated with vancomycin without preexisting renal injury. The main diagnosis, therapeutic interventions and medications administered in this period were evaluated. Generalized estimating equation models were used to assess the association between clinical covariates and the dependent variable pediatric risk, injury, failure, loss, end-stage renal disease (pRIFLE).

Results:

Hundred ten patients, representing 1177 vancomycin days, were analyzed. Vancomycin-associated nephrotoxicity was seen in 11.8%. In a multivariate model, higher vancomycin doses were not associated with poorer renal function (P = 0.08). Higher serum vancomycin levels were weakly associated with pRIFLE classification (OR: 1.05, 95% CI: 1.02–1.07). Furosemide or amphotericin B in addition to the vancomycin treatment was associated with impaired renal function (OR: 2.56, 95% CI: 1.38–4.8 and OR: 7.7 95% CI: 2.55–23, respectively).

Conclusions:

Vancomycin-associated nephrotoxicity in acute ill children without preexisting renal injury, measured with pRIFLE, is close to 11.8%. Furosemide and amphotericin B in addition to the vancomycin treatment are strong predictors of worse pRIFLE scores. The influence of acute kidney injury status at pediatric intensive care unit admission and the method used for renal function assessment might influence the incidence of vancomycin-associated nephrotoxicity and its associated risk factors.
Altered microbiome composition in individuals with fibromyalgia
Authors: Minerbi Amir , Gonzalez Emmanuel , Brereton Nicholas J.B. , Anjarkouchian Abraham , Dewar Ken , Fitzcharles Mary-Ann , Chevalier Stéphanie , Shir Yoram
Published: June 2019

Fibromyalgia (FM) is a prevalent syndrome, characterised by chronic widespread pain, fatigue, and impaired sleep, that is challenging to diagnose and difficult to treat. The microbiomes of 77 women with FM and that of 79 control participants were compared using 16S rRNA gene amplification and whole-genome sequencing. When comparing FM patients with unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa. Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM. In line with observed alteration in butyrate-metabolising species, targeted serum metabolite analysis verified differences in the serum levels of butyrate and propionate in FM patients. Using machine-learning algorithms, the microbiome composition alone allowed for the classification of patients and controls (receiver operating characteristic area under the curve 87.8%). To the best of our knowledge, this is the first demonstration of gut microbiome alteration in nonvisceral pain. This observation paves the way for further studies, elucidating the pathophysiology of FM, developing diagnostic aids and possibly allowing for new treatment modalities to be explored.
Preservation of Vestibular Function and Residual Hearing After Round Window Cochlear Implantation
Authors: Stuermer Konrad Johannes , Kluenter Heinz Dieter , Lang-Roth Ruth , Schwarz David , Hüttenbrink Karl-Bernd , Anagiotos Andreas
Published: June 2019

Objective:

To examine the possible correlation between the loss of short-term residual hearing and vestibular function after cochlear implantation (CI).

Study Design:

Retrospective patient review.

Setting:

Academic tertiary referral center.

Patients:

One hundred twenty patients with normal vestibular function (VF) in the caloric testing and residual hearing (RH) at the frequencies 250, 500, and 1000 Hz on the surgery side between 2008 and 2016 were included in the study.

Intervention:

Primary CI on the first side via round window with a conventional full-length electrode.

Main Outcome Measures:

Changes of RH and VF 7 weeks after surgery were analyzed. Preservation of RH was defined as measurable postoperative thresholds at the frequencies 250, 500, and 1000 Hz in the pure-tone audiogram. Preservation of the VF after CI was assessed both by an absolute and relative threshold in the caloric testing.

Results:

Seven weeks after implantation, the preservation of RH was achieved in 52 (43.3 %) patients and the preservation of VF in 95 (79.2 %) patients on the operated side. There was no significant statistical correlation between these two parameters.

Conclusion:

The loss of RH was more than twice as frequent as the loss of VF. However, no statistical correlation between the failure of the two inner ear functions was found. The exact causes are still unknown, but our data could give an indication that there may be different underlying pathomechanisms.
Bilateral Cochlear Implantation in Vogt-Koyanagi-Harada Syndrome: A Case Report
Authors: AlHelali Nora , Hajr Eman , Almuhawas Fida , Hagr Abdulrahman
Published: June 2019

Objective:

To evaluate cochlear implantation in Vogt-Koyanagi-Harada syndrome with regard to surgical difficulties and hearing outcomes.

Patients:

Single case report.

Intervention(s):

Therapeutic complete electrode insertion during surgery despite evident intra-cochlear fibrosis.

Main Outcome Measure(s):

Postoperative speech audiometry, categories of auditory performance, and speech intelligibility rating.

Results:

Vogt-Koyanagi-Harada syndrome is a multisystem autoimmune disease that affects tissues containing melanin. It is characterized by bilateral uveitis with auditory, vestibular, and dermatologic manifestations. Standard treatment comprises aggressive administration of systemic corticosteroids.

This report describes the use of bilateral cochlear implants in a 30-year-old Saudi woman who presented with uveitis and was diagnosed with Vogt-Koyanagi-Harada syndrome. She had progressive hearing loss in both ears and experienced minimal improvement with hearing aids. The patient underwent sequential cochlear implantation, which was challenging because it was difficult to insert the electrode in the right ear due to intra-cochlear fibrosis. After more than 5 years of follow-up, she has good hearing in both ears, despite the advancement of ocular disease and recurring visual complaints.

Conclusion:

This study suggests that patients with Vogt-Koyanagi-Harada syndrome could develop intra-cochlear fibrosis during cochlear implantation due to the autoimmune nature of disease. Moreover, cochlear implantation becomes more difficult with disease advancement. Therefore, it is essential that healthcare professionals consider early detection and prompt treatment of hearing loss in patients with this syndrome.
Negative Predictive Value of Non-Echo-Planar Diffusion Weighted MR Imaging for the Detection of Residual Cholesteatoma Done at 9 Months After Primary Surgery Is not High Enough to Omit Second Look Surgery
Authors: Horn Roelof J. , Gratama Jan Willem C. , van der Zaag-Loonen Hester J. , Droogh-de Greve Kitty E. , van Benthem Peter-Paul G.
Published: June 2019

Objectives:

To evaluate non echo-planar diffusion weighted magnetic resonance imaging (non-EP DW MRI) at 9 months after primary surgery to rule out residual cholesteatoma in patients scheduled before second-look-surgical exploration.

Study Design:

Prospective observational study.

Setting:

Secondary teaching hospital.

Patients/Interventions:

Patients who were scheduled for second-look-surgery after primary canal wall up repair of cholesteatoma underwent 1.5 T MRI including non-EP DWI and high-resolution coronal T1 and T2-FS SE sequences.

Main Outcome Measures:

Imaging studies were evaluated for the presence of cholesteatoma by three independent observers. Intraoperative observations were regarded the standard of reference. Ear, nose, throat (ENT) surgeons were blinded for imaging findings. The primary outcome was the negative predictive value (NPV) of MR imaging, secondary outcomes were sensitivity, specificity, and positive predictive value.

Results:

Thirty-three patients underwent both MRI and surgery, among whom 22 had a cholesteatoma. Mean time between primary surgery and MRI was 259 days (standard deviation [SD] 108). NPV of non-EP DW MRI in detecting recurrent cholesteatoma was 53% (95% CI: 32–73%). Sensitivity and specificity were 59% (39–77%) and 91% (62–98%), respectively. The positive predictive value was 93% (69–99%). In five out of nine false-negative cases, recurrent cholesteatoma measured 3 mm or less. Using a 3 mm detection threshold, NPV increased to 79%.

Conclusion:

Non-EP DW MRI cannot replace second look surgery in ruling-out residual cholesteatoma at 9 months after primary surgery. It could be used in a follow-up strategy in low risk patients. Further research is needed which types of residual cholesteatoma are not revealed by MRI.
A Validated Questionnaire to Assess the Severity of Persistent Postural-Perceptual Dizziness (PPPD): The Niigata PPPD Questionnaire (NPQ)
Authors: Yagi Chihiro , Morita Yuka , Kitazawa Meiko , Nonomura Yoriko , Yamagishi Tatsuya , Ohshima Shinsuke , Izumi Shuji , Takahashi Kuniyuki , Horii Arata
Published: June 2019

Objective:

To establish a questionnaire to diagnose and assess the severity of persistent postural-perceptual dizziness (PPPD).

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

Fifty PPPD patients and 50 consecutive control patients with other vestibular disorders.

Interventions:

Patients answered questions on three exacerbating factors of PPPD (upright posture/walking, movement, and visual stimulation), and each factor was evaluated using four questions scoring the severity from 0 (none) to 6 (unbearable). Somatic and psychological distress was evaluated by the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS), respectively.

Main Outcome Measures:

The questionnaire's reliability was tested by Cronbach's alpha, and it was validated by examining the differences in the questionnaire's scores between PPPD patients and controls. The area under the curve (AUC) of the receiver operating characteristic curve for each factor was calculated.

Results:

Cronbach's alpha coefficient was >0.8 for all factors, except the movement factor. There were no significant differences in the VAS and HADS scores between the two groups. However, the combined and individual questionnaire scores for each factor were higher in PPPD patients than in controls, indicating the questionnaire's high validity. The AUC was widest for the visual stimulation factor (0.830), and a score of 9 (full score 24) had the best sensitivity (82%) and specificity (74%) for discriminating PPPD patients from controls.

Conclusions:

We developed a questionnaire that exhibited high reliability and validity in evaluating PPPD severity. The visual stimulation factor may be the most characteristic among the three exacerbating factors.
Endre Hőgyes (1847–1906), Forgotten Father of the Vestibulo-Ocular Reflex
Authors: Tamás László T. , Mudry Albert
Published: June 2019

Objective:

Throughout the history of vestibular research, the discovery of the vestibulo-ocular reflex in 1881 by Endre Hőgyes (1847–1906) is rarely mentioned. The aim of this study is to review Hőgyes’ vestibular research articles, all originally written in Hungarian and emphasize their epoch-making content.

Main Data Sources:

Hőgyes’ vestibular publications, originally written in Hungarian, which describe various eye movements of the rabbit in response to vestibular stimulation by rotation about three axes.

Results:

Hőgyes was the first to use a three-axis turntable on an experimental animal, in this case a rabbit. He found that depending on the plane of rotation, different types of binocular eye movements were produced. He then demonstrated by destructive and excitatory experiments, the anatomical pathways and the physiological function producing this phenomenon. Ultimately, he explained the exact connections between the inner ear labyrinth and certain muscle contractions during eye movements. He identified this pathway as the “associating center of the ocular movements,” later defined as the vestibulo-ocular reflex. Hőgyes’ discovery was only superficially noted during his lifetime and ignored after his death.

Conclusion:

Hőgyes was the first to demonstrate the vestibulo-ocular reflex. He was forgotten during the ensuing 140 years probably because his articles were appeared only in Hungarian and because a short time later, Róbert Bárány's award of the Nobel Prize overshadowed many of Bárány's predecessors and contemporaries, including Hőgyes and relegated them to the background.
Efficacy and safety of treatment of chronic hepatitis C with sofosbuvir and ribavirin with or without peginterferon: a French prospective real-life cohort study of unselected 211 patients
Authors: Garioud Armand , Heng Ratmony , Amiot Xavier , Rémy André-Jean , Ollivier-Hourmand Isabelle , Mokhtari Camelia , Medmoun Mourad , Renou Christophe , Zougmoré Honoré , Pulwermacher Philippe , Lucidarme Damien , Rosa-Hézode Isabelle , Causse Xavier , Arotcarena Ramuntcho , Zanditenas David , Halfon Philippe , Pariente Alexandre , Cadranel Jean-François ,   Association Nationale des Hépato-gastroentérologues des Hôpitaux Généraux (ANGH), France
Published: June 2019

Introduction

Sofosbuvir is the first directly-acting antiviral for the treatment of hepatitis C virus. First, the regimens were combinations with sofosbuvir+ribavirin (SR) or with sofosbuvir+ribavirin and pegylated-interferon α-2a (SPR) with cure rates around 90%. The aim of this study was to report the results of these combinations in ‘real-life’ in France.

Materials and methods

Main features of patients treated with SR or SPR in 24 hospitals were collected. Undetectable hepatitis C virus week 12 viral load after treatment defined sustained virological response (SVR12). Statistics were performed using StatView software for descriptive analysis and χ
2 for the sub-groups comparisons.

Results

Two hundred and eleven patients were analyzed. The average age was 56.1. One hundred and seventy-one (89%) patients had a fibrosis score of at least 3. Seventy-nine patients were infected by a genotype 1 (G1). One hundred and thirteen patients were treated with SR and 95 with SPR. In naive patients: with SPR for 12 weeks, SVR12 was 93% in G1, 100% in G3 and 83% in G4. With SR for 12 weeks, SVR12 was 100% in G2 patients (6/6). The safety of these regimens was satisfactory with only two patients who had to stop P due to severe side effects. Multivariate analysis shows a higher SVR in SPR versus SR (odds ratio = 1.28; P = 0.05) and in G2 or G3 versus others (odds ratio = 1.56; P = 0.04). Moreover, Child–Pugh score B or C (P = 0.02), platelets count under 100G/l (P = 0.05) or a past event of ascites (P = 0.04) was independently associated with less SVR.

Conclusion

This multicenter large study confirms the good results of SR for 12 weeks in G2 naive patients. Finally, a decompensated cirrhosis, a past event of ascites and a baseline low platelet count were strongly associated with poor response.
Contemporary management of orbital blowout fractures
Authors: Homer Natalie , Huggins Alison , Durairaj Vikram D.
Published: June 2019

Purpose of review

Orbital floor blowout fractures may lead to significant morbidity, including debilitating double vision and globe malposition. Thorough evaluation and timely surgical intervention may prevent long-term sequelae.

Recent findings

New studies have demonstrated certain patients with orbital floor fractures to do well when managed conservatively. In those necessitating operative repair, precise surgical dissection and adequate fracture reduction are essential to restoring orbital anatomy and function. Novel surgical techniques and orbital floor reconstruction materials, described in this review, will further optimize patient outcomes.

A knowledgeable evaluation, thoughtful management strategy and modernized surgical technique can prevent long-term disability in patients with orbital floor blowout fractures.
The Work-Role Transition of Part-time Clinical Faculty
Authors: Wenner Teresa A. , Hakim Amy Cooper , Schoening Anne M.
Published: June 2019

Background

Part-time clinical nurse educators who simultaneously work in both a clinical and an academic setting experience a unique work-role transition. Identifying and addressing their needs during this time may assist in new faculty retention.

Purpose

As part of a larger study examining the work-role transition of part-time clinical nurse faculty, a specific research question was developed to determine how these individuals experience the phases of the Nurse Educator Transition (NET) model.

Methods

This qualitative phenomenological study used both purposive and snowball sampling to recruit 14 RNs who were part-time clinical educators.

Results

Study findings validated all 4 phases of the NET model. In addition, several participants indicated a sense of returning to the first 2 phases of transition at the beginning of new semesters and courses.

Conclusion

The NET model is applicable to the part-time clinical nurse educator population. This theory can be used as a framework to design orientation and mentorship programs that specifically target part-time clinical nurse educators.
Learning Preferences and Engagement Level of Generation Z Nursing Students
Authors: Hampton Debra , Welsh Darlene , Wiggins Amanda T.
Published: June 2019

Background

Minimal information exists about the educational environment that will foster learning and engage Generation Z students.

Purpose

The purposes of this study were to identify the teaching methods that Generation Z nursing students preferred and felt were the most engaging and effective for learning and to determine their engagement level in the classroom setting.

Methods

This study employed a descriptive, cross-sectional design.

Results

Lecture with audience response clickers was the most preferred/most engaging and effective method for helping Generation Z nursing students learn, whereas assigned reading was the least preferred method. Students preferred a traditional classroom model instead of a flipped classroom. Acquiring skills was the dimension of engagement rated the highest by this group of students.

Conclusions

Innovative lectures that incorporate applicable visual images and audience involvement combined with simulation, videos, and case studies may encompass a teaching formula that will engage and foster learning for Generation Z students.
Mantle Cell Lymphoma Involving Skin
Authors: Kim Do Hwan , Medeiros L. Jeffrey , Aung Phyu P. , Young Ken H. , Miranda Roberto N. , Ok Chi Young
Published: June 2019

Mantle cell lymphoma (MCL) rarely involves the skin and the histologic and immunohistochemical features of this neoplasm at this site are under described. In this study, we report 37 skin specimens involved by MCL, representing 1.4% of total MCL biopsy specimens in our institution. The median age at time of skin involvement was 66 years (range, 36 to 85 y) and there was a male predilection of 2.7 to 1. The most frequently involved site was the skin of extremities, in 59.3% of patients, and 30 (81.1%) patients had advanced stage (III/IV) disease. Eleven (29.7%) patients presented with skin lesions as the first manifestation of MCL and 26 (70.3%) patients presented as relapse or progression of previously documented MCL and despite therapy for systemic MCL. Multiple skin lesions were more common (81.8%) in the former group whereas a solitary skin lesion was more frequent (65.4%) in the relapse/progression group (P=0.01). Thirty (81.1%) patients had skin nodules. Microscopically, the epidermis was spared with a grenz zone in all cases. A diffuse pattern of involvement was the most common architectural pattern (66.7%). In 27 (72.9%) patients, the MCL was either blastoid or pleomorphic variant, in 9 (24.3%) patients classic variant, and the disease was not further classified in 1 (2.7%) patient. The Ki-67 proliferation rate was higher in aggressive variants as compared with classic variant MCL (median 90% vs. 20%, P <0.01). In patients who presented skin lesions as a manifestation of disease relapse or progression, 16 patients initially had classic variant MCL and in 10 of the patients the MCL evolved over time (median interval: 4.1 y) to an aggressive variant at progression or relapse. The overall survival of patients with aggressive variant MCH was inferior to that of patients with classic variant MCL (median: 59 vs. 155.8 mo, P<0.05). In summary, MCL rarely involves the skin and correlates with relapse or progression of disease, aggressive morphologic features, and a poorer prognosis.
The Effects of Functional Progressive Strength and Power Training in Children With Unilateral Cerebral Palsy
Authors: Kaya Kara Ozgun , Livanelioglu Ayse , Yardımcı Bilge Nur , Soylu Abdullah Ruhi
Published: June 2019

Purpose:

The purpose of this study was to investigate the effects of a novel functional strength and power-training program on gait and gross motor function in participants with unilateral cerebral palsy.

Methods:

This 12-week trial of functional strength and power training included 30 participants with cerebral palsy, randomly assigned to the experimental or comparison group. The primary outcomes, 1-minute walk test, muscle power, and the Gross Motor Function Measure, were assessed at baseline and 12 weeks after the intervention. Secondary outcomes included dynamic balance as measured by Timed Up and Go, muscle strength, and 1-repetition maximum measures.

Results:

Significantly greater improvements were seen in the experimental group for muscle power, Gross Motor Function Measure E score, and 1-minute walk test (P < .05), as well as for dynamic balance, 1-repetition maximum, and muscle strength.

Conclusion:

Functional strength training combined with plyometric exercises improved gait and gross motor function, dynamic balance, muscle strength, and power.

Video Abstract:

For more insights from the authors, access Supplemental Digital Content 1, available at: http://links.lww.com/PPT/A254