UW Neurological Surgery Recent PubMed Publications

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]

Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.

Am J Hum Genet. 2019 04 04;104(4):665-684

Authors: Ferreira MAR, Mathur R, Vonk JM, Szwajda A, Brumpton B, Granell R, Brew BK, Ullemar V, Lu Y, Jiang Y, 23andMe Research Team, eQTLGen Consortium, BIOS Consortium, Magnusson PKE, Karlsson R, Hinds DA, Paternoster L, Koppelman GH, Almqvist C

Abstract
The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n = 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h2g = 25.6%) than for AOA (onset at ages between 20 and 60 years; h2g = 10.6%). The genetic correlation (rg) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h2g = 5%), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n = 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA- than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n = 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.

PMID: 30929738 [PubMed - indexed for MEDLINE]

Frontotemporal Dermal Sinus Tract with 2 Connected Intradiploic Dermoid Cysts: A Rare Case and Review of the Literature.

World Neurosurg. 2019 Jul;127:350-353

Authors: Barkley AS, Susarla SM, Lee A

Abstract
BACKGROUND: Frontotemporal dermal sinus tracts with associated dermoid cysts are very rare, with only 1 found in the largest series to date and 10 total documented case reports.
CASE DESCRIPTION: We present the first case to our knowledge of a dermal sinus tract associated with 2 intradiploic dermoid cysts in the rare location of the pterion and sphenosquamosal suture. The patient was a 15-month-old girl presenting with periorbital cellulitis who was found to have 2 connected intradiploic cysts on radiographic imaging. The mass was excised, and pathology was consistent with a ruptured dermoid cyst.
CONCLUSIONS: We review of the literature and argue for early identification and prophylactic surgical resection to avoid complications associated with infection and to mitigate risk of subtotal resection.

PMID: 30930322 [PubMed - indexed for MEDLINE]

Enhanced perioperative care and decreased cost and length of stay after elective major spinal surgery.

Neurosurg Focus. 2019 04 01;46(4):E5

Authors: Carr DA, Saigal R, Zhang F, Bransford RJ, Bellabarba C, Dagal A

Abstract
OBJECTIVEThe purpose of this study was to compare total cost and length of stay (LOS) between spine surgery patients enrolled in an enhanced perioperative care (EPOC) pathway and patients receiving traditional perioperative care (TRDC).METHODSAll spine surgery candidates were screened for inclusion in the EPOC pathway. This cohort was compared to a retrospective cohort of patients who received TRDC and a concurrent group of patients who met inclusion criteria but did not receive the EPOC (no pathway care [NOPC] group). Direct and indirect costs as well as hospital and intensive care LOSs were analyzed between the 3 groups.RESULTSTotal costs after pathway implementation decreased by $19,344 in EPOC patients compared to a historical cohort of patients who received TRDC and $5889 in a concurrent cohort of patients who did not receive EPOC (NOPC group). Hospital and intensive care LOS were significantly lower in EPOC patients compared to TRDC and NOPC patients.CONCLUSIONSThe implementation of a multimodal EPOC pathway decreased LOS and cost in major elective spine surgeries.

PMID: 30933922 [PubMed - indexed for MEDLINE]

A spatially dynamic network underlies the generation of inspiratory behaviors.

Proc Natl Acad Sci U S A. 2019 04 09;116(15):7493-7502

Authors: Baertsch NA, Severs LJ, Anderson TM, Ramirez JM

Abstract
The ability of neuronal networks to reconfigure is a key property underlying behavioral flexibility. Networks with recurrent topology are particularly prone to reconfiguration through changes in synaptic and intrinsic properties. Here, we explore spatial reconfiguration in the reticular networks of the medulla that generate breathing. Combined results from in vitro and in vivo approaches demonstrate that the network architecture underlying generation of the inspiratory phase of breathing is not static but can be spatially redistributed by shifts in the balance of excitatory and inhibitory network influences. These shifts in excitation/inhibition allow the size of the active network to expand and contract along a rostrocaudal medullary column during behavioral or metabolic challenges to breathing, such as changes in sensory feedback, sighing, and gasping. We postulate that the ability of this rhythm-generating network to spatially reconfigure contributes to the remarkable robustness and flexibility of breathing.

PMID: 30918122 [PubMed - indexed for MEDLINE]

Targeted copy number analysis outperforms histologic grading in predicting patient survival for WHO grades II/III IDH-mutant astrocytomas.

Neuro Oncol. 2019 06 10;21(6):819-821

Authors: Cimino PJ, Holland EC

PMID: 30918961 [PubMed - indexed for MEDLINE]

Effects of intrastriatal dopamine D1 or D2 antagonists on methamphetamine-induced egocentric and allocentric learning and memory deficits in Sprague-Dawley rats.

Psychopharmacology (Berl). 2019 Jul;236(7):2243-2258

Authors: Gutierrez A, Regan SL, Hoover CS, Williams MT, Vorhees CV

Abstract
RATIONALE: Methamphetamine (MA) is an abused psychostimulant that causes cognitive deficits after chronic use. Neostriatal dopamine receptors play a role in MA monoamine neurotoxicity. Blocking dopamine receptors prior to MA exposure in adult rats attenuates monoamine reductions and reactive gliosis.
OBJECTIVES: We tested whether blocking dopamine receptors protects against cognitive deficits.
METHODS: First, we determined the effects of MA alone versus MA in combination with the dopamine receptor D1 antagonist SCH-23390 or the dopamine receptor D2 antagonist sulpiride on cFos expression and monoamines at the age when rats in the cognitive experiment were to begin testing and monoamines in rats after cognitive testing.
RESULTS: SCH-23390 infused into the neostriatum prior to systemic administration of MA attenuated MA-induced cFos activation while sulpiride induced cFos activation. Two weeks after MA, rats had dopamine and serotonin reductions that were attenuated by each antagonist. Other rats treated the same way, were tested for egocentric learning and memory in the Cincinnati water maze, for navigational strategy in a star water maze, and spatial learning and memory in a Morris water maze. Pre-treatment with SCH-23390 or sulpiride attenuated the effects of MA on egocentric and spatial learning and memory. MA-treated rats showed a shift from an egocentric to a disorganized strategy in the star maze that was less disorganized in groups receiving MA and an antagonist. Post-behavior monoamine reductions remained but were attenuated by the antagonists but not identically to what was seen in rats not behaviorally tested.
CONCLUSIONS: The results show for the first time that dopamine receptors are mediators of MA-induced cognitive deficits.

PMID: 30919007 [PubMed - indexed for MEDLINE]

High level of capture of coronary intervention and associated acute coronary syndromes in the all New Zealand acute coronary syndrome quality improvement cardiac registry and excellent agreement with national administrative datasets (ANZACS-QI 25).

N Z Med J. 2019 03 29;132(1492):19-29

Authors: Kerr AJ, Lee M, Jiang Y, Grey C, Wells S, Williams M, Jackson R, Poppe K

Abstract
BACKGROUND: The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry was designed to collect data on all coronary angiograms and percutaneous coronary interventions (PCI) in New Zealand, and all acute coronary syndromes (ACS) associated with these procedures. This study compares the completeness of capture in ANZACS-QI of coronary procedures and ACS admissions with those recorded in the National Hospitalisation Dataset and evaluates data quality by assessing agreement in ACS diagnoses and coronary procedures between datasets.
METHODS: The national dataset, which included all New Zealand public hospital admissions in 2015 (n=962,700 episodes), was anonymously linked with the ANZACS-QI CathPCI (n=14,649 coronary angiogram episodes) and ACS cohorts (n=8,141 episodes) for 2015. Total numbers of coronary angiogram, PCI and ACS admissions were used as denominators and calculated by combining unique episodes from both data sources.
RESULTS: Of all coronary angiogram episodes (n=15,377) and all PCI episodes (n=5,711), 92% were captured in both datasets, 5% in the national dataset only and 3% in ANZACS-QI only. Overall, 95% of coronary angiogram and PCI episodes were captured in ANZACS-QI. Of ACS episodes with associated coronary angiography (n=8,237), 85% were captured. Overall, 54% of all ACS episodes (n=15,167) were captured, including 71% in <70-year-olds. Seventy-five percent of all ST-elevation myocardial infarctions (STEMI) were captured. Ninety percent of ACS diagnoses in ANZACS-QI had a matching diagnosis in the national dataset. There was excellent agreement in recorded gender, date of birth and ethnicity (>99%). Sub-type of ACS was also highly concordant for STEMI and non-STEMI diagnoses (92% and 89% agreement, respectively).
CONCLUSIONS: Consistent with its aim, the ANZACS-QI registry captured almost all New Zealand public hospital coronary angiography and PCI procedures including those associated with an ACS diagnosis. The high level of agreement between the registry and national dataset supports the use of both datasets for ongoing quality improvement reporting and research.

PMID: 30921308 [PubMed - indexed for MEDLINE]

Malaria Parasite Density in Individuals with Different Rapid Diagnostic Test Results and Concentrations of HRP2 Antigen.

Am J Trop Med Hyg. 2019 05;100(5):1202-1203

Authors: Plucinski MM, Dimbu PR, Fortes F, Murphy SC, Smith NT, Cruz KR, Seilie AM, Halsey ES, Aidoo M, Rogier E

Abstract
Low-density malaria infections are a source of human morbidity in endemic settings and potentially contribute to ongoing malaria transmission. Conventional rapid diagnostic tests (RDTs) were designed to detect clinically relevant parasite and antigen levels, but it is largely unknown what proportion of parasite (and antigen positive) infections are missed by conventional RDTs. Furthermore, RDTs can also provide false positives from lingering histidine-rich protein 2 (HRP2) antigenemia from a past infection. We analyzed 207 samples from Angolan outpatients with a bead-based HRP2 antigen assay and by qRT-PCR for the presence of parasite nucleic acids. Among patients HRP2 positive but negative by conventional RDT, the rate of quantitative reverse transcription-PCR (qRT-PCR) positivity was 45% (95% CI: 35-56%), with a median parasitemia of 3.4 parasites/µL (interquartile range: 0.14-4.8). Only 15% (7-26%) of HRP2-negative samples were found to have parasite nucleic acids. A substantial proportion of persons with blood HRP2 antigen concentrations not detected by the conventional RDT were found to have evidence of active infection, but at low parasite density levels.

PMID: 30915959 [PubMed - indexed for MEDLINE]

Divergent 6-Month Functional Recovery Trajectories and Predictors after Traumatic Brain Injury: Novel Insights from the COBRIT Study.

J Neurotrauma. 2019 Mar 26;:

Authors: Gardner RC, Cheng J, Ferguson AR, Boylan R, Boscardin WJ, Zafonte RD, Manley GT, Bagiella E, Ansel BM, Novack TA, Friedewald WT, Hesdorffer DC, Timmons S, Jallo J, Eisenberg H, Hart T, Ricker JH, Diaz-Arrastia R, Merchant R, Temkin NR, Melton S, Dikmen S, Okonkwo DO

Abstract
Cross-sectional approaches to outcome assessment may not adequately capture heterogeneity in recovery after traumatic brain injury (TBI). Using latent class mixed models (LCMM), a data-driven analytic that identifies groups of patients with similar trajectories, we identified distinct 6-month functional recovery trajectories in a large cohort (n=1,046) of adults age 18-70 years with complicated mild to severe TBI who participated in the Citicoline Brain Injury Treatment Trial (COBRIT). We used multinomial logistic fixed effect models and backward elimination, forward selection, and forward stepwise selection with several stopping rules to explore baseline predictors of functional recovery trajectory. Based on statistical and clinical considerations, the 7-class model was deemed superior. Visualization of these 7 functional recovery trajectories revealed that each trajectory class started at one of 3 recovery levels at 1-month, which, for ease of reference we labeled groups A-C: Group A. good recovery (2 classes; A1 and A2), Group B. moderate disability (2 classes; B1 and B2), Group C. severe disability (3 classes; C1, C2, and C3). By 6-months, these 3 groups experienced dramatically divergent trajectories: A experienced stable good recovery (A1, n=115) or dramatic decline (A2, n=4); B, rapid complete recovery (B1, n=71) or gradual recovery (B2, n=742); C, dramatic rapid recovery (C1, n=12), no recovery (C2, n=91), or death (C3, n=11). Trajectory class membership was not predicted by citicoline treatment (p=0.57). The models identified demographic, pre-injury, and injury-related predictors of functional recovery trajectory, including: age, race, education, pre-injury employment, pre-injury diabetes, pre-injury psychiatric disorder, site, Glasgow Coma Scale (GCS), post-traumatic amnesia, TBI mechanism, major extracranial injury, hemoglobin, and acute CT findings. GCS was the most consistently selected predictor across all models. All models also selected at least one demographic or pre-injury medical predictor. LCMM successfully identified dramatically divergent, clinically meaningful 6-month recovery trajectories with utility to inform clinical trial design.

PMID: 30909795 [PubMed - as supplied by publisher]