Publications by authors named "David Wong"

935 Publications

Clinical Significance of Macula-Off Rhegmatogenous Retinal Detachment Preoperative Features on Optical Coherence Tomography.

Ophthalmic Surg Lasers Imaging Retina 2021 Jul 1;52(S1):S23-S29. Epub 2021 Jul 1.

Background And Objective: To evaluate the clinical significance of preoperative spectral-domain optical coherence tomography (OCT) features and their association with postoperative outcomes in eyes with primary macula-off rhegmatogenous retinal detachment (RRD).

Patients And Methods: This is a retrospective case series of all consecutive cases undergoing repair of primary macula-off RRD at two tertiary care academic centers between January 2018 to January 2021.

Results: Among 406 eyes, baseline visual acuity (β = 0.184, = .001) and time to surgery (β = 0.009, = .033) were predictive of postoperative visual acuity at 1-year follow-up after adjusting for age, sex and lens status, as well as presence of preoperative features on OCT such as outer retinal corrugations and height of the retinal detachment.

Conclusion: Baseline visual acuity and time to surgical repair are the best predictors of vision outcomes following macula-off RRD repair. .
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http://dx.doi.org/10.3928/23258160-20210518-05DOI Listing
July 2021

The Inflammatory Cytokine Profile Associated with Liver Damage is Broader and Stronger in Chronic Hepatitis B Patients Compared to Acute Hepatitis B Patients.

J Infect Dis 2021 Jul 21. Epub 2021 Jul 21.

Department of Immunology, University of Toronto, Ontario, Canada.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in acute hepatitis B, chronic hepatitis B patients with HBeAg seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL and TNF-α.
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http://dx.doi.org/10.1093/infdis/jiab373DOI Listing
July 2021

Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma.

Cancers (Basel) 2021 Jul 3;13(13). Epub 2021 Jul 3.

Thoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.

: We assessed whether serial ctDNA monitoring of plasma and saliva predicts response and resistance to osimertinib in EGFR-mutant lung adenocarcinoma. Three ctDNA technologies-blood-based droplet-digital PCR (ddPCR), next-generation sequencing (NGS), and saliva-based EFIRM liquid biopsy (eLB)-were employed to investigate their complementary roles. : Plasma and saliva samples were collected from patients enrolled in a prospective clinical trial of osimertinib and local ablative therapy upon progression (NCT02759835). Plasma was analyzed by ddPCR and NGS. Saliva was analyzed by eLB. : A total of 25 patients were included. We analyzed 534 samples by ddPCR ( = 25), 256 samples by NGS ( = 24) and 371 samples by eLB ( = 22). Among 20 patients who progressed, ctDNA progression predated RECIST 1.1 progression by a median of 118 days (range: 61-272 days) in 11 (55%) patients. Of nine patients without ctDNA progression by ddPCR, two patients had an increase in mutant by eLB and two patients were found to have ctDNA progression by NGS. Levels of ctDNA measured by ddPCR and NGS at early time points, but not volumetric tumor burden, were associated with PFS. // amplifications, C797S, E545K, V9del, and S45P were key resistance mechanisms identified by NGS. : Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles.
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http://dx.doi.org/10.3390/cancers13133342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268167PMC
July 2021

A new approach for health-oriented ozone control strategy: Adjoint-based optimization of NO emission reductions using metaheuristic algorithms.

J Clean Prod 2021 Aug;312(20):127533

Department of Geography and Resource Management, The Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong, China.

While levels of particulate matters in the Pearl River Delta Region (PRD) show a significant reduction, ozone (O) has an opposite increasing trend, becoming the critical air quality target in this decade. Emission control strategies are typically formulated sector by sector, spatial variability in emissions reductions and health impacts of air pollutants may not be taken into account, affecting the overall effectiveness of control strategies. This study proposes an adjoint-based optimization framework to facilitate health-oriented O control over PRD. The location-specific adjoint sensitivity coefficients, which reflect the spatiotemporal influences from emissions of nitrogen dioxide (NO) on O health impacts, are combined with metaheuristic algorithms to minimize the O-related premature mortalities over receptor regions. Using the proposed optimization methodology, the regional O health benefits under current emission reduction policy can be increased by 16-27%. The results show that relatively larger NO emissions reductions occurred at highly developed and populated areas. Particularly, significant reductions in NO emissions are observed at Shenzhen and urban Guangzhou. Furthermore, implementing regional NO emissions abatement has advantages to achieve an overall O health benefits for all cities. The interregional influences of NO emissions abatement between cities indicate a promising strategy of health-oriented O control in PRD.
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http://dx.doi.org/10.1016/j.jclepro.2021.127533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262626PMC
August 2021

"Crawling Attachment" during Periodontally Accelerated Osteogenic Orthodontics Procedure.

Contemp Clin Dent 2021 Apr-Jun;12(2):179-183. Epub 2021 Jun 14.

Department of Periodontology, University of Tennessee Health Sciences College of Dentistry, Memphis, TN, USA.

The present clinical case reports an increased zone of keratinized gingiva that was generated following surgical excision of the gingiva during periodontally accelerated osteogenic orthodontics. The present case consists of angle Class I with mal-aligned teeth and impacted #11. The patient was evaluated up to 2 years and 1 month (2.1) showing a stable increased zone of keratinized tissue. Possible causes for this event are discussed in this case report. Additional long-term clinical studies are necessary to support these results.
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http://dx.doi.org/10.4103/ccd.ccd_376_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237815PMC
June 2021

Development and validation of a quantitative, non-invasive, highly sensitive and specific, electrochemical assay for anti-SARS-CoV-2 IgG antibodies in saliva.

PLoS One 2021 1;16(7):e0251342. Epub 2021 Jul 1.

School of Dentistry, University of California, Los Angeles, CA, United States of America.

Amperial™ is a novel assay platform that uses immobilized antigen in a conducting polymer gel followed by detection via electrochemical measurement of oxidation-reduction reaction between H2O2/Tetrametylbenzidine and peroxidase enzyme in a completed assay complex. A highly specific and sensitive assay was developed to quantify levels of IgG antibodies to SARS-CoV-2 in saliva. After establishing linearity and limit of detection we established a reference range of 5 standard deviations above the mean. There were no false positives in 667 consecutive saliva samples obtained prior to 2019. Saliva was obtained from 34 patients who had recovered from documented COVID-19 or had documented positive serologies. All of the patients with symptoms severe enough to seek medical attention had positive antibody tests and 88% overall had positive results. We obtained blinded paired saliva and plasma samples from 14 individuals. The plasma was analyzed using an EUA-FDA cleared ELISA kit and the saliva was analyzed by our Amperial™ assay. All 5 samples with negative plasma titers were negative in saliva testing. Eight of the 9 positive plasma samples were positive in saliva and 1 had borderline results. A CLIA validation was performed as a laboratory developed test in a high complexity laboratory. A quantitative non-invasive saliva based SARS-CoV-2 antibody test was developed and validated with sufficient specificity to be useful for population-based monitoring and monitoring of individuals following vaccination.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251342PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248704PMC
July 2021

Canadian Airway Focus Group updated consensus-based recommendations for management of the difficult airway: part 1. Difficult airway management encountered in an unconscious patient.

Can J Anaesth 2021 Jun 18. Epub 2021 Jun 18.

Department of Emergency Medicine, QEII Health Sciences Centre, Dalhousie University, 1796 Summer Street, Halifax, NS, B3H 3A7, Canada.

Purpose: Since the last Canadian Airway Focus Group (CAFG) guidelines were published in 2013, the literature on airway management has expanded substantially. The CAFG therefore re-convened to examine this literature and update practice recommendations. This first of two articles addresses difficulty encountered with airway management in an unconscious patient.

Source: Canadian Airway Focus Group members, including anesthesia, emergency medicine, and critical care physicians, were assigned topics to search. Searches were run in the Medline, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL databases. Results were presented to the group and discussed during video conferences every two weeks from April 2018 to July 2020. These CAFG recommendations are based on the best available published evidence. Where high-quality evidence was lacking, statements are based on group consensus.

Findings And Key Recommendations: Most studies comparing video laryngoscopy (VL) with direct laryngoscopy indicate a higher first attempt and overall success rate with VL, and lower complication rates. Thus, resources allowing, the CAFG now recommends use of VL with appropriately selected blade type to facilitate all tracheal intubations. If a first attempt at tracheal intubation or supraglottic airway (SGA) placement is unsuccessful, further attempts can be made as long as patient ventilation and oxygenation is maintained. Nevertheless, total attempts should be limited (to three or fewer) before declaring failure and pausing to consider "exit strategy" options. For failed intubation, exit strategy options in the still-oxygenated patient include awakening (if feasible), temporizing with an SGA, a single further attempt at tracheal intubation using a different technique, or front-of-neck airway access (FONA). Failure of tracheal intubation, face-mask ventilation, and SGA ventilation together with current or imminent hypoxemia defines a "cannot ventilate, cannot oxygenate" emergency. Neuromuscular blockade should be confirmed or established, and a single final attempt at face-mask ventilation, SGA placement, or tracheal intubation with hyper-angulated blade VL can be made, if it had not already been attempted. If ventilation remains impossible, emergency FONA should occur without delay using a scalpel-bougie-tube technique (in the adult patient). The CAFG recommends all institutions designate an individual as "airway lead" to help institute difficult airway protocols, ensure adequate training and equipment, and help with airway-related quality reviews.
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http://dx.doi.org/10.1007/s12630-021-02007-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212585PMC
June 2021

SPINE20 A global advocacy group promoting evidence-based spine care of value.

Eur Spine J 2021 Jun 9. Epub 2021 Jun 9.

Ospedale Bambino Gesù, Roma, Italia.

Purpose: The Global Burden of Diseases (GBD) Studies have estimated that low back pain is one of the costliest ailments worldwide. Subsequent to GBD publications, leadership of the four largest global spine societies agreed to form SPINE20. This article introduces the concept of SPINE20, the recommendations, and the future of this global advocacy group linked to G20 annual summits.

Methods: The founders of SPINE20 advocacy group coordinated with G20 Saudi Arabia to conduct the SPINE20 summit in 2020. The summit was intended to promote evidence-based recommendations to use the most reliable information from high-level research. Eight areas of importance to mitigate spine disorders were identified through a voting process of the participating societies. Twelve recommendations were discussed and vetted.

Results: The areas of immediate concern were "Aging spine," "Future of spine care," "Spinal cord injuries," "Children and adolescent spine," "Spine-related disability," "Spine Educational Standards," "Patient safety," and "Burden on economy." Twelve recommendations were created and endorsed by 31/33 spine societies and 2 journals globally during a vetted process through the SPINE20.org website and during the virtual inaugural meeting November 10-11, 2020 held from the G20 platform.

Conclusions: This is the first time that international spine societies have joined to support actions to mitigate the burden of spine disorders across the globe. SPINE20 seeks to change awareness and treatment of spine pain by supporting local projects that implement value-based practices with healthcare policies that are culturally sensitive based on scientific evidence.
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http://dx.doi.org/10.1007/s00586-021-06890-5DOI Listing
June 2021

Canadian Airway Focus Group updated consensus-based recommendations for management of the difficult airway: part 2. Planning and implementing safe management of the patient with an anticipated difficult airway.

Can J Anaesth 2021 Jun 8. Epub 2021 Jun 8.

Department of Anesthesia & Perioperative Medicine, Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Rd., LHSC- University Hospital, London, ON, N6A 5A5, Canada.

Purpose: Since the last Canadian Airway Focus Group (CAFG) guidelines were published in 2013, the published airway management literature has expanded substantially. The CAFG therefore re-convened to examine this literature and update practice recommendations. This second of two articles addresses airway evaluation, decision-making, and safe implementation of an airway management strategy when difficulty is anticipated.

Source: Canadian Airway Focus Group members, including anesthesia, emergency medicine, and critical care physicians were assigned topics to search. Searches were run in the Medline, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL databases. Results were presented to the group and discussed during video conferences every two weeks from April 2018 to July 2020. These CAFG recommendations are based on the best available published evidence. Where high-quality evidence is lacking, statements are based on group consensus.

Findings And Key Recommendations: Prior to airway management, a documented strategy should be formulated for every patient, based on airway evaluation. Bedside examination should seek predictors of difficulty with face-mask ventilation (FMV), tracheal intubation using video- or direct laryngoscopy (VL or DL), supraglottic airway use, as well as emergency front of neck airway access. Patient physiology and contextual issues should also be assessed. Predicted difficulty should prompt careful decision-making on how most safely to proceed with airway management. Awake tracheal intubation may provide an extra margin of safety when impossible VL or DL is predicted, when difficulty is predicted with more than one mode of airway management (e.g., tracheal intubation and FMV), or when predicted difficulty coincides with significant physiologic or contextual issues. If managing the patient after the induction of general anesthesia despite predicted difficulty, team briefing should include triggers for moving from one technique to the next, expert assistance should be sourced, and required equipment should be present. Unanticipated difficulty with airway management can always occur, so the airway manager should have a strategy for difficulty occurring in every patient, and the institution must make difficult airway equipment readily available. Tracheal extubation of the at-risk patient must also be carefully planned, including assessment of the patient's tolerance for withdrawal of airway support and whether re-intubation might be difficult.
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http://dx.doi.org/10.1007/s12630-021-02008-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186352PMC
June 2021

Evaluation of a continuous glucose monitoring system in neonatal foals.

J Vet Intern Med 2021 Jul 6;35(4):1995-2001. Epub 2021 Jun 6.

Virginia Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.

Background: Monitoring blood glucose concentrations is common in critically ill neonatal foals, especially septic foals and those receiving naso-esophageal feedings or IV parenteral nutrition. Glucose typically is measured using a point-of-care (POC) glucometer but requires repeated restraint and blood collections, which may cause irritation at venipuncture sites and increased demands on nursing staff. Continuous glucose monitoring systems (CGMS) may provide an accurate alternative for monitoring blood glucose concentration.

Objectives: To determine the correlation and accuracy of a CGMS to monitor neonatal foals' blood glucose concentrations as compared to a POC glucometer and laboratory chemistry analysis (CHEM).

Animals: Samples from 4 healthy and 4 ill neonatal foals.

Methods: A CGMS was placed on each foal, and glucose measurements acquired from this device were compared to simultaneous measurements of blood glucose concentration using a POC glucometer and CHEM.

Results: Two-hundred matched glucose measurements were collected from 8 neonatal foals. The mean bias (95% limits of agreement) between CGMS and CHEM, CGMS and POC glucometer, and POC glucometer and CHEM was 3.97 mg/dL (-32.5 to 40.4), 18.2 mg/dL (-28.8 to 65.2), and 22.18 mg/dL (-9.3 to 53.67), respectively. The Pearson's correlation coefficient (r) was significantly correlated among all devices: GCMS and CHEM (r = 0.81), CGMS and POC glucometer (r = 0.77) and POC glucometer-CHEM (r = 0.92).

Conclusions And Clinical Importance: Within the blood glucose concentration ranges in this study (78-212 mg/dL), CGMS measurements were significantly correlated with CHEM, suggesting that it is an acceptable method to provide meaningful, immediate, and continuous glucose concentration measurements in neonatal foals while eliminating the need for repeated restraint and blood collection.
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http://dx.doi.org/10.1111/jvim.16186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295665PMC
July 2021

Cervical fusion for treatment of degenerative conditions: Development of appropriate use criteria.

Spine J 2021 Jun 1. Epub 2021 Jun 1.

Department of Neurosurgery, Lahey Hospital & Medical Center, 41 Mall Road Charles A, Tufts University School of Medicine, Burlington, MA 01805-0105, USA.

Background Context: High quality evidence is difficult to generate, leaving substantial knowledge gaps in the treatment of spinal conditions. Appropriate use criteria (AUC) are a means of determining appropriate recommendations when high quality evidence is lacking.

Purpose: Define appropriate use criteria (AUC) of cervical fusion for treatment of degenerative conditions of the cervical spine.

Study Design/setting: Appropriate use criteria for cervical fusion were developed using the RAND/UCLA appropriateness methodology. Following development of clinical guidelines and scenario writing, a one-day workshop was held with a multidisciplinary group of 14 raters, all considered thought leaders in their respective fields, to determine final ratings for cervical fusion appropriateness for various clinical situations.

Outcome Measures: Final rating for cervical fusion recommendation as either "Appropriate," "Uncertain" or "Rarely Appropriate" based on the median final rating among the raters.

Methods: Inclusion criteria for scenarios included patients aged 18 to 80 with degenerative conditions of the cervical spine. Key modifiers were defined and combined to develop a matrix of clinical scenarios. The median score among the raters was used to determine the final rating for each scenario. The final rating was compared between modifier levels. Spearman's rank correlation between each modifier and the final rating was determined. A multivariable ordinal regression model was fit to determine the adjusted odds of an "Appropriate" final rating while adjusting for radiographic diagnosis, number of levels and symptom type. Three decision trees were developed using decision tree classification models and variable importance for each tree was computed.

Results: Of the 263 scenarios, 47 (17.9 %) were rated as rarely appropriate, 66 (25%) as uncertain and 150 (57%) were rated as appropriate. Symptom type was the modifier most strongly correlated with the final rating (adjusted ρ2 = 0.58, p<.01). A multivariable ordinal regression adjusting for symptom type, diagnosis, and number of levels and showed high discriminative ability (C statistic = 0.90) and the adjusted odds ratio (aOR) of receiving a final rating of "Appropriate" was highest for myelopathy (aOR, 7.1) and radiculopathy (aOR, 4.8). Three decision tree models showed that symptom type and radiographic diagnosis had the highest variable importance.

Conclusions: Appropriate use criteria for cervical fusion in the setting of cervical degenerative disorders were developed. Symptom type was most strongly correlated with final rating. Myelopathy or radiculopathy were most strongly associated with an "Appropriate" rating, while axial pain without stenosis was most associated with "Rarely Appropriate."
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http://dx.doi.org/10.1016/j.spinee.2021.05.023DOI Listing
June 2021

Blood thiamine (vitamin B ), ascorbic acid (vitamin C), and cortisol concentrations in healthy and ill neonatal foals.

J Vet Intern Med 2021 Jul 30;35(4):1988-1994. Epub 2021 May 30.

North Carolina State University, College of Veterinary Medicine, Raleigh, NC, USA.

Background: Sepsis is common in foals and several treatments are used to facilitate recovery. Evidence in people suggests an association between low blood concentrations of thiamine, ascorbic acid, and cortisol and sepsis, with further evidence suggesting that administration of hydrocortisone, thiamine, and ascorbic acid may improve outcome. No information is available with regard to these treatments in foals.

Hypothesis/objectives: To compare blood concentrations of thiamine, ascorbic acid, and cortisol in healthy and ill foals.

Animals: Fifteen healthy and 27 ill (septic and sick-nonseptic [SNS]) foals were evaluated at admission. Fewer healthy and ill foals were available for sampling at 72 and 120 hours.

Methods: Prospective study. Blood was collected from healthy foals at 12 (n = 15), 72 (n = 11), and 120 (n = 9) hours of age and from ill foals <48 hours old at admission (n = 27), 72 (n = 8), and 120 (n = 8) hours after presentation. Thiamine, ascorbic acid, and cortisol concentrations were measured in blood samples and compared between groups of foals.

Results: Blood concentrations of thiamine were significantly lower in septic compared to healthy foals at 72 (median, 1.72 ng/mL; P = .02) and 120 (median, 2.0 ng/mL; P = .04) hours after admission; blood concentrations of ascorbic acid also were significantly lower in septic compared to healthy foals at 72 (median, 4.4 μg/mL; P = .02) and 120 hours (median, 4.8 μg/mL; P = .03). Blood concentrations of ascorbic acid were lower in SNS compared to healthy foals at 72 (median, 6.9 μg/mL; P = .03) and 120 (median, 6.4 μg/mL; P = .04) hours after admission. Serum cortisol concentrations were significantly higher at admission in septic (median, 4.23 μg/dL) compared to SNS (median, 1.8 μg/dL; P = .01) and healthy (median, 2.2 μg/dL; P = .002) foals.

Conclusions And Clinical Importance: A potential association exists between illness in foals and lower blood concentrations of thiamine and ascorbic acid during hospitalization. Additional studies are needed to examine a larger population of foals and determine the clinical impact of low vitamin concentrations, if any, on morbidity and mortality.
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http://dx.doi.org/10.1111/jvim.16188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295700PMC
July 2021

Face-to-face physiotherapy compared with a supported home exercise programme for the management of musculoskeletal conditions: protocol of a multicentre, randomised controlled trial-the REFORM trial.

BMJ Open 2021 05 18;11(5):e041242. Epub 2021 May 18.

Kolling Institute, The University of Sydney, Sydney, New South Wales, Australia

Introduction: Exercise, support and advice are considered core components of management for most musculoskeletal conditions and are typically provided by physiotherapists through regular face-to-face treatments. However, exercise can be provided remotely as part of a home exercise programme, while support and advice can be provided over the telephone. There is initial evidence from trials and systematic reviews to suggest that remotely provided physiotherapy can be used to manage a variety of musculoskeletal conditions safely and effectively.

Methods And Analysis: The aim of this single-blind randomised controlled non-inferiority trial is to determine whether a supported home exercise programme is as good as or better than face-to-face physiotherapy for the treatment of musculoskeletal conditions. Two hundred and ten participants will be recruited from five public hospitals in Sydney, Australia. Participants will be randomised to either the supported home exercise group or the face-to-face physiotherapy group. Participants allocated to the supported home exercise group will initially receive one face-to-face session with the trial physiotherapist and will then be managed remotely for the next 6 weeks. Participants allocated to the face-to-face physiotherapy group will receive a course of physiotherapy as typically provided in Sydney government hospitals. The primary outcome is function measured by the Patient Specific Functional Scale at 6 weeks. There will be nine secondary outcomes measured at 6 and 26 weeks. Separate analyses will be conducted on each outcome, and all analyses will be conducted on an intention-to-treat basis. A health economic evaluation will be conducted from a health funder plus patient perspective.

Ethics And Dissemination: Ethical approval was obtained on the 17 March 2017 from the Northern Sydney Local Health District HREC, trial number HREC/16HAWKE/431-RESP/16/287. The results of this study will be submitted for publication to peer-reviewed journals and be presented at national and international conferences. Recruitment commenced in March 2019, and it is anticipated that the trial will be completed by December 2021. This trial will investigate two different models of physiotherapy care for people with musculoskeletal conditions.

Trial Registration Number: CPMP/ICH-135/95.

Protocol Version: The most recent version of the protocol is V.1.2 dated November 2019.
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http://dx.doi.org/10.1136/bmjopen-2020-041242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130735PMC
May 2021

A scoping review to identify and map the multidimensional domains of pain in adults with advanced liver disease.

Can J Pain 2020 Sep 15;4(1):210-224. Epub 2020 Sep 15.

Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada.

: Pain is a significant problem in adults living with advanced liver disease, having limited guidance available for its clinical management. While pain is considered a multidimensional experience, there have been limited reviews of the pain literature in advanced liver disease conducted with a multidimensional framework. The goal of this scoping review was to identify and map the multidimensional domains of pain in adults with advanced liver disease using the biopsychosocial model. We used Arksey and O'Malley's scoping framework. A search was conducted in MEDLINE, Embase, AMED, and CINAHL databases and the gray literature using specific eligibility criteria (1990-2019). Citation selection and data extraction were performed by two independent reviewers and in duplicate. Of the 43 studies that met inclusion criteria, 51% were from North America and 93% utilized quantitative methods. The combined studies reported on 168,110 participants with ages ranging between 23 to 87 years. Only 9% reported an objective scoring system for liver disease severity. Few studies reported pain classification (9%) and intensity (16%). Pain prevalence ranged between 18% and 100%, with pain locations including joint, abdomen, back, head/neck, and upper/lower extremities. We identified and mapped 115 pain factors to the biopsychosocial model: physical (81%), psychological (65%), and sociocultural (5%). Only 9% measured pain using validated multidimensional tools. Pharmacological intervention (92%) prevailed among pain treatments. Pain is not well understood in patients with advanced liver disease, having limited multidimensional pain assessment and treatment approaches. There is a need to systematically examine the multidimensional nature of pain in this population.
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http://dx.doi.org/10.1080/24740527.2020.1785855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951148PMC
September 2020

Intracranial Metastasis from Prostate Cancer: Investigation, Incidence, and Imaging Findings in a Large Cohort of Australian Men.

J Clin Imaging Sci 2021 24;11:24. Epub 2021 Apr 24.

I-MED Radiology, The Wesley Hospital, Brisbane, Queensland, Australia.

Objectives: Prostate cancer metastasizing to the brain is remarkably uncommon, with the incidence never having been described in the modern setting. The objective of this study was to determine the incidence and imaging pattern of intracranial metastasis from prostate cancer in a large cohort of Australian men with prostate cancer.

Material And Methods: Retrospective review was undertaken of imaging reports for all known prostate cancer patients, who underwent an imaging examination inclusive of the brain, between July 1, 2014, and July 1, 2020. Once an intracranial lesion was identified, all available imaging and clinical notes were reviewed.

Results: A total of 5644 imaging examinations which included the brain were identified in 4341 prostate cancer patients. The majority (92.1%) of examinations were 68-Gallium-labeled prostate-specific membrane antigen (Ga-PSMA) positron emission tomography/computed tomography (PET/CT). Eight patients were identified as having an intracranial metastasis from prostate cancer, yielding an incidence of 0.18%. All patients had a Gleason score of 9 (where known), and the majority of patients (5/8) had a non-acinar variant of prostate cancer. At the time of diagnosis of intracranial metastasis, all patients had extensive metastatic disease. Imaging characteristics of the intracranial lesions were highly variable.

Conclusion: The incidence of intracranial metastasis in prostate cancer patients has never been well-established. In this study, we determined the incidence as being 0.18%. Given the majority of metastasis constituted unexpected findings on routine restaging Ga-PSMA PET/CT, the incidence determined in our study is arguably the most accurate and clinically relevant described to date.
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http://dx.doi.org/10.25259/JCIS_52_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088474PMC
April 2021

Lu177-PSMA therapy for men with advanced prostate cancer: 18 months survival analysis in a single Australian tertiary institution.

J Med Imaging Radiat Oncol 2021 Apr 22. Epub 2021 Apr 22.

I-MED Radiology, The Wesley Hospital, Auchenflower, Queensland, Australia.

Introduction: Radioligand therapies, or 'theranostics', have an emerging role in patients with metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177 (Lu), targeting prostate-specific membrane antigen (PSMA), has demonstrated promising outcomes including reduced disease progression and improved overall survival. We aim to determine overall survival demonstrated by our LuPSMA patient cohort to date.

Methods: Kaplan-Meier survival analysis and log-rank test were performed on all LuPSMA therapy patients with at least 12 months of follow-up data available (n = 68). Comparison across patients was made based on several variables including the baseline characteristics of prostate-specific antigen (PSA) level, maximum standard uptake value (SUV ) and metastasis site and by biochemical response.

Results: The 18-month overall survival estimate for the patient cohort was 63.8%. Patients with baseline serum PSA <20 µg/L had a greater 18-month survival estimate (79.9%) compared to PSA ≥20 µg/L (53.8%; P < 0.05). Patients with an SUV  >15 had an 18-month survival estimate of 56.0%, compared to 38.0% in patients with SUV  ≤15 (P < 0.05). No significant difference in overall survival was observed by metastasis site. Both a decrease in PSA after two LuPSMA therapy cycles and the maximum response over the treatment course being a decline in PSA were indicative of greater overall survival (P < 0.01 and P < 0.001 respectively).

Conclusion: Our study reported an 18-month overall survival of 64% in patients with mCRPC who have undergone LuPSMA therapy. Our study identified that baseline serum PSA, SUV and biochemical response to treatment are prognostic markers for increased overall survival.
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http://dx.doi.org/10.1111/1754-9485.13182DOI Listing
April 2021

Postoperative Photoreceptor Integrity Following Pneumatic Retinopexy vs Pars Plana Vitrectomy for Retinal Detachment Repair: A Post Hoc Optical Coherence Tomography Analysis From the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial.

JAMA Ophthalmol 2021 Jun;139(6):620-627

Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, England.

Importance: Pneumatic retinopexy (PnR) is associated with superior visual acuity and reduced vertical metamorphopsia compared with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). It is important to determine postoperative photoreceptor integrity with both surgical techniques.

Objective: To compare photoreceptor integrity on spectral domain-optical coherence tomography (SD-OCT) between PnR and PPV at 12 months postoperatively.

Design, Setting, And Participants: Post hoc analysis of the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) conducted between August 2012 and May 2017 at St Michael's Hospital, Toronto, Ontario, Canada. Primary RRDs with specific criteria were included. Data were analyzed between April and August 2020.

Intervention: Randomization to PnR vs PPV stratified by macular status.

Main Outcomes And Measures: Difference in proportion of patients with discontinuity of the ellipsoid zone (EZ) and external limiting membrane (ELM) between groups assessed independently by 2 masked graders at an external masked image reading center.

Results: A total of 150 participants completed the 12-month follow-up visit. A total of 145 patients (72 PPV and 73 PnR) had gradable spectral-domain optical coherence tomography at 12 months. Analysis of the central 3-mm (foveal) scans found that 24% (n = 17 of 72) vs 7% (n = 5 of 73) displayed EZ discontinuity (difference, 17%; odds ratio [OR], 4.204; 95% CI, 1.458-12.116; P = .005) and 20% (n = 14 of 71) vs 6% (n = 4 of 73) displayed ELM discontinuity (difference, 14%; OR, 4.237; 95% CI, 1.321-13.587; P = .01) in the PPV and PnR groups, respectively. Analysis of the 6-mm (foveal and nonfoveal) scans revealed that EZ and ELM discontinuity was greater in the PPV vs PnR groups (EZ, 32% [n = 23 of 72] vs 11% [n = 8 of 73]; difference, 21%; OR, 3.814; 95% CI, 1.573-9.249; P = .002; ELM, 32% [n = 23 of 71] vs 18% [n = 13 of 73]; difference, 14%; OR, 2.211; 95% CI, 1.015-4.819; P = .04).

Conclusions And Relevance: Discontinuity of the EZ and ELM was more common at 12 months postoperatively following PPV vs PnR for RRD repair. The findings of this post hoc analysis suggest that less discontinuity of the EZ and ELM may provide an anatomic basis for the previously reported superior functional outcomes with PnR, although the analysis does not prove a cause-and-effect relationship.

Trial Registration: ClinicalTrials.gov Identifier: NCT01639209.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209566PMC
June 2021

Role of sea fog over the Yellow Sea on air quality with the direct effect of aerosols.

J Geophys Res Atmos 2021 Mar;126(5)

Department of Safety and Environment Research, The Seoul Institute, Seoul, Republic of Korea.

In this study, we investigate the impact of sea fog over the Yellow Sea on air quality with the direct effect of aerosols for the entire year of 2016. Using the WRF-CMAQ two-way coupled model, we perform four model simulations with the up-to-date emission inventory over East Asia and dynamic chemical boundary conditions provided by hemispheric model simulations. During the spring of 2016, prevailing westerly winds and anticyclones caused the formation of a temperature inversion over the Yellow Sea, providing favorable conditions for the formation of fog. The inclusion of the direct effect of aerosols enhanced its strength. On foggy days, we find dominant changes of aerosols at an altitude of 150-200 m over the Yellow Sea resulted by the production through aqueous chemistry (~12.36% and ~3.08% increases in sulfate and ammonium) and loss via the wet deposition process (~-2.94% decrease in nitrate); we also find stronger wet deposition of all species occurring in PBL. Stagnant conditions associated with reduced air temperature caused by the direct effect of aerosols enhanced aerosol chemistry, especially in coastal regions, and it exceeded the loss of nitrate. The transport of air pollutants affected by sea fog extended to a much broader region. Our findings show that the Yellow Sea acts as not only a path of long-range transport but also as a sink and source of air pollutants. Further study should investigate changes in the impact of sea fog on air quality in conjunction with changes in the concentrations of aerosols and the climate.
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http://dx.doi.org/10.1029/2020jd033498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048130PMC
March 2021

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

Cell 2021 05 30;184(10):2587-2594.e7. Epub 2021 Mar 30.

Illumina, San Diego, CA 92122, USA.

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.
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http://dx.doi.org/10.1016/j.cell.2021.03.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009040PMC
May 2021

Airway Management in Surgical Patients With Obstructive Sleep Apnea.

Anesth Analg 2021 05;132(5):1321-1327

Department of Anesthesia, Toronto Western Hospital, University of Toronto, Ontario, Canada.

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder, and the difficult airway is perhaps the anesthesiologists' quintessential concern. OSA and the difficult airway share certain similar anatomical, morphological, and physiological features. Individual studies and systematic reviews of retrospective, case-control, and large database studies have shown a likely association between patients with OSA and the difficult airway; OSA patients have a 3- to 4-fold higher risk of difficult intubation, difficult mask ventilation, or a combination of both. The presence of OSA should initiate proactive perioperative management in anticipation of a difficult airway. Prudent intraoperative management comprises the use of regional anesthesia where possible and considering an awake intubation technique where there is the presence of notable difficult airway predictors and risk of rapid desaturation following induction of general anesthesia. Familiarity with difficult airway algorithms, cautious extubation, and appropriate postoperative monitoring of patients with OSA are necessary to mitigate perioperative risks.
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http://dx.doi.org/10.1213/ANE.0000000000005298DOI Listing
May 2021

Prehospital Trauma Care in Disasters and Other Mass Casualty Incidents - A Proposal for Hospital-Based Special Medical Response Teams.

Cureus 2021 Mar 2;13(3):e13657. Epub 2021 Mar 2.

Department of Surgery, Riverside Community Hospital, Riverside, USA.

Current mass casualty incident (MCI) response in the United States calls for rapid deployment of first responders, such as law enforcement, fire, and emergency medical services personnel, to the incident and simultaneous activation of trauma center disaster protocols. Past investigations demonstrated that the incorporation of advanced trauma-trained physicians and paramedics into prehospital teams resulted in improved mortality during routine emergency medical care in Europe and in the combat setting. To date, limited research exists on the incorporation of advanced trauma-trained physicians and paramedics into prehospital teams for civilian MCIs. We proposed the concept of Special Medical Response Teams, which would rapidly deploy advanced trauma-trained physicians and paramedics to deliver a higher level of medical and surgical care in the prehospital setting during civilian mass casualty incidents.
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http://dx.doi.org/10.7759/cureus.13657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016499PMC
March 2021

Development and evaluation of a deep learning model for the detection of multiple fundus diseases based on colour fundus photography.

Br J Ophthalmol 2021 Mar 30. Epub 2021 Mar 30.

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

Aim: To explore and evaluate an appropriate deep learning system (DLS) for the detection of 12 major fundus diseases using colour fundus photography.

Methods: Diagnostic performance of a DLS was tested on the detection of normal fundus and 12 major fundus diseases including referable diabetic retinopathy, pathologic myopic retinal degeneration, retinal vein occlusion, retinitis pigmentosa, retinal detachment, wet and dry age-related macular degeneration, epiretinal membrane, macula hole, possible glaucomatous optic neuropathy, papilledema and optic nerve atrophy. The DLS was developed with 56 738 images and tested with 8176 images from one internal test set and two external test sets. The comparison with human doctors was also conducted.

Results: The area under the receiver operating characteristic curves of the DLS on the internal test set and the two external test sets were 0.950 (95% CI 0.942 to 0.957) to 0.996 (95% CI 0.994 to 0.998), 0.931 (95% CI 0.923 to 0.939) to 1.000 (95% CI 0.999 to 1.000) and 0.934 (95% CI 0.929 to 0.938) to 1.000 (95% CI 0.999 to 1.000), with sensitivities of 80.4% (95% CI 79.1% to 81.6%) to 97.3% (95% CI 96.7% to 97.8%), 64.6% (95% CI 63.0% to 66.1%) to 100% (95% CI 100% to 100%) and 68.0% (95% CI 67.1% to 68.9%) to 100% (95% CI 100% to 100%), respectively, and specificities of 89.7% (95% CI 88.8% to 90.7%) to 98.1% (95%CI 97.7% to 98.6%), 78.7% (95% CI 77.4% to 80.0%) to 99.6% (95% CI 99.4% to 99.8%) and 88.1% (95% CI 87.4% to 88.7%) to 98.7% (95% CI 98.5% to 99.0%), respectively. When compared with human doctors, the DLS obtained a higher diagnostic sensitivity but lower specificity.

Conclusion: The proposed DLS is effective in diagnosing normal fundus and 12 major fundus diseases, and thus has much potential for fundus diseases screening in the real world.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316290DOI Listing
March 2021

Impact of Obesity on Mortality in Adult Trauma Patients.

Cureus 2021 Feb 15;13(2):e13352. Epub 2021 Feb 15.

Emergency Medicine, Arrowhead Regional Medical Center, Colton, USA.

Introduction Trauma is a major cause of morbidity and mortality amongst all populations in the United States. With the widespread increase of obesity in the United States, studies have been conducted to compare different body mass index (BMI) groups and their clinical outcomes for traumatic injuries. The goal of this study was to retrospectively compare mortality between adult trauma patients with a high BMI to those with a lower BMI as well as investigate whether the mechanism of trauma had an effect on the outcome. Methods This study was a retrospective review of all adult trauma patients presented to the emergency department at Arrowhead Regional Medical Center (ARMC) between January 2014 and October 2019. The outcome was all-cause mortality. Patients were grouped according to BMI and mechanisms of injury, including blunt trauma, low velocity penetrating trauma, and high velocity penetrating trauma. Patients were also stratified by injury severity scores (ISS). Results Among the 9642 patients assessed in this study, majority (88%) of patients sustained blunt trauma. The number of patients among the three different BMI groups was appropriately equal with 34.4% of normal BMI, 34.6% overweight, and 31.1% obese. The overall mortality of all patients studied was 2.6% (n=248). There was no statistically significant difference in mortality among the three different BMI groups for blunt trauma, penetrating trauma, and subgroup analyses stratified by ISS score (ISS<16 or ISS ≥ 16). Conclusion Our study found no statistically significant differences in mortality among the three BMI groups in regard to mortality, even when stratified by ISS, or mechanism of injury, and traumatic velocities.
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http://dx.doi.org/10.7759/cureus.13352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968702PMC
February 2021

A Prospective Study Evaluating Changes in Histology, Clinical and Virologic Outcomes in HBV-HIV Co-infected Adults in North America.

Hepatology 2021 Mar 20. Epub 2021 Mar 20.

National Cancer Institute, Bethesda.

Introduction: Histological and clinical outcomes in HBV-HIV coinfection in the era of combination antiretroviral therapy (cART) are poorly-defined.

Methods: Adult HBV-HIV co-infected patients from 8 North American sites were enrolled in this NIH-funded prospective observational study (n=139). Demographic, clinical, serological and virological data were collected at entry and every 24 weeks for ≤192 weeks. Paired liver biopsies were obtained at study entry and at ≥3 years of follow-up. Biopsies were assessed by a central pathology committee using Modified Ishak scoring system. Clinical outcome rate and changes in histology are reported.

Results: Among participants with follow-up data (n=114), median age was 49 years, 91% were male, 51% were non-Hispanic Black and 13% had at-risk alcohol use, with a median infection of 20 years. At entry, 95% were on anti-HBV cART. Median CD4 count was 562 cells/mm and 93% had HIV <400 copies/mL. HBeAg was positive in 61% and HBV DNA was below the limit of quantification (<20 IU/mL) in 61%; <1000 IU/mL in 80%. Clinical events were uncommon across follow-up: 1 hepatic decompensation, 2 hepatocellular carcinoma, no liver transplants and 1 HBV-related deaths, with a composite endpoint rate of 0.61/100 person-years. Incident cirrhosis (n=1), ALT flare (n=2), and HBeAg loss (n=13) rates were 0.40, 0.65 and 6.86/100 person-years, respectively. No participants had HBsAg loss. Paired biopsy (n=62; median 3.6 years apart) revealed minimal improvement in Histologic Activity Index (median [IQR]: 3 [2-4] to 3 [1-3]; P=.02) and no significant change in fibrosis score (1 [1-2] to 1 [0-3]; P=.58).

Conclusions: In a North American cohort of adults with HBV-HIV on cART with virological suppression, clinical outcomes and worsening histological disease were uncommon.
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http://dx.doi.org/10.1002/hep.31823DOI Listing
March 2021

Difficult Airway Management in Adult COVID-19 Patients: Statement by the Society of Airway Management.

Anesth Analg 2021 Mar 12. Epub 2021 Mar 12.

Department of Anesthesiology & Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The COVID-19 disease, caused by Coronavirus SARS-CoV-2, often results in severe hypoxemia requiring airway management. Because SARS CoV-2 virus is spread via respiratory droplets, bag-mask ventilation, intubation, and extubation may place health care workers (HCW) at risk. While existing recommendations address airway management in patients with COVID-19, no guidance exists specifically for difficult airway management. Some strategies normally recommended for difficult airway management may not be ideal in the setting of COVID-19 infection. To address this issue the Society for Airway Management (SAM) created a task force to review existing literature and current Practice Guidelines for management of the difficult airway by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. SAM task force created recommendations for management of known or suspected difficult airway in the setting of known or suspected COVID-19 infection. The goal of the task force was to optimize successful airway management while minimizing exposure risk. Each member conducted a literature review on specific clinical practice section utilizing standard search engines (PubMed, Ovid, Google Scholar). Existing recommendations and evidence for difficult airway management in COVID-19 context were developed. Each specific recommendation was discussed among task force members and modified until unanimously approved by all task force members. Elements of AGREE Reporting Checklist for dissemination of clinical practice guidelines were utilized to develop this statement. Airway management in the COVID-19 patient increases HCW exposure risk. and difficult airway management often takes longer, may involve multiple procedures with aerosolization potential, strict adherence to personal protective equipment (PPE) protocols is mandatory to reduce risk to providers. When patient's airway risk assessment suggests awake tracheal intubation is an appropriate choice of technique, procedures that may cause increased aerosolization of secretions should be avoided. Optimal preoxygenation before induction with tight seal facemask may be performed to reduce risk of hypoxemia. Unless the patient is experiencing oxygen desaturation, positive pressure bag-mask ventilation after induction may be avoided to reduce aerosolization. For optimal intubating conditions, patients should be anesthetized with full muscle relaxation. Videolaryngoscopy is recommended as first-line strategy for airway management. If emergent invasive airway access is indicated, we recommend a surgical technique such as scalpel-bougie-tube, rather than an aerosolizing generating procedure, such as transtracheal jet ventilation. This statement represents recommendations by SAM task force for the difficult airway management of adults with COVID-19 with the goal to optimize successful airway management while minimizing the risk of clinician exposure.
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http://dx.doi.org/10.1213/ANE.0000000000005554DOI Listing
March 2021

An in-vitro study of subretinal perfluorocarbon liquid (PFCL) droplets and the physics of their retention and evacuation.

Acta Ophthalmol 2021 Mar 5. Epub 2021 Mar 5.

Department of Eye and Vision Science, University of Liverpool, Liverpool, UK.

Purpose: To investigate the physics associated with the retention and removal of subretinal perfluorocarbon liquid (PFCL), as inspired by a series of anecdotal cases of spontaneous 'disappearance' of subretinal PFCL.

Methods: The profiles of subretinal PFCL in situ from published OCT images were studied and compared with that of PFCL droplets resting on a hydrophilic surface in vitro. A mathematical model based on Sampson's and Poiseuille's formula was developed to explain how evacuation of subretinal PFCL without aspiration could occur.

Results: The mathematical model suggested that in vivo subretinal PFCL can completely evacuate in less than a second via a 41-guage retinal hole. Perfluorocarbon liquid (PFCL) droplets in situ subretinally substantially varied in their aspect ratios (from 0.28 to 2.71) and their contact angles with the retinal pigment epithelium (from 98° to 155°). Conversely, PFCL in vitro had aspect ratios and contact angles close to 1 and 150° respectively.

Conclusion: This study showed evidence that stretching of the retina to accommodate subretinal PFCL occurs, which might be responsible for the varied profile of the droplets and resultant forces that can cause retinal holes, and spontaneous evacuation of large PFCL droplets. By filling the vitreous cavity with PFCL, a small retinotomy alone might allow spontaneous evacuation without the need for aspiration.
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http://dx.doi.org/10.1111/aos.14832DOI Listing
March 2021

Liver Injury Associated With Ezetimibe Monotherapy.

CJC Open 2021 Feb 28;3(2):195-197. Epub 2020 Sep 28.

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

Statin intolerance, primarily myalgia, is not uncommon in patients treated for elevated low-density lipoprotein cholesterol. Nonstatin drugs, such as ezetimibe, can spare patients from statin exposure, while still reducing low-density lipoprotein cholesterol. Ezetimibe is generally very well tolerated, although gastrointestinal and musculoskeletal symptoms have been occasionally reported. We describe an extremely rare case of an ezetimibe-associated liver injury who required protracted treatment with prednisone and azathioprine. Ezetimibe-associated liver injury should be suspected with development of hepatic abnormalities concurrent with the timing of ezetimibe treatment and in the absence of other possible precipitating factors.
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http://dx.doi.org/10.1016/j.cjco.2020.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893188PMC
February 2021

NKX3.1 immunohistochemistry is highly specific for the diagnosis of mesenchymal chondrosarcomas: experience in the Australian population.

Pathology 2021 Feb 24. Epub 2021 Feb 24.

Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park, NSW, Australia; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia; Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW, Australia.

Mesenchymal chondrosarcoma (MC) is a rare sarcoma that typically arises in adolescents and young adults and characteristically harbours a HEY1-NCOA2 gene fusion. A recent study has shown that NKX3.1 immunohistochemistry (IHC) is highly specific and sensitive in MCs. NKX3.1 is a nuclear marker expressed in prostatic tissue and is widely used in most laboratories to determine prostatic origin of metastatic tumours. In the current study we investigated whether this stain can be used in the diagnostic workup of MC, as it may assist in triaging cases for further molecular testing, by assessing its expression in a cohort of MCs and in a wide spectrum of sarcoma types. Furthermore, we aimed to elucidate if expression of NKX3.1 by MCs is related to androgen receptor (AR) expression. We identified NKX3.1 positive nuclear staining in 9 of 12 individual patients of MC (n=20 of 25 samples when taking into account separate episodes). Four of the five negative specimens had been previously subjected to acid-based decalcification. NKX3.1 was negative in 536 samples from 16 non-MC sarcomas derived from largely tissue microarrays (TMAs). Overall, we identified 80% sensitivity and 100% specificity for NKX3.1 IHC in MCs. The sensitivity increased to 95.2% when acid-based decalcified specimens were excluded from the analysis. No correlation between NKX3.1 expression and AR IHC was identified. In summary, our findings indicate that NKX3.1 nuclear positivity is highly sensitive and specific for MC, provided that ethylenediaminetetraacetic acid (EDTA)-based rather than acid-based decalcification is used for sample processing. NKX3.1 IHC in the right clinical and histopathological setting can potentially be sufficient for the diagnosis of MC, reserving molecular confirmation only for equivocal cases.
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http://dx.doi.org/10.1016/j.pathol.2020.11.007DOI Listing
February 2021
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