bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction to Genetic Counseling
Authors: Biesecker Barbara B. , Peters Kathryn F. , Resta Robert
Published: September 2019

A critical component of a genetic counselor’s professional growth is to develop the counseling skills to be able to “read” patients to gain a better understanding of the psychological underpinnings of their hopes, dreams, fears, choices, actions, suffering, reactions, strengths, and apparent weaknesses, as well as their cognitive understanding of genetic information. The purpose of this book is to help the reader to develop and expand some counseling skills that are key to the professional development of a genetic counselor. This chapter provides an overview of the issues to be addressed in the chapters that follow—counseling skills, and theories, how to critically think about ethical issues and how they may be addressed in clinical practice, laying a foundation for developing expertise to develop and investigate research questions relevant to the practice of genetic counseling, providing a sociological perspective on genetic counseling patients and genetic counselors, and offering a historical context to create a better understanding of why genetic counseling looks the way it does today.
Definitions and Goals of Genetic Counseling
Authors: Biesecker Barbara B. , Peters Kathryn F. , Resta Robert
Published: September 2019

The definition of genetic counseling has evolved from being proscriptive to the triumvirate of patient education, facilitating informed decision making, and adaptation to a risk or condition. This definition, endorsed by the National Society of Genetic Counselors, has been widely cited and used in graduate training around the globe. Despite significant advances in the roles of genetic counselors, the central tenets of counseling remain. Our practice model was previously described as psychoeducational but has evolved to psychotherapeutic to emphasize relational counseling. The goals of genetic counseling are specific, vary by subspecialty, and evolve with advances in genomic science. In the cancer setting much of genetic counseling is about cancer risk and the potential value of predictive testing to inform choices, whereas in the pediatric setting, the goal is to diagnose or determine a cause for a child’s condition.
Characteristics of Genetic Counselors
Authors: Biesecker Barbara B. , Peters Kathryn F. , Resta Robert
Published: September 2019

Beyond sensitivity to ones clients in genetic counseling, self-awareness by the genetic counselor is critical to effective patient care. Generally, genetic counselors are scientifically minded, optimistic, and high in emotional intelligence. These traits are assets to developing the skills to engage empathically with clients. Genetic counselors also hold personal beliefs about the inherent ability of clients to make good decisions for themselves and benefit from learning personalized genetic information. They value genomic science and are exuberant in sharing it, at times at the cost of effectively teaching clients. Theoretical and practical educational approaches can build strategically on counselors’ assets. Genetic counselors also value the lives of disabled adults and children, support reproductive freedoms, believe those at genetic risk should not be discriminated against, and that access to health care is a universal right. These values and beliefs propel counselors to do challenging work. Self-care is central to maintaining ones ability to care for clients. Risk of compassion fatigue can be offset with strategies to manage it, including use of professional or peer supervision.
Ruptured Middle Cerebral Artery Aneurysm Presenting with Hematoma
Authors: Zabramski Joseph M.
Published: September 2019

Abstract: This chapter reviews the surgical management of ruptured middle cerebral artery aneurysms associated with hematoma. Ruptured middle cerebral artery aneurysms occasionally present with mass effect from a large subarachnoid and/or intraparenchymal hematoma. In the case of significant hematoma size, midline shift, or increased intracranial pressure, these lesions are surgical emergencies. They can present significant management challenges because the presence of the hematoma makes operative management more difficult. Given the large and functionally critical territory supplied by the middle cerebral artery, preservation of the both the afferent and efferent branches is critical. Decision-making regarding the timing and strategy of clot evacuation is discussed.
Unruptured Ophthalmic Artery Aneurysm Presenting with Vision Loss
Authors: Loveren Harry Van , Ren Zeguang , Agarwalla Pankaj , Agazzi Siviero
Published: September 2019

Abstract: Intracranial aneurysms pose a significant clinical challenge for cerebrovascular and endovascular neurosurgeons both in treatment decision-making and in the technical aspects. The most important question is whether the aneurysm has ruptured, thereby necessitating urgent treatment. In the unruptured ophthalmic artery aneurysm case with vision loss, the decision to treat rests on understanding the risk of hemorrhage, the success in addressing neurological deficits, and the morbidity of any potential treatment. Computed tomography angiography, conventional angiography, and magnetic resonance imaging are critical and complementary in the diagnosis and management of ophthalmic artery aneurysms, which have also been termed paraclinoid or junctional aneurysms. Due to technological advances, multiple treatment methods are possible, including surgical clipping, endovascular coiling, and flow diversion. Flow diversion is emerging as an effective, less invasive technique with good vision outcomes. This chapter discusses the data behind decision-making, reviews the surgical technique of flow diversion, and emphasizes important aspects of perioperative management.
Acute Middle Cerebral Artery Occlusion
Authors: Bonney Phillip A. , Singh Parampreet , Yim Benjamin , Mack William J.
Published: September 2019

Abstract: This chapter addresses the neurosurgical management of stroke due to acute middle cerebral artery occlusion. Large vessel occlusion is a common mechanism of acute ischemic stroke. Mechanical thrombectomy has emerged as an important procedure that drastically improves outcomes in this disease. This chapter discusses the diagnosis and treatment of acute ischemic stroke from large vessel occlusion, including the rapid radiographic evaluation with CT, CTA, MRI, and perfusion imaging. The scoring of the stroke using scales such as the ASPECTS score and their use in decision-making is reviewed. The chapter then discusses treatment with both chemical thrombolysis and mechanical thrombectomy, including the technical aspects of the procedure.
Carotid Cavernous Fistula Presenting with Vision Loss
Authors: Sen Rajeev D. , Kim Louis , Levitt Michael R.
Published: September 2019

Abstract: Carotid cavernous fistulas (CCFs) are often a result of trauma, cavernous carotid artery aneurysm rupture, or arteriovenous fistulae. Although a proportion can be managed expectantly, CCFs that are under high flow can lead to rapid neurologic deterioration or visual loss requiring expeditious diagnosis and management. This chapter presents the case of a female patient who presented with subacute vision loss, chemosis, and proptosis and was treated for bilateral CCF using endovascular embolization. A strong understanding of the pathology and meticulous endovascular technique are necessary in deciding which endovascular approach and embolization agents to use in obliterating the fistula. Both transvenous and transarterial routes may be used. Legacy open intracranial methods exist for treating CCF, but are rarely needed now.
Large Temporal/Insular Cavernous Malformation Presenting with Headaches
Authors: Zhao Xiaochun , Cavallo Claudio , Belykh Evgenii , Nakaji Peter
Published: September 2019

Abstract: Cerebral cavernous malformations are often asymptomatic; however, acute symptoms may occur, suggesting a hemorrhagic episode. Surgical resection should be considered as the mainstay therapy among other treatment options when there is a symptomatic presentation. Particularly for those presenting without seizure, the decision to operate relies on a surgical approach that has acceptably low morbidity. Both the trans-temporal approach and the trans-sylvian trans-insular approach can be used for intra-axial lesions in the temporal–insular region. The trans-sylvian approach has been suggested to provide a short and straight trajectory to the surgical target and has been associated with a better postoperative outcome.
Spinal Dural Arteriovenous Fistula Presenting with Myelopathy
Authors: Narayan Vinayak , Nanda Anil
Published: September 2019

Abstract: Spinal dural arteriovenous fistulas are a rare cause of congestive myelopathy. Symptoms are insidious in onset and may be confused with degenerative spinal disease. MRI characteristically shows edema of the spinal cord with serpiginous flow voids that follow the surface of the spinal cord. Careful evaluation with spinal angiography is required to ensure accurate diagnosis. Spinal dural arteriovenous fistulas differ from spinal arteriovenous malformations in that most fistulas have only a single fistulous point without a nidus. Spinal dural arteriovenous fistulas may be treated successfully with either surgical resection or endovascular embolization depending on their anatomy. Earlier treatment is associated with better outcomes.
Gastroenterology
Authors: Kukreja Naveen
Published: September 2019

Gastrointestinal and hepatic disease is seen as a complicating factor for some of the most acute and chronically ill patients in the intensive care domain. These patients are not only academically challenging but also clinically challenging and commonly fall into the practice of general surgery as well as hepatology. This chapter reviews the laboratory and clinical presentations of these patients, along with discussion pertaining to common sources of morbidity. Furthermore, scoring systems and acuity markers for these patients are reviewed, along with practical management approaches. Disturbances in the gastrointestinal system are a hallmark of the perioperative patient and should be expected on the examination and in practice.
Sedation, Pain Management, and Pharmacology
Authors: Samuel Sophie , Cortes Jennifer
Published: September 2019

The study of pharmacology enables the principle method of intervention for critically ill patients. Because many variables exists that affect the efficacy and indications for drug intervention, a thorough knowledge of pharmacology is needed in the intensive care unit, just as it is needed in the operating room. Because pharmacology effects every system it may potentially be included in every type of question. In order to achieve a pharmacologic focus, much of this chapter emphasizes and infrequently seen but non-isoteric contact. Overall, chapter is designed to evaluate pharmacologic knowledge with highly clinical vignettes for the reader. Additionally, the reader will find an emphasis on practice pharmacologic elements of managing infectious diseases and complexities of sedation, which anesthesiologists will find reminiscent of the residency training with a critical care “twist”.
Cardiovascular II
Authors: Klick John C.
Published: September 2019

Cardiac dysfunction and hemodynamic instability comprise another hallmark pathology seen in the intensive care unit. Some could argue that cardiovascular compromise is the most common indication for intensive care management. This chapter aims to emphasize more non-traditional means of managing the patient with cardiac dysfunction up to and including mechanical devices. Additionally, the reader will find cases involving echocardiography which is commonly tested and growing in importance, particularly in the surgical population as volume assessment is challenging when only conventional means are applied. It is our hope that by the end of this chapter, the reader will have experienced a 360 degree perspective of the range of cardiac disease questions with an eye towards the types of questions which may be on the horizon for future examinations.
Renal Acid–Base
Authors: Idowu Olakunle
Published: September 2019

The renal system plays a critical role in maintaining normal blood pressure, acid–base and electrolyte balance, volume status, and clearance of metabolites. Impairments to kidney function directly affect all other organ systems and have significant implications for morbidity in the critical care setting. Understanding renal disease, it treatment and its replacement is imperative to effectively managing patients in the intensive care unit. This chapter focuses on diagnostic modalities for assessing renal function, acid–base disorders, infection, and electrolyte abnormalities. Here, the authors also focuses on differentiating prerenal, intrinsic renal, and postrenal causes of acute kidney failure, strategies for prevention, and the various forms of dialysis.
Criminal Procedure
Authors: Greenspan Michael , Mehta Amar , Rotter Merrill , Colley Jeremy
Published: September 2019

Chapter 21 includes cases that have helped to define basic principles of criminal procedure. The cases do not all involve individuals with mental illness, but the opinions significantly affect how those individuals are processed in the criminal justice system. Robinson v. California and Powell v. Texas were critical in establishing the scope of prosecution permitted against individual with substance use disorders. The other cases in the chapter are Miranda v. Arizona, North Carolina v. Alford and Colorado v. Connelly. The newest case (Commonwealth of Massachusetts v. Eldred) about an alleged violation of probation for recurrent drug use, revisits the Robinson and Powell issue of potentially punishing a person for the symptoms of her addiction (i.e. using drugs).
Diminished Capacity
Authors: Greenspan Michael
Published: September 2019

Chapter 24 describes cases that have played an important role in establishing reduced culpability by criminal defendants. People v. Patterson involves mitigation defense called Extreme Emotional Distress (EED), Ibn-Tamas v. U.S. involves evidence of Battered Woman Syndrome to reduce culpability, and the final two cases, People v. Saille and Montana v. Egelhoff involve voluntary intoxication.
Oxford Handbook of Clinical Immunology and Allergy
Authors: Spickett Gavin
Published: September 2019

The Oxford Handbook of Clinical Immunology and Allergy is a unique, practical and clinically relevant guide for clinicians and laboratory staff to assist with the diagnosis and management of immunological/allergic disease, and the correct selection and interpretation of immunological tests, and has been expanded to include the latest developments, drugs, diagnostic tests, and therapy options in the field.
Connective tissue disease
Authors: Spickett Gavin
Published: September 2019

This chapter covers the presentation, immunogenetics, immunopathology, diagnosis, treatment, and testing for a range of connective tissue diseases. It covers a range of rheumatic disorders, from rheumatoid arthritis to Raynaud’s phenomenon, and also covers the undifferentiated diseases, overlap syndromes, and mixed connective tissue disease.
Vasculitis
Authors: Spickett Gavin
Published: September 2019

The term vasculitis implies inflammation affecting predominantly the blood vessels. The effects of the process depend on the location of the inflammatory change and the size and type of the vessel involved. It is unclear why there is selectivity for vessels of a certain type, size, or location. This chapter covers the presentation, immunogenetics, immunopathology, diagnosis, treatment, and testing for a range of primary vasculitides.
Autoantibodies
Authors: Spickett Gavin
Published: September 2019

There are many hundreds of reported autoantibodies, not all of clinical value. The repertoire of the typical regional immunology laboratory will cover most of the ones described within this chapter. Some will only be available through specialist referral laboratories, or through research laboratories. This chapter covers techniques, then the units, principles, indications, and interpretation for tests for individual autoantibodies.
Allergy tests
Authors: Spickett Gavin
Published: September 2019

This chapter describes allergy tests, including their principles for testing, indications, and methods of interpreting the assays and tests. Limitations are also covered, along with key recombinant allergens for common substances that provoke an allergic reaction.
Mobilization of the Vertebral Artery—Surgical Option for C2 Screw Fixation in Cases With “High Riding” Vertebral Artery
Authors: Goel Atul , Rangnekar Ranjit , Shah Abhidha , Rai Survendra , Vutha Ravikiran
Published: September 2019

BACKGROUND

Mobilization of intraosseous course of vertebral artery for safe screw insertion into pedicle of axis in cases with high riding vertebral artery is discussed.

OBJECTIVE

To show drilling, exposure, and mobilization of the “high-riding” vertebral artery loop during its course in relationship with superior facet/pedicle of C2 vertebra can provide safety to techniques of atlantoaxial fixation that involve insertion of screws in the pars/pedicle/facet of C2.

METHODS

During the period June 2016 to April 2018, 15 patients operated for atlantoaxial stabilization underwent vertebral artery exposure and mobilization using the technique discussed. The ages of the patients ranged from 6 to 48 yrs. Four patients had mobile and reducible atlantoaxial dislocation. Seven patients had basilar invagination. Four patients had os-odontoideum. Gentle and precise drilling of bone that covers the “high-riding” vertebral artery can lead to its safe and wide surgical exposure. The arterial loop can then be either completely or partially mobilized out of the vertebral artery groove such that C2 screw insertion can be conducted under direct surgical visualization of the vertebral artery.

RESULTS

During the average follow-up period of 14 mo, there have been no complications related to the surgical procedure, metal implant, or vertebral artery.

CONCLUSION

Vertebral artery exposure and mobilization is rather simple and safe procedure and is remarkably effective in providing a space for C2 screw implantation.
A Multidisciplinary Patient-Specific Opioid Prescribing and Tapering Protocol Is Associated with a Decrease in Total Opioid Dose Prescribed for Six Weeks After Total Hip Arthroplasty
Authors: Tamboli Mallika , Mariano Edward R , Gustafson Kerianne E , Briones Beverly L , Hunter Oluwatobi O , Wang Rachel R , Harrison T Kyle , Kou Alex , Mudumbai Seshadri C , Kim T Edward , Indelli Pier F , Giori Nicholas J
Published: September 2019

Objective

This retrospective cohort study tested the hypothesis that implementing a multidisciplinary patient-specific discharge protocol for prescribing and tapering opioids after total hip arthroplasty (THA) will decrease the morphine milligram equivalent (MME) dose of opioids prescribed.

Methods

With institutional review board approval, we analyzed a Perioperative Surgical Home database and prescription data for all primary THA patients three months before (PRE) and three months after (POST) implementation of this new discharge opioid protocol based on patients’ prior 24-hour inpatient opioid consumption. The primary outcome was total opioid dosage in MME prescribed and opioid refills for six weeks after surgery. Secondary outcomes included the number of tablets and MME prescribed at discharge, in-hospital opioid consumption, length of stay, and postoperative complications.

Results

Forty-nine cases (25 PRE and 24 POST) were included. Total median (10th–90th percentiles) MME for six weeks postoperatively was 900 (57–2082) MME PRE vs 295 (69–741) MME POST (mean difference = 721, 95% confidence interval [CI] = 127–1316, P = 0.007, Mann-Whitney U test). Refill rates did not differ. The median (10th–90th percentiles) initial discharge prescription in MME was 675 (57–1035) PRE vs 180 (18–534) POST (mean difference = 387, 95% CI = 156–618, P = 0.003, Mann-Whitney U test) MME. There were no differences in other outcomes.

Conclusions

Implementation of a patient-specific prescribing and tapering protocol decreases the mean six-week dosage of opioid prescribed by 63% after THA without increasing the refill rate.
Extracting Benefits from Standardization of Digital Forensic Practices
Authors: Cusack Brian
Published: September 2019

Standardization offers consistencies for interoperability between jurisdictions and organizational entities. In some instances, accreditation and certification services are available to assure the reputational transfer of conformance and the compliance with best practice requirements. The impact of these benefits is a more predictable environment in which to deliver sensitive and high-risk services, leading to the reduction in failures and the enhancement of inter-party trust. In this article, the case of international standardization for digital forensic and related services is articulated as an example of structured planning for robust processes and practices that have user trust. Political and economic expediency has always reduced the implementation of standardization to functional attributes and short-term returns. The advocacy is for the long-term investment in standardization and the creation of trusted practices for predictable and robust scientific procedures in the transfer of operational knowledge and the preservation of digital evidences.
30. The paradox
Authors: Saleh Mohammed , Jenkins Charlotte
Published: September 2019

Introduction

Incidental findings on investigations is not uncommon in rheumatology practice. Here such an incidental finding has led to dramatic change in the management of the underlying disease.

Case description

A 38-year-old gentleman known to have ankylosing spondylitis (AS) since 2008, with radiologically evident sacroilitis on X-ray and MRI, was reviewed routinely in clinic and reported pain and restriction of neck movement and subsequent MRI cervical spine in April 2017 has shown incidental finding of apical fibrosis, but no AS activity.

He denied constitutional and respiratory symptoms apart from occasional dry cough. Chest X-ray and high resolution CT scan confirmed the same findings of apical fibrosis in addition to bilateral reticulonodular and fisural changes. Blood tests showed angiotensin converting Eezyme level ACE 65 U/L (normal range 8-65), C-reactive protein <5.

Bronchoscopy/biopsy showed non-caseating epitheliod granuloma. ZN stain and culture showed no TB infection. He was reviewed by the respiratory team and felt findings could conceivably fit with sarcoidosis.

His dry cough has improved after Benepali was discontinued in June 2017 and no steroids were given. However, had a flare of AS symptoms (ribs and lower back pain and stiffness, right SIJ pain) despite regular etoricoxib and required to start on secukinumab.

Discussion

Benepali (Etanercept biosimilar) sounds not different from the originator biologic in causing sarcoid-like reactions commonly present as skin rash and lung lesions. Etanercept is associated with a large majority of reported anti-TNF induced sarcoid-like cases, not effective in treating sarcoidosis and may even exacerbate it.

However, there are few reports of adalimumab induced sarcoid-like reactions that resolved when treated with etanercept. Paradoxical reaction to one TNF alfa inhibitor does not preclude the use of other TNF blocking agents including etanercept.

Key learning points

Lung lesions after exposure to anti-TNF warrants investigating a wide range of differential diagnoses. Paradoxical sarcoid-like reactions can occur with anti-TNF treatment and resolves on discounting it. Alternative biologic in ankylosing spondylitis might be a challenge.

Conflicts of interest

The authors have declared no conflicts of interest.
6. Treatment resistant ulcerating dermatomyositis in metastatic melanoma treated with checkpoint inhibitor therapy
Authors: Parker Lucy , Coull Philippa , Soliotis Fotini
Published: September 2019

Introduction

Paraneoplastic dermatomyositis is a well-recognised clinical entity, and should prompt investigation for an underlying malignancy. Immunosuppressive treatment can be effective in control of both skin and muscle disease. The effect of checkpoint inhibitors for control of solid tumours on autoimmune paraneoplastic phenomena is yet to be fully understood.

Case description

A 49-year-old female with a background of melanoma on the left thigh 2014 (Breslow thickness 1.9mm, treated with wide local excision only) presented with classical features of dermatomyositis; facial erythema, V-sign, Gottron’s papules, muscle weakness and elevated creatine kinase (CK) at 711 IU/L. An MRI of the upper arms was consistent with myositis. Myositis ENA panel was negative. She was initially treated with high dose oral prednisolone and weekly methotrexate. At presentation, there was no clinical or radiographic evidence of recurrent melanoma, but unfortunately after 7 months she developed a lump in the left groin which proved to be metastatic melanoma (stage IV M1a).

She was treated with 3 months palliative pembrolizumab, but this was discontinued due to lack of clinical response, when an interval CT scan showed increasing volume of disease (progressive left pelvic, retroperitoneal and left supra-clavicular fossa lymphadenopathy).

Her skin disease remained painful despite 20mg PO prednisolone and 25mg of subcutaneous methotrexate weekly, so she was treated with intravenous immunoglobulin (IVIG) 2g/kg planned to be given over 5 days. On day 3, she was found to be pyrexial at 38.2 degrees celcius prior to commencement of the infusion. Treatment was delayed by 2 days. On day 6 she was again apyrexial and the IVIG treatment was completed with IV paracetamol and 100mg IV hydrocortisone given alongside.

Following the IVIG, she has developed areas of painful localised ulceration over the dorsi of her feet, limbs and forehead. Her skin disease remains active with facial swelling and erythema, florid Gottron’s papules and periungual erythema. The ulcerated areas are discrete from the areas of known metastasis, and are considered to be secondary to severe dermal inflammation which is being treated with betnovate ointment, with a plan to introduce hydroxychloroquine if there is no clinical improvement.

Discussion

The use of checkpoint inhibitors to treat solid tumours is increasing. The autoimmune side effects of this group are well documented, and pembrolizumab is known to trigger dermatitis as a treatment related adverse event. However, the implications for checkpoint inhibitor use in an existing paraneoplastic autoimmune phenomenon is not yet understood.

Key learning points

Thorough investigation for underlying malignancy is paramount in new dermatomyositis. Patients treated with checkpoint inhibitors should be monitored closely for disease activity.

Conflicts of interest

The authors have declared no conflicts of interest.
The Effects of Genotype × Phenotype Interactions on Transcriptional Response to Silver Nanoparticle Toxicity in Organotypic Cultures of Murine Tracheal Epithelial Cells
Authors: Nicholas Tyler P , Haick Anoria K , Bammler Theo K , Workman Tomomi W , Kavanagh Terrance J , Faustman Elaine M , Gharib Sina A , Altemeier William A
Published: September 2019

The airway epithelium is critical for maintaining innate and adaptive immune responses, and occupational exposures that disrupt its immune homeostasis may initiate and amplify airway inflammation. In our previous study, we demonstrated that silver nanoparticles (AgNP), which are engineered nanomaterials used in multiple applications but primarily in the manufacturing of many antimicrobial products, induce toxicity in organotypic cultures derived from murine tracheal epithelial cells (MTEC), and those differentiated toward a “Type 2 [T2]-Skewed” phenotype experienced an increased sensitivity to AgNP toxicity, suggesting that asthmatics could be a sensitive population to AgNP exposures in occupational settings. However, the mechanistic basis for this genotype × phenotype (G × P) interaction has yet to be defined. In this study, we conducted transcriptional profiling using RNA-sequencing to predict the enrichment of specific canonical pathways and upstream transcriptional regulators to assist in defining a mechanistic basis for G × P effects on AgNP toxicity. Organotypic cultures were derived from MTEC across 2 genetically inbred mouse strains (A/J and C57BL/6J mice), 2 phenotypes (“Normal” and “T2-Skewed”), and 1 AgNP exposure (an acute 24 h exposure) to characterize G × P effects on transcriptional response to AgNP toxicity. The “T2-Skewed” phenotype was marked by increased pro-inflammatory T17 responses to AgNP toxicity, which are significant predictors of neutrophilic/difficult-to-control asthma and suggests that asthmatics could be a sensitive population to AgNP exposures in occupational settings. This study highlights the importance of considering G × P effects when identifying these sensitive populations, whose underlying genetics or diseases could directly modify their response to AgNP exposures.
Neuromelanin Modulates Heterocyclic Aromatic Amine-Induced Dopaminergic Neurotoxicity
Authors: Lawana Vivek , Um Se Young , Rochet Jean-Christophe , Turesky Robert J , Shannahan Jonathan H , Cannon Jason R
Published: September 2019

Heterocyclic aromatic amines (HAAs) are mutagens and potential human carcinogens. Our group and others have demonstrated that HAAs may also produce selective dopaminergic neurotoxicity, potentially relevant to Parkinson’s disease (PD). The goal of this study was to elucidate mechanisms of HAA-induced neurotoxicity through examining a translational biochemical weakness of common PD models. Neuromelanin is a pigmented byproduct of dopamine metabolism that has been debated as being both neurotoxic and neuroprotective in PD. Importantly, neuromelanin is known to bind and potentially release dopaminergic neurotoxicants, including HAAs (eg, β-carbolines such as harmane). Binding of other HAA subclasses (ie, aminoimidazoaazarenes) to neuromelanin has not been investigated, nor has a specific role for neuromelanin in mediating HAA-induced neurotoxicity been examined. Thus, we investigated the role of neuromelanin in modulating HAA-induced neurotoxicity. We characterized melanin from Sepia officinalis and synthetic dopamine melanin, proposed neuromelanin analogs with similar biophysical properties. Using a cell-free assay, we demonstrated strong binding of harmane and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to neuromelanin analogs. To increase cellular neuromelanin, we transfected SH-SY5Y neuroblastoma cells with tyrosinase. Relative to controls, tyrosinase-expressing cells exhibited increased neuromelanin levels, cellular HAA uptake, cell toxicity, and oxidative damage. Given that typical cellular and rodent PD models form far lower neuromelanin levels than humans, there is a critical translational weakness in assessing HAA-neurotoxicity. The primary impacts of these results are identification of a potential mechanism by which HAAs accumulate in catecholaminergic neurons and support for the need to conduct neurotoxicity studies in systems forming neuromelanin.
PML hyposumoylation is responsible for the resistance of pancreatic cancer
Authors: Swayden Mirna , Alzeeb George , Masoud Rawand , Berthois Yolande , Audebert Stéphane , Camoin Luc , Hannouche Laurent , Vachon Hortense , Gayet Odile , Bigonnet Martin , Roques Julie , Silvy Françoise , Carrier Alice , Dusetti Nelson , Iovanna Juan L. , Soubeyran Philippe
Published: September 2019

The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly due to its rapidly acquired resistance to all conventional treatments. Despite drug‐specific mechanisms of resistance, none explains how these cells resist the stress induced by any kind of anticancer treatment. Activation of stress‐response pathways relies on the post‐translational modifications (PTMs) of involved proteins. Among all PTMs, those mediated by the ubiquitin family of proteins play a central role. Our aim was to identify alterations of ubiquitination, neddylation, and sumoylation associated with the multiresistant phenotype and demonstrate their implications in the survival of PDAC cells undergoing treatment. This approach pointed at an alteration of promyelocytic leukemia (PML) protein sumoylation associated with both gemcitabine and oxaliplatin resistance. We could show that this alteration of PML sumoylation is part of a general mechanism of drug resistance, which in addition involves the abnormal activation of NF‐αB and cAMP response element binding pathways. Importantly, using patient‐derived tumors and cell lines, we identified a correlation between the levels of PML expression and sumoylation and the sensitivity of tumors to anticancer treatments.—Swayden, M., Alzeeb, G., Masoud, R., Berthois, Y., Audebert, S., Camoin, L., Hannouche, L., Vachon, H., Gayet, O., Bigonnet, M., Roques, J., Silvy, F., Carrier, A., Dusetti, N., Iovanna, J. L., Soubeyran, P. PML hyposumoylation is responsible for the resistance of pancreatic cancer. FASEB J. 33, 12447–12463 (2019). www.fasebj.org
Is It Correct to Correct for Prematurity? Theoretic Analysis of the Bayley-4 Normative Data
Authors: Aylward Glen P.
Published: September 2019

Objective:

To determine whether correction for prematurity is appropriate for cognitive, language, and motor function at varying degrees of prematurity and at different baseline functional levels.

Methods:

The newly published Bayley-4 normative data on 1700 normal children were used. Raw scores for baseline levels of function (−2 SD, −1 SD, and M) were identified at 6, 12, 24, and 36 months for receptive communication, expressive communication, fine motor, and gross motor scaled scores and cognitive, language, and motor composite scores. Differences between the baseline and uncorrected scores at 4, 3, 2, and 1 months of prematurity were evaluated at each age.

Results:

Using a cutoff of 3 points (1/5 SD), correction is needed for cognitive composite scores at all gestational ages for the first 2 years and in those born 4 months premature at 3 years of age; language and motor composite scores should be corrected to 3 years at all degrees of prematurity.

Conclusion:

Not correcting for prematurity in cognitive, language, and motor function at 3 years and younger places preterm infants at a distinct disadvantage when compared to peers with few exceptions, suggesting that such correction should be routine.
Threshold Automated Perimetry of the Full Visual Field in Patients With Glaucoma With Mild Visual Loss
Authors: Wall Michael , Lee Eric J. , Wanzek Robert J. , Zamba K.D. , Turpin Andrew , Chong Luke X. , Marin-Franch Ivan
Published: September 2019

Precis:

The authors used the Open Perimetry Interface to design a static automated perimetry test of the full field. Abnormal test locations in the nasal midperiphery and temporal inferior sector area best separated glaucomas from normals.

Purpose:

The peripheral visual field in glaucoma outside 30 degrees is largely unexplored with static perimetry. Their goal was to use threshold static automated perimetry to characterize the visual loss in glaucoma of the central 30 degrees and the far periphery.

Patients and Methods:

The authors administered the 30-2 perimetric test to 27 patients with early stage glaucoma (with mean deviation better than −4 dB) with the Goldmann III and V stimulus sizes and a custom test from 30 to up to 87 degrees with the size V stimulus twice within a month. The authors quantified (1) the retest variability, (2) the proportion of patients flagged as abnormal (at level 0.05) on the basis of pointwise probability distributions obtained from 63 ocular healthy observers, (3) the pointwise statistical distance using the Kullback-Leibler divergence between normal and glaucoma eyes, and (4) the effect of eccentricity on visual loss.

Results:

Size V 30-2 testing identified significantly more abnormal test locations (36%) than size III 30-2 (30%; P=0.004). Kullback-Leibler divergence between healthy and glaucoma distributions was greatest for the nasal midperipheral test locations and the inferior temporal sector area. A more pronounced decrease was found in visual sensitivity with eccentricity in the patients with glaucoma compared with the ocular healthy participants across the full visual field (P<0.001).

Conclusions:

Patients with glaucoma demonstrate a systematic decrease in sensitivity with eccentricity across the full visual field. Goldmann size V stimuli better detected visual loss in patients with glaucoma with mild loss than size III.
Changes in Intraocular Pressure in Single Ventricle Patients After the Glenn or Fontan Procedure
Authors: Kijima Riki , Sasaki Osamu , Shinmei Yasuhiro , Ohguchi Takeshi , Takeda Atsuhito , Chin Shinki , Ishida Susumu
Published: September 2019

Précis:

A positive correlation was observed between intraocular pressure (IOP) and central venous pressure (CVP) in patients with single ventricle (SV) during the perioperative period. IOP needs to be carefully monitored in the postoperative period after the Glenn and Fontan procedures, particularly the Glenn procedure.

Purpose:

SV is a cardiac malformation characterized by the existence of only 1 functional ventricle and is treated using the Glenn and Fontan procedures. Significant changes occur in CVP after these procedures. IOP has been reported to differ in the same individual when measured in a seated or supine position, which may be related to CVP. In the present study, we examined the relationship between CVP and IOP before and after surgery for SV.

Patients and Methods:

This study was a prospective, nonrandomized case series. All patients had SV and this study excluded those with eye diseases associated with ocular hypertension. We measured IOP before and after the Glenn or Fontan procedure. CVP was concurrently monitored.

Results:

Twenty-eight eyes of 14 patients with SV who underwent the Glenn (N=8) or Fontan (N=6) procedure were examined. Mean ages (±SD) were 2.6±0.7 months for the Glenn procedure and 24.0±2.7 months for the Fontan procedure. A correlation was observed between CVP and IOP in the perioperative period. IOP and CVP were both significantly higher after than before the Glenn and/or Fontan procedures. However, no relationship was noted between changes in IOP and CVP after the Glenn and/or Fontan procedures.

Conclusions:

Elevations in CVP significantly increased IOP in patients with SV who underwent the Glenn or Fontan procedure. IOP needs to be carefully monitored in the postoperative period after both procedures.
Duration of Pivalate-conjugated Antibiotics and Blood Glucose Levels Among Pediatric Inpatients
Authors: Sugitate Ryo , Okubo Yusuke , Matsui Atsushi
Published: September 2019

Background:

Several cases of hypoglycemia potentially induced by pivalate-conjugated antibiotics have been reported. However, no observational studies have investigated the associations among children.

Method:

A retrospective cohort study was conducted on 814 consecutive inpatients < 15 years of age with lower respiratory infections. We investigated whether the duration of lower respiratory symptoms and antibiotic use on blood glucose levels and their mediating/moderating effects using multivariable linear regression models and causal mediation analyses. Additionally, we performed a systematic review of the literature that reported the potential associations between pivalate-conjugated antibiotics and hypoglycemia.

Results:

Multivariable linear regression models showed that the duration of respiratory symptoms and fever had independent relationships with the reduction in blood glucose levels, whereas duration of pivalate-conjugated antibiotic use did not. Causal mediation analyses found that the controlled direct effects of respiratory symptom duration contributed to the reduction in blood glucose levels, but the mediating/moderating effects through antibiotic use did not. A systematic review of the literature included 7 reports written in English and 14 reports written in Japanese. No reports were observational studies; therefore, we were unable to conduct a meta-analysis.

Conclusions:

Our study failed to demonstrate an association between duration of pivalate-conjugated antibiotic use and blood glucose levels. Further studies are required to illuminate the relationship.
Prevalence of Bacterial Infection in Febrile Infant 61–90 Days Old Compared With Younger Infants
Authors: Bonilla Leire , Gomez Borja , Pintos Carla , Benito Javier , Mintegi Santiago
Published: September 2019

Background:

The objective is to compare the prevalence of serious bacterial infection (SBI) and invasive bacterial infection (IBI) in febrile infants <60 days of age and in those between 61 and 90 days.

Methods:

Prospective registry-based cohort study including all the infants ≤90 days with fever without a source evaluated in a pediatric emergency department between 2003 and 2017. We compared the prevalence of SBI and IBI in febrile infants <60 days of age and those between 61 and 90 days.

Results:

We included 3,301 infants. Overall, 605 (18.3%) had a SBI (mainly urinary tract infection), of these 81 (2.5%) had an IBI (bacteremia 60, meningitis 12, sepsis 9). The prevalence of SBI in infants >60 days old was 18.5% (95% CI: 16.4–20.7) versus 16.6% (95% CI: 14.7–18.7; n.s.) in those between 29 and 60 days and versus 21.5% (95% CI: 18.6–24.7; n.s.) in those <28 days of age. The prevalence of IBI among infants >60 days old was 1.1% (95% CI: 0.6–2.2) versus 2.3% (95% CI: 1.6–3.3; P < 0.05) in those between 29 and 60 days and 5.1% (95% CI: 3.7–7.0; P < 0.05) in those <28 days of age. The prevalence of IBI in well appearing >60 days was 1.0% (versus 4.5% in those <28 days old, P < 0.01; and 2.0% in those between 29 and 60 days, P = 0.06). All bacterial meningitis, except one, were diagnosed in infants <28 days.

Conclusions:

The prevalence of IBI in febrile infants between 61 and 90 days of age is high enough to support the recommendation for obtaining urine and blood tests in this population.
Comparison of the efficacy of continuous epidural block with epidural electrical stimulation and conventional continuous epidural block for management of zoster-associated pain beyond the acute phase
Authors: Lee Chung Hun , Choi Sang Sik , Lee Mi Kyoung , Lee Yeon Joo , Lee Mido , Park Jong Sun
Published: September 2019

Continuous epidural block (CEB) is a popular clinical method for controlling postherpetic neuralgia (PHN). However, the long-term effects of CEB on PHN have not yet been established. This study aimed to confirm the clinical efficacy of epidural electrical stimulation catheters in CEB to manage PHN.

Patients were classified into 2 groups: those with subacute PHN, between 30 and 180 days after the onset of the rash; and those with chronic PHN, over 180 days after the onset of the rash. On the basis of the type of catheter used, the patients were further divided into the following 2 groups: the esopocan group, in which the site of herpes zoster infection was confirmed using a contrast medium alone; and the epistim group, in which an additional method of electrical stimulation through a guide-wire in the catheter was used for detecting the site affected by herpes. Clinical efficacy was assessed with a numerical rating scale immediately 1, 3, and 6 months after the procedure. We also investigated whether additional interventional treatment was necessitated because of insufficient pain control during the 6-month follow-up.

We examined 88 patients. In the subacute PHN period, the numerical rating scale score was significantly lower in the epistim group than in the esopocan group until 6 months. In the chronic PHN period, no significant differences in the numerical rating scale scores were observed between the 2 groups until 6 months. In the subacute PHN period, the adjusted odds ratio for other interventional procedures within 6 months in the esopocan group versus the epistim group was 2.59 (95% confidence interval [CI] 0.83–8.09, P = .10), and in the chronic PHN period, it was 1.31 (95% CI 0.11–5.46, P = .79).

Epidural drug administration to specific segments using electrical stimulation catheters may be more useful in mitigating zoster-associated pain in subacute PHN.
Management of post-traumatic stress disorder
Authors: Rehman Yasir , Sadeghirad Behnam , Guyatt Gordon H. , McKinnon Margaret C. , McCabe Randi E. , Lanius Ruth A. , Richardson Donald J. , Couban Rachel , Sousa-Dias Helena , Busse Jason W.
Published: September 2019

Background:

Most systematic reviews have explored the efficacy of treatments on symptoms associated with post-traumatic stress disorder (PTSD), which is a chronic and often disabling condition. Previous network meta-analysis (NMA) had limitations such as focusing on pharmacological or psychotherapies. Our review is aims to explore the relative effectiveness of both pharmacological and psychotherapies and we will establish the differential efficacy of interventions for PTSD in consideration of both symptom reduction and functional recovery.

Methods:

We will conduct a network meta-analysis of randomized controlled trials evaluating treatment interventions for PTSD. We will systematically search Medline, PILOT, Embase, CINHAL, AMED, Psychinfo, Health Star, DARE and CENTRAL to identify trials that: (1) enroll adult patients with PTSD, and (2) randomize them to alternative interventions or an intervention and a placebo/sham arm. Independent reviewers will screen trials for eligibility, assess risk of bias using a modified Cochrane instrument, and extract data. Our outcomes of interest include PTSD symptom reduction, quality of life, functional recovery, social and occupational impairment, return to work and all-cause drop outs.

Results:

We will conduct frequentist random-effects network meta-analysis to assess relative effects of competing interventions. We will use a priori hypotheses to explore heterogeneity between studies, and assess the certainty of evidence using the GRADE approach.

Conclusion:

This network meta-analysis will determine the comparative effectiveness of therapeutic options for PTSD on both symptom reduction and functional recovery. Our results will be helpful to clinicians and patients with PTSD, by providing a high-quality evidence synthesis to guide shared-care decision making.
Interventional recanalization as a treatment of carotid stump syndrome caused by right internal carotid artery occlusion
Authors: Xu Ziqi , Wang Jinhua , Luo Benyan
Published: September 2019

Rationale:

Carotid stump syndrome is a cerebral infarction caused by an embolus formed subsequent to the vortex of blood flow from the occluded stump, which then moves through the collateral vessels into the brain. The covered stent and stent-assisted coil embolization stump are the effective interventions for the carotid artery stump.

Patient concerns:

A 71-year-old man twice experienced left limb weakness; diffusion weighted imaging confirmed the diagnosis of cerebral infarction. Cervical computed tomography angiography, intracranial magnetic resonance angiography, and digital subtraction angiography were conducted to evaluate collateral circulation, intraluminal composition, and shape of the carotid stump.

Diagnoses:

The patient was diagnosed with cerebral infarction and right carotid stump syndrome.

Intervention:

The patient underwent interventional recanalization of the occluded internal carotid artery, which relieved his symptoms and led to satisfactory therapeutic outcomes during the clinical follow-up.

Outcomes:

A 9-month clinical follow-up revealed no stroke recurrence.

Lessons:

Interventional recanalization for the carotid artery stump syndrome is feasible. Accurate preoperative evaluation including collateral circulation, intraluminal composition, and shape of the carotid stump can assure a successful vascularization and guided management.