UW Neurological Surgery Recent PubMed Publications

MetaBridge: An Integrative Multi-Omics Tool for Metabolite-Enzyme Mapping.

Curr Protoc Bioinformatics. 2020 Jun;70(1):e98

Authors: Blimkie T, Lee AH, Hancock REW

Abstract
MetaBridge is a web-based tool designed to facilitate the integration of metabolomics with other "omics" data types such as transcriptomics and proteomics. It uses data from the MetaCyc metabolic pathway database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to map metabolite compounds to directly interacting upstream or downstream enzymes in enzymatic reactions and metabolic pathways. The resulting list of enzymes can then be integrated with transcriptomics or proteomics data via protein-protein interaction networks to perform integrative multi-omics analyses. MetaBridge was developed to be intuitive and easy to use, requiring little to no prior computational experience. The protocols described here detail all steps involved in the use of MetaBridge, from preparing input data and performing metabolite mapping to utilizing the results to build a protein-protein interaction network. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Mapping metabolite data using MetaCyc identifiers Basic Protocol 2: Mapping metabolite data using KEGG identifiers Support Protocol 1: Converting compound names to HMDB IDs Support Protocol 2: Submitting mapped genes produced by MetaBridge for protein-protein interaction (PPI) network construction.

PMID: 32199034 [PubMed - as supplied by publisher]

Inflammation in Heart Failure: JACC State-of-the-Art Review.

J Am Coll Cardiol. 2020 03 24;75(11):1324-1340

Authors: Murphy SP, Kakkar R, McCarthy CP, Januzzi JL

Abstract
It has long been observed that heart failure (HF) is associated with measures of systemic inflammation. In recent years, there have been significant advancements in our understanding of how inflammation contributes to the pathogenesis and progression of HF. However, although numerous studies have validated the association between measures of inflammation and HF severity and prognosis, clinical trials of anti-inflammatory therapies have proven mostly unsuccessful. On this backdrop emerges the yet unmet goal of targeting precise phenotypes within the syndrome of HF; if such precise definitions can be realized, and with better understanding of the roles played by specific inflammatory mediators, the expectation is that targeted anti-inflammatory therapies may improve prognosis in patients whose HF is driven by inflammatory pathobiology. Here, the authors describe mechanistic links between inflammation and HF, discuss traditional and novel inflammatory biomarkers, and summarize the latest evidence from clinical trials of anti-inflammatory therapies.

PMID: 32192660 [PubMed - indexed for MEDLINE]

Slow release oral morphine versus methadone for opioid use disorder in the fentanyl era (pRESTO): Protocol for a non-inferiority randomized clinical trial.

Contemp Clin Trials. 2020 Mar 16;:105993

Authors: Socias ME, Wood E, Dong H, Brar R, Bach P, Murphy SM, Fairbairn N

Abstract
BACKGROUND: North America is facing an unprecedented public health crisis of opioid-related morbidity and mortality, increasingly as a result of the introduction of illicitly manufactured fentanyl into the street drug market. Although the treatment of opioid use disorder (OUD) is a key element in the response to the opioid overdose epidemic, currently available pharmacotherapies (e.g., methadone, buprenorphine) may not be acceptable to or effective in all patients. Available evidence suggests that slow-release oral morphine (SROM) has similar efficacy rates as methadone with respect to promoting abstinence, and with improvements in a number of patient-reported outcomes among persons using heroin. However, little is known about the relative effectiveness and acceptability of SROM compared to methadone in the context of fentanyl use. This study aims to address this research gap.
METHODS: pRESTO is a 24-week, open-label, two arm, non-inferiority, randomized controlled trial comparing SROM versus methadone for the treatment of OUD. Participants will be 298 clinically stable, non-pregnant adults with OUD, recruited from outpatient clinics in Vancouver, Canada, where the majority of the illicit opioids are contaminated with fentanyl. The primary outcome is suppression of illicit opioid use, measured by bi-weekly urine drug screens. Secondary outcomes include: treatment retention, medication safety, overdose events, treatment satisfaction, psychological functioning, changes in drug-related problems, changes in quality of life, opioid cravings, other substance use, and cost-effectiveness.
DISCUSSION: pRESTO will be among the first studies to evaluate treatment options for individuals primarily using synthetic street opioids, providing important evidence to guide treatment strategies for this population.

PMID: 32194251 [PubMed - as supplied by publisher]

Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants.

Front Hum Neurosci. 2020;14:66

Authors: Schimek N, Burke-Conte Z, Abernethy J, Schimek M, Burke-Conte C, Bobola M, Stocco A, Mourad PD

Abstract
Transcranial magnetic stimulation (TMS) of the visual cortex can induce phosphenes as participants look at a visual target. So can non-diagnostic ultrasound (nDU), delivered in a transcranial fashion, while participants have closed their eyes during stimulation. Here, we sought to determine if DU, aimed at the visual cortex, could alter the perception of a visual target. We applied a randomized series of actual or sham DU, transcranially and towards the visual cortex of healthy participants while they stared at a visual target (a white crosshair on a light-blue background), with the ultrasound device placed where TMS elicited phosphenes. These participants observed percepts seven out of ten times, which consisted of extra or extensions of lines relative to the original crosshair, and additional colors, an average of 53.7 ± 2.6% of the time over the course of the experiment. Seven out of ten different participants exposed to sham-only DU observed comparable percepts, but only an average of 36.3 ± 1.9% of the time, a statistically significant difference (p < 0.00001). Moreover, on average, participants exposed to a combination of sham and actual ultrasound reported a net increase of 47.9 percentage points in the likelihood that they would report a percept by the end of the experiment. Our results are consistent with the hypothesis that a random combination of sham-only and actual DU, applied directly over the visual cortex of participants, increased the likelihood that they would observe visual effects, but not the type of effects, with that likelihood increasing over the course of the experiment. From this, we conclude that repeated exposures by DU may make the visual cortex more responsive to stimulation of their visual cortex by the visual target itself. Future studies should identify the biophysical mechanism(s) and neural pathways by which DU, in our hands and others, can generate its observed effects on brain function. These observations, consistent with other's observation of effects of DU stimulation of the human motor cortex and amygdala, as well as the FDA approved nature of DU, may lead to increased use of DU as a means of altering brain function.

PMID: 32194387 [PubMed]

CCAP regulates feeding behavior via the NPF pathway in Drosophila adults.

Proc Natl Acad Sci U S A. 2020 03 31;117(13):7401-7408

Authors: Williams MJ, Akram M, Barkauskaite D, Patil S, Kotsidou E, Kheder S, Vitale G, Filaferro M, Blemings SW, Maestri G, Hazim N, Vergoni AV, Schiöth HB

Abstract
The intake of macronutrients is crucial for the fitness of any animal and is mainly regulated by peripheral signals to the brain. How the brain receives and translates these peripheral signals or how these interactions lead to changes in feeding behavior is not well-understood. We discovered that 2 crustacean cardioactive peptide (CCAP)-expressing neurons in Drosophila adults regulate feeding behavior and metabolism. Notably, loss of CCAP, or knocking down the CCAP receptor (CCAP-R) in 2 dorsal median neurons, inhibits the release of neuropeptide F (NPF), which regulates feeding behavior. Furthermore, under starvation conditions, flies normally have an increased sensitivity to sugar; however, loss of CCAP, or CCAP-R in 2 dorsal median NPF neurons, inhibited sugar sensitivity in satiated and starved flies. Separate from its regulation of NPF signaling, the CCAP peptide also regulates triglyceride levels. Additionally, genetic and optogenetic studies demonstrate that CCAP signaling is necessary and sufficient to stimulate a reflexive feeding behavior, the proboscis extension reflex (PER), elicited when external food cues are interpreted as palatable. Dopaminergic signaling was also sufficient to induce a PER. On the other hand, although necessary, NPF neurons were not able to induce a PER. These data illustrate that the CCAP peptide is a central regulator of feeding behavior and metabolism in adult flies, and that NPF neurons have an important regulatory role within this system.

PMID: 32179671 [PubMed - indexed for MEDLINE]

In defense of the AAN position on lawful physician-hastened death.

Neurology. 2020 04 14;94(15):641-643

Authors: Russell JA, Epstein LG, Bonnie RJ, Conwit R, Graf WD, Kirschen M, Kurek JA, Larriviere DG, Pascuzzi RM, Rizzo M, Sattin JA, Simmons Z, Taylor L, Williams MA, Ethics, Law, and Humanities Committee (a joint committee of the AAN, ANA, and CNS)

PMID: 32179699 [PubMed - indexed for MEDLINE]

Metabolic and evolutionary responses of Clostridium thermocellum to genetic interventions aimed at improving ethanol production.

Biotechnol Biofuels. 2020;13:40

Authors: Holwerda EK, Olson DG, Ruppertsberger NM, Stevenson DM, Murphy SJL, Maloney MI, Lanahan AA, Amador-Noguez D, Lynd LR

Abstract
Background: Engineering efforts targeted at increasing ethanol by modifying the central fermentative metabolism of Clostridium thermocellum have been variably successful. Here, we aim to understand this variation by a multifaceted approach including genomic and transcriptomic analysis combined with chemostat cultivation and high solids cellulose fermentation. Three strain lineages comprising 16 strains total were examined. Two strain lineages in which genes involved in pathways leading to organic acids and/or sporulation had been knocked out resulted in four end-strains after adaptive laboratory evolution (ALE). A third strain lineage recapitulated mutations involving adhE that occurred spontaneously in some of the engineered strains.
Results: Contrary to lactate dehydrogenase, deleting phosphotransacetylase (pta, acetate) negatively affected steady-state biomass concentration and caused increased extracellular levels of free amino acids and pyruvate, while no increase in ethanol was detected. Adaptive laboratory evolution (ALE) improved growth and shifted elevated levels of amino acids and pyruvate towards ethanol, but not for all strain lineages. Three out of four end-strains produced ethanol at higher yield, and one did not. The occurrence of a mutation in the adhE gene, expanding its nicotinamide-cofactor compatibility, enabled two end-strains to produce more ethanol. A disruption in the hfsB hydrogenase is likely the reason why a third end-strain was able to make more ethanol. RNAseq analysis showed that the distribution of fermentation products was generally not regulated at the transcript level. At 120 g/L cellulose loadings, deletions of spo0A, ldh and pta and adaptive evolution did not negatively influence cellulose solubilization and utilization capabilities. Strains with a disruption in hfsB or a mutation in adhE produced more ethanol, isobutanol and 2,3-butanediol under these conditions and the highest isobutanol and ethanol titers reached were 5.1 and 29.9 g/L, respectively.
Conclusions: Modifications in the organic acid fermentative pathways in Clostridium thermocellum caused an increase in extracellular pyruvate and free amino acids. Adaptive laboratory evolution led to improved growth, and an increase in ethanol yield and production due a mutation in adhE or a disruption in hfsB. Strains with deletions in ldh and pta pathways and subjected to ALE demonstrated undiminished cellulolytic capabilities when cultured on high cellulose loadings.

PMID: 32175007 [PubMed]

Single pedicle advancement flap for treatment of feline stenotic nares: technique and results in five cases.

J Feline Med Surg. 2020 Mar 16;:1098612X20910539

Authors: Berns CN, Schmiedt CW, Dickerson VM, Murphy SM

Abstract
OBJECTIVES: Brachycephalic obstructive airway syndrome (BOAS) is a common cause of upper airway obstruction in dogs, but is appreciated less commonly in cats. Of the components of BOAS, stenotic nares appear to play a major role in cats. However, the axial deviation of the alar wing, a common cause of nasal obstruction in dogs, is typically not present. We report a series of brachycephalic cats with a ventral nasal obstruction resulting from redundant skin along the floor of the nares. In these cats, surgical techniques developed for dogs were felt to be suboptimal. Our aim is to describe a novel surgical procedure designed specifically to surgically correct stenotic nares in cats with an obstructive fold of skin ventral to the nostril.
METHODS: Five brachycephalic cats presenting for clinical signs of stenotic nares underwent surgical repair. In each case, a resection of the skin fold followed by a bilateral single pedicle advancement flap technique was performed. Postoperative outcomes were obtained by contacting owners by telephone.
RESULTS: All cats had positive outcomes, resulting in immediate reduction of the nasal fold and opening of the nares. Owners noted resolution of stertor and no episodes of respiratory distress. No surgical complications were reported.
CONCLUSIONS AND RELEVANCE: In brachycephalic cats, the ventral skin fold may be a significant contributor to stenotic nares, unlike dogs. Resection of the skin fold, followed by bilateral single pedicle advancement flaps is a novel technique and appeared to be successful for treating stenotic nares in this series of brachycephalic cats.

PMID: 32175790 [PubMed - as supplied by publisher]

Another version of the truth.

J Neurointerv Surg. 2020 04;12(4):335-336

Authors: Levitt M

PMID: 32161165 [PubMed - indexed for MEDLINE]

Presynaptic calcium channels: specialized control of synaptic neurotransmitter release.

Nat Rev Neurosci. 2020 04;21(4):213-229

Authors: Dolphin AC, Lee A

Abstract
Chemical synapses are heterogeneous junctions formed between neurons that are specialized for the conversion of electrical impulses into the exocytotic release of neurotransmitters. Voltage-gated Ca2+ channels play a pivotal role in this process as they are the major conduits for the Ca2+ ions that trigger the fusion of neurotransmitter-containing vesicles with the presynaptic membrane. Alterations in the intrinsic function of these channels and their positioning within the active zone can profoundly alter the timing and strength of synaptic output. Advances in optical and electron microscopic imaging, structural biology and molecular techniques have facilitated recent breakthroughs in our understanding of the properties of voltage-gated Ca2+ channels that support their presynaptic functions. Here we examine the nature of these channels, how they are trafficked to and anchored within presynaptic boutons, and the mechanisms that allow them to function optimally in shaping the flow of information through neural circuits.

PMID: 32161339 [PubMed - indexed for MEDLINE]

Telephone-delivered cognitive behavioral therapy for veterans with chronic pain following traumatic brain injury: Rationale and study protocol for a randomized controlled trial study.

Contemp Clin Trials. 2019 01;76:112-119

Authors: Hoffman JM, Ehde DM, Dikmen S, Dillworth T, Gertz K, Kincaid C, Lucas S, Temkin N, Sawyer K, Williams R

Abstract
BACKGROUND AND OBJECTIVES: Chronic pain is a highly prevalent and potentially disabling condition in Veterans who have had a traumatic brain injury (TBI) and access to non-pharmacological pain treatments such as cognitive behavioral therapy is limited and variable. The purpose of this randomized controlled trial (RCT) is to evaluate the efficacy of a telephone-delivered cognitive behavioral therapy (T-CBT) for pain in Veterans with a history of TBI.
METHODS: Veterans with a history of TBI and chronic pain of at least six months duration (N = 160) will be randomized to either T-CBT or a telephone-delivered pain psychoeducational active control condition (T-Ed). The eight-week T-CBT intervention builds on other efficacious CBT interventions for chronic pain in the general population but is novel in that it is conducted via telephone and adapted for Veterans with a history of TBI. Outcome variables will be collected pre, mid-, and post-treatment, and 6 months following randomization (follow-up).
PROJECTED OUTCOMES: In addition to evaluating the effects of the interventions on pain intensity (primary outcome), this study will determine their effects on pain interference, sleep, depression, and life satisfaction. We will also examine potential moderators of treatment outcomes such as cognition, PTSD, and alcohol and drug use. This non-pharmacologic one-on-one therapeutic intervention has the potential to reduce pain and pain-related dysfunction, improve access to care, and reduce barriers associated with geography, finances, and stigma, without the negative effects on physical and cognitive performance and potential for addiction as seen with some pharmacologic treatments for pain. This trial is registered at ClinicalTrials.gov, protocol NCT01768650.

PMID: 30553077 [PubMed - indexed for MEDLINE]

Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome.

J Med Genet. 2020 Mar 10;:

Authors: Carroll MS, Ramirez JM, Weese-Mayer DE

Abstract
BACKGROUND: Rett syndrome is a severe neurological disorder with a range of disabling autonomic and respiratory symptoms and resulting predominantly from variants in the methyl-CpG binding protein 2 gene on the long arm of the X-chromosome. As basic research begins to suggest potential treatments, sensitive measures of the dynamic phenotype are needed to evaluate the results of these research efforts. Here we test the hypothesis that the physiological fingerprint of Rett syndrome in a naturalistic environment differs from that of controls, and differs among genotypes within Rett syndrome.
METHODS: A comprehensive array of heart rate variability, cardiorespiratory coupling and cardiac repolarisation measures were evaluated from an existing database of overnight and daytime inhome ambulatory recordings in 47 cases and matched controls.
RESULTS: Differences between girls with Rett syndrome and matched controls were apparent in a range of autonomic measures, and suggest a shift towards sympathetic activation and/or parasympathetic inactivation. Daily temporal trends analysed in the context of circadian rhythms reveal alterations in amplitude and phase of diurnal patterns of autonomic balance. Further analysis by genotype class confirms a graded presentation of the Rett syndrome phenotype such that patients with early truncating mutations were most different from controls, while late truncating and missense mutations were least different from controls.
CONCLUSIONS: Comprehensive autonomic measures from extensive inhome physiological measurements can detect subtle variations in the phenotype of girls with Rett syndrome, suggesting these techniques are suitable for guiding novel therapies.

PMID: 32156713 [PubMed - as supplied by publisher]

Diagnostic coronary angiography and percutaneous coronary intervention practices in New Zealand: The All New Zealand Acute Coronary Syndrome-Quality Improvement CathPCI registry 3-year study (ANZACS-QI 37).

Int J Cardiol. 2020 Feb 29;:

Authors: Wang TKM, Kasargod C, Chan D, Cicovic S, Dimalapang E, Webster M, Nunn C, Devlin G, El-Jack S, Fisher N, Simmonds M, Kneale B, Smyth D, Williams M, Kerr A, Somaratne J

Abstract
BACKGROUND: Coronary heart disease remains one of the leading causes of mortality and morbidity in New Zealand (NZ) and globally. The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) programme includes the CathPCI registry which records all those referred for diagnostic coronary angiography (DCA) and percutaneous coronary intervention (PCI) in NZ. We present the methods and three-years of data from the ANZACS-QI CathPCI registry.
METHODS: The data was extracted from the ANZACS QI CathPCI registry from 01/09/2014 to 24/09/2017. The ANZACS-QI data dictionary defines all the clinical, procedural and outcomes variables collected, and standard statistical analyses were applied.
RESULTS: 40,870 patients underwent cardiac catheterisation, with a mean age of 65 years, and males making up 67% of the cohort. Indications included acute coronary syndrome 55%, angina with suspected stable coronary disease 28%, valve surgery workup 8%, planned PCI 3%, heart failure/cardiomyopathy 3%, arrhythmia 1% and other 2%. For those undergoing DCA alone, radial access was used in 85% and two-thirds had at least one major artery with >50% stenosis. PCI was performed in 39% of patients. Drug-eluting stents were used in 97%.
CONCLUSION: The CathPCI registry records the characteristics and outcomes of all patients undergoing DCA and PCI in NZ hospitals. As part of the ANZACS-QI programme the registry provides an important platform for quality improvement, research and to inform clinical practice.

PMID: 32151441 [PubMed - as supplied by publisher]

Total copy number variation, somatic mutation burden, and histologic grade correlate with clinical outcome in oligodendroglioma.

Clin Neuropathol. 2020 Mar 08;:

Authors: Richardson TE, Williams M, Galbraith K, Mirchia K, Kumar A, Xing C, Walker JM

PMID: 32145756 [PubMed - as supplied by publisher]

Enhancing Medical Students' Interprofessional Teamwork Through Simulated Room of Errors Experience.

J Surg Res. 2020 07;251:137-145

Authors: Turrentine FE, Schroen AT, Hallowell PT, Quatrara BA, Smith PW, Williams MD, Haizlip JA

Abstract
BACKGROUND: Fostering medical students' appreciation for team members particularly those from other disciplines with varying levels of experience promotes a promising beginning to a health care career.
METHODS: During surgical clerkship orientation, third-year medical students completed 30-item TeamSTEPPS Teamwork Attitudes Questionnaire preintervention and postintervention, spent 7 min identifying errors in a simulated operating room, followed by recorded physician-led 30-min discussions.
RESULTS: Postintervention (67) compared with preintervention (141) mean TeamSTEPPS Teamwork Attitudes Questionnaire domain scores were statistically significantly higher for team structure (4.59, 4.70; P = 0.03) and higher but not significant for leadership (4.74, 4.75; P = 0.86), situation monitoring (4.62, 4.68; P = 0.32), communication (4.40, 4.50; P = 0.14), and decreased for mutual support (4.43, 4.36; P = 0.43). Medical students identified 2%-93% of 33 staged errors and 291 additional errors, which were placed into 14 categories. Soiled gloves in the operative field and urinary bag on the floor were the most frequently identified staged errors. Experienced nurses compared with medical students identified significantly more errors (mean, 17.7 versus 11.7, respectively; P < 0.001). Recognizing errors when lacking familiarity with the operative environment and appreciating teammates' perspectives were themes that emerged from discussions.
CONCLUSIONS: This well-received teamwork exercise enabled medical students to appreciate team members' contributions and other disciplines' perspectives, in addition to the synergy that occurs with multidisciplinary teams.

PMID: 32143058 [PubMed - indexed for MEDLINE]

Interplay of Staphylococcal and Host Proteases Promotes Skin Barrier Disruption in Netherton Syndrome.

Cell Rep. 2020 Mar 03;30(9):2923-2933.e7

Authors: Williams MR, Cau L, Wang Y, Kaul D, Sanford JA, Zaramela LS, Khalil S, Butcher AM, Zengler K, Horswill AR, Dupont CL, Hovnanian A, Gallo RL

Abstract
Netherton syndrome (NS) is a monogenic skin disease resulting from loss of function of lymphoepithelial Kazal-type-related protease inhibitor (LEKTI-1). In this study we examine if bacteria residing on the skin are influenced by the loss of LEKTI-1 and if interaction between this human gene and resident bacteria contributes to skin disease. Shotgun sequencing of the skin microbiome demonstrates that lesional skin of NS subjects is dominated by Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Isolates of either species from NS subjects are able to induce skin inflammation and barrier damage on mice. These microbes promote skin inflammation in the setting of LEKTI-1 deficiency due to excess proteolytic activity promoted by S. aureus phenol-soluble modulin α as well as increased bacterial proteases staphopain A and B from S. aureus or EcpA from S. epidermidis. These findings demonstrate the critical need for maintaining homeostasis of host and microbial proteases to prevent a human skin disease.

PMID: 32130897 [PubMed - in process]

Cytomorphologic findings of cervical Pap smears from female-to-male transgender patients on testosterone therapy.

Cancer Cytopathol. 2020 07;128(7):491-498

Authors: Williams MPA, Kukkar V, Stemmer MN, Khurana KK

Abstract
BACKGROUND: The cervical cancer screening recommendation for transgender female-to-male (FTM) patients is the same as that for cisgender females. A lack of literature on testosterone-induced changes in cervical cytology in these patients may result in interpretation errors, especially without a proper clinical history. The aim of this study was to delineate the Papanicolaou (Pap) test findings in this patient population.
METHODS: A pathology laboratory information system was used to obtain a cohort of FTM transgender patients on testosterone therapy (2009-2019). A cohort of age-matched, atrophic, control cisgender female patients (postpartum or menopausal) was selected. A retrospective review of the cytomorphologic findings on cervical Pap smears, pertinent follow-up, and human papillomavirus (HPV) test results was performed.
RESULTS: Fourteen transgender patients (age range, 21-64 years; mean age, 42.5 years) receiving testosterone therapy with 17 Pap smears were identified. One of the 5 available HPV tests was positive for HPV, and 4 were negative. A Pap smear review revealed the following: negative for intraepithelial lesion (NILM; 82.4%), unsatisfactory (5.9%), atypical squamous cells of undetermined significance (ASCUS; 5.9%), and low-grade squamous intraepithelial lesion (5.9%). The Pap smears of the atrophic cisgender cohort (102 patients) revealed the following: NILM (92.5%), unsatisfactory (0.9%), ASCUS (5.6%), and high-grade squamous intraepithelial lesion (0.9%). The difference between the rates of epithelial cell abnormality in the 2 cohorts was not statistically significant. Although atrophy was noted in both groups, cytomorphologic findings of transitional cell metaplasia (TCM; 88.2%) and "small cells" (82.4%) were characteristic of the testosterone-treated transgender cohort. Histologic correlates of TCM and small cells were noted in hysterectomy specimens from 6 patients.
CONCLUSIONS: Small cells and TCM are common cytomorphologic findings in Pap smears of testosterone-treated transgender (FTM) patients. On the basis of histologic follow-up, small cells most likely represent atrophic parabasal cells of cervical-vaginal epithelium.

PMID: 32125771 [PubMed - indexed for MEDLINE]

Factors associated with syrinx size in pediatric patients treated for Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

J Neurosurg Pediatr. 2020 Mar 06;:1-11

Authors: Hale AT, Adelson PD, Albert GW, Aldana PR, Alden TD, Anderson RCE, Bauer DF, Bonfield CM, Brockmeyer DL, Chern JJ, Couture DE, Daniels DJ, Durham SR, Ellenbogen RG, Eskandari R, George TM, Grant GA, Graupman PC, Greene S, Greenfield JP, Gross NL, Guillaume DJ, Heuer GG, Iantosca M, Iskandar BJ, Jackson EM, Johnston JM, Keating RF, Leonard JR, Maher CO, Mangano FT, McComb JG, Meehan T, Menezes AH, O'Neill B, Olavarria G, Park TS, Ragheb J, Selden NR, Shah MN, Smyth MD, Stone SSD, Strahle JM, Wait SD, Wellons JC, Whitehead WE, Shannon CN, Limbrick DD, Park-Reeves Syringomyelia Research Consortium Investigators

Abstract
OBJECTIVE: Factors associated with syrinx size in pediatric patients undergoing posterior fossa decompression (PFD) or PFD with duraplasty (PFDD) for Chiari malformation type I (CM-I) with syringomyelia (SM; CM-I+SM) are not well established.
METHODS: Using the Park-Reeves Syringomyelia Research Consortium registry, the authors analyzed variables associated with syrinx radiological outcomes in patients (< 20 years old at the time of surgery) with CM-I+SM undergoing PFD or PFDD. Syrinx resolution was defined as an anteroposterior (AP) diameter of ≤ 2 mm or ≤ 3 mm or a reduction in AP diameter of ≥ 50%. Syrinx regression or progression was defined using 1) change in syrinx AP diameter (≥ 1 mm), or 2) change in syrinx length (craniocaudal, ≥ 1 vertebral level). Syrinx stability was defined as a < 1-mm change in syrinx AP diameter and no change in syrinx length.
RESULTS: The authors identified 380 patients with CM-I+SM who underwent PFD or PFDD. Cox proportional hazards modeling revealed younger age at surgery and PFDD as being independently associated with syrinx resolution, defined as a ≤ 2-mm or ≤ 3-mm AP diameter or ≥ 50% reduction in AP diameter. Radiological syrinx resolution was associated with improvement in headache (p < 0.005) and neck pain (p < 0.011) after PFD or PFDD. Next, PFDD (p = 0.005), scoliosis (p = 0.007), and syrinx location across multiple spinal segments (p = 0.001) were associated with syrinx diameter regression, whereas increased preoperative frontal-occipital horn ratio (FOHR; p = 0.007) and syrinx location spanning multiple spinal segments (p = 0.04) were associated with syrinx length regression. Scoliosis (HR 0.38 [95% CI 0.16-0.91], p = 0.03) and smaller syrinx diameter (5.82 ± 3.38 vs 7.86 ± 3.05 mm; HR 0.60 [95% CI 0.34-1.03], p = 0.002) were associated with syrinx diameter stability, whereas shorter preoperative syrinx length (5.75 ± 4.01 vs 9.65 ± 4.31 levels; HR 0.21 [95% CI 0.12-0.38], p = 0.0001) and smaller pB-C2 distance (6.86 ± 1.27 vs 7.18 ± 1.38 mm; HR 1.44 [95% CI 1.02-2.05], p = 0.04) were associated with syrinx length stability. Finally, younger age at surgery (8.19 ± 5.02 vs 10.29 ± 4.25 years; HR 1.89 [95% CI 1.31-3.04], p = 0.01) was associated with syrinx diameter progression, whereas increased postoperative syrinx diameter (6.73 ± 3.64 vs 3.97 ± 3.07 mm; HR 3.10 [95% CI 1.67-5.76], p = 0.003), was associated with syrinx length progression. PFD versus PFDD was not associated with syrinx progression or reoperation rate.
CONCLUSIONS: These data suggest that PFDD and age are independently associated with radiological syrinx improvement, although forthcoming results from the PFDD versus PFD randomized controlled trial (NCT02669836, clinicaltrials.gov) will best answer this question.

PMID: 32114543 [PubMed - as supplied by publisher]

[Clinical practice guideline of integrated traditional Chinese and western medicine：atlantoaxial dislocation (AAD) (2019)].

Zhongguo Gu Shang. 2020 Jan 25;33(1):27-37

Authors: Professional Committee of Spine Medicine of Chinese Association of Integrated Traditional and Western Medicine, Tan MS, Atul G, Kuniyoshi A, Zhang F, Dong FH, Hao DJ, Zhao Y

Abstract
EDITOR'S NOTE: EDITOR'S NOTE In 2019, the clinical practice guideline of integrated traditional Chinese and western medicine atlantoaxial dislocation (ADD) was developed by the professional committee of spine medicine of the Chinese Association for Integration of Chinese and Western medicine, aiming at the major clinical problems of atlantoaxial dislocation (AAD) endangering the life center of the medulla oblongata in the field of spine surgery. More than 40 experts at home and abroad in the field of cervical spine surgery organized the first guide for the diagnosis and treatment of AAD. Guided by the principles of evidence based medicine and the consensus of experts, this guideline is based on the theory of "combination of disease and syndrome, from supervision to treatment" for the diagnosis and treatment of AAD；based on the treatment principles of "spinal cord decompression, reconstruction of atlantoaxial stability"；based on Tan technology, Goel technology, Abumi technology and other core technologies for surgical treatment. The main content includes four parts：AAD diagnosis standard, TCM syndrome differentiation, clinical classification, treatment strategy and method. It provides academic guidance to solve the clinical situation of AAD, which is "unclear definition of diagnosis and classification, confused choice of treatment strategy".
ABSTRACT: Clinical Practice Guideline of Integrated Traditional Chinese and Western Medicine：Atlantoaxial Dislocation (AAD) was enacted by the academic committee of spine surgery of integrated traditional Chinese and Western medicine. The guideline's recommendations forms by evidence-based medicine and the expert consensus of Integrative Medicine. The guidement principles is "spinal cord decompression, reconstruction of atlantoaxial stability". The objective of the guideline is providing an academic suggestion. The main contents include diagnostic criteria, traditional Chinese medicine's (TCM) dialectical method, clinical classification, treatment strategies and methods.

PMID: 32115921 [PubMed - indexed for MEDLINE]

Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis.

Eur Heart J. 2020 Feb 29;:

Authors: Zhang L, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zlotoff DA, Murphy SP, Stone JR, Golden DLA, Alvi RM, Rokicki A, Jones-O'Connor M, Cohen JV, Heinzerling LM, Mulligan C, Armanious M, Barac A, Forrestal BJ, Sullivan RJ, Kwong RY, Yang EH, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Moslehi JJ, Coelho-Filho OR, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Mercurio V, Mahmoudi M, Lawrence DP, Reynolds KL, Weinsaft JW, Baksi AJ, Ederhy S, Groarke JD, Lyon AR, Fradley MG, Thavendiranathan P, Neilan TG

Abstract
AIMS: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.
METHODS AND RESULTS: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.
CONCLUSION: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

PMID: 32112560 [PubMed - as supplied by publisher]