UW Neurological Surgery Recent PubMed Publications

Traumatic Fetal Subdural Hematoma and Unstable Maternal Spine Fracture.

World Neurosurg. 2020 10;142:368-370

Authors: Young CC, Hofstetter CP

Abstract
We present a remarkable image of a woman, 24 weeks pregnant, who sustained polytrauma after a high-speed motor vehicle collision. Evaluation revealed traumatic bilateral subdural hematoma in the fetus and an unstable T12-L1 fracture in the patient. The standard of care for her unstable fracture was surgical fixation; however, this was hampered by the desire to continue the pregnancy in the interest of the premature fetus. This case presented a unique additional consideration in the management of the polytrauma neurosurgery patient and underscores the importance of coordinated team work and patient counseling to achieve the optimal patient outcome.

PMID: 32683009 [PubMed - indexed for MEDLINE]

Percutaneous cervical cordotomy for cancer-related pain: national data (response to letter by Professor S Mercadante).

BMJ Support Palliat Care. 2020 12;10(4):414

Authors: Poolman M, Makin M, Briggs J, Scofield K, Campkin N, Williams M, Sharma ML, Laird B, Mayland CR, INPIC Group

PMID: 32680892 [PubMed - indexed for MEDLINE]

Managing central venous access during a health care crisis.

J Vasc Surg. 2020 Oct;72(4):1184-1195.e3

Authors: Chun TT, Judelson DR, Rigberg D, Lawrence PF, Cuff R, Shalhub S, Wohlauer M, Abularrage CJ, Anastasios P, Arya S, Aulivola B, Baldwin M, Baril D, Bechara CF, Beckerman WE, Behrendt CA, Benedetto F, Bennett LF, Charlton-Ouw KM, Chawla A, Chia MC, Cho S, Choong AMTL, Chou EL, Christiana A, Coscas R, De Caridi G, Ellozy S, Etkin Y, Faries P, Fung AT, Gonzalez A, Griffin CL, Guidry L, Gunawansa N, Gwertzman G, Han DK, Hicks CW, Hinojosa CA, Hsiang Y, Ilonzo N, Jayakumar L, Joh JH, Johnson AP, Kabbani LS, Keller MR, Khashram M, Koleilat I, Krueger B, Kumar A, Lee CJ, Lee A, Levy MM, Lewis CT, Lind B, Lopez-Pena G, Mohebali J, Molnar RG, Morrissey NJ, Motaganahalli RL, Mouawad NJ, Newton DH, Ng JJ, O'Banion LA, Phair J, Rancic Z, Rao A, Ray HM, Rivera AG, Rodriguez L, Sales CM, Salzman G, Sarfati M, Savlania A, Schanzer A, Sharafuddin MJ, Sheahan M, Siada S, Siracuse JJ, Smith BK, Smith M, Soh I, Sorber R, Sundaram V, Sundick S, Tomita TM, Trinidad B, Tsai S, Vouyouka AG, Westin GG, Williams MS, Wren SM, Yang JK, Yi J, Zhou W, Zia S, Woo K

Abstract
OBJECTIVE: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic.
METHODS: We conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19.
RESULTS: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group).
CONCLUSIONS: Implementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises.

PMID: 32682063 [PubMed - indexed for MEDLINE]

Comparison of tumor-associated YAP1 fusions identifies a recurrent set of functions critical for oncogenesis.

Genes Dev. 2020 Jul 16;:

Authors: Szulzewsky F, Arora S, Hoellerbauer P, King C, Nathan E, Chan M, Cimino PJ, Ozawa T, Kawauchi D, Pajtler KW, Gilbertson RJ, Paddison PJ, Vasioukhin V, Gujral TS, Holland EC

Abstract
YAP1 is a transcriptional coactivator and the principal effector of the Hippo signaling pathway, which is causally implicated in human cancer. Several YAP1 gene fusions have been identified in various human cancers and identifying the essential components of this family of gene fusions has significant therapeutic value. Here, we show that the YAP1 gene fusions YAP1-MAMLD1, YAP1-FAM118B, YAP1-TFE3, and YAP1-SS18 are oncogenic in mice. Using reporter assays, RNA-seq, ChIP-seq, and loss-of-function mutations, we can show that all of these YAP1 fusion proteins exert TEAD-dependent YAP activity, while some also exert activity of the C'-terminal fusion partner. The YAP activity of the different YAP1 fusions is resistant to negative Hippo pathway regulation due to constitutive nuclear localization and resistance to degradation of the YAP1 fusion proteins. Genetic disruption of the TEAD-binding domain of these oncogenic YAP1 fusions is sufficient to inhibit tumor formation in vivo, while pharmacological inhibition of the YAP1-TEAD interaction inhibits the growth of YAP1 fusion-expressing cell lines in vitro. These results highlight TEAD-dependent YAP activity found in these gene fusions as critical for oncogenesis and implicate these YAP functions as potential therapeutic targets in YAP1 fusion-positive tumors.

PMID: 32675324 [PubMed - as supplied by publisher]

Glucose promotes epithelial-mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ.

J Cell Mol Med. 2020 Jul 17;:

Authors: Li S, Zhu H, Chen H, Xia J, Zhang F, Xu R, Lin Q

Abstract
Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial-mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high-glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC-3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT-associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High-glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high-glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D.

PMID: 32678516 [PubMed - as supplied by publisher]

Prenatal exposure to PCBs in Cyp1a2 knock-out mice interferes with F1 fertility, impairs long-term potentiation, reduces acoustic startle and impairs conditioned freezing contextual memory with minimal transgenerational effects.

J Appl Toxicol. 2019 04;39(4):603-621

Authors: Hufgard JR, Sprowles JLN, Pitzer EM, Koch SE, Jiang M, Wang Q, Zhang X, Biesiada J, Rubinstein J, Puga A, Williams MT, Vorhees CV

Abstract
Polychlorinated biphenyls (PCBs) are toxic environmental pollutants. Humans are exposed to PCB mixtures via contaminated food or water. PCB exposure causes adverse effects in adults and after exposure in utero. PCB toxicity depends on the congener mixture and CYP1A2 gene activity. For coplanar PCBs, toxicity depends on ligand affinity for the aryl hydrocarbon receptor (AHR). Previously, we found that perinatal exposure of mice to a three-coplanar/five-noncoplanar PCB mixture induced deficits in novel object recognition and trial failures in the Morris water maze in Cyp1a2-/- ::Ahrb1 C57BL6/J mice compared with wild-type mice (Ahrb1  = high AHR affinity). Here we exposed gravid Cyp1a2-/- ::Ahrb1 mice to a PCB mixture on embryonic day 10.5 by gavage and examined the F1 and F3 offspring (not F2 ). PCB-exposed F1 mice exhibited increased open-field central time, reduced acoustic startle, greater conditioned contextual freezing and reduced CA1 hippocampal long-term potentiation with no change in spatial learning or memory. F1 mice also had inhibited growth, decreased heart rate and cardiac output, and impaired fertility. F3 mice showed few effects. Gene expression changes were primarily in F1 PCB males compared with wild-type males. There were minimal RNA and DNA methylation changes in the hippocampus from F1 to F3 with no clear relevance to the functional effects. F0 PCB exposure during a period of rapid DNA de-/remethylation in a susceptible genotype produced clear F1 effects with little evidence of transgenerational effects in the F3 generation. While PCBs show clear developmental neurotoxicity, their effects do not persist across generations for effects assessed herein.

PMID: 30561030 [PubMed - indexed for MEDLINE]

Factors Associated With Medication Adherence in Vascular Surgery Patients.

Vasc Endovascular Surg. 2020 Oct;54(7):625-632

Authors: Minami HR, Zemela MS, Ring AC, Williams MS, Smeds MR

Abstract
INTRODUCTION: Patients with vascular disease have higher mortality rates than age-matched peers and medical management of coexisting diseases may alter these outcomes. We sought to understand factors associated with medication nonadherence in vascular surgery patients at a single University vascular surgery clinic over a 3-month period.
MATERIALS AND METHODS: Consecutive vascular surgery patients were surveyed from June to August 2019. The survey included demographic questions, the validated Morisky Medication Adherence Scale, the 4-item Patient Health Questionnaire for Anxiety and Depression scales, and other medication-related questions. Medical and surgical histories were retrospectively collected from charts. Univariate and multivariate analyses were used to compare among high, intermediate, and low adherence.
RESULTS: A total of 128 (74%) of 174 patients met study inclusion criteria. On univariate analysis, lower medication adherence was associated with younger age (P = .004), anxiety and depression (P = .001), higher daily pain (P < .001), and patients who believed their medications were less important for treating their vascular disease (P < .001). Adherence was not associated with symptomatic vascular disease, gender, education level, marital status, employment, insurance, or the use of medication usage reminders. Multivariate analysis significantly predicted high adherence relative to low adherence with 5-year increase in age (odds ratio [OR] = 1.252, P = .021) and low adherence relative to high adherence with greater perceived pain (OR = 0.839, P = .016).
CONCLUSIONS: Younger age and high level of pain were associated with lower medication adherence. Informing patients of the importance of prescribed medication and addressing anxiety or depression symptoms may improve adherence.

PMID: 32666902 [PubMed - indexed for MEDLINE]

"Do Not Ignore Musculoskeletal Pain"-Initial Presentation of a Rare Malignant Disease: Case Report and Literature Review.

J Investig Med High Impact Case Rep. 2020 Jan-Dec;8:2324709620941316

Authors: Patel I, Akoluk A, Upadhyaya V, Makadia S, Douedi S, Farooq T, Flynn D, Levitt M, Hossain MA

Abstract
Gray zone lymphoma, also known as B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a rare malignancy with overlapping features of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma. Most commonly mediastinal involvement is seen. Extranodal involvement is rare. In this case report, we present the case of a 59-year-old male who presented with stress-related left shoulder pain, ultimately diagnosed with gray zone lymphoma. The patient was treated with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin-rituximab (EPOCH-R) regimen followed by consolidation radiotherapy resulting in complete response. We are highlighting this case as rare and atypical presentation of a rare disease.

PMID: 32660277 [PubMed - in process]

Impact of lordotic cages in the restoration of spinopelvic parameters after dorsal lumbar interbody fusion: a retrospective case control study.

Int Orthop. 2020 Jul 13;:

Authors: Oikonomidis S, Heck V, Bantle S, Scheyerer MJ, Hofstetter C, Budde S, Eysel P, Bredow J

Abstract
PURPOSE: Aim of this study was to compare the reconstruction of radiological sagittal spinopelvic parameters between lordotic (10°) and normal cages (0°) after dorsal lumbar spondylodesis.
METHODS: This retrospective monocentric study included patients who received dorsal lumbar spondylodesis between January 2014 and December 2018. Inclusion criteria were degenerative lumbar diseases and mono- or bi-segmental fusions in the middle and lower lumbar region. Exclusion criteria were long-distance fusions (3 segments and more) and infectious and tumour-related diseases. The sagittal spinopelvine parameters (lumbar lordosis, segmental lordosis, sacral slope, pelvic incidence, and pelvic tilt) were measured pre- and post-operatively by two examiners at two different times. The patients were divided into 2 groups (group 1: lordotic cage, group 2: normal cage).
RESULTS: One hundred thirty-eight patients (77 female, 61 male) with an average age of 66.6 ± 11.2 years (min.: 26, max.: 90) were included in the study based on the inclusion criteria. Ninety-two patients (66.7%) received 0° cages and 46 (33.3%) lordotic cages (10°). Segmental lordosis was increased by 4.2° on average in group 1 and by 6.5° in group 2 (p = 0.074). Average lumbar lordosis was increased by 2.1° in group 1 and by 0.6° in group 2 (p = 0.378). There was no significant difference in the correction of sagittal spinopelvic parameters. Inter- and inter-class reliability was between 0.887 and 0.956.
CONCLUSION: According to the results of our study, no advantages regarding sagittal radiological parameters for the implantation of a lordotic cage could be demonstrated.

PMID: 32661634 [PubMed - as supplied by publisher]

Do Counter-Narratives Reduce Support for ISIS? Yes, but Not for Their Target Audience.

Front Psychol. 2020;11:1059

Authors: Bélanger JJ, Nisa CF, Schumpe BM, Gurmu T, Williams MJ, Putra IE

Abstract
The purpose of this research is to experimentally test whether counter-narratives are effective to reduce people's support and willingness to join Islamic State of Iraq and Syria (ISIS). Integrating psychological reactance theory (Brehm, 1966) and need for closure (NFC; Kruglanski, 2004), we predicted that exposing people to counter-narratives when they are at greater risk of radicalization (high NFC individuals) would be counterproductive and enhance their support for ISIS. Participants (N = 886 American Muslims) were randomly assigned to a 3 × 3 factorial experimental design varying the source (United States Government, Imam, ISIS defector), and the content (social, political, and religious) of the counter-narrative while comparing these groups to a control message. Results show an overall small positive effect of counter-narratives (β = -0.107, p = 0.043), but also evidence for greater support for ISIS in individuals at greater risk of radicalization (β = 0.154, p = 0.005). Results also show that the content was more important than the source: A political narrative was the most effective, and this result is consistent across different sources although an ISIS defector is the most effective messenger. These findings challenge the widespread assumption that counter-narratives are effective against violent extremism. In fact, they accelerate the very phenomenon that governments and policy makers are trying to undermine. Therefore, policy makers should avoid including them in their armamentarium to tackle violent extremism.

PMID: 32655429 [PubMed]

Full endoscopic unilateral laminotomy for bilateral decompression of the cervical spine: surgical technique and early experience.

J Spine Surg. 2020 Jun;6(2):447-456

Authors: Carr DA, Abecassis IJ, Hofstetter CP

Abstract
Background: Full-endoscopic decompression surgery has been shown to be safe and efficacious in the lumbar spine, while its role remains to be determined in the cervical spine. We describe the utility of cervical endoscopic unilateral laminotomy for bilateral decompression (CE-ULBD) in a series of elderly patients with severe central stenosis, significant medical comorbidity, and existing cervical deformity.
Methods: A prospectively collected spine surgery registry at the University of Washington was retrospectively queried for patients with cervical spondylotic myelopathy receiving CE-ULBD. Demographic data, operative details, imaging, and patient reported outcomes, including visual analogue scale (VAS) for neck and upper extremity pain, Nurick grade, and the modified Japanese Orthopedic Association (mJOA) score, were reviewed. Description of the surgical technique is provided. Descriptive statistics were calculated.
Results: From 2014 through 2018, 10 patients with an average age of 70.2±5.0 years underwent CE-ULBD for symptomatic upper cervical stenosis due to ligamentum flavum buckling. Half of these patients had one stenotic segment, the other half had two stenotic segments. The most commonly affected segment was C3/4 (5/10 patients). Average length of surgery was 128±18.4 minutes. Average length of stay was 1.2±0.2 days. Average clinical follow-up time was 22.0±4.7 months; clinical outcomes at most recent follow-up were improved via both the Nurick grade (1.2±0.4, P<0.01) and modified Japanese Orthopedic Association (14.6±1.0, P<0.001) compared with pre-operative values. One patient experienced a transient loss of motor evoked potentials intraoperatively, but there were no cases of permanent neurological deficit.
Conclusions: Severe central cervical stenosis is a safe and viable target for full-endoscopic decompression via an interlaminar approach.

PMID: 32656382 [PubMed]

Microsurgical Resection of a Primary Intraosseous Meningioma Encasing the Superior Sagittal Sinus.

J Craniofac Surg. 2020 Jul 10;:

Authors: Ene CI, Kurnik N, Vellimana AK, Liu Y, Susarla SM, Sekhar LN

Abstract
Primary intraosseous meningiomas (PIMs) are an infrequent variant of meningiomas characterized by hyperostosis and brain compression. En bloc surgical resection of giant PIMs involving critical structures such as venous sinuses or cranial nerves could be associated with significant morbidity. The objective of this report is to demonstrate the safety and feasibility of piecemeal resection of PIMs involving the superior sagittal sinus and frontal sinus. A 54-year-old female with a large 5 cm thick bifrontal primary intra-osseous meningioma encasing the anterior segment of the superior sagittal sinus and frontal sinus underwent a bifrontal craniotomy with piecemeal microsurgical resection of the lesion, complete frontal sinus exoneration, and a synthetic cranioplasty. Clinical outcome was measured by extent of resection, preservation of cortical draining veins and postoperative course. A Simpson grade I resection of the lesion was achieved following piecemeal resection of the giant PIM without clinical or radiographic evidence of venous infarct or injury. The postoperative course was uncomplicated, and the patient was discharged home 3 days after cranioplasty. A complete resection of a giant bifrontal PIM with superior sagittal sinus encasement and frontal sinus involvement can be achieved safely via a piecemeal approach without significant intra-operative morbidity.

PMID: 32657980 [PubMed - as supplied by publisher]

Unnecessary hesitancy on human vaccine tests-Response.

Science. 2020 07 10;369(6500):151

Authors: Shah SK, Miller FG, Darton TC, Duenas D, Emerson C, Lynch HF, Jamrozik E, Jecker NS, Kamuya D, Kapulu M, Kimmelman J, MacKay D, Memoli MJ, Murphy SC, Palacios R, Richie TL, Roestenberg M, Saxena A, Saylor K, Selgelid MJ, Vaswani V, Rid A

PMID: 32646992 [PubMed - indexed for MEDLINE]

Multicenter phase II study of Cabazitaxel in advanced gastroesophageal cancer: Association of HER2 Expression and M2-like Tumor Associated Macrophages with Patient Outcome.

Clin Cancer Res. 2020 Jul 08;:

Authors: Shah MA, Enzinger P, Ko AH, Ocean AJ, Philip PA, Thakkar PV, Cleveland K, Lu Y, Kortmansky J, Christos PJ, Zhang C, Kaur N, Elmonshed D, Galletti G, Sarkar S, Bhinder B, Pittman ME, Plotnikova OM, Kotlov N, Frenkel FE, Bagaev AV, Elemento O, Betel D, Giannakakou P, Lenz HJ

Abstract
PURPOSE: Purpose: We examined cabazitaxel, a novel next generation taxoid, in patients with metastatic gastric cancer in a multicenter phase II study.
EXPERIMENTAL DESIGN: Patients that have progressed on 1 or more prior therapies for locally advanced, unresectable or metastatic disease, were eligible and prior taxane therapy was allowed. Taxane-naïve and pretreated cohorts were analyzed independently for efficacy. The primary endpoint for both cohorts was progression-free survival (PFS) using RECIST 1.1, using a Simon's two-stage design (10% significance, 80% power) for both cohorts. Comprehensive molecular annotation included whole exome and bulk RNA sequencing.
RESULTS: Fifty-three patients enrolled in the taxane-naïve cohort (Arm A), and 23 patients in the prior-taxane cohort (Arm B), from January 8, 2013 to April 8, 2015: median age 61.7 years (range 35.5 - 91.8 years), 66% male, 66% Caucasian. The most common adverse events included neutropenia (17% Arm A, 39% Arm B), fatigue/muscle weakness (13%), and hematuria (12%). In Arm A, the 3-month PFS rate was 28% (95%CI 17-42%), and did not meet the pre-specified efficacy target. The 3-month PFS rate in Arm B was 35% (95% CI 16-57%), and surpassed its efficacy target. HER2 amplification or over-expression was associated with improved disease control (P=0.003), PFS (p=0.04) and overall survival (p=0.002). An M2 macrophage signature was also associated with improved survival (p=0.031).
CONCLUSIONS: Cabazitaxel has modest activity in advanced gastric cancer, including in patients previously treated with taxanes. Her2 amplification/overexpression and M2 high macrophage signature are potential biomarkers for taxane efficacy that warrant further evaluation.

PMID: 32641434 [PubMed - as supplied by publisher]

A quick and reliable estimate of extended high-frequency hearing.

Int J Audiol. 2020 Jul 09;:1-5

Authors: Prendergast G, Hymers M, Lee A

Abstract
Objective: To encourage researchers to perform high-frequency threshold estimation using a technique outlined by Rieke and colleagues, described as fixed-level frequency threshold estimation. Their method used a Bekesy-style roving tone to estimate the highest audible frequency of a listener. The tone was fixed in its intensity (SPL) and changed in frequency as the participant indicated whether they could perceive the tone, or not. This was developed specifically for ototoxicity monitoring in the extended high-frequency region. Rieke and colleagues established that this approach to measuring hearing thresholds is both fast and reliable.Design: The current article extends this approach to using a simple PC-soundcard-transducer setup and the method of limits to rapidly establish the highest audible frequency of a listener.Study sample: 24 listeners performed standard and fixed-level audiometry in the extended high-frequency range.Results: The method described is rapid and reliable and a single summary metric is obtained for each listener.Conclusions: The advantage of the described approach over standard pure-tone audiometry in the extended high-frequency range is the time taken, the ability to avoid missing data points and the risk of distortions or electrical noise when close to maximal system output.

PMID: 32643465 [PubMed - as supplied by publisher]

Extended lumbar drainage in idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis of diagnostic test accuracy.

Br J Neurosurg. 2020 Jul 09;:1-7

Authors: Nunn AC, Jones HE, Morosanu CO, Singleton WGB, Williams MA, Nagel SJ, Luciano MG, Zwimpfer TJ, Holubkov R, Wisoff JH, McKhann GM, Hamilton MG, Edwards RJ

Abstract
BACKGROUND: When appropriately selected, a high proportion of patients with suspected idiopathic normal pressure hydrocephalus (iNPH) will respond to cerebrospinal fluid diversion with a shunt. Extended lumbar drainage (ELD) is regarded as the most accurate test for this condition, however, varying estimates of its accuracy are found in the current literature. Here, we review the literature in order to provide summary estimates of sensitivity, specificity, positive- and negative predictive value for this test through meta-analysis of suitably rigorous studies.
METHODS: Studies involving a population of NPH patients with predominantly idiopathic aetiology (>80%) in which the intention of the study was to shunt patients regardless of the outcome of ELD were included in the review. Various literature databases were searched to identify diagnostic test accuracy studies addressing ELD in the diagnosis of iNPH. Those studies passing screening and eligibility were assessed using the QUADAS-2 tool and data extracted for bivariate random effects meta-analysis.
RESULTS: Four small studies were identified. They showed disparate results concerning diagnostic test accuracy. The summary estimates for sensitivity and specificity were 94% (CI 41-100%) and 85% (CI 33-100%), respectively. The summary estimates of positive and negative predictive value were both 90% (CIs 65-100% and 48-100%, respectively).
CONCLUSION: Large, rigorous studies addressing the diagnostic accuracy of ELD are lacking, and little robust evidence exists to support the use of ELD in diagnostic algorithms for iNPH. Therefore, a large cohort study, or ideally an RCT, is needed to determine best practice in selecting patients for shunt surgery.

PMID: 32643967 [PubMed - as supplied by publisher]

Safety, pharmacokinetics and causal prophylactic efficacy of KAF156 in a Plasmodium falciparum human infection study.

Clin Infect Dis. 2020 Jul 09;:

Authors: Kublin JG, Murphy SC, Maenza J, Seilie AM, Jain JP, Berger D, Spera D, Zhao R, Soon RL, Czartoski JL, Potochnic MA, Duke E, Chang M, Vaughan A, Kappe SHI, Leong FJ, Pertel P, Prince WT

Abstract
BACKGROUND: KAF156 is a novel antimalarial drug that is active against both liver- and blood- stage Plasmodium parasites, including drug-resistant strains. Here, we investigated the causal prophylactic efficacy of KAF156 in a controlled human malaria infection (CHMI) model.
METHODS: In Part 1, healthy, malaria-naïve participants received 800 mg KAF156 or placebo three hr before CHMI with Pf-infected mosquitoes. In Part 2, KAF156 was administered as single doses of 800, 300, 100, 50, or 20 mg 21 hr post-CHMI. All participants received atovaquone/proguanil treatment if blood-stage infection was detected or on day 29. For each cohort, 7-14 subjects were enrolled to KAF156 treatment and up to four subjects to placebo.
RESULTS: KAF156 at all dose levels was safe and well tolerated. Two serious adverse events were reported - both resolved without sequelae and neither was considered related to KAF156. In Part 1, all participants treated with KAF156 and none of those randomized to placebo were protected against malaria infection. In Part 2, all participants treated with placebo or 20 mg KAF156 developed malaria infection. In contrast, 50 mg KAF156 protected 3/14 participants from infection, and doses of 800, 300, and 100 mg KAF156 protected all subjects against infection. An exposure-response analysis suggested that a 24-hr post-dose concentration of KAF156 of 21·5 ng/mL (90% CI 17.66 to 25.32 ng/mL) would ensure a 95% chance of protection from malaria parasite infection.
CONCLUSIONS: KAF156 was safe and well tolerated and demonstrated high levels of pre- and post-CHMI protective efficacy.

PMID: 32644127 [PubMed - as supplied by publisher]

Changes in the Preterm Heart From Birth to Young Adulthood: A Meta-analysis.

Pediatrics. 2020 08;146(2):

Authors: Telles F, McNamara N, Nanayakkara S, Doyle MP, Williams M, Yaeger L, Marwick TH, Leeson P, Levy PT, Lewandowski AJ

Abstract
CONTEXT: Preterm birth is associated with incident heart failure in children and young adults.
OBJECTIVE: To determine the effect size of preterm birth on cardiac remodeling from birth to young adulthood.
DATA SOURCES: Data sources include Medline, Embase, Scopus, Cochrane databases, and clinical trial registries (inception to March 25, 2020).
STUDY SELECTION: Studies in which cardiac phenotype was compared between preterm individuals born at <37 weeks' gestation and age-matched term controls were included.
DATA EXTRACTION: Random-effects models were used to calculate weighted mean differences with corresponding 95% confidence intervals.
RESULTS: Thirty-two observational studies were included (preterm = 1471; term = 1665). All measures of left ventricular (LV) and right ventricular (RV) systolic function were lower in preterm neonates, including LV ejection fraction (P = .01). Preterm LV ejection fraction was similar from infancy, although LV stroke volume index was lower in young adulthood. Preterm LV peak early diastolic tissue velocity was lower throughout development, although preterm diastolic function worsened with higher estimated filling pressures from infancy. RV longitudinal strain was lower in preterm-born individuals of all ages, proportional to the degree of prematurity (R 2 = 0.64; P = .002). Preterm-born individuals had persistently smaller LV internal dimensions, lower indexed LV end-diastolic volume in young adulthood, and an increase in indexed LV mass, compared with controls, of 0.71 g/m2 per year from childhood (P = .007).
LIMITATIONS: The influence of preterm-related complications on cardiac phenotype could not be fully explored.
CONCLUSIONS: Preterm-born individuals have morphologic and functional cardiac impairments across developmental stages. These changes may make the preterm heart more vulnerable to secondary insults, potentially underlying their increased risk of early heart failure.

PMID: 32636236 [PubMed - indexed for MEDLINE]

Evaluation of the Patient-Practitioner Consultation on Surgical Treatment Options for Patients With Craniosynostosis.

J Craniofac Surg. 2020 Jul-Aug;31(5):1186-1190

Authors: Pfeifauf KD, Said AM, Naidoo SD, Skolnick GB, Kestle JRW, Lee A, Birgfeld C, Anderson RCE, Gociman B, Siddiqi FA, Pollack IF, Goldstein JA, Tamber M, Imahiyerobo T, Smyth MD, Patel KB, Synostosis Research Group

Abstract
INTRODUCTION: Endoscope-assisted craniectomy and spring-assisted cranioplasty with post-surgical helmet molding are minimally invasive alternatives to the traditional craniosynostosis treatment of open cranial vault remodeling. Families are often faced with deciding between techniques. This study aimed to understand providers' practice patterns in consulting families about surgical options.
METHODS: An online survey was developed and distributed to 31 providers. The response rate was 84% (26/31).
RESULTS: Twenty-six (100%) respondents offer a minimally invasive surgical option for sagittal craniosynostosis, 21 (81%) for coronal, 20 (77%) for metopic, 18 (69%) for lambdoid, and 12 (46%) for multi-suture. Social issues considered in determining whether to offer a minimally invasive option include anticipated likelihood of compliance (23 = 88%), distance traveled for care (16 = 62%) and financial considerations (6 = 23%). Common tools to explain options include verbal discussion (25 = 96%), 3D reconstructed CT scans (17 = 65%), handouts (13 = 50%), 3D models (12 = 46%), hand drawings (11 = 42%) and slides (10 = 38%). Some respondents strongly (7 = 27%) or somewhat (3 = 12%) encourage a minimally invasive option over open repair. Others indicate they remain neutral (7 = 27%) or tailor their approach to meet perceived needs (8 = 31%). One (4%) somewhat encourages open repair. Despite this variation, all completely (17 = 65%), strongly (5 = 19%) or somewhat agree (4 = 15%) they use shared decision making in presenting surgical options.
CONCLUSION: This survey highlights the range of practice patterns in presenting surgical options to families and reveals possible discrepancies in the extent providers believe they use shared decision making and the extent it is actually used.

PMID: 32634133 [PubMed - indexed for MEDLINE]

Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis.

J Allergy Clin Immunol. 2020 Jul 04;:

Authors: Cau L, Williams MR, Butcher AM, Nakatsuji T, Kavanaugh JS, Cheng JY, Shafiq F, Higbee K, Hata TR, Horswill AR, Gallo RL

Abstract
BACKGROUND: S. aureus and S. epidermidis are the most abundant bacteria found on the skin of patients with atopic dermatitis (AD). S. aureus is known to exacerbate AD while S. epidermidis was considered as a beneficial commensal organism.
OBJECTIVE: In this study, we hypothesized that S. epidermidis could promote skin damage in AD by the production of a protease that damages the epidermal barrier.
METHODS: Protease activity of S. epidermidis isolates was compared with other staphylococcal species. The capacity of S. epidermidis to degrade the barrier and induce inflammation was examined using human keratinocyte tissue culture and mouse models. Skin swabs from atopic and healthy adult subjects were analyzed for the presence of S. epidermidis genomic DNA and mRNA.
RESULTS: S. epidermidis strains were observed to produce strong cysteine protease activity when grown at high density. The enzyme responsible for this activity was identified to be EcpA, a cysteine protease under quorum sensing control. EcpA was shown to degrade desmoglein-1 and LL-37 in vitro and disrupted the physical barrier and induced skin inflammation in mice. The abundance of S. epidermidis and expression of ecpA mRNA were increased on the skin of some patients with AD and this correlated with disease severity. Another commensal skin bacterial species, S. hominis, can inhibit EcpA production by S. epidermidis.
CONCLUSION: S. epidermidis was commonly regarded as a beneficial skin microbe while S. aureus considered to be deleterious. This study suggests that the overabundance of S. epidermidis found on some atopic patients can act similarly to S. aureus and damage the skin by expression of a cysteine protease.

PMID: 32634452 [PubMed - as supplied by publisher]