bluuebunny/crossref_metadata_2025 huggingface dataset:
The predator odor avoidance model of post-traumatic stress disorder in rats
Authors: Albrechet-Souza Lucas , Gilpin Nicholas W.
Published: January 2019

Individuals with post-traumatic stress disorder avoid trauma-related stimuli and exhibit blunted hypothalamic–pituitary–adrenal axis response at the time of trauma. Our laboratory uses predator odor (i.e. bobcat urine) stress to divide adult Wistar rats into groups that exhibit high (avoiders) or low (nonavoiders) avoidance of a predator odor-paired context, modeling the fact that not all humans exposed to traumatic events develop psychiatric conditions. Male avoiders exhibit lower body weight gain after stress, as well as extinction-resistant avoidance that persists after a second stress exposure. These animals also show attenuated hypothalamic–pituitary–adrenal axis response to predator odor that predicts subsequent avoidance of the odor-paired context. Avoiders exhibit unique brain activation profiles relative to nonavoiders and controls (as measured by Fos immunoreactivity), and higher corticotropin-releasing factor levels in multiple brain regions. Furthermore, avoider rats exhibit escalated and compulsive-like alcohol self-administration after traumatic stress. Here, we review the predator odor avoidance model of post-traumatic stress disorder and its utility for tracking behavior and measuring biological outcomes predicted by avoidance. The major strengths of this model are (i) etiological validity with exposure to a single intense stressor, (ii) established approach distinguishing individual differences in stress reactivity, and (iii) robust behavioral and biological phenotypes during and after trauma.
Stress reactivity after traumatic brain injury: implications for comorbid post-traumatic stress disorder
Authors: Hoffman Ann N. , Taylor Anna N.
Published: January 2019

Most people have or will experience traumatic stress at some time over the lifespan, but only a subset of traumatized individuals develop post-traumatic stress disorder (PTSD). Clinical research supports high rates of traumatic brain injury (TBI)–PTSD comorbidity and demonstrates TBI as a significant predictor of the development of PTSD. Biological factors impacted following brain injury that may contribute to increased PTSD risk are unknown. Heightened stress reactivity and dysregulated hypothalamic–pituitary–adrenal (HPA) axis function are common to both TBI and PTSD, and affect amygdalar structure and function, which is implicated in PTSD. In this review, we summarize a growing body of literature that shows HPA axis dysregulation, as well as enhanced fear and amygdalar function after TBI. We present the hypothesis that altered stress reactivity as a result of brain injury impacts the amygdala and defense systems to be vulnerable to increased fear and PTSD development from traumatic stress. Identifying biological mechanisms that underlie this vulnerability, such as dysregulated HPA axis function, may lead to better targeted treatments and preventive measures to support psychological health after TBI.
Ganciclovir Therapeutic Drug Monitoring: A Case Series
Authors: Märtson Anne-Grete , Touw Daan , Damman Kevin , Bakker Martijn , Oude Lansink-Hartgring Annemieke , van der Werf Tjip , Knoester Marjolein , Alffenaar Jan-Willem C.
Published: January 2019

This article presents 3 cases of immunocompromised patients for whom therapeutic drug monitoring of ganciclovir in combination with cytomegalovirus viral load measurement was used to guide treatment. The first patient is diagnosed with thymoma A, the second is a heart transplant recipient, and the third is an HIV-positive patient. These patients were all diagnosed with cytomegalovirus and treated with ganciclovir. Our case studies illustrate how therapeutic drug monitoring–guided dosing can be helpful in the management of these complex cases.
Keratometric, Pachymetric, and Surface Elevation Characterization of Corneas With Fuchs Endothelial Corneal Dystrophy Treated With DMEK
Authors: Arnalich-Montiel Francisco , Mingo-Botín David , Diaz-Montealegre Ana
Published: January 2019

Purpose:

To characterize pachymetric, keratometric, and surface elevation parameters in pseudophakic eyes with Fuchs dystrophy that underwent Descemet membrane endothelial keratoplasty (DMEK) and to compare these characteristics with those in normal pseudophakic eyes.

Methods:

Postoperative corneal tomography with a median follow-up of 20 months was evaluated using the Pentacam tomographer on 46 DMEK eyes. Results were compared with data from an age-matched cohort of 46 normal eyes. Parameters included curvature analysis, keratometry values, corneal thickness (CT), pachymetric progression index, Ambrósio relational thickness, posterior elevation, and D-index values. Bonferroni correction was used for multiple comparisons.

Results:

CT at the apex (mean difference 41 μm; 95% confidence interval 28–54) and CT at the thinnest point (46 μm; 33–60) were statistically significantly lower in the DMEK group (P < 0.001), whereas pachymetric progression index average (0.47; 0.32–0.62), Ambrósio relational thickness maximum (172; 126–228), IHD (0.096; 0.005–0.014), and the global D-index (1.03; 0.51–1.56) were significantly higher in eyes with DMEK (P < 0.001). The mean CT along the vertical and horizontal meridians was significantly lower in the DMEK group within the central 5 mm. A quarter and one half of the DMEK eyes had a CT of less than 500 μm at the apex or at the thinnest point, respectively.

Conclusions:

Resolution of corneal edema after DMEK was associated with a thinner-than-normal central cornea, steeper pachymetric progression from the thinnest point to the periphery, and some high-end outliers for posterior elevation values. Caution should be exerted in planning corneal refractive surgery for residual refractive errors.
Small-Incision Femtosecond Laser–Assisted Intracorneal Concave Lenticule Implantation in Patients With Keratoconus
Authors: Jin He , He Miao , Liu Hongshan , Zhong Xiaoying , Wu Junshu , Liu Liangping , Ding Hui , Zhang Chi , Zhong Xingwu
Published: January 2019

Purpose:

To evaluate the feasibility and efficacy of small-incision femtosecond laser–assisted intracorneal concave lenticule implantation (SFII) and penetrating keratoplasty (PKP) in patients with progressive keratoconus.

Methods:

All the patients were clinically diagnosed with progressive keratoconus. Twenty patients underwent PKP (PKP group), and 11 patients underwent SFII (SFII group). Visual acuity, intraocular pressure, corneal topography, corneal visualization Scheimpflug technology, anterior segment optical coherence tomography, and in vivo confocal microscopy were analyzed.

Results:

Vision improved at 3 months postoperatively in the SFII group. In the PKP group, corrected distance visual acuity improved 1 week after surgery. Corneal topography showed a statistically significant decrease in the anterior K1 and K2. Corneal visualization Scheimpflug technology showed that changes in the biomechanical parameters of the SFII group were also statistically different from those of the PKP group. All the grafts from both groups were clearly visible by anterior segment optical coherence tomography observation. The central corneal thickness of both groups was stable during the 24-month study period. In vivo confocal microscopy showed a few dendritic cells in the subepithelial region in the SFII group. At 3 months after surgery, many dendritic cells and inflammatory cells were observed in the basal epithelium and stroma in the PKP group.

Conclusions:

Both SFII and PKP surgical procedures resulted in a stable corneal volume and improved visual acuity in this long-term study. SFII was less invasive and more efficient compared with PKP.
Postoperative Complications of Ab Interno Gelatin Microstent
Authors: Rooney David M. , Shadid Husam R. , Siegel Les I. , Watnick Richard L. , Lesser G. Robert , Obertynski Thomas , Siegel Marc J. , Citron Matthew E. , Hasbrook Madeline , Siegel Michael J.
Published: January 2019

Purpose:

To report 4 previously undescribed postoperative complications in 4 cases of ab interno XEN45 Gel Stent (XEN) implantation following uncomplicated surgeries.

Patients and Methods:

A total of 51 consecutive XEN implantations performed between July 1, 2017 and April 30, 2018 were reviewed. All cases were performed by 7 experienced glaucoma surgeons affiliated with the William Beaumont Hospital, Department of Ophthalmology. Cases with postoperative complications were identified, and a literature review was performed on PubMed.gov between April 5, 2018 and June 2, 2018 to identify previously unreported XEN complications.

Results:

Case 1 consisted of an 86-year-old woman who suffered a suprachoroidal hemorrhage and associated rhegmatogenous retinal detachment following XEN implantation. One month after sclerotomy drainage and pars plana vitrectomy repair, an amputated XEN was found to have eroded through the conjunctiva. Case 2 consisted of a 68-year-old man with persistent elevated intraocular pressure due to recurrent Tenon’s capsule fibrosis who developed complete XEN retraction into the subconjunctival space. Cases 3 and 4 consisted of a 68-year-old man and a 78-year-old woman who developed occlusion of the microstent’s internal ostium by a partially detached Descemet’s membrane. Case 3 maintained normal intraocular pressure on timolol, whereas case 4 resulted in bleb failure, despite Nd:YAG laser lysis of the occluded XEN internal ostium.

Conclusions:

Although the XEN is a promising new surgical option for the management of primary open-angle glaucoma, it can present unique postoperative challenges that are still being elucidated. Timely intervention or prevention of these complications can be improved by early surgeon recognition and effective communication with comanaging ophthalmologists.
A Comparison of Deep Sclerectomy Trainer Versus Trainee Outcomes
Authors: Karaconji Tanya , Mercieca Karl , Romera Pau , McNaught Andrew , Anand Nitin
Published: January 2019

Purpose:

The aim of this study was to compare the results of deep sclerectomy (DS) and combined deep sclerectomy with phacoemulsification (phaco-DS) performed by clinical fellows with those by an experienced glaucoma surgeon and DS trainer.

Patients and Methods:

This is a retrospective nonrandomized study of 266 eyes of 226 consecutive patients who had DS or phaco-DS between March 2014 and December 2016 which were included from a database of all glaucoma surgery performed in our department. A minimum of 9 months follow-up was required. The cases were recorded as to whether a fellow or consultant performed the entire procedure. Overall, 114 surgeries were performed by the consultant and 164 surgeries were performed by the fellow, in which 91 cases received no assistance from the consultant. Intraocular pressure (IOP) success criteria were: (A) IOP<22 mm Hg and/or 20% decrease from baseline off any glaucoma medications and (B) IOP<16 mm Hg and/or 30% drop from baseline off any glaucoma medications.

Results:

No statistically significant difference was noted by any criteria (P<0.05) between the 2 groups. The Kaplan-Meir IOP success rates at 2 years with criteria B (IOP<16 mm Hg without medications) were 64% for consultant, 76% for independent surgeries done by a fellow and 72% for surgeries with assistance from the consultant trainer (P=0.15). There were no significant differences between measured IOPs at any time after surgery. Intraoperative perforation of trabeculo-Descemet membrane was noted in 4 cases (3.5%) done by the consultant and 12 cases (7.3%) performed by fellows (Fisher exact P=0.19).

Conclusions:

IOP outcomes of DS and phaco-DS were not adversely affected if fellows performed surgery, whether under supervision or independently.
Spinal somatostatin-positive interneurons transmit chemical itch
Authors: Fatima Mahar , Ren Xiangyu , Pan Haili , Slade Hannah F.E. , Asmar Alyssa J. , Xiong Cynthia M. , Shi Angela , Xiong Ailin E. , Wang Lijing , Duan Bo
Published: January 2019

Recent studies have made significant progress in identifying distinct populations of peripheral neurons involved in itch transmission, whereas the cellular identity of spinal interneurons that contribute to itch processing is still a debate. Combining genetic and pharmacological ablation of spinal excitatory neuronal subtypes and behavioral assays, we demonstrate that spinal somatostatin-positive (SOM+) excitatory interneurons transmit pruritic sensation. We found that the ablation of spinal SOM+/Lbx1+ (SOMLbx1) neurons caused significant attenuation of scratching responses evoked by various chemical pruritogens (chemical itch). In an attempt to identify substrates of spinal itch neural circuit, we observed that spinal SOM+ neurons partially overlapped with neurons expressing natriuretic peptide receptor A (Npra), the receptor of peripheral itch transmitter B-type natriuretic peptide. Spinal SOM+ neurons, however, did not show any overlap with itch transmission neurons expressing gastrin-releasing peptide receptor in the dorsal spinal cord, and the gastrin-releasing peptide–triggered scratching responses were intact after ablating spinal SOM+ neurons. Dual ablation of SOMLbx1 and Npra+ neurons in the spinal cord reduced chemical itch responses to a greater extent than ablation of SOMLbx1 or Npra+ neurons alone, suggesting the existence of parallel spinal pathways transmitting chemical itch. Furthermore, we showed that SOM peptide modulated itch processing through disinhibition of somatostatin receptor 2A–positive inhibitory interneuron. Together, our findings reveal a novel spinal mechanism for sensory encoding of itch perception.
The serum protease network—one key to understand complex regional pain syndrome pathophysiology
Authors: König Simone , Bayer Malte , Dimova Violeta , Herrnberger Myriam , Escolano-Lozano Fabiola , Bednarik Josef , Vlckova Eva , Rittner Heike , Schlereth Tanja , Birklein Frank
Published: January 2019

Complex regional pain syndrome (CRPS) develops after fracture. The acute CRPS phenotype resembles exaggerated inflammation, which is explained by local and systemic activation of a proinflammatory network including peptides and cytokines. Epidemiologic data suggest that inactivation of the peptidase angiotensin-converting enzyme in patients treated for hypertension increases the odds to develop CRPS. This hint leads us to investigate the serum protease network activity in patients with CRPS vs respective controls. For this purpose, we developed a dabsyl-bradykinin (DBK)-based assay and used it to investigate patients with CRPS, as well as healthy and pain (painful diabetic neuropathy [dPNP]) controls. The major result is that the degradation of DBK to fragments 1-8 and 1-5 in healthy control and dPNP is shifted to higher values for DBK1-8 and lower values for DBK1-5 at 1 hour of incubation in patients with CRPS. Using this novel reporter peptide assay, we have been able to show that the resolving protease network for mediators such as BK might be different in patients with CRPS; having a look at the clinical signs, which resemble inflammation, this resolving protease network is probably less effective in CRPS.
Milk Thistle Treatment for Children and Adults with Trichotillomania
Authors: Grant Jon E. , Redden Sarah A. , Chamberlain Samuel R.
Published: January 2019

Background

Data on the pharmacological treatment of trichotillomania are limited. Milk thistle has antioxidant properties and showed promise in trichotillomania in a prior case report. The goal of the current study was to determine the efficacy and tolerability of silymarin in children and adults with trichotillomania.

Methods

Twenty individuals (19 [95.0%] women; 16 adults; mean age, 27.9 [11.5] years) with trichotillomania entered a 12-week, double-blind, placebo-controlled crossover study (6 weeks of milk thistle and 6 weeks of placebo with a 1-week wash-out in between). Dosing of milk thistle ranged from 150 mg twice a day to 300 mg twice a day. Subjects were assessed with the National Institute of Mental Health Trichotillomania Severity Scale (primary outcome), the Massachusetts General Hospital Hair Pulling Scale, Clinical Global Impression scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using linear mixed models with a random intercept for subject and t tests.

Results

There were no statistically significant treatment type-by-time interactions for the main outcome measure, but significant effects were seen for secondary measures (eg, time spent pulling per day for the past week). From baseline to week 6, there was a significant decrease in Clinical Global Impression severity for the milk thistle group but not in the placebo group.

Conclusions

This trial failed to show that milk thistle was more effective than placebo on the main outcome measure, but milk thistle did demonstrate significant improvements on select secondary outcome measures. These findings may shed light on important neurochemical targets worthy of future investigation.
A Psychometric Analysis of CIWA-Ar in Acutely Ill and Injured Hospitalized Patients
Authors: Higgins Jacob , Bugajski Andrew A. , Church Dirk , Oyler Doug , Parli Sara , Halcomb Paula , Fryman Lisa , Bernard Andrew C.
Published: January 2019

Alcohol withdrawal syndrome (AWS) manifests after alcohol-dependent individuals suddenly cease alcohol consumption. Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) is a widely used tool to assess and guide treatment of AWS. CIWA-Ar was developed in voluntarily detoxification centers, and the reliability and validity of CIWA-Ar have been minimally evaluated in hospitalized patients. We performed a retrospective chart review of 479 cases of screening and treatment of AWS using CIWA-Ar, of which 118 were admitted to a trauma/orthopedic (T/O) service and 361 to an internal medicine (IM) service. Exploratory factor analyses with varimax rotation were applied for each population, and reliability testing was performed on the determined subscales. Exploratory factor analyses yielded 2 unique structures, each explaining 56% of the variance of CIWA-Ar. The IM group had a 3-factor structure with the Physical Disturbances (23%), Anxiety (19%), and Confusion (14%) subscales. The T/O group had a 2-factor structure with the Neurological Disturbances (36%) and Physical Disturbances (20%) subscales. Overall, Cronbach's alphas were acceptable (0.74 and 0.82 for IM and T/O, respectively); however, Cronbach's alphas for the IM subscales were 0.66 and 0.69 for physical disturbances and anxiety, respectively. Cronbach's alpha for the Confusion subscale was not calculated because only 1 scale item loaded. The subscales of the T/O factor structure yielded Cronbach's alphas of 0.81 for neurological disturbances and 0.62 for physical disturbances. Our analyses did not support the reliability or validity of CIWA-Ar in acutely ill or injured patients, warranting further investigation and tool development for AWS management in the hospital setting.
Increasing Referrals to a Community Paramedicine Fall Prevention Program Through Implementation of a Daily Management System
Authors: Ontengco Julianne B.
Published: January 2019

This quality improvement project was undertaken to improve trauma service referral compliance to an existing home-based elderly fall prevention program through the implementation of a daily management system (DMS). Operational excellence, a hospital-wide initiative, provided the foundation for improvement efforts. This initiative went through a series of 5 plan, do, study, and act (PDSA) cycles and demonstrated significant improvement in referrals from 0% to 100%. Compliance with referrals after the retirement of the key performance indicator remained high at 95.5%. Results from this project provided support for the framework set forth in DMS and PDSA improvement methodologies as a feasible option to implement quality and process improvement projects. Further study in this area is warranted.
Evaluation of Functional Outcomes for Adult Patients After Distal Radius Fracture Treated With Volar Plate Fixation Versus Nonsurgical Care
Authors: Heidgerd Rachel , Morgan Jacqueline , Schentrup Denise
Published: January 2019

Distal radius fractures are one of the most common fractures patients experience. Although there are a variety of treatments, there is a lack of standardization as it relates to treatment of such fractures. The purpose of this study was to compare treatment outcomes between surgical and nonsurgical care of distal radius fractures to inform evidence-based guidelines for the management of distal radius fractures. A retrospective chart analysis was performed in the public university hospital setting on a sample of 60 patient health records divided equally into those treated surgically and nonsurgically. Data were analyzed related to specific variables in those patients who met specific inclusion/exclusion criteria. Analysis identified that patients treated surgically experienced improved healing and return of range of motion. There was no statistical significance comparing pain in both the surgical and nonsurgical groups. Diabetes and smoking were found to have a negative impact on healing and clinical outcomes. Despite limitations, this pilot project serves as a baseline for future research regarding best practices in the treatment of distal radius fractures. It also demonstrates the negative impact that diabetes and smoking can have on clinical outcomes.
Cohorting Trauma Patients in a Medical/Surgical Unit at a Level I Pediatric Trauma Center to Enhance Interdisciplinary Collaboration and Documentation
Authors: Meyer Loreen K. , Nanassy Autumn D. , Lavella Heather , Arthur L. Grier , Grewal Harsh
Published: January 2019

Medical errors are a significant issue in health care that may be avoided through enhanced communication and documentation. This study examines interdisciplinary communication and compliance with trauma standards of care demonstrated through following the implementation of cohorting trauma patients to one medical/surgical unit and instituting daily interdisciplinary trauma patient rounds. Potential benefits include enhanced communication, improved nursing satisfaction, and increased compliance with trauma standards of care demonstrated through documentation, which the literature suggests improves quality of care. Pre- and postcohorting surveys related to safety attitudes, comfort with caring for trauma patients, and the efficacy of cohorting were administered to the nursing staff. As a marker for increased compliance with trauma standards of care, medical records were reviewed for completion of substance abuse screening upon admission and Functional Independence Measure screening at discharge. The results were compared after the cohorting initiative with 2 years prior. The rate of compliance with substance abuse screening increased from an average of 62.5% in 2015 and 2016 to 84% in 2017. Functional Independence Measure compliance increased from an average of 72.5% in 2015 and 2016 to 94% in 2017 following the cohorting intervention. Nursing perceptions of teamwork, safety climate, and staff support significantly improved (p < .05) from pre- to postcohorting surveys. Improvements were noted in comfort with performing tasks associated with caring for trauma patients but were not statistically significant. Cohorting trauma patients to one medical/surgical unit resulted in positive perceptions of professional relationships, improved communication, and compliance with trauma standards of care for documentation.
Fostering promotion and protection of the professional nurse practitioner role: A call to action
Authors: Berg Judith A. , Ruppert Susan D.
Published: January 2019

The professional obligations to protect and promote nursing professional roles stem from the American Nurses Association Code of Ethics. Nurturing new generations of NPs to assume leadership role is foundational to succession planning and is critical to assuring NPs’ continued contributions to health care. Making professional role development a priority at various points in educational programs, modeling ways to contribute to the profession, and encouraging professional organization membership are a few of the suggestions presented for the academic environment. In clinical settings, NP meetings are opportunities to engage NPs in legislative and policy issues important to practice. Attaining employee benefits, such as conference attendance, can promote commitment; and precepting NP students forges professional bonds. Present and future generations of NPs must assume responsibility for protecting and promoting the role. Many threats to NPs’ scope of practice and other professional conundrums are ongoing. Instilling the values of protecting and promoting the NP role in students and colleagues and then identifying leaders to direct these efforts are essential to succession planning.
Electric-Acoustic Stimulation After Reimplantation: Hearing Preservation and Speech Perception
Authors: Thompson Nicholas J. , Dillon Margaret T. , Bucker Andrea L. , King English R. , Pillsbury Harold C. , Brown Kevin D.
Published: January 2019

Objective:

Hearing preservation after cochlear implantation allows for fitting of acoustic and cochlear implant technologies in the same ear, known as Electric-Acoustic Stimulation (EAS). Cochlear implant recipients with EAS who experience an internal device failure face the additional risk of residual hearing loss during reimplantation. This report reviews the case of an EAS recipient with long-term hearing preservation and significant benefit who experienced a device failure and underwent cochlear reimplantation.

Patient:

Case study who presented with an internal device failure after nearly 10 years of hearing preservation and significant benefit with an EAS device.

Intervention:

Reimplantation with hearing preservation electrode array.

Main Outcome Measures:

Unaided residual hearing and aided speech perception with an EAS device using CNC words in quiet and CUNY sentences in noise.

Results:

Low-frequency thresholds were similar when comparing residual hearing pre- and post-reimplantation. The patient does not use the acoustic portion of the EAS device due to normal low-frequency hearing sensitivity—even after two cochlear implantation procedures. At the 3-month follow-up interval, the patient demonstrated restoration of aided speech perception performance with the EAS device.

Conclusions:

Hearing preservation can be maintained with long-term use of EAS devices. Those with preserved low-frequency hearing who experience a device failure may maintain hearing preservation after reimplantation. Normal low-frequency hearing thresholds were maintained in the present case, and the patient continued to listen with the EAS device without the acoustic component. EAS recipients may experience rapid restoration in speech perception after reimplantation in the presence of hearing preservation.
Linked-read Sequencing Analysis Reveals Tumor-specific Genome Variation Landscapes in Neurofibromatosis Type 2 (NF2) Patients
Authors: Roberts Daniel S. , Maurya Rahul , Takemon Yuka , Vitte Jeremie , Gong Liang , Zhao Juanjuan , Wong Chee-Hong , Slattery William , Peng Kevin A. , Lekovic Gregory , Schwartz Marc S. , Bulsara Ketan , Ngan Chew Yee , Giovannini Marco , Wei Chia-Lin
Published: January 2019

Hypothesis:

We hypothesize that genomic variants including deletions, insertions, inversions, and tandem duplications beyond the changes in tumor suppressor NF2 gene affect gene expression of tumor-specific pathways in vestibular schwannomas (VS) patients with Neurofibromatosis type 2 (NF2), thus contributing to their clinical behavior.

Background:

Genomic variation could reconfigure transcription in NF2 transformation process. Therefore, genome-wide high-resolution characterization of structural variants (SV) landscapes in NF2 tumors can expand our understanding of the genes regulating the clinical phenotypes in NF2-associated VS.

Methods:

We performed whole-genome haplotype-specific structural variation analysis using synthetic linked reads generated through microfluidics-based barcoding of high molecular weight DNA followed by high-coverage Illumina paired-end whole-genome sequencing from 10 patients’ tumors of different growth rates and their matching blood samples.

Results:

NF2 tumor-specific deletions and large SVs were detected and can be classified based on their association with tumor growth rates. Through detailed annotation of these mutations, we uncover common alleles affected by these deletions and large SVs that can be associated with signaling pathways implicated in cell proliferation and tumorigenesis.

Conclusion:

The genomic variation landscape of NF2-related VS was investigated through whole-genome linked-read sequencing. Large SVs, in addition to deletions, were identified and may serve as modulators of clinical behavior.
Intraoperative Evaluation of Cochlear Implant Electrodes Using Mobile Cone-Beam Computed Tomography
Authors: Yamamoto Norio , Okano Takayuki , Yamazaki Hiroshi , Hiraumi Harukazu , Sakamoto Tatsunori , Ito Juichi , Omori Koichi
Published: January 2019

Objective:

To evaluate the electrode status during cochlear implantation (CI) using mobile cone-beam CT (mCBCT).

Study Design:

Retrospective case review.

Setting:

Tertiary referral hospital.

Patients:

Fifty-seven patients (7 bilateral surgeries, 64 ears) who underwent CI and who received intraoperative mCBCT imaging.

Intervention:

CI and CBCT during surgery.

Main Outcome Measure:

Electrode location and angular insertion depth determined by intraoperative mCBCT images.

Results:

There were six cases with cochlear malformation where intraoperative mCBCT was useful to confirm electrode location. Of 58 ears with a normal cochlear morphology, perimodiolar, straight, and mid-scalar electrodes were used in 30 (cochleostomy; 14 advance off-stylet technique cases), 27 (26 round window [RW] insertion, 1 extended round window [ERW] insertion), and 1 (RW insertion) ears, respectively. Complete scala-tympani (ST) insertion was achieved in 35 ears (14 cochleostomy, 21 RW or ERW insertion). The complete ST-insertion rate was significantly higher with RW or ERW insertion than that for cochleostomy insertion (p = 0.03), although cochleostomy insertion using the advanced off-stylet technique had a similar rate to RW or ERW insertion. The angular insertion depth values (average ± standard deviation) for perimodiolar electrodes (354.4 ± 29.44 degrees) were significantly smaller than those for Flex24 (464.8 ± 43.09 degrees) and Flex28 (518.2 ± 61.91 degrees) electrodes (p < 0.05).

Conclusions:

Evaluation of CI electrodes using intraoperative mCBCT was comparable to that with fan-beam CT or c-arm-based CBCT. Considering the low radiation dose of mCBCT and its availability in any operation room, mCBCT is the better modality for evaluating cochlear implant electrode arrays.
Facial Rehabilitation as Noninvasive Treatment for Chronic Facial Nerve Paralysis
Authors: Karp Emily , Waselchuk Emily , Landis Cynthia , Fahnhorst Jill , Lindgren Bruce , Lyford-Pike Sofia
Published: January 2019

Objectives:

This study aims to evaluate the effectiveness of facial rehabilitation (FR) in patients with chronic facial nerve paralysis (FNP) and describe factors that predict improved facial nerve function after FR in this patient population.

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Around 241 patients were referred to a university hospital facial rehabilitation (FR) program for FNP between 1995 and 2016. Seventy-six patients met criteria, defined as diagnosis of FNP ≥12 months prior to initiation of FR.

Interventions:

Each received at least two sessions of directed FR by a single therapist. Techniques employed: neuromuscular retraining, stretching/massage, and active exercise.

Main Outcomes:

Variables affecting outcomes were analyzed to determine association with success of FR as measured by improvement in Facial Grading System (FGS) scale.

Results:

Onset of FNP to initiation of FR ranged 12 to 384 months (mean latency = 64.7 months). All patients, age 20 to 89, showed improvement in FGS after FR (mean, 16.54 points, SD 9.35). Positive predictors of FGS improvement after therapy (p-values < 0.05): increased the number of therapy sessions, right side of face being treated for FNP, lower starting FGS score. When controlling for these important variables, time from diagnosis to initiation of therapy was not significantly associated with improvement in FGS score.

Conclusion:

Facial rehabilitation was associated with improved FGS score regardless of patient age, gender, or latency to facial rehabilitation. As a noninvasive treatment option with positive outcomes, it should be offered to patients with facial nerve paralysis regardless of chronicity.
Dual-Propeller Cavopulmonary Pump for Assisting Patients with Hypoplastic Right Ventricle
Authors: Jagani Jakin N. , Untaroiu Alexandrina , Kalaria Amit D.
Published: January 2019

Various congenital heart defects (CHDs) are characterized by the existence of a single functional ventricle, which perfuses both the systemic and pulmonary circulation. A three-stage palliation procedure, including the final Fontan completion, is often adopted by surgeons to treat patients with such CHDs. The completion Fontan involves the creation of a total cavopulmonary connection (TCPC), commonly accomplished with an extracardiac conduit. This TCPC results in nonphysiologic flow conditions that can lead to systemic venous hypertension, reduced cardiac output, and ultimately the need for heart transplantation. A modest pressure rise of 5–6 mm Hg could correct the abnormal flow dynamics in these patients. To achieve this, we propose a novel conceptual design of a dual-propeller pump inside a flared TCPC. The TCPC dual-propeller conjunction was examined for hydraulic performance, blood flow pattern, and potential for hemolysis inside the TCPC using computational fluid dynamics (CFD). The effect of axial distance between the two propellers on the blood flow interference and energy loss was studied to determine the optimal separation distance. Both the inferior vena cava (IVC) and superior vena cava (SVC) propellers provided a pressure rise of 1–20 mm Hg at flow rates ranging from 0.4 to 7 lpm while rotating at speeds of 6,000–12,000 rpm. Larger separation distance provided favorable performance in terms of flow interference, energy loss, and blood damage potential. The ability of a dual-propeller micropump to provide the required pressure rise would help to augment the cavopulmonary flow and mimic flows seen in normal biventricular circulation.
Risk Assessment in Patients with a Left Ventricular Assist Device Across INTERMACS Profiles Using Bayesian Analysis
Authors: Kanwar Manreet K. , Lohmueller Lisa C. , Teuteberg Jeffrey , Kormos Robert L. , Rogers Joseph G. , Benza Raymond L. , Lindenfeld Joann , McIlvennan Colleen , Bailey Stephen H. , Murali Srinivas , Antaki James F.
Published: January 2019

Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types, and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012 to 2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort), we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3, and 12 months post implant according to disease severity (IM profiles), device type (axial versus centrifugal) and strategy (bridge to transplantation or destination therapy). Fifteen percentage (n = 308) were categorized as IM profile 1, 36% (n = 752) as profile 2, 33% (n = 672) as profile 3, and 15% (n = 311) as profile 4–7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long-term (1 year) mortality for patients with severe HF (Profiles 1–3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC, 0.68–0.74), as well as bridge to transplantation or destination therapy indication (AUC, 0.66–0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models. Bayesian algorithms allow for risk stratification after LVAD implantation across different IM profiles, device types, and implant strategies.
Clinical Courses of HeartMate II Left Ventricular Assist Device Thrombosis
Authors: Kittipibul Veraprapas , Xanthopoulos Andrew , Hurst Thomas E. , Fukamachi Kiyotaka , Blackstone Eugene H. , Soltesz Edward , Starling Randall C.
Published: January 2019

We observed different temporal patterns of HeartMate II left ventricular assist device (LVAD) thrombosis regarding clinical manifestations and lactate dehydrogenase (LDH) trends. We propose nomenclature for classification of LVAD thrombosis and compare patient characteristics and outcomes in each pattern of LVAD thrombosis. We reviewed electronic medical records of 362 consecutive HeartMate II devices implanted at Cleveland Clinic from October 2008 to July 2014. We categorized clinical courses of confirmed device thrombosis based on clinical manifestations and LDH patterns. Patients’ characteristics, clinical variables, and outcomes were collected for comparison. From a total of 19 confirmed device thromboses, we categorized the patterns of thrombosis into three distinctive types; abrupt thrombosis (Type 1), subacute thrombosis (Type 2), and asymptomatic hemolysis (Type 3). Abrupt thrombosis (Type 1) tended to be the most morbid clinical course with acute-onset thrombosis at 56.5 (interquartile range: 44–71) days, all New York Heart Association functional class III or IV at presentation. Death and need for surgical intervention were not different in each pattern. Asymptomatic hemolysis had unique comorbidities of preexisting cardiac thrombi and preoperative bacteremia. Confirmed LVAD thrombosis has different patterns of clinical presentation and each pattern of thrombosis has unique characteristics and clinical manifestations.
Effect of Heart Rate Reserve on Exercise Capacity in Patients Treated with a Continuous Left Ventricular Assist Device
Authors: Mirza Kiran K. , Cuomo Kimberly , Jung Mette H. , Russell Stuart D. , Gustafsson Finn
Published: January 2019

We hypothesized that an inadequate increase in heart rate (HR) during exercise was associated with low peak oxygen uptake (VO2 peak) seen in left ventricular assist device (LVAD) recipients and aimed to analyze the potential relation between HR and VO2 peak and use of drugs with negative chronotropic effect. Sixty-eight LVAD recipients (44 Heartmate 2 and 24 HeartWare Ventricular Assist Device) with support duration >1 month and a VO2 peak were included from two centers. Patients were 57 ± 13 years at time of VO2 peak and LVAD support duration was 483 ± 545 days. Peak oxygen uptake was 12 ± 4 ml/kg/min (40% ± 13% of predicted). Heart rate reserve (HRR = maximal HR − resting HR) was 59 ± 22 min−
1 (75% ± 15% of predicted for age, %HRR) and was significantly associated with VO2 peak (r = 0.244, p = 0.045). Predicted heart rate reserve was associated with %Predicted VO2 peak (P = 0.011). Chronotropic incompetence (CI) was observed in 44% and VO2 peak was clearly lower in patients with CI (10 ± 2.7 vs. 13 ± 4.6 ml/kg/min, p = 0.005). Beta-blockers (BB) were prescribed to 85% and adjusting for being on target BB-dose did not affect the correlation between %predicted VO2 peak and %HRR (r = 0.33, p = 0.024). In conclusion, almost half of LVAD recipients suffer from CI which is associated with lower VO2 peak. This relation did not seem to be affected by BB therapy.
The evolution of genetic-based risk scores for lipids and cardiovascular disease
Authors: Dron Jacqueline S. , Hegele Robert A.
Published: January 2019

Purpose of review

With improved next-generation sequencing technology, open-access genetic databases and increased awareness of complex trait genetics, we are entering a new era of risk assessment in which genetic-based risk scores (GRSs) will play a clinical role. We review the concepts underlying polygenic models of disease susceptibility and challenges in clinical implementation.

Recent findings

Polygenic risk scores are currently used in genetic research on dyslipidemias and cardiovascular disease (CVD). Although the underlying principles for constructing polygenic scores for lipids are established, the lack of consensus on which score to use is indicated by the large number — about 50 — that have been published. Recently, large-scale polygenic scores for CVD appear to afford superior risk prediction compared to small-scale scores. Despite the potential benefits of GRSs, certain biases towards ethnicity and sex need to be worked through.

We are on the verge of clinical application of GRSs to provide incremental information on dyslipidemia and CVD risk above and beyond traditional clinical variables. Additional work is required to develop a consensus of how such scores will be constructed and measured in a validated manner, as well as clinical indications for their use.
Prophylactic human papilloma virus vaccination in head and neck: indications and future perspectives
Authors: Wierzbicka Małgorzata , Berkhof Johannes Hans , Dikkers Frederik G.
Published: January 2019

Purpose of review

To gain the evidence-based knowledge concerning the efficacy of HPV vaccination for oropharyngeal sites and to highlight the trials and strategies for vaccine administration in HPV-dependent head and neck diseases.

Recent findings

Vaccination can be provided in two injections. There is increasing anecdotal evidence that therapeutic vaccination is effective in treatment of recurrent respiratory papillomatosis.

The availability and broadening spectrum of HPV vaccines make possible the prevention of cervical and other HPV-dependent diseases. Vaccination is now included in the national immunization programs of most industrial countries and will be used, it is hoped, in developing countries within the next few years. In developing countries, few women are screened for cervical precancerous lesions, making immunization even more important. In affluent countries and matured societies, with high coverage of cervical screening, the focus of interest will shift to other HPV-related diseases. The HPV vaccination is effective in preventing oral infection with types targeted by the vaccines.
The devil is in the detail: current management of perioperative surgical complications after liver transplantation
Authors: Patel Priyal , DiNorcia Joseph
Published: January 2019

Purpose of review

Despite advances in the field, perioperative morbidity is common after liver transplantation. This review examines the current literature to provide up-to-date management of common surgical complications associated with liver transplantation.

Recent findings

Research focuses on problems with anastomoses of the vena cava, portal vein, hepatic artery, and bile ducts. Interventional endoscopic and radiological techniques are used more frequently to avoid reoperation.

Advances in the management of perioperative surgical complications have focused on minimally invasive measures that successfully treat technical problems with implantation of liver allografts from both living and deceased donors.
Donor-specific antibody management in intestine transplantation: hope for improving the long-term durability of the intestine allograft?
Authors: Hawksworth Jason S. , Matsumoto Cal S.
Published: January 2019

Purpose of review

In this review, we appraise the current status of donor-specific antibody (DSA) monitoring and treatment in the literature and highlight the current challenges in DSA management for the intestine transplant community.

Recent findings

Sensitizing events are common in patients referred for intestinal transplant, as these patients universally are repeatedly exposed to immune activation and inflammatory events. Both preformed and de novo DSA have been shown to increase rejection and graft loss in intestine recipients. Avoidance of preformed DSA with the use of virtual crossmatch (VXM) and antibody monitoring protocols to detect and treat de novo DSA may improve intestine transplant outcomes. There is no consensus on the clinical and pathologic criteria that are required to diagnose antibody-mediated rejection (AMR) in the intestine recipient. Therefore, many clinicians treat AMR based on the coincidence of DSA and acute biopsy-proven rejection. Inclusion of the liver in the intestine allograft appears to be immunologically protective in the setting of DSA with improved outcomes and a higher rate of preformed DSA clearance. Critically, DSA has been linked to chronic rejection and poor long-term outcomes in the intestine recipient.

On the basis of increasing evidence in the intestine transplant literature, it appears that avoidance of preformed DSA and aggressive monitoring and treatment of de novo DSA is a key to long-term survival following intestine transplantation.
Menin Upregulates FOXO1 Protein Stability by Repressing Skp2-Mediated Degradation in β Cells
Authors: Jiang Zongzhe , Xing Bowen , Feng Zijie , Ma Jian , Ma Xiaosong , Hua Xianxin
Published: January 2019

Objectives

Menin, a chromatin binding protein, interacts with various epigenetic regulators to regulate gene transcription, whereas forkhead box protein O1 (FOXO1) is a transcription factor that can be regulated by multiple signaling pathways. Both menin and FOXO1 are crucial regulators of β-cell function and metabolism; however, whether or how they interplay to regulate β cells is not clear.

Methods

To examine whether menin affects expression of FOXO1, we ectopically expressed menin complementary DNA and small hairpin RNA targeting menin via a retroviral vector in INS-1 cells. Western blotting was used to analyze protein levels.

Results

Our current work shows that menin increases the expression of FOXO1. Menin stabilizes FOXO1 protein level in INS-1 cells, as shown by increased half-life of FOXO1 by menin expression. Moreover, menin represses ubiquitination of FOXO1 protein and AKT phosphorylation, We found that menin stabilizes FOXO1 by repressing FOXO1 degradation mediated by S-phase kinase-associated protein 2 (Skp2), an E3 ubiquitin ligase, promoting caspase 3 activation and apoptosis.

Conclusions

Because FOXO1 upregulates the menin gene transcription, our findings unravel a crucial menin and FOXO1 interplay, with menin and FOXO1 upregulating their expression reciprocally, forming a positive feedback loop to sustain menin and FOXO1 expression.