UW Neurological Surgery Recent PubMed Publications

A retrospective descriptive study of cranioplasty failure rates and contributing factors in novel 3D printed calcium phosphate implants compared to traditional materials.

3D Print Med. 2020 Jun 17;6(1):14

Authors: Koller M, Rafter D, Shok G, Murphy S, Kiaei S, Samadani U

Abstract
BACKGROUND: Failure rates with cranioplasty procedures have driven efforts to improve graft material and reduce reoperation. One promising allograft source is a 3D-printed titanium mesh with calcium phosphate filler. This study evaluated failure rates and pertinent characteristics of these novel 3D-grafts compared to traditional materials.
METHODS: Sixty patients were retrospectively identified who underwent a cranioplasty between January 2015-December 2017. Specific data points related to graft failure were collected for all surgical admissions, from the primary injury to their most recent. These included, but were not limited to, initial physical exam findings, vitals, comorbid conditions, surgery length, estimated blood loss, incision type, and need for revision. Failure rates of 3D-printed allografts were compared to traditional grafts.
RESULTS: A total of 60 subjects were identified who underwent 71 unique cranioplasty procedures (3D = 13, Synthetic = 12, Autologous = 46). There were 14 total failures, demonstrating a 19.7% overall failure rate. Specifically, 15.4% (n = 2) of 3D, 19.6% (n = 9) of autologous, and 25.0% (n = 3) of synthetic grafts required revision. Patients receiving 3D-grafts had the shortest overall mean surgery times (200.8 ± 54.3 min) and lowest infection rates (7.7%) compared to autologous (210.5 ± 47.9 min | 25.0%) and synthetic models (217.6 ± 77.3 min | 8.7%), though significance was unable to be determined. Tobacco use and trap-door incisions were associated with increased failure rates relative to straight or curved incisions in autologous grafts. Cranioplasties performed less than 3 months after craniectomy appeared to fail more often than those performed at least three months after craniectomy, for the synthetic group.
CONCLUSION: We concluded that 3D-printed cranioplasty grafts may lead to lower failure rates and shorter surgery times compared to traditional cranioplasty materials in our limited population. 3D-implants hold promise for cranial reconstruction after TBI.

PMID: 32556704 [PubMed]

Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children's Hospital experience.

J Neurooncol. 2020 Jun 16;:

Authors: Crotty EE, Leary SES, Geyer JR, Olson JM, Millard NE, Sato AA, Ermoian RP, Cole BL, Lockwood CM, Paulson VA, Browd SR, Ellenbogen RG, Hauptman JS, Lee A, Ojemann JG, Vitanza NA

Abstract
INTRODUCTION: Beyond focal radiation, there is no consensus standard therapy for pediatric high-grade glioma (pHGG) and outcomes remain dismal. We describe the largest molecularly-characterized cohort of children with pHGG treated with a 3-drug maintenance regimen of temozolomide, irinotecan, and bevacizumab (TIB) following radiation.
METHODS: We retrospectively reviewed 36 pediatric patients treated with TIB at Seattle Children's Hospital from 2009 to 2018 and analyzed survival using the Kaplan-Meier method. Molecular profiling was performed by targeted DNA sequencing and toxicities, steroid use, and palliative care utilization were evaluated.
RESULTS: Median age at diagnosis was 10.9 years (18 months-18 years). Genetic alterations were detected in 26 genes and aligned with recognized molecular subgroups including H3 K27M-mutant (12), H3F3A G34-mutant (2), IDH-mutant (4), and hypermutator profiles (4). Fifteen patients (42%) completed 12 planned cycles of maintenance. Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified. Median event-free survival (EFS) and overall survival (OS) was 16.2 and 20.1 months, with shorter survival seen in DIPG (9.3 and 13.3 months, respectively). Survival at 1, 2, and 5 years was 80%, 10% and 0% for DIPG and 85%, 38%, and 16% for other pHGG.
CONCLUSION: Our single-center experience demonstrates tolerability of this 3-drug regimen, with prolonged survival in DIPG compared to historical single-agent temozolomide. pHGG survival was comparable to analogous 3-drug regimens and superior to historical agents; however, cure was rare. Children with pHGG remain excellent candidates for the study of novel therapeutics combined with standard therapy.

PMID: 32556862 [PubMed - as supplied by publisher]

Management of benign prostatic hyperplasia in the 21st century: temporal trends in Australian population-based data.

BJU Int. 2020 09;126 Suppl 1:18-26

Authors: Morton A, Williams M, Perera M, Teloken PE, Donato P, Ranasinghe S, Chung E, Bolton D, Yaxley J, Roberts MJ

Abstract
OBJECTIVE: To examine national trends in the medical and surgical treatment of benign prostatic hyperplasia (BPH) using Australian Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) population data from 2000 to 2018.
PATIENTS AND METHODS: Annual data was extracted from the MBS, PBS and Australian Institute of Health and Welfare databases for the years 2000-2018. Population-adjusted rates of BPH procedures and medical therapies were calculated and compared in relation to age. Cost analysis was performed to estimate financial burden due to BPH.
RESULTS: Overall national hospital admissions due to BPH declined between 2000 and 2018, despite an increased proportion of admissions due to private procedures (42% vs 77%). Longitudinal trends in the medical management of BPH showed an increased prescription rate of dutasteride/tamsulosin combined therapy (111 vs 7649 per 100 000 men) and dutasteride monotherapy (149 vs 336 per 100 000 men) since their introduction to the PBS in 2011. Trends in BPH surgery showed an overall progressive increase in rate of total procedures between 2000 and 2018 (92 vs 133 per 100 000 men). Transurethral resection of the prostate (TURP) remained the most commonly performed surgical procedure, despite reduced utilisation since 2009 (118 vs 89 per 100 000 men), offset by a higher uptake of photoselective vaporisation of prostate, holmium:YAG laser enucleation of prostate, and later likely due to minimally invasive surgical therapies including prostatic urethral lift and ablative technologies (including Rezūm™). Financial burden due to BPH surgery has remained steady since 2009, whilst the burden due to medical therapy has risen sharply.
CONCLUSION: Despite reduced national BPH-related hospitalisations, overall treatment for BPH has increased due to medical therapy and surgical alternatives to TURP. Further exploration into motivators for particular therapies and effect of medical therapy on BPH progression in clinical practice outside of clinical trials is warranted.

PMID: 32558340 [PubMed - indexed for MEDLINE]

Regional Dichotomy in Enteric Mucosal Immune Responses to a Persistent Mycobacterium avium ssp. paratuberculosis Infection.

Front Immunol. 2020;11:1020

Authors: Facciuolo A, Lee AH, Gonzalez Cano P, Townsend HGG, Falsafi R, Gerdts V, Potter A, Napper S, Hancock REW, Mutharia LM, Griebel PJ

Abstract
Chronic enteric Mycobacterium avium ssp. paratuberculosis (MAP) infections are endemic in ruminants globally resulting in significant production losses. The mucosal immune responses occurring at the site of infection, specifically in Peyer's patches (PP), are not well-understood. The ruminant small intestine possesses two functionally distinct PPs. Discrete PPs function as mucosal immune induction sites and a single continuous PP, in the terminal small intestine, functions as a primary lymphoid tissue for B cell repertoire diversification. We investigated whether MAP infection of discrete vs. continuous PPs resulted in the induction of significantly different pathogen-specific immune responses and persistence of MAP infection. Surgically isolated intestinal segments in neonatal calves were used to target MAP infection to individual PPs. At 12 months post-infection, MAP persisted in continuous PP (n = 4), but was significantly reduced (p = 0.046) in discrete PP (n = 5). RNA-seq analysis revealed control of MAP infection in discrete PP was associated with extensive transcriptomic changes (1,707 differentially expressed genes) but MAP persistent in continuous PP elicited few host responses (4 differentially expressed genes). Cytokine gene expression in tissue and MAP-specific recall responses by mucosal immune cells isolated from PP, lamina propria and mesenteric lymph node revealed interleukin (IL)22 and IL27 as unique correlates of protection associated with decreased MAP infection in discrete PP. This study provides the first description of mucosal immune responses occurring in bovine discrete jejunal PPs and reveals that a significant reduction in MAP infection is associated with specific cytokine responses. Conversely, MAP infection persists in the continuous ileal PP with minimal perturbation of host immune responses. These data reveal a marked dichotomy in host-MAP interactions within the two functionally distinct PPs of the small intestine and identifies mucosal immune responses associated with the control of a mycobacterial infection in the natural host.

PMID: 32547548 [PubMed - in process]

Analysis of Normal High-Frequency Intracranial Pressure Values and Treatment Threshold in Neurocritical Care Patients: Insights into Normal Values and a Potential Treatment Threshold.

JAMA Neurol. 2020 Jun 15;:

Authors: Hawryluk GWJ, Nielson JL, Huie JR, Zimmermann L, Saigal R, Ding Q, Hirschi R, Zeiler FA, Ferguson A, Manley G

Abstract
Importance: Intracranial pressure (ICP) elevation is a compartment syndrome that impairs blood flow to the brain. Despite the importance of ICP values in neurocritical care, normal ICP values and the precise ICP threshold at which treatment should be initiated remain uncertain.
Objective: To refine our understanding of normal ICP values and determine the ICP threshold most strongly associated with outcome.
Design, Setting, and Participants: Prospective observational study (2004-2010), with outcomes determined at hospital discharge. The study included neurocritical care patients from a single level I trauma center, San Francisco General Hospital. Three hundred eighty-three patients had a traumatic brain injury with or without craniectomy; 140 patients had another indication for ICP monitoring. Consecutive patients were studied. Data analyses were completed between March 2015 and December 2019.
Exposures: Five hundred twenty-three ICP-monitored patients.
Main Outcomes and Measures: A computer system prospectively and automatically collected 1-minute physiologic data from patients in the intensive care unit during a 6-year period. Mean ICP was calculated, as was the proportion of ICP values greater than thresholds from 1 to 80 mm Hg in 1-mm Hg increments. The association between these measures and outcome was explored for various epochs up to 30 days from the time of injury. A principal component analysis was used to explore physiologic changes at various ICP thresholds, and elastic net regression was used to identify ICP thresholds most strongly associated with Glasgow Outcome Scale score at discharge.
Results: Of the 523 studied patients, 70.7% of studied patients were men (n = 370) and 72.1% had a traumatic brain injury (n = 377). A total of 4 090 964 1-minute ICP measurements were recorded for the included patients (7.78 years of recordings). Intracranial pressure values of 8 to 9 mm Hg were most commonly recorded and could possibly reflect normal values. The principal component analysis suggested state shifts in the physiome occurred at ICPs greater than 19 mm Hg and 24 mm Hg. Elastic net regression identified an ICP threshold of 19 mm Hg as most robustly associated with outcome when considering all neurocritical care patients, patients with TBI, and patients with TBI who underwent craniectomy. Intracranial pressure values greater than 19 mm Hg were associated with mortality, while lower values were associated with outcome in surviving patients.
Conclusions and Relevance: This study provides insight into what normal ICP values could be. An ICP threshold of 19 mm Hg was robustly associated with outcome in studied patients, although lower ICP values were associated with outcome in surviving patients.

PMID: 32539101 [PubMed - as supplied by publisher]

Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis.

Circulation. 2020 Jun 16;141(24):2031-2034

Authors: Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zubiri L, Chen CL, Sullivan RJ, Alvi RM, Rokicki A, Murphy SP, Jones-O'Connor M, Heinzerling LM, Barac A, Forrestal BJ, Yang EH, Gupta D, Kirchberger MC, Shah SP, Rizvi MA, Sahni G, Mandawat A, Mahmoudi M, Ganatra S, Ederhy S, Zatarain-Nicolas E, Groarke JD, Tocchetti CG, Lyon AR, Thavendiranathan P, Cohen JV, Reynolds KL, Fradley MG, Neilan TG

PMID: 32539614 [PubMed - in process]

CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection.

Cell. 2020 07 09;182(1):38-49.e17

Authors: Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ

Abstract
cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are immune sensors that synthesize nucleotide second messengers and initiate antiviral responses in bacterial and animal cells. Here, we discover Enterobacter cloacae CD-NTase-associated protein 4 (Cap4) as a founding member of a diverse family of >2,000 bacterial receptors that respond to CD-NTase signals. Structures of Cap4 reveal a promiscuous DNA endonuclease domain activated through ligand-induced oligomerization. Oligonucleotide recognition occurs through an appended SAVED domain that is an unexpected fusion of two CRISPR-associated Rossman fold (CARF) subunits co-opted from type III CRISPR immunity. Like a lock and key, SAVED effectors exquisitely discriminate 2'-5'- and 3'-5'-linked bacterial cyclic oligonucleotide signals and enable specific recognition of at least 180 potential nucleotide second messenger species. Our results reveal SAVED CARF family proteins as major nucleotide second messenger receptors in CBASS and CRISPR immune defense and extend the importance of linkage specificity beyond mammalian cGAS-STING signaling.

PMID: 32544385 [PubMed - indexed for MEDLINE]

The stress-inducible molecular chaperone GRP78 as potential therapeutic target for coronavirus infection.

J Infect. 2020 09;81(3):452-482

Authors: Ha DP, Van Krieken R, Carlos AJ, Lee AS

PMID: 32535155 [PubMed - indexed for MEDLINE]

A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways.

Nat Commun. 2020 06 12;11(1):2977

Authors: Pattwell SS, Arora S, Cimino PJ, Ozawa T, Szulzewsky F, Hoellerbauer P, Bonifert T, Hoffstrom BG, Boiani NE, Bolouri H, Correnti CE, Oldrini B, Silber JR, Squatrito M, Paddison PJ, Holland EC

Abstract
Independent scientific achievements have led to the discovery of aberrant splicing patterns in oncogenesis, while more recent advances have uncovered novel gene fusions involving neurotrophic tyrosine receptor kinases (NTRKs) in gliomas. The exploration of NTRK splice variants in normal and neoplastic brain provides an intersection of these two rapidly evolving fields. Tropomyosin receptor kinase B (TrkB), encoded NTRK2, is known for critical roles in neuronal survival, differentiation, molecular properties associated with memory, and exhibits intricate splicing patterns and post-translational modifications. Here, we show a role for a truncated NTRK2 splice variant, TrkB.T1, in human glioma. TrkB.T1 enhances PDGF-driven gliomas in vivo, augments PDGF-induced Akt and STAT3 signaling in vitro, while next generation sequencing broadly implicates TrkB.T1 in the PI3K signaling cascades in a ligand-independent fashion. These TrkB.T1 findings highlight the importance of expanding upon whole gene and gene fusion analyses to include splice variants in basic and translational neuro-oncology research.

PMID: 32532995 [PubMed - indexed for MEDLINE]

Variation in hospital charges in patients with external ventricular drains: comparison between the intensive care and surgical floor settings.

J Neurosurg Pediatr. 2019 04 19;24(1):29-34

Authors: Chu JK, Feroze AH, Collins K, McGrath LB, Young CC, Williams JR, Browd SR

Abstract
OBJECTIVE: Placement of an external ventricular drain (EVD) is a common and potentially life-saving neurosurgical procedure, but the economic aspect of EVD management and the relationship to medical expenditure remain poorly studied. Similarly, interinstitutional practice patterns vary significantly. Whereas some institutions require that patients with EVDs be monitored strictly within the intensive care unit (ICU), other institutions opt primarily for management of EVDs on the surgical floor. Therefore, an ICU burden for patients with EVDs may increase a patient's costs of hospitalization. The objective of the current study was to examine the expense differences between the ICU and the general neurosurgical floor for EVD care.
METHODS: The authors performed a retrospective analysis of data from 2 hospitals within a single, large academic institution-the University of Washington Medical Center (UWMC) and Seattle Children's Hospital (SCH). Hospital charges were evaluated according to patients' location at the time of EVD management: SCH ICU, SCH floor, or UWMC ICU. Daily hospital charges from day of EVD insertion to day of removal were included and screened for days that would best represent baseline expenses for EVD care. Independent-samples Kruskal-Wallis analysis was performed to compare daily charges for the 3 settings.
RESULTS: Data from a total of 261 hospital days for 23 patients were included in the analysis. Ten patients were cared for in the UWMC ICU and 13 in the SCH ICU and/or on the SCH neurosurgical floor. The median values for total daily hospital charges were $19,824.68 (interquartile range [IQR] $12,889.73-$38,494.81) for SCH ICU care, $8,620.88 (IQR $6,416.76-$11,851.36) for SCH floor care, and $10,002.13 (IQR $8,465.16-$12,123.03) for UWMC ICU care. At SCH, it was significantly more expensive to provide EVD care in the ICU than on the floor (p < 0.001), and the daily hospital charges for the UWMC ICU were significantly greater than for the SCH floor (p = 0.023). No adverse clinical event related to the presence of an EVD was identified in any of the settings.
CONCLUSIONS: ICU admission solely for EVD care is costly. If safe EVD care can be provided outside of the ICU, it would represent a potential area for significant cost savings. Identifying appropriate patients for EVD care on the floor is multifactorial and requires vigilance in balancing the expenses associated with ICU utilization and optimal patient care.

PMID: 31003227 [PubMed - indexed for MEDLINE]

Correlation between epicardial adipose tissue and body mass index in New Zealand ethnic populations.

N Z Med J. 2020 06 12;133(1516):22-32

Authors: Moharram MA, Aitken-Buck HM, Reijers R, Hout IV, Williams MJ, Jones PP, Whalley GA, Lamberts RR, Coffey S

Abstract
AIM: We aimed to investigate the correlation between epicardial adipose tissue (EAT) and body mass index (BMI) in different ethnic groups in New Zealand.
METHODS: The study included 205 individuals undergoing open heart surgery. Māori and Pacific groups were combined to increase statistical power. EAT was measured using 2D echocardiography.
RESULTS: There were 164 New Zealand Europeans (NZE) and 41 Māori/Pacific participants. The mean (SD) age of the study group was 67.9 (10.1) years, 69.1 (9.5) for NZE and 63.5 (11.4) for Māori/Pacific. BMI was 29.6 (5.5) kg/m2 for NZE and 31.8 (6.2) for Māori/Pacific. EAT thickness was 6.2 (2.2) mm and 6.0 (1.8) mm for NZE and Māori/Pacific, respectively. Using univariate linear regression, BMI showed moderate correlation with EAT in NZE (R2=0.26, p<0.001); however, there was no significant correlation between BMI and EAT in Māori/Pacific patients (R2=0.05, p=0.17). Using multivariate analysis, BMI remained a significant predictor of EAT thickness in NZE (R2 =0.27, p<0.001).
CONCLUSIONS: BMI was associated with EAT thickness in NZE patients, but not in Māori/Pacific patients. The same level of BMI can carry different connotations of risk in different ethnic groups, with BMI likely being an inconsistent measure of obesity in in Māori/Pacific patients.

PMID: 32525859 [PubMed - indexed for MEDLINE]

AOSpine Consensus Paper on Nomenclature for Working-Channel Endoscopic Spinal Procedures.

Global Spine J. 2020 Apr;10(2 Suppl):111S-121S

Authors: Hofstetter CP, Ahn Y, Choi G, Gibson JNA, Ruetten S, Zhou Y, Li ZZ, Siepe CJ, Wagner R, Lee JH, Sairyo K, Choi KC, Chen CM, Telfeian AE, Zhang X, Banhot A, Lokhande PV, Prada N, Shen J, Cortinas FC, Brooks NP, Van Daele P, Kotheeranurak V, Hasan S, Keorochana G, Assous M, Härtl R, Kim JS

Abstract
Study Design: International consensus paper on a unified nomenclature for full-endoscopic spine surgery.
Objectives: Minimally invasive endoscopic spinal procedures have undergone rapid development during the past decade. Evolution of working-channel endoscopes and surgical instruments as well as innovation in surgical techniques have expanded the types of spinal pathology that can be addressed. However, there is in the literature a heterogeneous nomenclature defining approach corridors and procedures, and this lack of common language has hampered communication between endoscopic spine surgeons, patients, hospitals, and insurance providers.
Methods: The current report summarizes the nomenclature reported for working-channel endoscopic procedures that address cervical, thoracic, and lumbar spinal pathology.
Results: We propose a uniform system that defines the working-channel endoscope (full-endoscopic), approach corridor (anterior, posterior, interlaminar, transforaminal), spinal segment (cervical, thoracic, lumbar), and procedure performed (eg, discectomy, foraminotomy). We suggest the following nomenclature for the most common full-endoscopic procedures: posterior endoscopic cervical foraminotomy (PECF), transforaminal endoscopic thoracic discectomy (TETD), transforaminal endoscopic lumbar discectomy (TELD), transforaminal lumbar foraminotomy (TELF), interlaminar endoscopic lumbar discectomy (IELD), interlaminar endoscopic lateral recess decompression (IE-LRD), and lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD).
Conclusions: We believe that it is critical to delineate a consensus nomenclature to facilitate uniformity of working-channel endoscopic procedures within academic scholarship. This will hopefully facilitate development, standardization of procedures, teaching, and widespread acceptance of full-endoscopic spinal procedures.

PMID: 32528794 [PubMed]

Development of a Curriculum for Minimally Invasive Spine Surgery (MISS).

Global Spine J. 2020 Apr;10(2 Suppl):122S-125S

Authors: Schmidt FA, Wong T, Kirnaz S, Taboada N, Assaker R, Hofstetter C, Kim JS, Parajón A, Taylor P, Assous M, Härtl R

Abstract
The purpose of this review is to describe how a curriculum for minimally invasive spine surgery (MISS) was developed and implemented. The authors discuss the curriculum roadmap, its target audience, and the educational process for teaching general skills and specific procedures in MISS. Initiated by AOSpine, a panel of experts within spinal surgery from multiple centers formed the minimally invasive spine surgery task force. Together, task force members redefined the standards and milestones of the MISS education and training. Therefore, we conclude that the MISS task force created a structured curriculum which will have a positive influence on daily practice for surgeons and patients worldwide.

PMID: 32528795 [PubMed]

Pay-it-forward gonorrhoea and chlamydia testing among men who have sex with men in China: a randomised controlled trial.

Lancet Infect Dis. 2020 08;20(8):976-982

Authors: Yang F, Zhang TP, Tang W, Ong JJ, Alexander M, Forastiere L, Kumar N, Li KT, Zou F, Yang L, Mi G, Wang Y, Huang W, Lee A, Zhu W, Luo D, Vickerman P, Wu D, Yang B, Christakis NA, Tucker JD

Abstract
BACKGROUND: WHO recommends that men who have sex with men (MSM) receive gonorrhoea and chlamydia testing, but many evidence-based preventive services are unaffordable. The pay-it-forward strategy offers an individual a gift (eg, a test for sexually transmitted diseases) and then asks whether they would like to give a gift (eg, a future test) to another person. This study examined the effectiveness of a pay-it-forward programme to increase gonorrhoea and chlamydia testing among MSM in China.
METHODS: We did a randomised controlled superiority trial at three HIV testing sites run by MSM community-based organisations in Guangzhou and Beijing, China. We included MSM aged 16 years or older who were seeking HIV testing and met indications for gonorrhoea and chlamydia testing. Restricted randomisation was done using computer-generated permuted blocks. 30 groups were randomised into three arms (1:1:1): a pay-it-forward arm in which men were offered free gonorrhoea and chlamydia testing and then asked whether they would like to donate for testing of prospective participants, a pay-what-you-want arm in which men were offered free testing and given the option to pay any desired amount for the test, and a standard-of-care arm in which testing was offered at ¥150 (US$22). There was no masking to arm assignment. The primary outcome was gonorrhoea and chlamydia test uptake ascertained by administrative records. We used generalised estimating equations to estimate intervention effects with one-sided 95% CIs and a prespecified superiority margin of 20%. The trial is registered with ClinicalTrials.gov, NCT03741725.
FINDINGS: Between Dec 8, 2018, and Jan 19, 2019, 301 men were recruited and included in the analysis. 101 were randomly assigned to the pay-it-forward group, 100 to the pay-what-you-want group, and 100 to the standard-of-care group. Test uptake for gonorrhoea and chlamydia was 56% (57 of 101 participants) in the pay-it-forward arm, 46% (46 of 100 participants) in the pay-what-you-want arm, and 18% (18 of 100 participants) in the standard-of-care arm. The estimated difference in test uptake between the pay-it-forward and standard-of-care group was 38·4% (95% CI lower bound 28·4%). Among men in the pay-it-forward arm, 54 of 57 (95%) chose to donate to support testing for others.
INTERPRETATION: The pay-it-forward strategy can increase gonorrhoea and chlamydia testing uptake among Chinese MSM and could be a useful tool for scaling up preventive services that carry a mandatory fee.
FUNDING: US National Institute of Health; Special Programme for Research and Training in Tropical Diseases, sponsored by UNICEF, UNDP, World Bank, and WHO; the National Key Research and Development Program of China; Doris Duke Charitable Foundation; and Social Entrepreneurship to Spur Health.

PMID: 32530426 [PubMed - indexed for MEDLINE]

Adverse Childhood Experiences in Trainees and Physicians With Professionalism Lapses: Implications for Medical Education and Remediation.

Acad Med. 2020 Jun 09;:

Authors: Williams BW, Welindt D, Hafferty FW, Stumps A, Flanders P, Williams MV

Abstract
PURPOSE: Unprofessional behavior, which can include failure to engage, dishonest and/or disrespectful behavior, and poor self-awareness, can be demonstrated by medical trainees and practicing physicians. In the authors' experience, these types of behaviors are associated with exposure to adverse childhood experiences (ACEs). Given this overlap, the authors studied the percentage of ACEs among trainees and physicians referred for fitness-for-duty evaluations and patterns between the types of ACEs experienced and the reason for referral.
METHOD: A final sample of 123 cases of U.S. trainees and physicians who had been referred to a Midwestern center for assessment and remediation of professionalism issues from 2013 to 2018 was created. Included professionalism lapses fell within 3 categories: boundary violation, disruptive behavior, or potential substance use disorder concerns. All participants completed a psychosocial developmental interview, which includes questions about ACE exposure. Overall rate of reported ACEs and types of ACEs reported were explored.
RESULTS: Eighty-six (70%) participants reported at least 1 ACE, while 27 (22%) reported 4 or more. Compared to national data, these results show significantly higher occurrence rates of 1 or more ACEs and a lower occurrence rate of 0 ACEs. ACEs that predicted reasons for referral were physical or sexual abuse, feeling unwanted or unloved, witnessing abuse of their mother or stepmother, or caretaker substance use.
CONCLUSIONS: In this sample, ACE exposure was associated with professionalism issues. Remediating individuals with professionalism issues and exposure to ACEs can be complicated by heightened responses to stressful stimuli, difficulties with collaboration and trust, and decreased self-efficacy. Adoption of a trauma-informed medical education approach may help those that have been impacted by trauma rebuild a sense of control and empowerment. The findings of this study may be useful predictors in identifying those at risk of problematic behavior and recidivism prior to a sentinel event.

PMID: 32520753 [PubMed - as supplied by publisher]

Risks for cold frequency vary by sex: role of asthma, age, TLR7 and leukocyte subsets.

Eur Respir J. 2020 Jun 08;:

Authors: Murray LM, Yerkovich ST, Ferreira MA, Upham JW

Abstract
Viral respiratory infections are usually benign but can trigger asthma exacerbations. The factors associated with upper respiratory tract infection (cold) frequency are not fully understood, nor is it clear whether such factors differ between women and men.To determine which immunological and clinical variables associate with the frequency of self-reported respiratory infections (colds), 150 asthma cases and 151 controls were recruited. Associations between antiviral immune response variables - TLR7/8 gene expression, plasmacytoid dendritic cell (pDC) numbers and interferon-alpha, TNF and IL-12 production - and asthma were then examined that might explain cold frequency.People with asthma cases reported more colds per year (median 3 versus 2, p<0.001) and had lower baseline TLR7 gene expression (odds ratio (OR)=0.12, p=0.02) than controls. Associations between many variables and cold frequency differed between women and men. In women, high blood neutrophil counts (beta=0.096, p=0.002), and younger age (beta= -0.017, p<0.001), but not exposure to children, were independently associated with more frequent colds. In men, low TLR7 expression (beta= -0.96, p=0.041) and high CLEC4C gene expression (a marker of pDC; beta=0.88, p=0.008) were independently associated with more frequent colds. Poor asthma symptom control was independently associated with reduced TLR8 gene expression (beta= -1.4, p=0.036) and high BMI (beta=0.041, p=0.004).Asthma, age and markers of inflammation and antiviral immunity in peripheral blood are associated with frequent colds. Interestingly, the variables associated with cold frequency differed between women and men.

PMID: 32513781 [PubMed - as supplied by publisher]

Screening for Drug Use in Primary Care: Practical Implications of the New USPSTF Recommendation.

JAMA Intern Med. 2020 08 01;180(8):1050-1051

Authors: Bradley KA, Lapham GT, Lee AK

PMID: 32515790 [PubMed - indexed for MEDLINE]

Editorial overviews: Editorial matters - point of clarification.

Curr Opin Pharmacol. 2020 02;50:107-108

Authors: Williams M

PMID: 32506004 [PubMed - indexed for MEDLINE]

Antiepileptic Drugs and Bone Health: Current Concepts.

Psychopharmacol Bull. 2020 May 19;50(2):36-44

Authors: Siniscalchi A, Murphy S, Cione E, Piro L, Sarro G, Gallelli L

Abstract
Chronic use of antiepileptic drugs (AEDs) can induce the development of adverse effects on bone metabolism. In epileptic patients treated with AED, the monitoring of biochemical markers of bone turnover, such as the measurement of serum 25 (OH) vitamin D, bone mineral density, before the beginning of the treatment and during the follow-up is not routinely required. In the future, monitoring of biochemical markers in epileptic patients treated with AED may help us for adequate prevention therapy.

PMID: 32508365 [PubMed - in process]

Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides.

Front Cell Infect Microbiol. 2020;10:228

Authors: Choi KG, Wu BC, Lee AH, Baquir B, Hancock REW

Abstract
Host defense peptides (HDPs), also known as antimicrobial peptides, are naturally occurring polypeptides (~12-50 residues) composed of cationic and hydrophobic amino acids that adopt an amphipathic conformation upon folding usually after contact with membranes. HDPs have a variety of biological activities including immunomodulatory, anti-inflammatory, anti-bacterial, and anti-biofilm functions. Although HDPs have the potential to address the global threat of antibiotic resistance and to treat immune and inflammatory disorders, they have yet to achieve this promise. Indeed, there are several challenges associated with bringing peptide-based drug candidates from the lab bench to clinical practice, including identifying appropriate indications, stability, toxicity, and cost. These challenges can be addressed in part by the development of innate defense regulator (IDR) peptides and peptidomimetics, which are synthetic derivatives of HDPs with similar or better efficacy, increased stability, and reduced toxicity and cost of the original HDP. However, one of the largest gaps between basic research and clinical application is the validity and translatability of conventional model systems, such as cell lines and animal models, for screening HDPs and their derivatives as potential drug therapies. Indeed, such translation has often relied on animal models, which have only limited validity. Here we discuss the recent development of human organoids for disease modeling and drug screening, assisted by the use of omics analyses. Organoids, developed from primary cells, cell lines, or human pluripotent stem cells, are three-dimensional, self-organizing structures that closely resemble their corresponding in vivo organs with regards to immune responses, tissue organization, and physiological properties; thus, organoids represent a reliable method for studying efficacy, formulation, toxicity and to some extent drug stability and pharmacodynamics. The use of patient-derived organoids enables the study of patient-specific efficacy, toxicogenomics and drug response predictions. We outline how organoids and omics data analysis can be leveraged to aid in the clinical translation of IDR peptides.

PMID: 32509598 [PubMed - in process]