bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation Approaches to Pain and Applications in Outpatient Practice
Authors: Gonzalez-Fernandez Marlis , Wright Katherine S. , Abrams Bernard , Yao Ada L. , Noles Amira , Hogans Beth B.
Published: November 2019

Chapter 12 introduces a broad range of considerations, alternatives, and coordination of nonpharmacologic pain management. Rehabilitation approaches to pain include somatic, biopsychosocial, and changes in neurochemical pathways in response to exercise, psychological interventions, and other therapeutic aspects. Rehabilitation occurs after injury, trauma, disease, or dysfunction leads to pain and the need for functional restoration. Prehabilitation is now being used in anticipation of planned procedures to reduce the impact of decreased activity in the operative setting and to increase the likelihood of successful return to function. Complementary and alternative therapies are often incorporated into rehabilitative pain management plans. In the process of providing clinical care for patients with persistent or disabling pain-associated conditions, questions of impairment, disability, and pending legal action may arise, and these are discussed. Applications in outpatient pain care address the coordination of pharmacologic and nonpharmacologic approaches and the challenges of planning and organizing effective evidence-based pain self-management plans in the outpatient setting.
Basics of Pediatric Pain Management
Authors: Rappold Tommy , Digiusto Matthew , Suleman M-Irfan
Published: November 2019

Chapter 18 covers the basics of pediatric pain management. Pediatric pain is a significant public health problem leading to lost days of school, increased use of the healthcare system, and multifactorial impact on all aspects of a child’s life. Pediatric patients present special clinical challenges because of variabilities in metabolism, susceptibility to disease and side effects, ability to communicate, developmental stage, coping skills, and support systems. This chapter serves as an introduction to the main features of pediatric pain management and reviews pain assessment, common causes of pain both acute and chronic, and basic nonpharmacologic and pharmacologic strategies in patients ranging from neonates to adolescents.
A null test to probe the scale dependence of the growth of structure as a test of general relativity
Authors: Franco Felipe Oliveira , Bonvin Camille , Clarkson Chris
Published: November 2019

The main science driver for the coming generation of cosmological surveys is understanding dark energy that relies on testing general relativity on the largest scales. Once we move beyond the simplest explanation for dark energy of a cosmological constant, the space of possible theories becomes both vast and extremely hard to compute realistic observables. A key discriminator of a cosmological constant, however, is that the growth of structure is scale invariant on large scales. By carefully weighting observables derived from distributions of galaxies and a dipole pattern in their apparent sizes, we construct a null test that vanishes for any model of gravity or dark energy where the growth of structure is scale independent. It relies only on very few assumptions about cosmology, and does not require any modelling of the growth of structure. We show that with a survey like the Dark Energy Spectroscopic Instrument (DESI) a scale dependence of the order of 10–20 per cent can be detected at 3σ with the null test, which will drop by a factor of 2 for a survey like the Square Kilometre Array. We also show that the null test is very insensitive to typical uncertainties in other cosmological parameters including massive neutrinos and scale-dependent bias, making this a key null test for dark energy.
Multiple Subpial Transections in Eloquent Cortex for Refractory Epilepsy: 2-Dimensional Operative Video
Authors: Whiting Alexander C , Cavallo Claudio , Rubel Nicholas , Catapano Joshua S , Walker Corey T , Smith Kris A
Published: November 2019

Although the epilepsy refractory to medical therapy can potentially be cured by the resection of epileptogenic tissue, many patients do not qualify for surgery, because epileptogenic tissue can arise from eloquent areas of the brain, where surgical resection would result in severe neurological deficits. Palliative surgical treatments currently used in these situations include deep brain stimulation, responsive neurostimulation, and vagal nerve stimulation.
1
A previously developed technique, multiple subpial transections (MSTs), although used infrequently, is another effective tool.
2
Our patient, a 34-yr-old man, had epilepsy that was refractory to medical management. His preoperative work-up demonstrated a potential seizure focus in the left pars opercularis and left superior temporal gyrus, which was verified using invasive stereoelectroencephalography. Functional magnetic resonance imaging demonstrated a significant verbal and motor function in this region. After informed consent was obtained, the patient underwent a left-sided craniotomy. The central portion of the seizure focus was resected using the subpial technique. The surrounding presumed epileptogenic cortex, which was considered functionally eloquent, was then horizontally disconnected with MSTs. For each transection, a small puncture incision was made in the pia, and a vertical cut was completed using Morrell dissectors.
2
MSTs were performed circumferentially around the entire resection cavity in 5-mm increments. All hemostasis was achieved with irrigation instead of electrocautery, although noncauterizing hemostatic agents are also acceptable. The patient was neurologically intact after the operation and was discharged home on postoperative day 2. He was free of seizures at 11-month follow-up. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Scrub typhus in patients with acute febrile illness: a 5-year study from India
Authors: Thakur C K , Chaudhry R , Gupta N , Vinayaraj E V , Singh V , Das B K , Jadon R S , Wig N , Lodha R , Kabra S K , Dey A B , Chhabra M
Published: November 2019

Background

Scrub typhus was once thought to be a disease of rural origin and was confined to specific pockets in South Asia. Early diagnosis and treatment is extremely important as it is associated with high mortality if left untreated.

Aim

To delineate the clinical and molecular epidemiology of scrub typhus in patients presenting with acute febrile illness from various parts of India.

Methods

During the study period of 5 years (October 2013 to October 2018), a total of 1742 patients with acute febrile illness <15 days were enrolled after taking informed consent. Patients were diagnosed using IgM Enzyme-linked immunosorbent assay (ELISA) based on the pre-determined region specific cut offs. Patients with positive IgM ELISA were also subjected to IgM Immunofluorescence assay and nested polymerase chain reaction (PCR) assay. The demographic and relevant clinical details of the patients were documented and analyzed.

Results

A total of 210 (12.1%) patients were diagnosed with scrub typhus. Of these, nested PCR was positive in only 85 patients. Sequencing and phylogenetic analysis showed that the predominant circulating genotypes were Gilliam and Karp. On multivariate analysis, acute respiratory distress syndrome, myocarditis, encephalitis/encephalopathy, jaundice and splenomegaly were significantly more common in those patients who were diagnosed with scrub typhus. A total of 14 patients diagnosed with scrub typhus succumbed to the illness.

Conclusion

Patients with fever, headache, pulmonary manifestations, CNS manifestations, myocarditis, transaminitis or thrombocytopenia presenting in the monsoon and post-monsoon season should be evaluated for scrub typhus irrespective of the geographical location in India.
The Risk of Sexually Transmitted Infections Following First-Episode Schizophrenia Among Adolescents and Young Adults: A Cohort Study of 220 545 Subjects
Authors: Liang Chih-Sung , Bai Ya-Mei , Hsu Ju-Wei , Huang Kai-Lin , Ko Nai-Ying , Chu Hsuan-Te , Yeh Ta-Chuan , Tsai Shih-Jen , Chen Tzeng-Ji , Chen Mu-Hong
Published: November 2019

Young people are disproportionately affected by sexually transmitted infections (STIs). The risk of STIs in young people following first-episode schizophrenia is unknown. This study using Taiwan’s National Health Insurance Research Database enrolled 44 109 adolescents and young adults with first-episode schizophrenia and 176 436 age- and sex-matched controls without schizophrenia from 2001 through 2009 and followed to the end of 2011. New-onset STIs were identified. Survival analysis was performed. Cox regression analysis was used to examine the effects of comorbid substance use disorder (SUD), schizophrenia medications, and schizophrenia severity. The E value for causality of evidence was calculated. We found that young people had a higher risk of STIs following first-episode schizophrenia compared with controls without schizophrenia (hazard ratio [HR] = 2.35, 95% CI = 2.08–2.64); these STIs included human immunodeficiency virus (HIV) (3.70, 2.60–5.28) and syphilis (5.35, 3.96–7.23). They also showed a disproportionate distribution of STIs, with an increased proportion of syphilis (20.4% vs 8.2%) and HIV (9.1% vs 6.0%). When presenting with SUD, the risks of HIV (11.00, 7.02–17.25) and syphilis (9.11, 6.16–13.47) were further increased. The severe schizophrenia group had an extremely high risk of syphilis (41.26, 27.69–61.47) and HIV (7.50, 3.85–14.62). Schizophrenia medications may provide beneficial effects against contracting STIs (0.77, 0.68–0.89). We concluded that following first-episode schizophrenia, young patients are at higher risk of STIs, particularly HIV and syphilis. The risk further increased when subjects presented with SUD or severe schizophrenia. Importantly, antipsychotic treatment may lower the risk of STIs.
Whose Bodies? Bringing Gender Into Interaction Ritual Chain Theory
Authors: Ferguson Todd W
Published: November 2019

The goal of this paper is to bring gender into the theory of interaction ritual chains. While this theory focuses on how bodies emotionally respond within interactions, it ignores how the sex–gender system impacts bodies. The cultural norms for women and men shape how bodies react emotionally in rituals. To demonstrate the need for interaction rituals to account for gender, I explore how gendered feeling rules affect ritual outcomes in religious congregations. Using multilevel regressions to analyze data from the 2001 US Congregational Life Survey, I show that men have lower levels of emotional energy than women. Additionally, the gender ratio has an effect, and individuals who are in congregations with higher percentages of men experience lower levels of emotional energy. This effect is more powerful for men than it is for women. I conclude by stating that interaction ritual theory must account for the gendered identities of its participants.
Secular Evangelicals: Faith-Based Organizing and Four Modes of Public Religion
Authors: Markofski Wes , Fulton Brad R , Wood Richard L
Published: November 2019

We present four modes of public religion—secularist, generalist pluralist, particularist pluralist, and exclusivist—and discuss conditions under which white evangelicals employ these different modes. Ethnographic research on white evangelicals participating in multifaith initiatives in Los Angeles, Portland, Boston, and Atlanta indicates that they prefer the secularist mode that avoids religious expression. In addition, the research indicates that when white evangelicals do participate in multifaith contexts where religious expression is encouraged, they prefer the particularist mode that uses faith-specific language rather than the generalist mode that invokes interfaith language. Quantitative data from a national study of community organizing organizations confirms that white evangelicals are more likely to participate in multifaith initiatives that operate in the secularist rather than a religious mode of public engagement. We anticipate that our analytic typology describing four modes of public religion will be valuable for future studies that examine the public engagement of religious actors.
Biosensor-based enzyme engineering approach applied to psicose biosynthesis
Authors: Armetta Jeremy , Berthome Rose , Cros Antonin , Pophillat Celine , Colombo Bruno Maria , Pandi Amir , Grigoras Ioana
Published: December 2019

Bioproduction of chemical compounds is of great interest for modern industries, as it reduces their production costs and ecological impact. With the use of synthetic biology, metabolic engineering and enzyme engineering tools, the yield of production can be improved to reach mass production and cost-effectiveness expectations. In this study, we explore the bioproduction of D-psicose, also known as D-allulose, a rare non-toxic sugar and a sweetener present in nature in low amounts. D-psicose has interesting properties and seemingly the ability to fight against obesity and type 2 diabetes. We developed a biosensor-based enzyme screening approach as a tool for enzyme selection that we benchmarked with the Clostridium cellulolyticum D-psicose 3-epimerase for the production of D-psicose from D-fructose. For this purpose, we constructed and characterized seven psicose responsive biosensors based on previously uncharacterized transcription factors and either their predicted promoters or an engineered promoter. In order to standardize our system, we created the Universal Biosensor Chassis, a construct with a highly modular architecture that allows rapid engineering of any transcription factor-based biosensor. Among the seven biosensors, we chose the one displaying the most linear behavior and the highest increase in fluorescence fold change. Next, we generated a library of D-psicose 3-epimerase mutants by error-prone PCR and screened it using the biosensor to select gain of function enzyme mutants, thus demonstrating the framework’s efficiency.
Exchange of information: the challenges ahead
Authors: Oberson Xavier , Papadopoulos Lysandre
Published: December 2019

Rules governing the exchange of information in tax matters with Switzerland have been essentially amended in recent years, in order to align with the Organisation for Economic Co-operation and Development standards. Provisions at both the international and domestic levels provide for more transparency. In this context, to what extent have taxpayers’ rights been considered? The abundant Swiss case law provides for some answers—not always satisfactory, though.
Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish
Authors: Nath Anjali K. , Ma Junyan , Chen Zsu‐Zsu , Li Zhuyun , Vitery Maria del Carmen , Kelley Michelle L. , Peterson Randall T. , Gerszten Robert E. , Yeh Jing‐Ruey J.
Published: December 2019

G protein‐coupled receptors (GPCRs) comprise the largest group of membrane receptors in eukaryotic genomes and collectively they regulate nearly all cellular processes. Despite the widely recognized importance of this class of proteins, many GPCRs remain understudied. G protein‐coupled receptor 27 (Gpr27) is an orphan GPCR that displays high conservation during vertebrate evolution. Although, GPR27 is known to be expressed in tissues that regulate metabolism including the pancreas, skeletal muscle, and adipose tissue, its functions are poorly characterized. Therefore, to investigate the potential roles of Gpr27 in energy metabolism, we generated a whole body gpr27 knockout zebrafish line. Loss of gpr27 potentiated the elevation in glucose levels induced by pharmacological or nutritional perturbations. We next leveraged a mass spectrometry metabolite profiling platform to identify other potential metabolic functions of Gpr27. Notably, genetic deletion of gpr27 elevated medium‐chain acylcarnitines, in particular C6‐hexanoylcarnitine, C8‐octanoylcarnitine, C9‐nonanoylcarnitine, and C10‐decanoylcarnitine, lipid species known to be associated with insulin resistance in humans. Concordantly, gpr27 deletion in zebrafish abrogated insulin‐dependent Akt phosphorylation and glucose utilization. Finally, loss of gpr27 increased the expression of key enzymes in carnitine shuttle complex, in particular the homolog to the brain‐specific isoform of CPT1C which functions as a hypothalamic energy senor. In summary, our findings shed light on the biochemical functions of Gpr27 by illuminating its role in lipid metabolism, insulin signaling, and glucose homeostasis.
Therapeutic administration of the recombinant antimicrobial peptide microcin J25 effectively enhances host defenses against gut inflammation and epithelial barrier injury induced by enterotoxigenic Escherichia coli infection
Authors: Yu Haitao , Wang Yuming , Zeng Xiangfang , Cai Shuang , Wang Gang , Liu Lu , Huang Shuo , Li Ning , Liu Hongbin , Ding Xiuliang , Song Qinglong , Qiao Shiyan
Published: November 2019

Recombinant antimicrobial peptide microcin J25 (MccJ25) causes potent antimicrobial activity against enterotoxigenic Escherichia coli (ETEC) in vitro; however, independently of this activity, its role in suppressing intestinal inflammation and epithelial barrier injury in vivo remains unclear. We investigated the therapeutic effects of MccJ25 on intestinal inflammation and epithelial barrier dysfunction and the underlying mechanism, using gentamicin for comparison. In a mouse model of intestinal inflammation, therapeutic administration of either MccJ25 or gentamicin after ETEC K88 infection attenuated clinical symptoms, reduced intestinal pathogen colonization, improved intestinal morphology, and decreased inflammatory pathologies and intestinal permeability, ultimately improving the hosts’ health. MccJ25 also attenuated ETEC‐induced mouse intestinal barrier dysfunction by enhancing tight junction proteins (TJPs). Using the human epithelial cell line Caco‐2, we verified the epithelial barrier‐strengthening and mucosal injury‐alleviating effects of MccJ25 on ETEC infection: increased expression of TJPs by activating the p38/MAPK pathway, balancing the microbiota, and improving short‐chain fatty acid concentrations in the cecum of ETEC‐infected mice. Although gentamicin and MccJ25 had similar effects in the inflamed gut, MccJ25 was superior to gentamicin with regard to defending the host from ETEC infection. Overall, MccJ25 may be a promising therapeutic drug for treating enteric pathogen‐induced intestinal inflammation diseases.
Membrane‐type frizzled‐related protein regulates lipidome and transcription for photoreceptor function
Authors: Kautzmann Marie‐Audrey I. , Gordon William C. , Jun Bokkyoo , Do Khanh V. , Matherne Blake J. , Fang Zhide , Bazan Nicolas G.
Published: November 2019

Molecular decision‐makers of photoreceptor (PRC) membrane organization and gene regulation are critical to understanding sight and retinal degenerations that lead to blindness. Using Mfrprd6 mice, which develop PRC degeneration, we uncovered that membrane‐type frizzled‐related protein (MFRP) participates in docosahexaenoic acid (DHA, 22:6) enrichment in a manner similar to adiponectin receptor 1 (AdipoR1). Untargeted imaging mass spectrometry demonstrates cell‐specific reduction of phospholipids containing 22:6 and very long‐chain polyunsaturated fatty acids (VLC‐PUFAs) in Adipor1−/− and Mfrprd6 retinas. Gene expression of pro‐inflammatory signaling pathways is increased and gene‐encoding proteins for PRC function decrease in both mutants. Thus, we propose that both proteins are necessary for retinal lipidome membrane organization, visual function, and to the understanding of the early pathology of retinal degenerative diseases.
A Diagnostic Approach to Various Fat-Containing Lesions in Thoracic Imaging
Authors: Mu Weiya , Son Hongju
Published: November 2019

Fat-containing lesions may involve any compartment of the chest, and the differential diagnosis for these lesions primarily depends on location, imaging features, and patient demographics. Although many fat-containing lesions of the chest are benign, they may be manifestations of pathologic and malignant conditions. Therefore, interval growth of the lesions and any morphological changes of the adjacent structures over time also should be evaluated.
Current advances on the microbiome and role of probiotics in upper airways disease
Authors: Yamanishi Shingo , Pawankar Ruby
Published: November 2019

Purpose of review

The prevalence of chronic upper airway inflammatory diseases such as allergic rhinitis and chronic rhinosinusitis (CRS) is increasing markedly posing a potential health threat globally. The involvement of the upper respiratory microbiota in chronic inflammatory diseases of the upper airways has been of considerable interest. The purpose of this review is to understand the characteristics of upper respiratory microbiota in both healthy and chronic inflammatory diseases of the upper airways like allergic rhinitis and CRS and to know the potential role of interventions with probiotics.

Recent findings

We present here the studies on the nasal microbiota in healthy infants, allergic rhinitis, and CRS. The results demonstrate that there are stable and unstable profiles of microbiota during infancy. Decreased diversity or an imbalance of the microbial composition could be an important factor in the development of both allergic rhinitis and CRS. We also discuss here several recent animal and human studies that demonstrate the effect of probiotics in allergic rhinitis and chronic rhinosinusitis. Results from human studies (clinical trials) have demonstrated that probiotics may be effective for allergic rhinitis, but there are no consistent results in human CRS trials.

Several strains of probiotics revealed potential efficacy for allergic rhinitis but not for CRS. Large clinical trials are essential to establish robust data on probiotics for chronic inflammatory upper airways diseases like allergic rhinitis and CRS.
Redesigning the Learning Environment to Promote Learner Well-Being and Professional Development
Authors: Dyrbye Liselotte N. , Lipscomb Wanda , Thibault George
Published: December 2019

There is a high prevalence of burnout and depression among medical students and residents (or learners), which can negatively impact them personally, their professional development, and the patients to whom they provide care. Educators have a responsibility for the system-level factors that influence learners’ well-being. In this Invited Commentary, the authors outline strategies institutions and affiliated training sites responsible for educating learners can take to pursue the recommended goal related to learners, their well-being, and the learning environment in the National Academies of Sciences, Engineering, and Medicine consensus study report, Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being.
Does an Uninstrumented Level Increase the Rate of Revision Surgery in a Multilevel Posterior Cervical Decompression and Fusion?
Authors: Schroeder Gregory D. , McKenzie James C. , Casper David S. , Mangan John J. , Stull Justin , Kepler Christopher K. , Nicholson Kristen J. , Kurd Mark F. , Hilibrand Alan S. , Murphy Hamadi , Woods Barrett I. , Radcliff Kris E. , Anderson David G. , Vaccaro Alexander R. , Rihn Jeffery A.
Published: November 2019

Study Design:

This was a retrospective cohort study.

Objective:

The goal of this study is to determine if skipping a single level affects the revision rate for patients undergoing multilevel posterior cervical decompression and fusion (PCDF).

Summary of Background Data:

A multilevel PCDF is a common procedure for patients with cervical spondylotic myelopathy. With advanced pathology, it can be difficult to safely place screw instrumentation at every level increasing the risk of intraoperative and perioperative morbidity. It is unclear whether skipping a level during PCDF affects fusion and revision rates.

Patients and Methods:

A cervical spine surgeries database at a single institution was used to identify patients who underwent ≥3 levels of PCDF. Inclusion criteria consisted of patients who had screws placed at every level or if they had a single level without screws bilaterally. Patients were excluded if the surgery was performed for tumor, trauma, or infection, and age below 18 years, or if there was <1 year of follow-up.

Results:

A total of 157 patients met inclusion criteria, with 86 undergoing a PCDF with instrumentation at all levels and 71 that had a single uninstrumented level. Overall mean follow-up was 46.5±22.8 months. In patients with or without a skipped level, the revision rate was 25% and 26%, respectively (P<1.00). Univariate regression analysis demonstrated that proximal fixation level in the upper cervical region, having the fusion end at C7, prior surgery, and myelopathy were significant predictors of revision. Skipping a single level, however, was not predictive of revision.

Conclusions:

When performing a multilevel PCDF, there is no increase in the rate of revision surgery if a single level is uninstrumented. Conversely, other surgical factors, including the cranial and caudal levels, affect revision rates. In contrast to other reports, the C2 sagittal vertical axis did not affect reoperation rates.

Level of Evidence:

Level IV.
Surviving an Active Shooter Incident in the Intensive Care Unit
Authors: Akiyama Cliff
Published: November 2019

Staff members in the intensive care unit expect to deal with medical emergencies and are typically well-educated and trained to manage these. However, when faced with unusual threats such as an active shooter in the environment, they may be less well-prepared to take prompt and definitive actions. This brief article outlines the active shooter scenario and suggests strategies to ensure the safety of patients, staff members, and visitors who are in the unit. Hospital shootings are rarely anticipated on the basis of a known threat, and there is limited time to prepare for this terrorizing event. This article describes mass shooting scenarios in hospitals and offers some definitive ways to ensure survival of those involved.
An Uncommon Cause of Chest Pain
Authors: Fasolka Brian J. , Chen Leon L.
Published: November 2019

Chest pain is a common and high-risk chief complaint in the emergency department. There is an array of cardiac and non–cardiac-related conditions that could lead to this symptom. It is important for the clinician to have a broad perspective when treating patients complaining of chest pain so that dangerous and potentially life-threatening conditions are not overlooked. Here, we present one such cause of chest pain that can be detrimental if the clinician fails to correctly identify the underlying condition. A brief review of hypertriglyceridemia-induced acute pancreatitis is provided, and challenges faced by the treatment team are discussed.
An Initiative Using Simulation to Aid in Retention of Advanced Cardiac Life Support Knowledge and Skills in an Emergency Department Nurse Residency Program
Authors: Campbell Denise , Clark Patricia C.
Published: November 2019

Introduction

Cardiac arrest is the most urgent type of emergency, and favorable outcomes are best achieved by early resuscitation. Advanced Cardiac Life Support (ACLS) certification enables nurses to provide care to patients who are at a high risk of life-threatening emergencies.

Objective

The objective of this quality improvement project was to explore the retention of knowledge and skills of 20 graduate nurses who participated in a nurse residency program using an ACLS simulation-based learning experience (SBLE) at 2 and 8 weeks post completion of an ACLS provider course.

Methods

A pretest-posttest design was used with 2 emergency department graduate nurse cohorts who participated in an SBLE focused on ACLS components at 2 and 8 weeks after attending the ACLS provider course. Simulation-based learning experiences were videotaped, and outcome measures (ie, time to shock) were measured in seconds. The nurses completed the ACLS written test before and after the SBLE.

Results

Most ACLS outcomes improved after SBLE except time to shock. Pretest-posttest ACLS average scores decreased from 93.5% to 77.8% (first cohort) and from 94.5% to 86.7% (second cohort).

Discussion

Simulation-based learning experience may be an important adjunct instructing method for teaching new graduates ACLS skills.
Precision in Oculofacial Surgery: Made-To-Specification Cast-Molded Implants in Orbital Reconstruction
Authors: Chen Allison J. , Chung Natalie N. , Liu Catherine Y. , MacIntosh Peter W. , Korn Bobby S. , Kikkawa Don O.
Published: November 2019

Purpose:

To describe the utilization of customized made-to-specification porous polyethylene implants and to evaluate clinical characteristics and outcomes of patients who received these implants for unilateral orbital defects.

Methods:

A retrospective review of 9 patients was performed. Three-dimensional surface models were generated from high-resolution computed tomography scans. Orbital constructs were modeled after the normal, contralateral orbits and mirrored across the vertical midline to generate the target orbital implant. Measured outcomes included globe position, extraocular motility, facial symmetry, and diplopia.

Results:

Patients ranged 25–56 years old (mean: 37) and included 6 males and 3 females. Cases consisted of 6 orbital floor fractures due to trauma, 1 lateral wall defect after neurofibroma resection, 1 floor/medial wall defect after myxoma resection, and 1 superior orbital rim defect after intraosseous hemangioma resection. Seven patients had ≥1 prior repair. All patients had previous hard and soft tissue defects and varying degrees of restrictive globe motility. Patients exhibited improved ductions after implant placement and improved facial appearance and symmetry. Post-operatively, 1 patient was found to have a small orbital hematoma between the implant and orbital floor, resolving within weeks.

Conclusions:

Precision, personalized oculofacial surgery is the next wave in tailoring surgical care to the individual patient. Customizable implants are manufactured to specifically mold to an individual patient’s unique bony architecture, which can lead to superior outcomes in reconstructing orbital and craniofacial bony defects. This technique is particularly useful in patients with prior unsuccessful repair.
Clinical-Radiological Patterns and Histopathological Outcomes in Non-Thyroid Extraocular Muscle Enlargement: Retrospective Case Series and Current Concepts
Authors: Savino Gustavo , Midena Giulia , Tartaglione Tommaso , Milonia Luca , Caputo Carmela Grazia , Grimaldi Gabriela
Published: November 2019

Purpose:

To report a single-center experience with non-thyroid causes of extraocular muscle enlargement (EME), describing the association between clinical-radiological findings at presentation and the final histopathological diagnosis.

Methods:

Retrospective consecutive case series of 59 patients with single or multiple EME on orbital imaging, in the absence of an etiological diagnosis at the time of presentation. All patients were submitted to orbital muscle biopsy in order to achieve a final etiological diagnosis. Patients with a confirmed diagnosis of thyroid-associated orbitopathy and vascular causes of EME which were angiographically and clinically diagnosed were excluded. Orbital ultrasound and radiologic evaluation (CT and/or MRI) were performed before surgery in all cases. Main outcomes measured included initial clinical-radiological findings and final histopathological features of EME.

Results:

A diagnosis of lymphoma was confirmed in 13 cases (22%). Sixteen cases (27%) were diagnosed as orbital inflammatory disease including nonspecific idiopathic orbital inflammatory disease in 9 cases, IgG4-related disease in 4 cases, and sclerosing idiopathic orbital inflammatory disease in 3 cases. In 11 patients (18%), a diagnosis of metastatic tumor was made, whereas sarcoidosis, vascular malformations, Erdheim-Chester, and necrobiotic xanthogranuloma were diagnosed in 8 eyes (13.5%). Three patients (5%) with single muscle enlargement developed Graves disease 10 months later. Four patients (6.7%) were diagnosed with granulomatosis with polyangiitis. In 2 cases (3.3%), the diagnosis was unknown, with inconclusive biopsy results. Differential patterns for inflammatory/vascular, lymphomatous and metastatic EME were identified based on age and gender distribution and clinical-radiological characteristics at presentation.

Conclusions:

Initial clinical and radiological features may orientate the differential diagnosis of non-thyroid EME.
CPI-17 Overexpression and Its Correlation With the NF2 Mutation Spectrum in Sporadic Vestibular Schwannomas
Authors: Xu Jianhui , Zhang Yang , Shi Yuxuan , Yin Dongming , Dai Peidong , Zhao Weidong , Zhang Tianyu
Published: November 2019

Hypothesis:

We hypothesized that CPI-17 expression and NF2 mutations are correlated with merlin phosphorylation in the etiology of sporadic vestibular schwannoma (VS).

Background:

NF2 gene mutations have been identified in the majority of sporadic and NF2-associated schwannomas and NF2 gene mutations have been shown to result in merlin protein phosphorylation. CPI-17 can drive Ras activity and promote tumorigenic transformation by inhibiting the tumor suppressor merlin. The aim of this study was to determine the correlation between CPI-17 overexpression and the NF2 mutation spectrum in sporadic VS.

Methods:

In this study, we measured CPI-17 expression and identified NF2 gene alterations in a series of sporadic VS samples. Freshly frozen tumor and matched peripheral blood leukocytes from 44 individuals with sporadic VS were analyzed using next-generation sequencing and Sanger sequencing. Western blotting was used to determine the level of merlin phosphorylation, and immunohistochemistry and Western blotting were used to measure CPI-17 expression in the sporadic VS samples. CCK-8 and wound-healing assays were used to determine the influence of CPI-17 overexpression on cell proliferation.

Results:

NF2 mutations were identified in 79.5% of sporadic vestibular schwannomas, with all mutations being exclusively somatic. IHC and WB showed the expression of CPI-17 is upregulated in the sporadic VS. NF2 mutation and CPI-17 are positively correlated with merlin phosphorylation. CPI-17 overexpression induces the proliferation of HEI193 cells.

Conclusion:

NF2 mutations and CPI-17 expression together induce merlin phosphorylation, which is correlated with the tumorigenesis of sporadic VSs.
Feasibility of Pediatric Robotic Cochlear Implantation in Phantoms
Authors: Bom Braga Gabriela O’Toole , Schneider Daniel , Muller Fabian , Hermann Jan , Weber Stefan , Caversaccio Marco
Published: November 2019

Objective:

To demonstrate the feasibility of robotic cochlear implant surgery in subject specific pediatric phantoms.

Study Design:

Pilot study.

Materials and Methods:

Computed tomographic preoperative encrypted data of 10 pediatric subjects (total of 20 sides) between 8 months and 48 months old, who underwent cochlear implant surgery were studied. Four datasets (n = 8 sides) were selected for investigation of the complete robotic procedure including middle and inner ear access and electrode insertion.

Results:

The planning of the safe trajectory for the robotic approach was possible in 17 of the cases. In three sides, planning the trajectory was not possible due to the small size of the facial recess. Bone thickness study demonstrated average sufficient bone thickness at the site of screw implantation in general. The complete robotic procure including the drilling and insertion was successfully carried out on all the created phantoms.

Conclusion:

With this work we have demonstrated the feasibility of planning and performing a robotic middle and inner ear access and cochlear implantation (CI) in phantom models of pediatric subjects. To develop and validate the proposed procedure for use in children, next stage optimization of the current surgical workflow and adaptation of the surgical material to pediatric population is necessary.
Efficacy of Vestibular Rehabilitation Following Acute Vestibular Neuritis: A Randomized Controlled Trial
Authors: Tokle Guri , Mørkved Siv , Bråthen Geir , Goplen Frederik Kragerud , Salvesen Øyvind , Arnesen Haakon , Holmeslet Berit , Nordahl Stein Helge Glad , Wilhelmsen Kjersti Thulin
Published: November 2019

Objective:

To investigate whether a vestibular rehabilitation program started early after diagnosis of vestibular neuritis combined with standard care reduces dizziness and improves functions of daily life more effectively than standard care alone in patients with acute vestibular neuritis.

Study Design:

Non-blinded, randomized controlled trial with 2 parallel groups.

Setting:

Specialist centers in 2 university hospitals.

Patients:

Patients, 18–70 years, with acute vestibular neuritis confirmed by videonystagmography.

Intervention:

Standard care was 10 days of prednisolone, general information, and counseling given to all patients. In addition to standard care, the intervention group received supervised exercise therapy (vestibular rehabilitation). Vestibular rehabilitation was given in a group format, individually tailored, and supported by home exercises.

Main Outcome Measure:

Perceived dizziness during head motion. Secondary outcomes were walking speed, standing balance, Hospital Anxiety and Depression Scale (HADS), Vertigo Symptom Scale, Visual Analog Scales (VASs), Dizziness Handicap Inventory (DHI), The University of California Los Angeles Dizziness Questionnaire.

Results:

Sixty-five patients were included, 27 participated in the vestibular rehabilitation group. There was a statistically significant difference in favor of the vestibular rehabilitation group in overall perceived dizziness at 3 (p = 0.007) and 12 months (p = 0.001). No statistically significant differences were found in standing balance and walking speed. Results from self-report measures showed a statistically significant difference at 12 months in HADS (p = 0.039), DHI (p = 0.049) and VAS-C (p = 0.012).

Conclusion:

A vestibular rehabilitation program started early after confirmed vestibular neuritis diagnosis in addition to standard care reduces the perception of dizziness and improves functions of daily life more effectively than standard care alone.
Relations Between Scalar Shift and Insertion Depth in Human Cochlear Implantation
Authors: Zelener Freddi , Majdani Omid , Roemer Ariane , Lexow G. Jakob , Giesemann Anja , Lenarz Thomas , Warnecke Athanasia
Published: November 2019

Objective:

The intracochlear position of an electrode array may influence the outcome after cochlear implantation. The design of the electrode array can increase the risk of trauma causing penetration of the basilar membrane or shift of the electrode array into the scala vestibuli. The aim of the present study was to identify a scalar shift after implantation of two different electrode arrays developed by one manufacturer.

Study Design:

Retrospective analysis.

Setting:

Tertiary referral center.

Patients and Intervention:

Cochlear implant recipients implanted between 2010 and 2014 and receiving either a mid-scala (n = 30) or a perimodiolar (n = 30) electrode array.

Main Outcome Measure:

Occurrence of scalar shift in association with the electrode type.

Results:

Scalar shift occurred in 26.7% (8 of 30) of the patients implanted with a perimodiolar electrode array and in 6.7% (2 of 30) of the patients implanted with the mid-scala electrode array. The mean insertion depth in the patients experiencing scalar shift after implantation of the mid-scala electrode was much deeper (21.59 ± 0.34 mm) when compared with the mean insertion depth of the patients with scalar shift after implantation with a perimodiolar electrode array (17.85 ± 2.19 mm). There tends to be a correlation between the cochlear length and the occurrence of a scalar shift. However, the number of patients with scalar shift in the mid-scala group is rather small.

Conclusion:

Based on the presented data, more patients implanted with a perimodiolar electrode array have a scalar shift when compared with the midscalar electrode array.
Sex-based Differences in Hearing Loss: Perspectives From Non-clinical Research to Clinical Outcomess
Authors: Villavisanis Dillan F. , Berson Elisa R. , Lauer Amanda M. , Cosetti Maura K. , Schrode Katrina M.
Published: November 2019

Introduction:

It is estimated over 466 million people worldwide have disabling hearing loss, and untreated hearing loss is associated with poorer health outcomes. The influence of sex as a biological variable on hearing loss is not well understood, especially for differences in underlying mechanisms which are typically elucidated through non-clinical research. Although the inclusion of sex as a biological variable in clinical studies has been required since 1993, sex reporting has only been recently mandated in National Institutes of Health funded non-clinical studies.

Objective:

This article reviews the literature on recent non-clinical and clinical research concerning sex-based differences in hearing loss primarily since 1993, and discusses implications for knowledge gaps in the translation from non-clinical to clinical realms.

Conclusions:

The disparity between sex-based requirements for non-clinical versus clinical research may inhibit a comprehensive understanding of sex-based mechanistic differences. Such disparities may play a role in understanding and explaining clinically significant sex differences and are likely necessary for developing robust clinical treatment options.
Long-term outcomes in the treatment of acquired hemophilia A: a 16-year single institution prospective cohort experience
Authors: Loloi Justin , Moroi Morgan K. , Songdej Natthapol , Al-Mondhiry Hamid A.
Published: November 2019

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against coagulation factor VIII. We conducted a single institution prospective cohort study to assess treatment strategies and long-term outcomes in AHA patients and provide further evidence for effective treatment and relapse timing. A total of 25 patients diagnosed with AHA between 2001 and 2017 at Penn State Hershey Medical Center were prospectively followed. Information was collected on factor VIII activity and inhibitor titer at diagnosis, treatment regimen(s), complete remission, and relapse time. For immunosuppressive therapy (IST), 19 patients were treated initially with prednisone and cyclophosphamide, four were treated with prednisone, one with prednisone and rituximab, and one with prednisone and second-line rituximab. 13/17 (76%) evaluable patients treated with prednisone and cyclophosphamide achieved complete remission. Four patients received rituximab as second-line therapy (inhibitor titers 34, 122, 416, and 768 BU); three achieved complete remission and one died from sepsis. Both evaluable patients receiving initial prednisone alone achieved complete remission. Five relapses occurred from 17 days to 7 years; all were treated with prednisone and cyclophosphamide and achieved complete remission. IST with prednisone and cyclophosphamide is highly effective in achieving and maintaining complete remission, even for relapsed patients. Despite dual IST with prednisone and cyclophosphamide, some patients, particularly with extremely high inhibitor titers, required addition of second-line rituximab to achieve complete remission. This supports rituximab as effective salvage treatment, including for patients with inhibitor titers at least 100–200 BU. Those who experienced relapse often did so years after complete remission, signifying importance of continued monitoring and vigilance.
Update on congenital hypothyroidism
Authors: Cherella Christine E. , Wassner Ari J.
Published: November 2019

Purpose of review

The present review summarizes recent advances in the diagnosis and management of patients with congenital hypothyroidism.

Recent findings

Although most newborn screening strategies are designed to detect severe primary hypothyroidism that presents shortly after birth, some infants display a pattern of delayed TSH rise despite normal initial newborn screening. Recent studies suggest that delayed TSH rise may be more common and more severe than previously recognized. Although much less common than primary hypothyroidism, central congenital hypothyroidism is as likely to be of moderate or severe degree, which has implications for its detection and treatment. The discovery of new genetic causes of central congenital hypothyroidism, including the X-linked genes IGSF1, TBL1X, and IRS4, has begun to expand our understanding of thyroid axis regulation. Recent long-term data indicate that current treatment recommendations for congenital hypothyroidism result in grossly normal neurocognitive outcomes even in severely affected patients, and that overtreatment may not be as harmful as previously suspected. Liquid levothyroxine is now commercially available in the United States, but more studies are needed to determine optimal dosing using this formulation.

Prompt identification and adequate treatment of patients with congenital hypothyroidism is critical to optimize outcomes. New information continues to accumulate about how to improve detection of congenital hypothyroidism in specific subgroups of infants (particularly those with delayed TSH rise and central hypothyroidism) and about treatment of patients with this disorder.
Irritable bowel syndrome and gut microbiota
Authors: Canakis Andrew , Haroon Mustafa , Weber H. Christian
Published: November 2019

Purpose of review

To provide an overview of recent studies exploring the gut microbiota in pathogenesis and treatment of irritable bowel syndrome (IBS).

Recent findings

Primary bacterial gut disturbances have been linked to the development and severity of IBS. Dysbiosis, or alteration in the normal intestinal flora, modulates intestinal permeability, inflammation, gut motility and likely quality of life. These biomechanical changes are associated with enteric and central nervous system processing as well. When compared to healthy controls, IBS patients display poor quality of life measures and are at increased risk of depression and anxiety. The severity of psychological and gastrointestinal symptoms in IBS has been linked with a distinct intestinal microbiota signature. Efforts to modulate intestinal dysbiosis in IBS have shown little improvement in large systematic reviews. The low FODMAP diet reduces bacteria, such as Bifidobacterum and Actinobacteria. Although rifaximin improves symptoms, it may only stimulate a transient effect on the gut microbiota. Fecal microbiota transplant does not provide prolonged symptom relief in IBS.

This review elucidates recent advances in IBS and the gut microbiota. Microbiota changes are one underlying factor in perpetuating global IBS symptoms. The opportunity to exploit this disturbance through treatment modalities requires further investigation.