UW Neurological Surgery Recent PubMed Publications

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Nat Commun. 2019 04 15;10(1):1741

Authors: Ferreira MA, Gamazon ER, Al-Ejeh F, Aittomäki K, Andrulis IL, Anton-Culver H, Arason A, Arndt V, Aronson KJ, Arun BK, Asseryanis E, Azzollini J, Balmaña J, Barnes DR, Barrowdale D, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Białkowska K, Blomqvist C, Bogdanova NV, Bojesen SE, Bolla MK, Borg A, Brauch H, Brenner H, Broeks A, Burwinkel B, Caldés T, Caligo MA, Campa D, Campbell I, Canzian F, Carter J, Carter BD, Castelao JE, Chang-Claude J, Chanock SJ, Christiansen H, Chung WK, Claes KBM, Clarke CL, EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, de la Hoya M, Dennis J, Devilee P, Diez O, Dörk T, Dunning AM, Dwek M, Eccles DM, Ejlertsen B, Ellberg C, Engel C, Eriksson M, Fasching PA, Fletcher O, Flyger H, Friedman E, Frost D, Gabrielson M, Gago-Dominguez M, Ganz PA, Gapstur SM, Garber J, García-Closas M, García-Sáenz JA, Gaudet MM, Giles GG, Glendon G, Godwin AK, Goldberg MS, Goldgar DE, González-Neira A, Greene MH, Gronwald J, Guénel P, Haiman CA, Hall P, Hamann U, He W, Heyworth J, Hogervorst FBL, Hollestelle A, Hoover RN, Hopper JL, Hulick PJ, Humphreys K, Imyanitov EN, ABCTB Investigators, HEBON Investigators, BCFR Investigators, Isaacs C, Jakimovska M, Jakubowska A, James PA, Janavicius R, Jankowitz RC, John EM, Johnson N, Joseph V, Karlan BY, Khusnutdinova E, Kiiski JI, Ko YD, Jones ME, Konstantopoulou I, Kristensen VN, Laitman Y, Lambrechts D, Lazaro C, Leslie G, Lester J, Lesueur F, Lindström S, Long J, Loud JT, Lubiński J, Makalic E, Mannermaa A, Manoochehri M, Margolin S, Maurer T, Mavroudis D, McGuffog L, Meindl A, Menon U, Michailidou K, Miller A, Montagna M, Moreno F, Moserle L, Mulligan AM, Nathanson KL, Neuhausen SL, Nevanlinna H, Nevelsteen I, Nielsen FC, Nikitina-Zake L, Nussbaum RL, Offit K, Olah E, Olopade OI, Olsson H, Osorio A, Papp J, Park-Simon TW, Parsons MT, Pedersen IS, Peixoto A, Peterlongo P, Pharoah PDP, Plaseska-Karanfilska D, Poppe B, Presneau N, Radice P, Rantala J, Rennert G, Risch HA, Saloustros E, Sanden K, Sawyer EJ, Schmidt MK, Schmutzler RK, Sharma P, Shu XO, Simard J, Singer CF, Soucy P, Southey MC, Spinelli JJ, Spurdle AB, Stone J, Swerdlow AJ, Tapper WJ, Taylor JA, Teixeira MR, Terry MB, Teulé A, Thomassen M, Thöne K, Thull DL, Tischkowitz M, Toland AE, Torres D, Truong T, Tung N, Vachon CM, van Asperen CJ, van den Ouweland AMW, van Rensburg EJ, Vega A, Viel A, Wang Q, Wappenschmidt B, Weitzel JN, Wendt C, Winqvist R, Yang XR, Yannoukakos D, Ziogas A, Kraft P, Antoniou AC, Zheng W, Easton DF, Milne RL, Beesley J, Chenevix-Trench G

Abstract
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

PMID: 30988301 [PubMed - indexed for MEDLINE]

Colour profile analysis of Port wines by various instrumental and visual methods.

J Sci Food Agric. 2019 May;99(7):3563-3571

Authors: Soares-da-Silva FA, Campos FM, Ferreira ML, Ribeiro N, Amaral B, Simões T, Silva CL

Abstract
BACKGROUND: Wine colour is an important quality parameter, being the first sensorial attribute evaluated during wine tasting. The perception of wine colour can be different depending on many factors, including the depth of the sample under observation. The main objectives of the present study were to measure the colour of Port wines using CIE L*, a*, b* parameters at different depths with various instrumental techniques (spectrophotometry and colorimetry), and to compare the obtained results with the sensory (visual) perception of colour samples.
RESULTS: Representative profiles of lightness (L*), hue (H*) and chroma (C*) at different depths were obtained using Port wine samples from various categories and ages. In general, relatively good correlations between the colorimetric and spectrophotometric methods were obtained for the L* and H* parameters. The results of the sensory tests also showed good correlations between the visually assessed hue scores and the colorimetric measurements of the H* parameter, particularly at the lower depths tested (up to 4.0 mm).
CONCLUSIONS: Overall, the results indicate that the colorimetric method can be used for estimating wine colour parameters, providing useful information about the colour profile of wines at different depths. © 2019 Society of Chemical Industry.

PMID: 30628078 [PubMed - indexed for MEDLINE]

Associations between lung and endothelial function in early middle age.

Respirology. 2020 01;25(1):89-96

Authors: Hancox RJ, Thomas L, Williams MJA, Sears MR

Abstract
BACKGROUND AND OBJECTIVE: Chronic lung disease is associated with impaired endothelial function and this may be a risk factor for poor cardiovascular health. It is unknown if there is an association between lung and endothelial function in the general population. We investigated associations between lung and endothelial function in a population-based cohort of 38-year-old men and women.
METHODS: Systemic endothelial function was measured using peripheral arterial tonometry to calculate the Framingham reactive hyperaemia index. Lung function was assessed using spirometry, plethysmographic lung volumes, airway conductance and gas transfer. Associations between lung and endothelial function were assessed with and without adjustment for potential confounding factors using regression analyses.
RESULTS: Sex modified the association between lung and endothelial function. Among women, lower values of pre- and post-bronchodilator spirometry, total lung capacity and functional residual capacity (FRC) were associated with worse endothelial function (P < 0.05). These associations persisted after adjustment for smoking, asthma diagnoses, fitness and body mass index. Associations were weaker among men: only FRC, airway conductance and post-bronchodilator forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) ratios were associated with endothelial function. Endothelial function was not associated with gas transfer in either sex.
CONCLUSION: Lower lung volumes and airflow obstruction are associated with endothelial dysfunction among women. There is weaker evidence for an association between airway and endothelial function in men. These findings may partly explain the increased risk of cardiovascular disease among people with poor lung function, but suggest that there are sex differences in this association.

PMID: 30985946 [PubMed - indexed for MEDLINE]

Biodentine™ Boosts, WhiteProRoot®MTA Increases and Life® Suppresses Odontoblast Activity.

Materials (Basel). 2019 Apr 11;12(7):

Authors: Paula A, Laranjo M, Marto CM, Abrantes AM, Casalta-Lopes J, Gonçalves AC, Sarmento-Ribeiro AB, Ferreira MM, Botelho MF, Carrilho E

Abstract
(1) Background: When pulp exposure occurs, reparative dentinogenesis can be induced by direct pulp capping to maintain the vitality and function of the tissue. The aim of this work was to assess the cytotoxicity and bioactivity of three different direct pulp capping materials, calcium hydroxide (Life®), mineral trioxide aggregate (WhiteProRoot®MTA) and calcium silicate (Biodentine™), in an odontoblast-like mouse cell line (MDPC-23). (2) Methods: Metabolic activity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT)assay, viability by the sulforhodamine B (SRB) assay, and the type of death and cell cycle analysis by flow cytometry. Alkaline phosphatase was evaluated by polymerase chain reaction (PCR), and dentin sialoprotein expression was assessed by immunocytochemistry. Mineralization was determined by the Alizarin Red S colorimetric assay and quantified by spectrophotometry. (3) Results: Life® induced a decrease in metabolic activity and viability, which is associated with an increase cell death. WhiteProRoot®MTA and Biodentine™ induced similar effects in cytotoxicity assays, with an increase in the expression of dentin sialoprotein (DSP) and formation of mineralized deposits, especially with Biodentine™. (4) Conclusions: The results of WhiteProRoot®MTA confirm its indication for these therapies, justifying its recognition as the "gold standard". Biodentine™ may be an alternative, since they promote the same cellular response that mineral trioxide aggregate (MTA) does.

PMID: 30978943 [PubMed]

Genetic correlates of wall shear stress in a patient-specific 3D-printed cerebral aneurysm model.

J Neurointerv Surg. 2019 Oct;11(10):999-1003

Authors: Levitt MR, Mandrycky C, Abel A, Kelly CM, Levy S, Chivukula VK, Zheng Y, Aliseda A, Kim LJ

Abstract
OBJECTIVES: To study the correlation between wall shear stress and endothelial cell expression in a patient-specific, three-dimensional (3D)-printed model of a cerebral aneurysm.
MATERIALS AND METHODS: A 3D-printed model of a cerebral aneurysm was created from a patient's angiogram. After populating the model with human endothelial cells, it was exposed to media under flow for 24 hours. Endothelial cell morphology was characterized in five regions of the 3D-printed model using confocal microscopy. Endothelial cells were then harvested from distinct regions of the 3D-printed model for mRNA collection and gene analysis via quantitative polymerase chain reaction (qPCR.) Cell morphology and mRNA measurement were correlated with computational fluid dynamics simulations.
RESULTS: The model was successfully populated with endothelial cells, which survived under flow for 24 hours. Endothelial morphology showed alignment with flow in the proximal and distal parent vessel and aneurysm neck, but disorganization in the aneurysm dome. Genetic analysis of endothelial mRNA expression in the aneurysm dome and distal parent vessel was compared with the proximal parent vessels. ADAMTS-1 and NOS3 were downregulated in the aneurysm dome, while GJA4 was upregulated in the distal parent vessel. Disorganized morphology and decreased ADAMTS-1 and NOS3 expression correlated with areas of substantially lower wall shear stress and wall shear stress gradient in computational fluid dynamics simulations.
CONCLUSIONS: Creating 3D-printed models of patient-specific cerebral aneurysms populated with human endothelial cells is feasible. Analysis of these cells after exposure to flow demonstrates differences in both cell morphology and genetic expression, which correlate with areas of differential hemodynamic stress.

PMID: 30979845 [PubMed - indexed for MEDLINE]

A randomized controlled trial of WATAAP to promote physical activity in colorectal and endometrial cancer survivors.

Psychooncology. 2019 07;28(7):1420-1429

Authors: Maxwell-Smith C, Hince D, Cohen PA, Bulsara MK, Boyle T, Platell C, Tan P, Levitt M, Salama P, Tan J, Salfinger S, Makin G, Mohan GRKA, Jiménez-Castuera R, Hardcastle SJ

Abstract
OBJECTIVE: The objective of this study was to ascertain whether wearable technology coupled with action planning was effective in increasing physical activity (PA) in colorectal and endometrial cancer survivors at cardiovascular risk.
METHODS: Sixty-eight survivors who had cardiovascular risk factors and were insufficiently active were randomized to intervention and control arms. Intervention participants were given a wearable tracker for 12 weeks, two group sessions, and a support phone call. Participants in the control arm received print materials describing PA guidelines. Assessments at baseline and 12 weeks measured triaxial and uniaxial estimates of moderate-vigorous physical activity (MVPA), sedentary behaviour, blood pressure, and body mass index (BMI).
RESULTS: The intervention group significantly increased MVPA by 45 min/wk compared with a reduction of 21 min/wk in the control group. Group by time interactions were significant for minutes of MVPA (F1,126  = 5.14, P = 0.025). For those with diastolic hypertension, there was a significant group by time interaction (F1,66  = 4.89, P = 0.031) with a net reduction of 9.89 mm Hg in the intervention group.
CONCLUSIONS: Significant improvements in MVPA were observed following the intervention. The results display promise for the use of pragmatic, low-intensity interventions using wearable technology.

PMID: 30980691 [PubMed - indexed for MEDLINE]

Current state of transfusion in traumatic brain injury and associated coagulopathy.

Transfusion. 2019 04;59(S2):1522-1528

Authors: Stolla M, Zhang F, Meyer MR, Zhang J, Dong JF

Abstract
Traumatic brain injury (TBI)-induced coagulopathy has long been recognized as a significant risk for poor outcomes in patients with TBI, but its pathogenesis remains poorly understood. As a result, current treatment options for the condition are limited and ineffective. The lack of information is most significant for the impact of blood transfusions on patients with isolated TBI and in the absence of confounding influences from trauma to the body and limbs and the resultant hemorrhagic shock. Here we discuss recent progress in understanding the pathogenesis of TBI-induced coagulopathy and the current state of blood transfusions for patients with TBI and associated coagulopathy.

PMID: 30980753 [PubMed - indexed for MEDLINE]

A Randomized Trial Evaluating the Prophylactic Activity of DSM265 Against Preerythrocytic Plasmodium falciparum Infection During Controlled Human Malarial Infection by Mosquito Bites and Direct Venous Inoculation.

J Infect Dis. 2018 02 14;217(5):693-702

Authors: Murphy SC, Duke ER, Shipman KJ, Jensen RL, Fong Y, Ferguson S, Janes HE, Gillespie K, Seilie AM, Hanron AE, Rinn L, Fishbaugher M, VonGoedert T, Fritzen E, Kappe SH, Chang M, Sousa JC, Marcsisin SR, Chalon S, Duparc S, Kerr N, Möhrle JJ, Andenmatten N, Rueckle T, Kublin JG

Abstract
Background: DSM265 is a selective inhibitor of Plasmodium dihydroorotate dehydrogenase that fully protected against controlled human malarial infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites when administered 1 day before challenge and provided partial protection when administered 7 days before challenge.
Methods: A double-blinded, randomized, placebo-controlled trial was performed to assess safety, tolerability, pharmacokinetics, and efficacy of 1 oral dose of 400 mg of DSM265 before CHMI. Three cohorts were studied, with DSM265 administered 3 or 7 days before direct venous inoculation of sporozoites or 7 days before 5 bites from infected mosquitoes.
Results: DSM265-related adverse events consisted of mild-to-moderate headache and gastrointestinal symptoms. DSM265 concentrations were consistent with pharmacokinetic models (mean area under the curve extrapolated to infinity, 1707 µg*h/mL). Placebo-treated participants became positive by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and were treated 7-10 days after CHMI. Among DSM265-treated subjects, 2 of 6 in each cohort were sterilely protected. DSM265-treated recipients had longer times to development of parasitemia than placebo-treated participants (P < .004).
Conclusions: This was the first CHMI study of a novel antimalarial compound to compare direct venous inoculation of sporozoites and mosquito bites. Times to qRT-PCR positivity and treatment were comparable for both routes. DSM265 given 3 or 7 days before CHMI was safe and well tolerated but sterilely protected only one third of participants.

PMID: 29216395 [PubMed - indexed for MEDLINE]

Extracellular mitochondria released from traumatized brains induced platelet procoagulant activity.

Haematologica. 2019 Apr 11;:

Authors: Zhao Z, Zhou Y, Hilton T, Li F, Han C, Liu L, Yuan H, Li Y, Xu X, Wu X, Zhang F, Thiagarajan P, Cap A, Shi FD, Zhang J, Dong JF

Abstract
Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing the hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive oxygen species. These extracellular mitochondria bound platelets through the phospholipid-CD36 interaction and induced α-granule secretion, microvesiculation, and procoagulant activity in an oxidant-dependent manner, but failed to induce aggregation. These results define an extracellular mitochondria-induced and redox-dependent intermediate phenotype of platelets that contribute to the pathogenesis of traumatic brain injury-induced coagulopathy and inflammation.

PMID: 30975909 [PubMed - as supplied by publisher]

Genetic Screen in Chlamydia muridarum Reveals Role for an Interferon-Induced Host Cell Death Program in Antimicrobial Inclusion Rupture.

MBio. 2019 04 09;10(2):

Authors: Giebel AM, Hu S, Rajaram K, Finethy R, Toh E, Brothwell JA, Morrison SG, Suchland RJ, Stein BD, Coers J, Morrison RP, Nelson DE

Abstract
Interferon-regulated immune defenses protect mammals from pathogenically diverse obligate intracellular bacterial pathogens of the genus Chlamydia Interferon gamma (IFN-γ) is especially important in controlling the virulence of Chlamydia species and thus impacts the modeling of human chlamydial infection and disease in mice. How IFN-γ contributes to cell-autonomous defenses against Chlamydia species and how these pathogens evade IFN-γ-mediated immunity in their natural hosts are not well understood. We conducted a genetic screen which identified 31 IFN-γ-sensitive (Igs) mutants of the mouse model pathogen Chlamydia muridarum Genetic suppressor analysis and lateral gene transfer were used to map the phenotype of one of these mutants, Igs4, to a missense mutation in a putative chlamydial inclusion membrane protein, TC0574. We observed the lytic destruction of Igs4-occupied inclusions and accompanying host cell death in response to IFN-γ priming or various proapoptotic stimuli. However, Igs4 was insensitive to IFN-γ-regulated cell-autonomous defenses previously implicated in anti-Chlamydia trachomatis host defense in mice. Igs4 inclusion integrity was restored by caspase inhibitors, indicating that the IFN-γ-mediated destruction of Igs4 inclusions is dependent upon the function of caspases or related prodeath cysteine proteases. We further demonstrated that the Igs4 mutant is immune restricted in an IFN-γ-dependent manner in a mouse infection model, thereby implicating IFN-γ-mediated inclusion destruction and host cell death as potent in vivo host defense mechanisms to which wild-type C. muridarum is resistant. Overall, our results suggest that C. muridarum evolved resistance mechanisms to counter IFN-γ-elicited programmed cell death and the associated destruction of intravacuolar pathogens.IMPORTANCE Multiple obligatory intracellular bacteria in the genus Chlamydia are important pathogens. In humans, strains of C. trachomatis cause trachoma, chlamydia, and lymphogranuloma venereum. These diseases are all associated with extended courses of infection and reinfection that likely reflect the ability of chlamydiae to evade various aspects of host immune responses. Interferon-stimulated genes, driven in part by the cytokine interferon gamma, restrict the host range of various Chlamydia species, but how these pathogens evade interferon-stimulated genes in their definitive host is poorly understood. Various Chlamydia species can inhibit death of their host cells and may have evolved this strategy to evade prodeath signals elicited by host immune responses. We present evidence that chlamydia-induced programmed cell death resistance evolved to counter interferon- and immune-mediated killing of Chlamydia-infected cells.

PMID: 30967464 [PubMed - indexed for MEDLINE]

The molecular landscape of adult diffuse gliomas and relevance to clinical trials.

Oncotarget. 2019 Mar 05;10(19):1758-1759

Authors: Cimino PJ, Holland EC

PMID: 30956755 [PubMed]

Mouse knockout of guanylyl cyclase C: Recognition memory deficits in the absence of activity changes.

Genes Brain Behav. 2019 06;18(5):e12573

Authors: Mann EA, Sugimoto C, Williams MT, Vorhees CV

Abstract
Guanylyl cyclase C (GC-C) is found in brain regions where dopamine is expressed. We characterized a mouse in which GC-C was knocked out (KO) that was reported to be a model of attention deficit hyperactivity disorder (ADHD). We re-examined this model and controlled for litter effects, used 16 to 23 mice per genotype per sex and assessed an array of behavioral and neurochemical outcomes. GC-C KO mice showed no phenotypic differences from wild-type mice on most behavioral tests, or on striatal or hippocampal monoamines, and notably no evidence of an ADHD-like phenotype. KO mice were impaired on novel object recognition, had decreased tactile startle but not acoustic startle, and females had increased latency on cued training trials in the Morris water maze, but not hidden platform spatial learning trials. Open-field activity showed small differences in females but not males. The data indicate that the GC-C KO mouse with proper controls and sample sizes has a moderate cognitive and startle phenotype but has no ADHD-like phenotype.

PMID: 30953414 [PubMed - indexed for MEDLINE]

Lingual liability: macroglossia and dyspnoea as the harbinger of systemic AL (light-chain) cardiac amyloidosis.

BMJ Case Rep. 2018 Dec 22;11(1):

Authors: Williams MU, Murphy CE, Gore RS, Fentanes E

Abstract
A 58-year-old man presented with a chief complaint of tongue indentations and discomfort. Otolaryngology treated him for oral thrush with counselling to avoid tongue biting. In addition, the patient reported dyspnoea described as a decrease in tolerance of his physical activities. Due to continued increase in tongue size and worsening dyspnoea, he underwent a tissue biopsy with findings consistent with amyloidosis. Further evaluation with a bone marrow biopsy revealed underlying multiple myeloma. Echocardiography revealed abnormal ventricular wall thickness, with a reduced left ventricular chamber size, dilated atria and Doppler findings with restrictive filling patterns indicative of cardiac amyloidosis. The patient was initiated on chemotherapy for his multiple myeloma and supportive therapy for his cardiac amyloidosis. Light-chain amyloidosis (AL) is a systemic disease characterised by irreversible deposition of amyloid in tissues throughout the body; when there is cardiac involvement, it can result in heart failure with a poor prognosis. Early diagnosis of cardiac amyloidosis can lead to prolonged survival.

PMID: 30580294 [PubMed - indexed for MEDLINE]

Reliability and Construct Validity of the TBI-QOL Communication Short Form as a Parent-Proxy Report Instrument for Children With Traumatic Brain Injury.

J Speech Lang Hear Res. 2019 01 30;62(1):84-92

Authors: Cohen ML, Tulsky DS, Boulton AJ, Kisala PA, Bertisch H, Yeates KO, Zonfrillo MR, Durbin DR, Jaffe KM, Temkin N, Wang J, Rivara FP

Abstract
Purpose The purpose of this study was to evaluate the internal consistency and construct validity of the Traumatic Brain Injury Quality of Life Communication Item Bank (TBI-QOL COM) short form as a parent-proxy report measure. The TBI-QOL COM is a patient-reported outcome measure of functional communication originally developed as a self-report measure for adults with traumatic brain injury (TBI), but it may also be valid as a parent-proxy report measure for children who have sustained TBI. Method One hundred twenty-nine parent-proxy raters completed the TBI-QOL COM short form 6 months postinjury as a secondary aim of a multisite study of pediatric TBI outcomes. The respondents' children with TBI were between 8 and 18 years old ( M age = 13.2 years old) at the time of injury, and the proportion of TBI severity mirrored national trends (73% complicated-mild; 27% moderate or severe). Results The parent-proxy report version of the TBI-QOL COM displayed strong internal consistency (ordinal α = .93). It also displayed evidence of known-groups validity by virtue of more severe injuries associated with more abnormal scores. The instrument also showed evidence of convergent and discriminant validity by displaying a pattern of correlations with other constructs according to their conceptual relatedness to functional communication. Conclusions This preliminary psychometric investigation of the TBI-QOL COM supports the further development of a parent report version of the instrument. Future development of the TBI-QOL COM with this population may include expanding the content of the item bank and developing calibrations specifically for parent-proxy raters. Supplemental Material https://doi.org/10.23641/asha.7616534.

PMID: 30950756 [PubMed - indexed for MEDLINE]

Cystic Fibrosis Inflammation: Hyperinflammatory, Hypoinflammatory, or Both?

Am J Respir Cell Mol Biol. 2019 Sep;61(3):273-274

Authors: Murphy SV, Ribeiro CMP

PMID: 30951377 [PubMed - indexed for MEDLINE]

Anger and aggression treatments: a review of meta-analyses.

Curr Opin Psychol. 2018 02;19:65-74

Authors: Lee AH, DiGiuseppe R

Abstract
In the last several decades, researchers have begun to recognize dysregulated anger as a common and debilitating psychological problem among various psychiatric populations. Accordingly, the treatment of anger and aggression has received increasing attention in the literature. The current article reviews existing meta-analyses of psychosocial intervention for anger and aggression with the aims of (1) synthesizing current research evidence for these interventions, and (2) identifying interventions characteristics associated with effectiveness in specific populations of interest. Results demonstrate that cognitive behavioral treatments are the most commonly disseminated intervention for both anger and aggression. Anger treatments have consistently demonstrated at least moderate effectiveness among both non-clinical and psychiatric populations, whereas aggression treatment results have been less consistent. We discuss the implication of these findings and provide directions for future research in the treatment of anger and aggression.

PMID: 29279226 [PubMed - indexed for MEDLINE]

Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors): Results of a Retrospective Study.

J Clin Med Res. 2019 Apr;11(4):225-236

Authors: Bajwa R, Cheema A, Khan T, Amirpour A, Paul A, Chaughtai S, Patel S, Patel T, Bramson J, Gupta V, Levitt M, Asif A, Hossain MA

Abstract
In recent years the use of immunomodulating therapy to treat various cancers has been on the rise. Three checkpoint inhibitors have been approved by the Food and Drug Administration (ipilimumab, pembrolizumab and nivolumab). The use of these drugs comes with serious adverse events related to excessive immune activation, collectively known as immune-related adverse events (irAEs). We conducted a system-based review of 139 case reports/case series that have described these adverse events between January 2016 and April 2018, found in the PubMed database. There was a broad spectrum of presentations, doses and checkpoint inhibitors used. The most common check point inhibitor observed in our literature review was nivolumab. The most common adverse effects encountered were colitis (14/139), hepatitis (11/139), adrenocorticotropic hormone insufficiency (12/139), hypothyroidism (7/139), type 1 diabetes (22/139), acute kidney injury (16/139) and myocarditis (10/139). The treatment most commonly consisted of cessation of the immune checkpoint inhibitor, initiation of steroids and supportive therapy. This approach provided a complete resolution in a majority of cases; however, there were many that developed long-term adverse events with deaths reported in a few cases. The endocrine system was the mostly commonly affected with the development of type 1 diabetes mellitus or diabetic ketoacidosis being the most frequently reported adverse events. While immunomodulating therapy is a significant advance in the management of various malignancies, it is capable of serious adverse effects. Because the majority of the cases developed pancreatic dysfunction within five cycles of therapy, in addition to the evaluation of other systems, pancreatic function should be closely monitored to minimize adverse impact on patients.

PMID: 30937112 [PubMed]

Type A aortic dissection secondary to a left common carotid artery dissection.

Radiol Case Rep. 2019 Jun;14(6):647-651

Authors: Doran S, Llamas Osorio Y, Murphy M, Kavanagh E, Murphy S

Abstract
Common carotid artery dissection is an unusual clinical event that most commonly occurs secondary to type A aortic dissection. We present a rare case of spontaneous common carotid artery dissection temporally preceding aortic dissection. Our case highlights the careful attention that cases of common carotid dissection should be given; our knowledge base regarding their natural history and evidence-based management is distinctly lacking compared to dissection of other cervical vessels. It also demonstrates the importance of imaging the entire aorta at the time of, a seemingly isolated, common carotid dissection to exclude other potential synchronous dissections.

PMID: 30937125 [PubMed]

Enantioselective Synthesis of 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) via Enzymatic Desymmetrization.

Org Lett. 2017 02 17;19(4):926-929

Authors: McLaughlin M, Kong J, Belyk KM, Chen B, Gibson AW, Keen SP, Lieberman DR, Milczek EM, Moore JC, Murray D, Peng F, Qi J, Reamer RA, Song ZJ, Tan L, Wang L, Williams MJ

Abstract
An enantioselective synthesis of the potent anti-HIV nucleoside EFdA is presented. Key features of stereocontrol include construction of the fully substituted 4'-carbon via a biocatalytic desymmetrization of 2-hydroxy-2-((triisopropylsilyl)ethynyl)propane-1,3-diyl diacetate and a Noyori-type asymmetric transfer hydrogenation to control the stereochemistry of the 3'-hydroxyl bearing carbon. The discovery of a selective crystallization of an N-silyl nucleoside intermediate enabled isolation of the desired β-anomer from the glycosylation step.

PMID: 28165251 [PubMed - indexed for MEDLINE]

Reinfection after treatment of first cerebrospinal fluid shunt infection: a prospective observational cohort study.

J Neurosurg Pediatr. 2018 04;21(4):346-358

Authors: Simon TD, Kronman MP, Whitlock KB, Gove NE, Mayer-Hamblett N, Browd SR, Cochrane DD, Holubkov R, Kulkarni AV, Langley M, Limbrick DD, Luerssen TG, Oakes WJ, Riva-Cambrin J, Rozzelle C, Shannon C, Tamber M, Wellons JC, Whitehead WE, Kestle JRW

Abstract
OBJECTIVE CSF shunt infection requires both surgical and antibiotic treatment. Surgical treatment includes either total shunt removal with external ventricular drain (EVD) placement followed by new shunt insertion, or distal shunt externalization followed by new shunt insertion once the CSF is sterile. Antibiotic treatment includes the administration of intravenous antibiotics. The Hydrocephalus Clinical Research Network (HCRN) registry provides a unique opportunity to understand reinfection following treatment for CSF shunt infection. This study examines the association of surgical and antibiotic decisions in the treatment of first CSF shunt infection with reinfection. METHODS A prospective cohort study of children undergoing treatment for first CSF infection at 7 HCRN hospitals from April 2008 to December 2012 was performed. The HCRN consensus definition was used to define CSF shunt infection and reinfection. The key surgical predictor variable was surgical approach to treatment for CSF shunt infection, and the key antibiotic treatment predictor variable was intravenous antibiotic selection and duration. Cox proportional hazards models were constructed to address the time-varying nature of the characteristics associated with shunt surgeries. RESULTS Of 233 children in the HCRN registry with an initial CSF shunt infection during the study period, 38 patients (16%) developed reinfection over a median time of 44 days (interquartile range [IQR] 19-437). The majority of initial CSF shunt infections were treated with total shunt removal and EVD placement (175 patients; 75%). The median time between infection surgeries was 15 days (IQR 10-22). For the subset of 172 infections diagnosed by CSF culture, the mean ± SD duration of antibiotic treatment was 18.7 ± 12.8 days. In all Cox proportional hazards models, neither surgical approach to infection treatment nor overall intravenous antibiotic duration was independently associated with reinfection. The only treatment decision independently associated with decreased infection risk was the use of rifampin. While this finding did not achieve statistical significance, in all 5 Cox proportional hazards models both surgical approach (other than total shunt removal at initial CSF shunt infection) and nonventriculoperitoneal shunt location were consistently associated with a higher hazard of reinfection, while the use of ultrasound was consistently associated with a lower hazard of reinfection. CONCLUSIONS Neither surgical approach to treatment nor antibiotic duration was associated with reinfection risk. While these findings did not achieve statistical significance, surgical approach other than total removal at initial CSF shunt infection was consistently associated with a higher hazard of reinfection in this study and suggests the feasibility of controlling and standardizing the surgical approach (shunt removal with EVD placement). Considerably more variation and equipoise exists in the duration and selection of intravenous antibiotic treatment. Further consideration should be given to the use of rifampin in the treatment of CSF shunt infection. High-quality studies of the optimal duration of antibiotic treatment are critical to the creation of evidence-based guidelines for CSF shunt infection treatment.

PMID: 29393813 [PubMed - indexed for MEDLINE]