Publications by authors named "Andrew Nguyen"

246 Publications

Catch me if you can: Under-detection of Trypanosoma cruzi (Kinetoplastea: Trypanosomatida) infections in Triatoma dimidiata s.l. (Hemiptera: Reduviidae) from Central America.

Acta Trop 2021 Sep 15:106130. Epub 2021 Sep 15.

The Walter Reed Biosystematics Unit, Smithsonian Institution Museum Support Center, MD, USA; Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.

Assays for parasite detection in insect vectors provide important information for disease control. American Trypanosomiasis (Chagas disease) is the most devastating vector-borne illness and the fourth most common in Central America behind HIV/AIDS and acute respiratory and diarrheal infections (Peterson et al., 2019). Under-detection of parasites is a general problem which may be influenced by parasite genetic variation; however, little is known about the genetic variation of the Chagas parasite, especially in this region. In this study we compared six assays for detecting the Chagas parasite, Trypanosoma cruzi: genomic reduced representation sequencing (here referred to as genotype-by-sequencing or GBS), two with conventional PCR (i.e., agarose gel detection), two with qPCR, and microscopy. Our results show that, compared to GBS genomic analysis, microscopy and PCR under-detected T. cruzi in vectors from Central America. Of 94 samples, 44% (50/94) were positive based on genomic analysis. The lowest detection, 9% (3/32) was in a subset assayed with microscopy. Four PCR assays, two with conventional PCR and two with qPCR showed intermediate levels of detection. Both qPCR tests and one conventional PCR test targeted the 195 bp repeat of satellite DNA while the fourth test targeted the 18S gene. Statistical analyses of the genomic and PCR results indicate that the PCR assays significantly under detect infections of Central American T. cruzi genotypes.
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http://dx.doi.org/10.1016/j.actatropica.2021.106130DOI Listing
September 2021

Resolving severe oligohydramnios as an early prenatal presentation of renal coloboma syndrome-A report of two generations.

Clin Case Rep 2021 Sep 7;9(9):e04758. Epub 2021 Sep 7.

Schulich School of Medicine and Dentistry University of Western Ontario London ON Canada.

This report suggests that self-resolving oligohydramnios is an early sign of malfunctioning kidney in individuals with renal coloboma syndrome (RCS) and demonstrates how a genetic diagnosis can impact patient and fetal management as it outlines two generations of RCS.
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http://dx.doi.org/10.1002/ccr3.4758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423080PMC
September 2021

Inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen: a case report and approach to differential diagnosis.

Radiol Case Rep 2021 Nov 26;16(11):3213-3216. Epub 2021 Aug 26.

Body Imaging Division, Department of Radiology, Stanford University, 300 Pasteur Drive, H1307, Stanford, CA 94305, USA.

We present a case of an inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen. The patient is a 44-year-old woman, without significant underlying history, who presented with nonspecific abdominal pain for a few months. Both a contrast enhanced computed tomography and magnetic resonance imaging revealed a new 2.5 cm enhancing splenic lesion, which demonstrated hypermetabolic activity on subsequent positron emission tomography and computed tomography scan. Since the lesion was new compared to more remote imaging and hypermetabolic, a splenectomy was performed.  Pathology confirmed the diagnosis and demonstrated positivity for Epstein-Barr Virus .
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http://dx.doi.org/10.1016/j.radcr.2021.07.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405940PMC
November 2021

Presentation and survival of gastro-entero-pancreatic neuroendocrine tumors in young adults versus older patients.

Am J Surg 2021 Aug 28. Epub 2021 Aug 28.

Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA. Electronic address:

Background: A minority of patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) is diagnosed at younger age. This population-based study explores the broad clinical and pathologic features of the youngest 5% of adult patients with GEP-NETs.

Methods: A retrospective study of the National Cancer Database (NCDB) of patients with a primary GEP-NET was performed. Patients were stratified by age. Kaplan-Meier and multivariate Cox proportional hazards analyses were performed.

Results: We identified 31,983 patients with a diagnosis of a GEP-NET and only 5% of patients were under the age of 35. Young patients were found to have greater proportions of localized, well differentiated disease. On multivariate analysis, young age, well differentiated histology, early stage, and surgical intervention were associated with lower risk of mortality.

Conclusions: Young patients with GEP-NETs tend to have earlier stage of presentation and well differentiated tumors, which may be most amenable to surgical intervention.
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http://dx.doi.org/10.1016/j.amjsurg.2021.08.030DOI Listing
August 2021

The Additive Diagnostic Value of Prostate-specific Membrane Antigen Positron Emission Tomography Computed Tomography to Multiparametric Magnetic Resonance Imaging Triage in the Diagnosis of Prostate Cancer (PRIMARY): A Prospective Multicentre Study.

Eur Urol 2021 Aug 28. Epub 2021 Aug 28.

Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Background: Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for false negative concerns. In addition, Ga-PSMA-11 positron emission tomography/computed tomography (prostate-specific membrane antigen [PSMA]) may also identify csPCa accurately.

Objective: This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa.

Design, Setting, And Participants: A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy.

Outcome Measurements And Statistical Analysis: Sensitivity, specificity, and predictive values (negative predictive value [NPV] and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy.

Results And Limitations: Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3-5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 [1.11-1.39], p < 0.001). Sensitivity also improved (97% vs 83%, p < 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall.

Conclusions: PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging.

Patient Summary: The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.
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http://dx.doi.org/10.1016/j.eururo.2021.08.002DOI Listing
August 2021

Adropin correlates with aging-related neuropathology in humans and improves cognitive function in aging mice.

NPJ Aging Mech Dis 2021 Aug 30;7(1):23. Epub 2021 Aug 30.

Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA.

The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevant to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40 y and 'old-old' (>75 y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the 'old-old' without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the 'old-old' also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18-month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines in cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential therapy against neurological aging.
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http://dx.doi.org/10.1038/s41514-021-00076-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405681PMC
August 2021

Hypothyroidism - A Causal Approach to Testing Assumptions against Empirical Results.

AMIA Annu Symp Proc 2021 17;2021:257-266. Epub 2021 May 17.

University of San Francisco, San Francisco, CA.

There is a controversy in the diagnosis and treatment of hypothyroidism. We propose the disagreement is fueled by statistical paradoxes, and sampling biases that provide different perspectives depending upon the sample selection criteria. The statistical inconsistencies become more apparent when viewed using a causal lens. Foundational hypothyroid research does not reflect the current Levothyroxine treated population. Exploration of empirical data demonstrates an apparent breakdown of the T4 to T3 causal pathway in the treated population. This use case demonstrates the difficulty of translating controlled research into clinical practices for patients with multiple comorbid conditions. We make the case for redundancy in data collection, ongoing attempts to falsify current assumptions and the need for causal approaches to validate the results of controlled research in clinical settings, in order to avoid confirmation bias from statistically insufficient biometrics.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378658PMC
September 2021

Chronic social isolation signals starvation and reduces sleep in Drosophila.

Nature 2021 09 18;597(7875):239-244. Epub 2021 Aug 18.

Laboratory of Genetics, The Rockefeller University, New York, NY, USA.

Social isolation and loneliness have potent effects on public health. Research in social psychology suggests that compromised sleep quality is a key factor that links persistent loneliness to adverse health conditions. Although experimental manipulations have been widely applied to studying the control of sleep and wakefulness in animal models, how normal sleep is perturbed by social isolation is unknown. Here we report that chronic, but not acute, social isolation reduces sleep in Drosophila. We use quantitative behavioural analysis and transcriptome profiling to differentiate between brain states associated with acute and chronic social isolation. Although the flies had uninterrupted access to food, chronic social isolation altered the expression of metabolic genes and induced a brain state that signals starvation. Chronically isolated animals exhibit sleep loss accompanied by overconsumption of food, which resonates with anecdotal findings of loneliness-associated hyperphagia in humans. Chronic social isolation reduces sleep and promotes feeding through neural activities in the peptidergic fan-shaped body columnar neurons of the fly. Artificial activation of these neurons causes misperception of acute social isolation as chronic social isolation and thereby results in sleep loss and increased feeding. These results present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness.
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http://dx.doi.org/10.1038/s41586-021-03837-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429171PMC
September 2021

Chromophobe Renal Cell Carcinoma with Radiologic-Pathologic Correlation.

Radiographics 2021 Sep-Oct;41(5):1408-1419. Epub 2021 Aug 13.

From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Md, and American Institute for Radiologic Pathology, Silver Spring, Md (J.M.); F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md (R.C.); George Washington University School of Medicine and Health Sciences, Washington, DC (A.N.); Department of Pathology, University of Michigan Medical School, Ann Arbor, Mich (A.M.U.); and Department of Radiology, Johns Hopkins Hospital and Health System, 5255 Loughboro Rd NW, Washington, DC 20016 (D.J.W.).

Renal cell carcinoma (RCC) is a heterogeneous group of neoplasms derived from the renal tubular epithelial cells. Chromophobe RCC (chRCC) is the third most common subtype of RCC, accounting for 5% of cases. chRCC may be detected as an incidental finding or less commonly may manifest with clinical symptoms. The mainstay of therapy for chRCC is surgical resection. chRCC has a better prognosis compared with the more common clear cell RCC. At gross pathologic analysis, chRCC is a solid well-defined mass with lobulated borders. Histologic findings vary by subtype but include large pale polygonal cells with abundant transparent cytoplasm, crinkled "raisinoid" nuclei with perinuclear halos, and prominent cell membranes. Pathologic analysis reveals only moderate vascularity. The most common imaging pattern is a predominantly solid renal mass with circumscribed margins and enhancement less than that of the renal cortex. The authors discuss chRCC with emphasis on correlative pathologic findings and illustrate the multimodality imaging appearances of chRCC by using cases from the Radiologic Pathology Archives of the American Institute for Radiologic Pathology. RSNA, 2021.
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http://dx.doi.org/10.1148/rg.2021200206DOI Listing
August 2021

Follow-up rates for patients needing regular intravitreal therapy in rural north-western Western Australia.

Rural Remote Health 2021 08 11;21(3):6001. Epub 2021 Aug 11.

Lions Outback Vision, Lions Eye Institute, Nedlands, WA 6009, Australia

Introduction: Regular intravitreal injections are an important treatment for significant vision impairment caused by diabetic macular oedema. Barriers to intravitreal treatment for rural Australian patients include travel time to appointments, especially as patients face a high volume of other medical appointments for their diabetes and related co-morbidities. This audit addresses intravitreal injection compliance by identifying patients lost to follow up in north-western Western Australia.

Methods: A retrospective audit of all injections was performed in the Pilbara and Kimberley between January and December 2018. Outcome measures included total injections, number of injection patients, rates of patients lost to follow-up by region, Aboriginal and Torres Strait Islander status and diagnosis. The audit was extended to include the first 6 months of 2019 to ensure further treatment plan timeframes had lapsed.

Results: A total of 140 patients received injections, resulting in 346 injections. Ten patients were excluded due to relocation to another region and three patients were deceased. Seventeen patients were lost to follow-up (12.1%). Of those lost to follow-up, 14.3% were in the Pilbara region and 10% in the Kimberley region. Similar rates with respect to Indigenous status with 12.6% identifying as Aboriginal and 11.4% not. 15.8% were treated for diabetic macular oedema and 3.8% for age-related macular degeneration.

Conclusion: The logistics of providing appropriate intravitreal therapy, including scheduling timely visits and working in hospital and community-controlled settings, requires a specific focus on those needing intravitreal treatment. The study highlights the importance of coordination and systems to enable patients to receive injections in remote settings. Further analysis of optimal patient management plans for appropriate frequency and treatment outcomes is required.
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http://dx.doi.org/10.22605/RRH6001DOI Listing
August 2021

Rapid, Large-Scale Wastewater Surveillance and Automated Reporting System Enable Early Detection of Nearly 85% of COVID-19 Cases on a University Campus.

mSystems 2021 Aug 10;6(4):e0079321. Epub 2021 Aug 10.

Department of Pediatrics, School of Medicine, University of California, San Diegogrid.266100.3, La Jolla, California, USA.

Wastewater-based surveillance has gained prominence and come to the forefront as a leading indicator of forecasting COVID-19 (coronavirus disease 2019) infection dynamics owing to its cost-effectiveness and its ability to inform early public health interventions. A university campus could especially benefit from wastewater surveillance, as universities are characterized by largely asymptomatic populations and are potential hot spots for transmission that necessitate frequent diagnostic testing. In this study, we employed a large-scale GIS (geographic information systems)-enabled building-level wastewater monitoring system associated with the on-campus residences of 7,614 individuals. Sixty-eight automated wastewater samplers were deployed to monitor 239 campus buildings with a focus on residential buildings. Time-weighted composite samples were collected on a daily basis and analyzed on the same day. Sample processing was streamlined significantly through automation, reducing the turnaround time by 20-fold and exceeding the scale of similar surveillance programs by 10- to 100-fold, thereby overcoming one of the biggest bottlenecks in wastewater surveillance. An automated wastewater notification system was developed to alert residents to a positive wastewater sample associated with their residence and to encourage uptake of campus-provided asymptomatic testing at no charge. This system, integrated with the rest of the "Return to Learn" program at the University of California (UC) San Diego-led to the early diagnosis of nearly 85% of all COVID-19 cases on campus. COVID-19 testing rates increased by 1.9 to 13× following wastewater notifications. Our study shows the potential for a robust, efficient wastewater surveillance system to greatly reduce infection risk as college campuses and other high-risk environments reopen. Wastewater-based epidemiology can be particularly valuable at university campuses where high-resolution spatial sampling in a well-controlled context could not only provide insight into what affects campus community as well as how those inferences can be extended to a broader city/county context. In the present study, a large-scale wastewater surveillance was successfully implemented on a large university campus enabling early detection of 85% of COVID-19 cases thereby averting potential outbreaks. The highly automated sample processing to reporting system enabled dramatic reduction in the turnaround time to 5 h (sample to result time) for 96 samples. Furthermore, miniaturization of the sample processing pipeline brought down the processing cost significantly ($13/sample). Taken together, these results show that such a system could greatly ameliorate long-term surveillance on such communities as they look to reopen.
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http://dx.doi.org/10.1128/mSystems.00793-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409724PMC
August 2021

RNA-Based Therapies for Neurodegenerative Diseases.

Mo Med 2021 Jul-Aug;118(4):340-345

Departments of Internal Medicine and Pharmacology & Physiology, Saint Louis University School of Medicine, St. Louis, Missouri.

Most neurodegenerative disorders afflict the ageing population and are often incurable. Therefore, therapeutic development is a major focus in biomedical research. We highlight a new class of drugs, RNA molecules, to control gene expression and decrease neurotoxicity. Their efficacy is shown in pre-clinical studies, clinical trials and in cases of approved patient treatment. As the number of RNA-based strategies increases, so does the promise of targeting more disease-associated genes through a variety of different mechanisms.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343627PMC
August 2021

Recurrence and treatment of adult primary nonmetastatic bladder rhabdomyosarcoma: A systematic review.

Urol Oncol 2021 Jul 28. Epub 2021 Jul 28.

The George Washington University School of Medicine, Washington, District of Columbia.

Introduction: While survival for pediatric bladder rhabdomyosarcoma (RMS) has recently improved with risk-based multimodality treatment protocols, survival for adult bladder RMS remains to be poor. Survival is poor likely because adult bladder RMS is rare, understudied, and consequently lacking in high-level evidence to inform standardization of treatment. In addition, adult bladder RMS exhibits high rates of recurrence. The purpose of this systematic review is to determine associations between patient clinicopathologic factors and recurrence for adult primary bladder RMS, as well as to provide an updated survey of the various treatments employed for this disease in adults.

Material And Methods: Studies involving adult primary bladder RMS were acquired from MEDLINE (OVID), Scopus, and Cochrane Central Register of Controlled Trials from 1947 to 2018. Cases with no metastatic disease at diagnosis and at least 6 months follow-up were included. Multivariable Cox-regression hazard analysis was utilized to determine associations of age, sex, histology, and TNM stage with recurrence. Kaplan-Meier analysis and log-rank testing was used to calculate overall survival (OS) for patients who underwent surgical treatment only, and to evaluate differences in survival between radical cystectomy and partial cystectomy.

Results: 20 articles were selected for the review, and 22 cases were obtained. The mean age of the patients was 55.7 ± 18.4 (range = 28-83). With a mean follow-up time of 21.4 ± 18.6 months, 36.4% of the patients experienced disease recurrence. Recurrence was not associated with age, sex, histology, or stage (p = 0.366, p = 0.754, p = 0.889, and p = 0.590, respectively). Most patients underwent surgery only as their initial therapy (n = 12), while the remaining had chemotherapy, radiation, or some combination of these therapies (including surgery). The median OS of patients who underwent surgery only was 21.0 months (95% CI: 0.0-44.6 months). Among these patients, no difference in OS between radical cystectomy and partial cystectomy was found (p = 0.841).

Conclusion: Adult bladder RMS is a rare, lethal tumor with a high proclivity for recurrence. No association between age, sex, histology, or stage and recurrence was found. Radical cystectomy is not superior to partial cystectomy in terms of survival, suggesting a role for bladder preservation in select patients. Our study is the first to provide a comprehensive summary of the various treatments employed with clinical outcomes for adult primary bladder RMS.
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http://dx.doi.org/10.1016/j.urolonc.2021.07.008DOI Listing
July 2021

Lutetium PSMA-617 and idronoxil (NOX66) in men with end-stage metastatic castrate-resistant prostate cancer (LuPIN): Patient outcomes and predictors of treatment response of a Phase I/II trial.

J Nucl Med 2021 Jul 29. Epub 2021 Jul 29.

Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Australia.

Lutetium PSMA-617 (Lu-PSMA-617) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently and combination therapies may improve outcomes. We report the final safety and efficacy results of a phase I/II study combining Lu-PSMA-617 with idronoxil (NOX66), a radiosensitiser, and examined potential clinical, blood-based and imaging biomarkers. 56 men with progressive mCRPC previously treated with taxane chemotherapy and novel androgen signaling inhibitor (ASI) were enrolled. Patients received up to six doses of Lu-PSMA-617 (7.5Gbq) day 1 in combination with NOX66 suppository days 1-10 each 6-week cycle. Cohort 1 ( = 8) received 400mg NOX66, cohort 2 ( = 24) received 800mg and cohort 3 ( = 24) received 1200mg. Ga-PSMA and FDG PET/CT were performed at study entry and semi-quantitative imaging analysis was undertaken. Blood samples were collected for blood-based biomarkers including androgen receptor splice variant 7 expression. The primary outcomes were safety and tolerability; secondary outcomes included efficacy, pain scores and xerostomia. Regression analyses were performed to explore the prognostic value of baseline clinical, blood-based and imaging parameters. 56/100 men screened were enrolled (56%) with a screen failure rate of 26% (26/100) for PET imaging criteria. All men had received prior treatment with ASI and docetaxel, and 95% (53/56) had received cabazitaxel. 96% (54/56) patients received ≥2 cycles of combination NOX66 and Lu-PSMA-617, and 46% (26/56) completed six cycles. Common adverse events were anaemia, fatigue and xerostomia. Anal irritation attributable to NOX66 occurred in 38%. 48/56 had a reduction in prostate-specific antigen (PSA) (86%, 95% CI 74-94), 34/56 (61%, 95% CI 47-74) had a PSA reduction ≥50% (PSA50). Median PSA progression-free survival was 7.5 months (95% CI 5.9-9) and median overall survival 19.7 months (95% CI 9.5-30). Higher PSMA SUVmean correlated with treatment response, while higher PSMA tumour volume and prior treatment with ASI for less than 12 months were associated with worse overall survival. NOX66 with Lu-PSMA-617 is a safe and feasible therapeutic strategy in men treated 3rd line and beyond for mCRPC. PSMA SUVmean, PSMA avid tumour volume and duration of treatment with ASI were independently associated with outcome.
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http://dx.doi.org/10.2967/jnumed.121.262552DOI Listing
July 2021

Immune checkpoint inhibitor cardiotoxicity: Breaking barriers in the cardiovascular immune landscape.

J Mol Cell Cardiol 2021 Jul 22;160:121-127. Epub 2021 Jul 22.

Department of Medicine, Stanford University, Stanford, California 94305, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, California 94305, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. Electronic address:

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy, but their use carries a high risk of cardiac immune related adverse events (iRAEs). With the expanding utilization of ICI therapy, there is a growing need to understand the underlying mechanisms behind their anti-tumor activity as well as their immune-mediated toxicities. In this review, we will focus on clinical characteristics and immune pathways of ICI cardiotoxicity, with an emphasis on single-cell technologies used to gain insights in this field. We will focus on three key areas of ICI-mediated immune pathways, including the anti-tumor immune response, the augmentation of the immune response by ICIs, and the pathologic "autoimmune" response in some individuals leading to immune-mediated toxicity, as well as local factors in the myocardial immune environment predisposing to autoimmunity. Discerning the underlying mechanisms of these immune pathways is necessary to inform the development of targeted therapies for ICI cardiotoxicities and reduce treatment related morbidity and mortality.
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http://dx.doi.org/10.1016/j.yjmcc.2021.07.006DOI Listing
July 2021

PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer.

Sci Rep 2021 Jul 21;11(1):14841. Epub 2021 Jul 21.

NIBR Biologics Center, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.

High-grade serous ovarian cancers (HGSOC) represent the most common subtype of ovarian malignancies. Due to the frequency of late-stage diagnosis and high rates of recurrence following standard of care treatments, novel therapies are needed to promote durable responses. We investigated the anti-tumor activity of CD3 T cell engaging bispecific antibodies (TCBs) directed against the PAX8 lineage-driven HGSOC tumor antigen LYPD1 and demonstrated that anti-LYPD1 TCBs induce T cell activation and promote in vivo tumor growth inhibition in LYPD1-expressing HGSOC. To selectively target LYPD1-expressing tumor cells with high expression while sparing cells with low expression, we coupled bivalent low-affinity anti-LYPD1 antigen-binding fragments (Fabs) with the anti-CD3 scFv. In contrast to the monovalent anti-LYPD1 high-affinity TCB (VHP354), the bivalent low-affinity anti-LYPD1 TCB (QZC131) demonstrated antigen density-dependent selectivity and showed tolerability in cynomolgus monkeys at the maximum dose tested of 3 mg/kg. Collectively, these data demonstrate that bivalent TCBs directed against LYPD1 have compelling efficacy and safety profiles to support its use as a treatment for high-grade serous ovarian cancers.
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http://dx.doi.org/10.1038/s41598-021-93992-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295318PMC
July 2021

Impact of postoperative complications on long-term survival after esophagectomy in older adults: A SEER-Medicare analysis.

J Surg Oncol 2021 Oct 5;124(5):751-766. Epub 2021 Jul 5.

Thoracic Surgical Services, RWJBarnabas Health, West Orange, New Jersey, USA.

Background: Esophagectomy is a complex procedure associated with a high rate of postoperative complications. It is not clear whether postoperative complications effect long-term survival. Most studies report the results from single institutions.

Methods: We examined the Surveillance, Epidemiology and End Results (SEER)-Medicare database to assess whether long-term overall and cancer-specific mortality of patients undergoing esophagectomy for cancer is impacted by postoperative complications.

Results: Nine hundred and forty patients underwent esophagectomy from 2007 to 2014, of which 50 died, resulting in a cohort of 890 patients. Majority were males (n = 764, 85.8%) with adenocarcinoma of the lower esophagus. Almost 60% of the group had no neoadjuvant therapy. Four hundred and fifty-five patients had no major complications (51.1%), while 285 (32.0%) and 150 (16.9%) patients had one, two, or more major complications, respectively. Overall survival at 90 days was 93.1%. Multivariate analysis of patients followed up for a minimum of 90 days demonstrated that the number of complications was significantly associated with decreased overall survival but no impact on cancer-specific survival.

Conclusions: Our population-based analysis with its inherent limitations suggests that patients undergoing esophagectomy who experience complications have worse overall survival but not cancer-specific survival if they survive at least 90 days from the date of surgery.
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http://dx.doi.org/10.1002/jso.26587DOI Listing
October 2021

Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults.

Sci Rep 2021 Jun 28;11(1):13394. Epub 2021 Jun 28.

Gérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalo-Universitaire de Toulouse, 37 Allées Jules Guesdes, 31000, Toulouse, France.

Neurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer's Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β =  - 0.007, 95% CI [- 0.013, - 0.001]; CCS: β =  - 0.003, 95% CI [- 0.006, - 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β =  - 0.003, 95% CI [- 0.005, - 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β =  - 0.07, 95% CI [- 0.12, - 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI.
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http://dx.doi.org/10.1038/s41598-021-91038-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238930PMC
June 2021

Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy.

J Immunother Cancer 2021 Jun;9(6)

Department of Internal Medicine 5, Hematology/Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

Background: Therapeutic regimens designed to augment the immunological response of a patient with breast cancer (BC) to tumor tissue are critically informed by tumor mutational burden and the antigenicity of expressed neoepitopes. Herein we describe a neoepitope and cognate neoepitope-reactive T-cell identification and validation program that supports the development of next-generation immunotherapies.

Methods: Using GPS Cancer, NantOmics research, and The Cancer Genome Atlas databases, we developed a novel bioinformatic-based approach which assesses mutational load, neoepitope expression, human leukocyte antigen (HLA)-binding prediction, and in vitro confirmation of T-cell recognition to preferentially identify targetable neoepitopes. This program was validated by application to a BC cell line and confirmed using tumor biopsies from two patients with BC enrolled in the Tumor-Infiltrating Lymphocytes and Genomics (TILGen) study.

Results: The antigenicity and HLA-A2 restriction of the BC cell line predicted neoepitopes were determined by reactivity of T cells from HLA-A2-expressing healthy donors. For the TILGen subjects, tumor-infiltrating lymphocytes (TILs) recognized the predicted neoepitopes both as peptides and on retroviral expression in HLA-matched Epstein-Barr virus-lymphoblastoid cell line and BC cell line MCF-7 cells; PCR clonotyping revealed the presence of T cells in the periphery with T-cell receptors for the predicted neoepitopes. These high-avidity immune responses were polyclonal, mutation-specific and restricted to either HLA class I or II. Interestingly, we observed the persistence and expansion of polyclonal T-cell responses following neoadjuvant chemotherapy.

Conclusions: We demonstrate our neoepitope prediction program allows for the successful identification of neoepitopes targeted by TILs in patients with BC, providing a means to identify tumor-specific immunogenic targets for individualized treatment, including vaccines or adoptively transferred cellular therapies.
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http://dx.doi.org/10.1136/jitc-2021-002605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237736PMC
June 2021

VISTA is an activating receptor in human monocytes.

J Exp Med 2021 Aug 9;218(8). Epub 2021 Jun 9.

AbbVie Biotherapeutics Inc., Redwood City, CA.

As indicated by its name, V-domain Ig suppressor of T cell activation (VISTA) is thought to serve primarily as an inhibitory protein that limits immune responses. VISTA antibodies can dampen the effects of several concomitantly elicited activation signals, including TCR and TLR activation, but it is currently unclear if VISTA agonism could singly affect immune cell biology. In this study, we discovered two novel VISTA antibodies and characterized their effects on human peripheral blood mononuclear cells by scRNA/CITE-seq. Both antibodies appeared to agonize VISTA in an Fc-functional manner to elicit transcriptional and functional changes in monocytes consistent with activation. We also used pentameric VISTA to identify Syndecan-2 and several heparan sulfate proteoglycan synthesis genes as novel regulators of VISTA interactions with monocytic cells, adding further evidence of bidirectional signaling. Together, our study highlights several novel aspects of VISTA biology that have yet to be uncovered in myeloid cells and serves as a foundation for future research.
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http://dx.doi.org/10.1084/jem.20201601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193568PMC
August 2021

The Role for Simulation in Professional Identity Formation in Medical Students.

Simul Healthc 2021 Jun 1. Epub 2021 Jun 1.

From the Virginia Commonwealth University School of Medicine, Center for Human Simulation and Patient Safety, Richmond, VA.

Introduction: Authentic clinical experiences and reflection are critical for medical student professional identity formation (PIF). Individualized learning plans and competency-based education accelerate time to graduation, thus creating more demand for students to gain PIF experiences early in medical education. This pilot study investigated student professional identity experiences related to participation in a clinical simulation during the first week of medical school.

Methods: All first-year medical students at an academic health center participated in a clinically relevant simulation-based orientation to medical school (SOMS). Participants completed evaluation surveys measuring PIF-related experiences during the SOMS.

Results: All participants completed the survey (N = 186). Students agreed that the SOMS helped them feel what it is like to be a doctor (90%) and transition to the role of student-physician (91%). Student comments about the SOMS-reflected PIF-related processes, such as building a sense of a community of practice among their peers in their roles as a healthcare team. Students also valued the opportunity to engage in reflection about their roles as student-physicians.

Conclusions: Simulation experiences can be used as a trigger for self-reflection to assist in medical student professional identity development as early as the first weeks of medical school. Simulation exercises may improve PIF and could further enhance medical student PIF by adding them longitudinally into the curriculum.
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http://dx.doi.org/10.1097/SIH.0000000000000583DOI Listing
June 2021

Residential proximity to plant nurseries and risk of childhood leukemia.

Environ Res 2021 09 29;200:111388. Epub 2021 May 29.

Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, 90095-1772, USA. Electronic address:

Background: Pesticides are a potential risk factor for childhood leukemia. Studies evaluating the role of prenatal and/or early life exposure to pesticides in the development of childhood leukemia have produced a range of results. In addition to indoor use of pesticides, higher risks have been reported for children born near agricultural crops. No studies have looked at pesticide exposure based on proximity of birth residence to commercial plant nurseries, even though nurseries are located much closer to residences than agricultural crops and can potentially result in chronic year-round pesticide exposure.

Objectives: To evaluate whether risk of childhood leukemia is associated with pesticide use as determined by distance of residence at birth to commercial, outdoor plant nurseries.

Methods: We conducted a large statewide, record-based case-control study of childhood leukemia in California, which included 5788 childhood leukemia cases and an equal number of controls. Pesticide exposure was based on a spatial proximity model, which combined geographic information system data with aerial satellite imagery.

Results: Overall, the results supported an increased childhood leukemia risk only for birth residences very close to nurseries. For birth residences less than 75 m from plant nurseries, we found an increased risk of childhood leukemia (odds ratio (OR) 2.40, 95% confidence interval (CI) 0.99-5.82) that was stronger for acute lymphocytic leukemia (OR 3.09, 95% CI 1.14-8.34).

Discussion: The association was robust to choices of reference group, cut points and data quality. Our findings suggest that close proximity to plant nurseries may be a risk factor for childhood leukemia and that this relationship should be further evaluated.
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http://dx.doi.org/10.1016/j.envres.2021.111388DOI Listing
September 2021

Biennial Analysis of Medication Guide Length and Estimated Readability for New Molecular Entity Drugs, 2011-2017.

Ther Innov Regul Sci 2021 09 10;55(5):918-925. Epub 2021 May 10.

Center for Drug Evaluation and Research, Office of Medical Policy, Office of Medical Policy Initiatives, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, WO Bldg 51, Third Floor, Silver Spring, MD, 20993, USA.

Background: A medication guide (MG) is a form of FDA-approved labeling that provides patients with information about certain prescribed drugs so that patients can use these drugs safely and effectively. Given ongoing efforts by FDA and industry to continuously improve MG content and format, we hypothesized that more recently approved MGs for new molecular entities (NMEs) would be shorter and more readable compared to NME MGs approved earlier.

Methods: We analyzed 53 NME MGs that were either approved in 2011 (n = 16), 2013 (n = 9), 2015 (n = 12), or 2017 (n = 16) to determine whether MG page length, word count, and readability scores differed by year. Readability was estimated by Flesch Reading Ease, Flesch-Kincaid Grade Level (FKGL), Fry graph (FRY), and Gunning's Fog Index (FOG) scores.

Results: Mean page length was significantly lower in 2017 than in 2011 and 2013 (ps < .0001). Mean FKGL scores reflected sentences and words found in 8th grade textbooks, but mean FOG and FRY scores were consistent with sentences and words found in 10th and 11th grade textbooks.

Conclusions: Although more recent NME MGs were shorter than older NME MGs, additional research is warranted to determine whether shorter MGs lead to improved readability. Developers choosing to estimate MG readability with equations should consider using multiple readability formulas and weigh the strengths and weaknesses of this approach. Using validated tools to more comprehensively assess MG readability should also be considered.
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http://dx.doi.org/10.1007/s43441-021-00270-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338801PMC
September 2021

Associations Between Physical Activity, Blood-Based Biomarkers of Neurodegeneration, and Cognition in Healthy Older Adults: The MAPT Study.

J Gerontol A Biol Sci Med Sci 2021 Jul;76(8):1382-1390

Gérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalo-Universitaire de Toulouse, France.

Physical activity (PA) demonstrated benefits on brain health, but its relationship with blood biomarkers of neurodegeneration remains poorly investigated. We explored the cross-sectional associations of PA with blood concentrations of neurofilament light chain (NFL) and beta amyloid (Aβ)42/40. We further examined whether the interaction between PA and these biomarkers was longitudinally related to cognition. Four-hundred and sixty-five nondemented older adults engaged in an interventional study and who had a concomitant assessment of PA levels and blood measurements of NFL (pg/mL) and Aβ 42/40 were analyzed. A composite Z-score combining 4 cognitive tests was used for cognitive assessment up to a 4-year follow-up. Multiple linear regressions demonstrated that people achieving 500-999 and 2000+ MET-min/week of PA had lower (ln)NFL concentrations than their inactive peers. Logistic regressions revealed that achieving at least 90 MET-min/week of PA was associated with a lower probability of having high NFL concentrations (ie, ≥91.961 pg/mL [third quartile]). PA was not associated with (Aβ)42/40. Mixed-model linear regressions demonstrated that the reverse relationship between PA and cognitive decline tended to be more pronounced as Aβ 42/40 increased, while it was dampened with increasing levels of (ln)NFL concentrations. This study demonstrates that PA is associated with blood NFL but not with Aβ 42/40. Furthermore, it suggests that PA may attenuate the negative association between amyloid load and cognition, while having high NFL levels mitigates the favorable relationship between PA and cognition. More investigations on non demented older adults are required for further validation of the present findings.
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http://dx.doi.org/10.1093/gerona/glab094DOI Listing
July 2021

Functional Analysis of Tumor-Infiltrating Myeloid Cells by Flow Cytometry and Adoptive Transfer.

J Vis Exp 2021 03 5(169). Epub 2021 Mar 5.

Department of Pathology and Molecular Medicine, McMaster University.

The tumor-infiltrating myeloid cell compartment represents a heterogeneous population of broadly immunosuppressive cells that have been exploited by the tumor to support its growth. Their accumulation in tumor and secondary lymphoid tissue leads to the suppression of antitumor immune responses and is thus a target for therapeutic intervention. As it is known that the local cytokine milieu can dictate the functional programming of tumor-infiltrating myeloid cells, strategies have been devised to manipulate the tumor microenvironment (TME) to express a cytokine landscape more conducive to antitumor myeloid cell activity. To evaluate therapy-induced changes in tumor-infiltrating myeloid cells, this paper will outline the procedure to dissociate intradermal/subcutaneous tumor tissue from solid tumor-bearing mice in preparation for leukocyte recovery. Strategies for flow cytometric analysis will be provided to enable the identification of heterogeneous myeloid populations within isolated leukocytes and the characterization of unique myeloid phenotypes. Lastly, this paper will describe a means of purifying viable myeloid cells for functional assays and determining their therapeutic value in the context of adoptive transfer.
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http://dx.doi.org/10.3791/61511DOI Listing
March 2021

Associations of acetylcholinesterase inhibition between pesticide spray seasons with depression and anxiety symptoms in adolescents, and the role of sex and adrenal hormones on gender moderation.

Expo Health 2021 Mar 21;13(1):51-64. Epub 2020 May 21.

Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA 92093, USA.

Background: Cholinesterase inhibitor pesticides, especially organophosphates, are endocrine disruptors and a few existing studies have linked self-reports of exposure with increased depression and anxiety. Some evidence suggests that associations may be stronger in women, but the mechanism of this gender difference is unclear. We assessed whether acetylcholinesterase (AChE) inhibition between 2 time points (reflecting greater cholinesterase inhibitor exposure) during different agricultural seasons in the year was associated with anxiety/depression symptoms.

Methods: We examined 300 adolescents (ages 11-17y, 51% female) living near agricultural settings in Ecuador (ESPINA study) twice in 2016: April and July-October. We assessed AChE activity (finger stick), estradiol, testosterone, dehydroepiandrosterone, cortisol (saliva) and anxiety and depression scales (CDI-2 and MASC-2).

Results: The mean (SD) depression and anxiety scores were 52.8 (9.3) and 58.1 (9.6), respectively. The median (25, 75 percentile) AChE change (July-October vs April) was -3.94% (-10.45%, 5.13%). For every 10% decrease in AChE activity, there was a 0.96 unit (95%CI: 0.01, 1.90) increase in depression symptoms and an OR of elevated depression score of 1.67 (1.04, 2.66). These associations were stronger in girls (OR=2.72 [1.23, 6.00]) than boys (1.18 [0.59, 2.37]). Adjustment for cortisol, testosterone and dehydroepiandrosterone reduced gender differences by 18-62%. No associations were observed with anxiety.

Discussion: Inhibition of AChE activity at 2 points in time during different pesticide spray periods was associated with greater depression symptoms, affecting girls more than boys. Gender differences may be partly explained by endocrine disruption. These findings suggest that AChE inhibition may transiently affect the mood of adolescents.
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http://dx.doi.org/10.1007/s12403-020-00361-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968045PMC
March 2021

EUS-guided gastroenterostomy versus enteral stenting for gastric outlet obstruction: Systematic review and meta-analysis.

Endosc Int Open 2021 Mar 22;9(3):E496-E504. Epub 2021 Feb 22.

Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, United States.

 Endoscopic and surgical techniques have been utilized for palliation of gastric outlet obstruction (GOO). Enteral stenting (ES) is an established technique with high clinical success and low morbidity rate. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a novel approach that aims to provide sustained palliation of GOO. We conducted a comprehensive review and meta-analysis to evaluate the effectiveness in terms of clinical and technical success, as well as the safety profile of EUS-GE and ES.  We searched multiple databases from inception through July 2020 to identify studies that reported on safety and effectiveness of EUS-GE in comparison to ES. Pooled rates of technical success, clinical success, and adverse events (AEs) were calculated. Study heterogeneity was assessed using I % and 95 % confidence interval.  Five studies including 659 patients were included in our final analysis. Pooled rate of technical and clinical success for EUS-GE was 95.2 % (CI 87.2-.98.3, I  = 42) and 93.3 % (CI 84.4-97.3, I  = 59) while for ES it was 96.9 % (CI 90.9-99, I  = 64) and 85.6 % (CI 73-92.9, I  = 85), respectively. Pooled rate of re-intervention was significantly lower with EUS-GE i. e. 4 % (CI 1.8-8.7, I  = 35) compared to ES, where it was 23.6 % (CI 17.5-31, I  = 35), p = 0.001 Pooled rates of overall and major AEs were comparable between the two techniques.  EUS-GE is comparable in terms of technical and clinical effectiveness and has a similar safety profile when compared to ES for palliation of GOO.
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http://dx.doi.org/10.1055/a-1341-0788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899789PMC
March 2021

Sphenopalatine ganglion block for the treatment of acute headache: An old treatment revisited.

Am J Emerg Med 2021 Feb 6. Epub 2021 Feb 6.

Spectrum Health - Michigan State University Emergency Medicine Residency Program, 15 Michigan St NE, Suite 701, Grand Rapids, MI 49503, United States. Electronic address:

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http://dx.doi.org/10.1016/j.ajem.2021.02.007DOI Listing
February 2021

Characteristics to consider when selecting a positive control material for an in vitro assay

ALTEX 2021 24;38(2):365-376. Epub 2021 Feb 24.

Empa, Swiss Federal Laboratories for Material Testing and Research, Particles-Biology Interactions Laboratory, St. Gallen, Switzerland.

The use of in vitro assays to inform decision-making requires robust and reproducible results across studies, laboratories, and time. Experiments using positive control materials are an integral component of an assay procedure to demonstrate the extent to which the measurement system is performing as expected. This paper reviews ten characteristics that should be considered when selecting a positive control material for an in vitro assay: 1) the biological mechanism of action, 2) ease of preparation, 3) chemical purity, 4) verifiable physical properties, 5) stability, 6) ability to generate responses spanning the dynamic range of the assay, 7) technical or biological interference, 8) commercial availability, 9) user toxicity, and 10) disposability. Examples and a case study of the monocyte activation test are provided to demonstrate the application of these characteristics for identification and selection of potential positive control materials. Because specific positive control materials are often written into testing standards for in vitro assays, selection of the positive control material based on these characteristics can aid in ensuring the long-term relevance and usability of these standards.
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http://dx.doi.org/10.14573/altex.2102111DOI Listing
February 2021

Mitigating the Youth Vaping Epidemic through Increasing Screening Rates for Youth Vaping/E-Cigarette Use in Pediatrics.

Perm J 2020 12;25

Department of Pediatrics, Kaiser Permanente San Jose Medical Center, San Jose, CA.

Introduction: E-cigarette/vaping use in adolescents has increased 77.8% among high schoolers and 48.5% among middle schoolers in 2017-2018. As such, there is need for an effective workflow for screening for vaping. We aimed to increase screening rates of e-cigarette/vaping users from less than 1% to at least 50% in 6 months.

Methods: Screening for vaping in youth was implemented in a pediatric clinic in Northern California beginning in the summer of 2019 for 6 months. Depending on comorbidity, severity, and readiness to quit, patients were referred to treatment. Outcomes included screening rates, process measure included positive screening rates, and balancing measure was provider time.

Results: The clinic completed 1414 physicals with an average screening rate of 76% and a positive rate of 7.9%. The average age of patients was 15 (standard deviation = 1.3), 48% were female and 29% were Asian/Pacific Islander, 23% Hispanic, and 23% White. After 6 months, we met our goal in all but 1 plan-do-study-act (PDSA) cycle.

Discussion: We created a standardized workflow that identified teens who vaped. When compared to other studies, the positive rate for this study was low which is likely due to misinterpretation by staff of screening questions as well as the fact that data were collected during a clinic visit.

Conclusions: It is important to find ways in which providers can mitigate this epidemic given the alarming increase in e-cigarette/vaping use among adolescents. This study furthers the effort to develop a screening method that is simple and brief, allowing physicians to intervene if necessary.
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http://dx.doi.org/10.7812/TPP/20.064DOI Listing
December 2020
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