Deep Learning-Based Analysis of Aortic Morphology From Three-Dimensional MRI.

BACKGROUND: Quantification of aortic morphology plays an important role in the evaluation and follow-up assessment of patients with aortic diseases, but often requires labor-intensive and operator-dependent measurements. Automatic solutions would help enhance their quality and reproducibility. PURPOSE: To design a deep learning (DL)-based automated approach for aortic landmarks and lumen detection derived from three-dimensional (3D) MRI. STUDY TYPE: Retrospective. POPULATION: Three hundred ninety-one individuals (female: 47%, age = 51.9 ± 18.4) from three sites, including healthy subjects and patients (hypertension, aortic dilation, Turner syndrome), randomly divided into training/validation/test datasets (N = 236/77/78). Twenty-five subjects were randomly selected and analyzed by three operators with different levels of expertise. FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T, 3D spoiled gradient-recalled or steady-state free precession sequences. ASSESSMENT: Reinforcement learning and a two-stage network trained using reference landmarks and segmentation from an existing semi-automatic software were used for aortic landmark detection and segmentation from sinotubular junction to coeliac trunk. Aortic segments were defined using the detected landmarks while the aortic centerline was extracted from the segmentation and morphological indices (length, aortic diameter, and volume) were computed for both the reference and the proposed segmentations. STATISTICAL TESTS: Segmentation: Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetrical surface distance (ASSD); landmark detection: Euclidian distance (ED); model robustness: Spearman correlation, Bland-Altman analysis, Kruskal-Wallis test for comparisons between reference and DL-derived aortic indices; inter-observer study: Williams index (WI). A WI 95% confidence interval (CI) lower bound >1 indicates that the method is within the inter-observer variability. A P-value <0.05 was considered statistically significant. RESULTS: DSC was 0.90 ± 0.05, HD was 12.11 ± 7.79 mm, and ASSD was 1.07 ± 0.63 mm. ED was 5.0 ± 6.1 mm. A good agreement was found between all DL-derived and reference aortic indices (r >0.95, mean bias <7%). Our segmentation and landmark detection performances were within the inter-observer variability except the sinotubular junction landmark (CI = 0.96;1.04). DATA CONCLUSION: A DL-based aortic segmentation and anatomical landmark detection approach was developed and applied to 3D MRI data for achieve aortic morphology evaluation. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Long-term outcomes of SARS-CoV-2 variants and other respiratory infections: evidence from the Virus Watch prospective cohort in England.

This study compared the likelihood of long-term sequelae following infection with SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals. Participants (n=5,630) were drawn from Virus Watch, a prospective community cohort investigating SARS-CoV-2 epidemiology in England. Using logistic regression, we compared predicted probabilities of developing long-term symptoms (>2 months) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status. SARS-CoV-2 infection during early variant periods up to Omicron BA.1 was associated with greater probability of long-term sequalae (adjusted predicted probability (PP) range 0.27, 95% CI = 0.22-0.33 to 0.34, 95% CI = 0.25-0.43) compared with later Omicron sub-variants (PP range 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, all post-infection estimates substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00, 0.02 to 0.03, 95% CI 0.01-0.06). Variant was an important predictor of SARS-CoV-2 post-infection sequalae, with recent Omicron sub-variants demonstrating similar probabilities to other contemporaneous ARIs. Further aetiological investigation including between-pathogen comparison is recommended.

Estimate of the hydraulic force in the aging heart: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Coupling between left ventricle (LV) and left atrium (LA) plays a central role in the process of cardiac remodeling during aging and development of cardiac disease. The hydraulic force (HyF) is related to variation in size between LV and LA. The objectives of this study were to: (1) derive an estimate of left atrioventricular HyF using cine- Magnetic Resonance Imaging (MRI) in healthy subjects with a wide age range, and (2) study its relationship with age and conventional diastolic function parameters, as estimated by reference echocardiography. METHODS: We studied 119 healthy volunteers (mean age 44 ± 17 years, 58 women) who underwent Doppler echocardiography and MRI on the same day. Conventional transmitral flow early (E) and late (A) LV filling peak velocities as well as mitral annulus diastolic longitudinal peak velocity (E') were derived from echocardiography. MRI cine SSFP images in longitudinal two and four chamber views were acquired, and analyzed using feature tracking (FT) software. In addition to conventional LV and LA strain measurements, FT-derived LV and LA contours were further used to calculate chamber cross-sectional areas. HyF was approximated as the difference between the LV and LA maximal cross-sectional areas in the diastasis phase corresponding to the lowest LV-LA pressure gradient. Univariate and multivariate analyses while adjusting for appropriate variables were used to study the associations between HyF and age as well as diastolic function and strain indices. RESULTS: HyF decreased significantly with age (R²=0.34, p < 0.0001). In addition, HyF was significantly associated with conventional indices of diastolic function and LA strain: E/A: R²=0.24, p < 0.0001; E': R²=0.24, p < 0.0001; E/E': R²=0.12, p = 0.0004; LA conduit longitudinal strain: R²=0.27, p < 0.0001. In multivariate analysis, associations with E/A (R2 = 0.39, p = 0.03) and LA conduit strain (R2 = 0.37, p = 0.02) remained significant after adjustment for age, sex, and body mass index. CONCLUSIONS: HyF, estimated using FT contours, which are primarily used to quantify LV/LA strain on standard cardiac cine MRI, varied significantly with age in association with subclinical changes in ventricular filling. Its usefulness in cohorts of patients with left heart disease to detect LV-LA uncoupling remains to be evaluated.

Validation of the Canadian Institute for Health Information Diagnostic Codes for Benign Gynaecologic Surgery.

We investigated the validity of the 10th Revision Canadian modification of International Statistical Classification of Disease and Related Health Problems (ICD-10-CA) diagnostic codes for surgery for benign gynaecologic conditions in the Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD), the main source of routinely collected data in Canada. Reabstracted data from patient charts was compared to ICD-10-CA codes and measures of validity were calculated with 95% confidence intervals. A total of 1068 procedures were identified. More objective, structural diagnoses (fibroids, prolapse) had higher sensitivity and near-perfect Kappa coefficients, while more subjective, symptomatic diagnoses (abnormal uterine bleeding, pelvic pain) had lower sensitivity and moderate-substantial Kappa coefficients. Specificity, positive predictive values, and negative predictive values were generally high for all diagnoses. These findings support the use of CIHI-DAD data for gynaecologic research.

Bayesian reconstruction of household transmissions to infer the serial interval of COVID-19 by variants of concern: analysis from a prospective community cohort study (Virus Watch).

BACKGROUND: The serial interval is a key epidemiological measure that quantifies the time between an infector's and an infectee's onset of symptoms. This measure helps investigate epidemiological links between cases, and is an important parameter in transmission models used to estimate transmissibility and inform control strategies. The emergence of multiple variants of concern (VOC) during the SARS-CoV-2 pandemic has led to uncertainties about potential changes in the serial interval of COVID-19. We estimated the household serial interval of multiple VOC using data collected by the Virus Watch study. This online, prospective, community cohort study followed-up entire households in England and Wales since mid-June 2020. METHODS: This analysis included 5842 symptomatic individuals with confirmed SARS-CoV-2 infection among 2579 households from Sept 1, 2020, to Aug 10, 2022. SARS-CoV-2 variant designation was based upon national surveillance data of variant prevalence by date and geographical region. We used a Bayesian framework to infer who infected whom by exploring all transmission trees compatible with the observed dates of symptoms, given assumptions on the incubation period and generation time distributions using the R package outbreaker2. FINDINGS: We characterised the serial interval of COVID-19 by VOC. The mean serial interval was shortest for omicron BA5 (2·02 days; 95% credible interval [CrI] 1·26-2·84) and longest for alpha (3·37 days; 2·52-4·04). The mean serial interval before alpha (wild-type) was 2·29 days (95% CrI 1·39-2·94), 3·11 days (2·28-3·90) for delta, 2·72 days (2·01-3·47) for omicron BA1, and 2·67 days (1·90-3·46) for omicron BA2. We estimated that 17% (95% CrI 5-26) of serial interval values are negative across all variants. INTERPRETATION: Most methods estimating the reproduction number from incidence time series do not allow for a negative serial interval by construction. Further research is needed to extend these methods and assess biases introduced by not accounting for negative serial intervals. To our knowledge, this study is the first to use a Bayesian framework to estimate the serial interval of all major SARS-CoV-2 VOC from thousands of confirmed household cases. FUNDING: UK Medical Research Council and Wellcome Trust.

Live birth rates after resolution of endometrial cavity fluid in frozen embryo transfer cycles.

RESEARCH QUESTION: Are live birth rates affected in frozen embryo transfer cycles that develop transient endometrial cavity fluid that resolves by day of embryo transfer? DESIGN: The first frozen blastocyst transfer cycle between January 1st, 2016 and December 31st, 2019 were included in this retrospective cohort study at an academic fertility center. The presence or absence of endometrial cavity fluid (ECF) detected on initial ultrasound and at time of transfer was recorded. Patients who had persistent ECF at time of transfer were excluded from the study. The primary outcome was live birth rate in the group with resolved ECF relative to the group without ECF. RESULTS: A total of 1034 frozen blastocyst transfer cycles were included, 54 with resolved ECF and 980 without ECF. Adjusted analyses were performed using a log-binomial regression model. Live birth rates were 35.2% and 34.2%, adjusted risk ratio 1.00 [95% CI 0.70-1.50] in the two groups, respectively. CONCLUSION: Live birth rates in frozen embryo transfer cycles are equivalent between patients with resolved endometrial cavity fluid compared to those who never had endometrial cavity fluid. Our findings suggest that the presence of endometrial cavity fluid is likely not detrimental to live birth rates if the fluid spontaneously resolves by the time of embryo transfer.

Baseline Characteristics and Predictive Factors of Intravenous Immunoglobulin Response in Drug and Device Refractory Gastroparesis Symptoms.

INTRODUCTION: Intravenous immunoglobulin (IVIG) has been shown in a small pilot series to be helpful for some patients with gastroparesis that is refractory to drugs, devices, and surgical therapies. Many but not all patients have serologic neuromuscular markers. We hypothesize that those patients with serologic markers and/or longer duration of therapy would have better responses to IVIG. MATERIALS AND METHODS: We studied 47 patients with a diagnosis of gastroparesis and gastroparesis-like syndrome that had all failed previous therapies including available and investigational drugs, devices, and/or pyloric therapies. Patients had a standardized 12-week course of IVIG, dosed as 400 mg/kg per week intravenously. Symptom assessment was done with Food and Drug Administration (FDA) compliant traditional patient-reported outcomes. Success to IVIG was defined as 20% or greater reduction in average symptom scores from baseline to the latest evaluation. RESULTS: Fourteen patients (30%) had a response, and 33 (70%) had no response per our definition. Patients responding had a higher glutamic acid decarboxylase 65 positivity (64% vs. 30%, P =0.049, missing=3) and longer duration of therapy (>12 wk/continuous: 86% vs. 48%, P =0.09). CONCLUSIONS: In this moderately sized open-label series of refractory patients with gastroparesis symptoms treated with IVIG, 30% of patients responded. While serologic markers and extended therapies show a trend to greater response, neither was statistically significant, except for glutamic acid decarboxylase 65 which showed a higher positivity rate in responders. We conclude that a clinical trial of IVIG may be warranted in severely refractory patients with gastroparesis symptoms.

Cilostazol for the management of moyamoya disease: a systematic review of the early evidence, efficacy, safety, and future directions.

Surgical revascularization remains the standard treatment for symptomatic moyamoya disease (MMD). As with any major surgical treatment, revascularization is associated with risks and limitations, denoting the need for noninvasive treatments to improve ischemic symptoms and prevent strokes. Cilostazol is a selective phosphodiesterase III inhibitor with antiplatelet, antithrombotic, and vasodilatory effects commonly used in peripheral vascular disease. Clinical studies assessing the efficacy of cilostazol in the management of stroke and MMD were recently reported, although a comprehensive assessment of the overall evidence is lacking. A systematic scoping review was conducted to assess the early evidence on cilostazol administration in patients with MMD. The inclusion criteria encompassed original human studies primarily focused on cilostazol's safety, efficacy, or utilization in managing MMD patients. A search of the PubMed database was conducted in June 2023, yielding 5 peer-reviewed publications that satisfied the inclusion criteria and were subjected to narrative synthesis. Risk of bias assessment was not applicable due to the scoping nature of this review. East Asian studies demonstrate increasing rates of cilostazol prescriptions for patients with MMD. In a large population-based study, cilostazol was compared to other antiplatelet medications and yielded the largest decrease in mortality among patients with newly diagnosed MMD. Other studies reported significant improvements in cerebral blood flow and cognitive function, which were deemed to be independent of one another. There are limited data on the safety profile of cilostazol in the MMD population, although the evidence derived from various studies performed in the general stroke population can likely provide insights into its potential utility in MMD patients. Cilostazol targets several critical pathways involved in the pathophysiology of MMD. The evidence corroborates the potential benefits of cilostazol for the management of MMD, although these findings should be interpreted with caution due to the small number of studies and lack of randomized trials. Subgroups of patients need to be identified who can safely undergo medical management in lieu of revascularization surgery or to improve surgical outcomes. Additional studies are needed to assess the efficacy and safety of cilostazol therapy, especially in Western populations.

Inequalities in access to paid sick leave among workers in England and Wales.

BACKGROUND: It is poorly understood which workers lack access to sick pay in England and Wales. This evidence gap has been of particular interest in the context of the Covid-19 pandemic given the relationship between presenteeism and infectious disease transmission. METHOD: This cross-sectional analysis (n = 8874) was nested within a large community cohort study based across England and Wales (Virus Watch). An online survey in February 2021 asked participants in work if they had access to paid sick leave. We used logistic regression to examine sociodemographic factors associated with lacking access to sick pay. RESULTS: Only 66% (n = 5864) of participants reported access to sick pay. South Asian workers (adjusted odds ratio [OR] 1.40, 95% confidence interval [CI] 1.06-1.83) and those from Other minority ethnic backgrounds (OR 2.93, 95% CI 1.54-5.59) were more likely to lack access to sick pay compared to White British workers. Older workers (OR range 1.72 [1.53-1.93]-5.26 [4.42-6.26]), workers in low-income households (OR 2.53, 95% CI 2.15-2.98) and those in transport, trade, and service occupations (OR range 2.03 [1.58-2.61]-5.29 [3.67-7.72]) were also more likely to lack access to sick pay compared respectively to workers aged 25-44, those in high income households and managerial occupations. DISCUSSION: Unwarranted age and ethnic inequalities in sick pay access are suggestive of labour market discrimination. Occupational differences are also cause for concern. Policymakers should consider expanding access to sick pay to mitigate transmission of Covid-19 and other endemic respiratory infections in the community, and in the context of pandemic preparation.

Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD).

9'-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of BIO203, a novel norbixin amide conjugate. Compared to norbixin, BIO203 displays improved stability at all temperatures tested for up to 18 months. In vitro, BIO203 and norbixin share a similar mode of action involving the inhibition of PPARs, NF-κB, and AP-1 transactivations. The two compounds also reduce IL-6, IL-8, and VEGF expression induced by A2E. In vivo, ocular maximal concentration and BIO203 plasma exposure are increased compared to those of norbixin. Moreover, BIO203 administered systemically protects visual functions and retinal structure in albino rats subjected to blue-light illumination and in the retinal degeneration model of Abca4-/- Rdh8-/- double knock-out mice following 6 months of oral complementation. In conclusion, we report here that BIO203 and norbixin share similar modes of action and protective effects in vitro and in vivo. BIO203, with its improved pharmacokinetic and stability properties, could be developed for the treatment of retinal degenerative diseases such as AMD.

Direct, Indirect, and Combined Extracranial-to-Intracranial Bypass for Adult Moyamoya Disease: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Moyamoya disease is a chronic, progressive cerebrovascular disease involving occlusion or stenosis of the terminal portion of the internal carotid artery. We conducted an updated systematic review and meta-analysis to investigate clinical and angiographic outcomes comparing direct, combined, and indirect bypass for the treatment of moyamoya disease in adults. METHODS: Two independent authors performed Preferred Reporting Items for Systematic reviews and Meta-Analyses guided literature searches in December 2021 to identify articles reporting clinical/angiographic outcomes in adult moyamoya disease patients undergoing bypass. Primary end points used were ischemic and hemorrhagic strokes, clinical outcomes, and angiographic revascularization. Study quality was evaluated with Newcastle-Ottawa and the Oxford Center for Evidence-Based Medicine scales. RESULTS: Four thousand four hundred fifty seven articles were identified in the initial search; 143 articles were analyzed. There were 3827 direct, 3826 indirect, and 3801 combined bypasses. Average length of follow-up was 3.59±2.93 years. Pooled analysis significantly favored direct (odds ratio [OR], 0.62 [0.48-0.79]; P<0.0001; OR, 0.44 [0.32-0.59]; P<0.0001; OR, 0.56 [0.42-0.74]; P<0.0001; OR, 3.1 [2.5-3.8]; P=0.0001) and combined (OR, 0.53 [0.41-0.69]; P<0.0001; OR, 0.28 [0.2-0.41]; P<0.0001; OR, 0.41 [0.3-0.56]; P<0.0001; OR, 3.1 [2.8-4.3]; P=0.0001) over indirect bypass for early stroke, late stroke, late intracerebral hemorrhage, and favorable outcomes, respectively. Indirect bypass was favored over combined (OR, 3.1 [1.7-5.6]; P<0.0001) and direct (OR, 4.12 [2.34-7.25]; P<0.0001) for early intracerebral hemorrhage. The meta-analysis significantly favored direct (OR, 0.37 [0.23-0.60]; P<0.001; OR, 0.49 [0.31-0.77]; P=0.002) and combined (OR, 0.23 [0.12-0.43]; P<0.00001; OR, 0.30 [0.18-0.49]; P<0.00001) bypass over indirect bypass for late stroke and late hemorrhage, respectively. Combined bypass was favored over indirect bypass for favorable outcomes (OR, 2.06 [1.18-3.58]; P=0.01). CONCLUSIONS: Based on combined meta-analysis (43 articles) and pooled analysis (143 articles), the existing literature indicates that combined and direct bypasses have significant benefits for patients suffering from late stroke and hemorrhage versus indirect bypass. Combined bypass was favored over indirect bypass for favorable outcomes. This is a strong recommendation based on low-quality evidence when utilizing the Grades of Recommendation, Assessment, Development, and Evaluation system. These findings have important implications for bypass strategy selection.

Relative contribution of essential and non-essential activities to SARS-CoV-2 transmission following the lifting of public health restrictions in England and Wales.

PURPOSE: We aimed to understand which non-household activities increased infection odds and contributed greatest to SARS-CoV-2 infections following the lifting of public health restrictions in England and Wales. PROCEDURES: We undertook multivariable logistic regressions assessing the contribution to infections of activities reported by adult Virus Watch Community Cohort Study participants. We calculated adjusted weighted population attributable fractions (aPAF) estimating which activity contributed greatest to infections. FINDINGS: Among 11 413 participants (493 infections), infection was associated with: leaving home for work (aOR 1.35 (1.11-1.64), aPAF 17%), public transport (aOR 1.27 (1.04-1.57), aPAF 12%), shopping once (aOR 1.83 (1.36-2.45)) vs. more than three times a week, indoor leisure (aOR 1.24 (1.02-1.51), aPAF 10%) and indoor hospitality (aOR 1.21 (0.98-1.48), aPAF 7%). We found no association for outdoor hospitality (1.14 (0.94-1.39), aPAF 5%) or outdoor leisure (1.14 (0.82-1.59), aPAF 1%). CONCLUSION: Essential activities (work and public transport) carried the greatest risk and were the dominant contributors to infections. Non-essential indoor activities (hospitality and leisure) increased risk but contributed less. Outdoor activities carried no statistical risk and contributed to fewer infections. As countries aim to 'live with COVID', mitigating transmission in essential and indoor venues becomes increasingly relevant.

Search like an expert: Reducing expertise disparity using a hybrid neural index for COVID-19 queries.

Consumers from non-medical backgrounds often look for information regarding a specific medical information need; however, they are limited by their lack of medical knowledge and may not be able to find reputable resources. As a case study, we investigate reducing this knowledge barrier to allow consumers to achieve search effectiveness comparable to that of an expert, or a medical professional, for COVID-19 related questions. We introduce and evaluate a hybrid index model that allows a consumer to formulate queries using consumer language to find relevant answers to COVID-19 questions. Our aim is to reduce performance degradation between medical professional queries and those of a consumer. We use a universal sentence embedding model to project consumer queries into the same semantic space as professional queries. We then incorporate sentence embeddings into a search framework alongside an inverted index. Documents from this index are retrieved using a novel scoring function that considers sentence embeddings and BM25 scoring. We find that our framework alleviates the expertise disparity, which we validate using an additional set of crowdsourced-consumer-queries even in an unsupervised setting. We also propose an extension of our method, where the sentence encoder is optimised in a supervised setup. Our framework allows for a consumer to search using consumer queries to match the search performance with that of a professional.

Occupation, work-related contact and SARS-CoV-2 anti-nucleocapsid serological status: findings from the Virus Watch prospective cohort study.

OBJECTIVES: Risk of SARS-CoV-2 infection varies across occupations; however, investigation into factors underlying differential risk is limited. We aimed to estimate the total effect of occupation on SARS-CoV-2 serological status, whether this is mediated by workplace close contact, and how exposure to poorly ventilated workplaces varied across occupations. METHODS: We used data from a subcohort (n=3775) of adults in the UK-based Virus Watch cohort study who were tested for SARS-CoV-2 anti-nucleocapsid antibodies (indicating natural infection). We used logistic decomposition to investigate the relationship between occupation, contact and seropositivity, and logistic regression to investigate exposure to poorly ventilated workplaces. RESULTS: Seropositivity was 17.1% among workers with daily close contact vs 10.0% for those with no work-related close contact. Compared with other professional occupations, healthcare, indoor trade/process/plant, leisure/personal service, and transport/mobile machine workers had elevated adjusted total odds of seropositivity (1.80 (1.03 to 3.14) - 2.46 (1.82 to 3.33)). Work-related contact accounted for a variable part of increased odds across occupations (1.04 (1.01 to 1.08) - 1.23 (1.09 to 1.40)). Occupations with raised odds of infection after accounting for work-related contact also had greater exposure to poorly ventilated workplaces. CONCLUSIONS: Work-related close contact appears to contribute to occupational variation in seropositivity. Reducing contact in workplaces is an important COVID-19 control measure.

The evolution of intracranial aneurysm treatment techniques and future directions.

Treatment techniques and management guidelines for intracranial aneurysms (IAs) have been continually developing and this rapid development has altered treatment decision-making for clinicians. IAs are treated in one of two ways: surgical treatments such as microsurgical clipping with or without bypass techniques, and endovascular methods such as coiling, balloon- or stent-assisted coiling, or intravascular flow diversion and intrasaccular flow disruption. In certain cases, a single approach may be inadequate in completely resolving the IA and successful treatment requires a combination of microsurgical and endovascular techniques, such as in complex aneurysms. The treatment option should be considered based on factors such as age; past medical history; comorbidities; patient preference; aneurysm characteristics such as location, morphology, and size; and finally the operator's experience. The purpose of this review is to provide practicing neurosurgeons with a summary of the techniques available, and to aid decision-making by highlighting ideal or less ideal cases for a given technique. Next, we illustrate the evolution of techniques to overcome the shortfalls of preceding techniques. At the outset, we emphasize that this decision-making process is dynamic and will be directed by current best scientific evidence, and future technological advances.

A Validation of Hysterectomy Procedural Codes in the Canadian Institute for Health Information Discharge Abstract Database.

OBJECTIVE: The Canadian Institute of Health Information (CIHI) Discharge Abstract Database (DAD) is the main source of routinely collected data for gynaecologic surgery in Canada and is increasingly used for research. These data are prone to error as they were originally collected for administrative purposes, and they therefore should be validated for clinical research. The objective of this study was to validate hysterectomy codes from the DAD at a single institution. METHODS: This was a retrospective observational study using an existing hospital database. We obtained a consecutive sample of all gynaecologic procedures performed at The Ottawa Hospital from April 2016 to March 2017 using the DAD. Patient data, including diagnosis, procedure type, concomitant procedure, and surgical approach, were reabstracted from records. These data were compared with the DAD Canadian Classification of Health Interventions (CCI) codes using sensitivity, specificity, positive predictive value (PPV), and κ coefficient with associated 95% confidence intervals (CIs). RESULTS: Of 1068 gynaecologic procedures, 639 hysterectomies were performed: 39.2% vaginally, 35.4% laparoscopically, and 25.4% abdominally. Median patient age was 46 years (IQR 41-54 y). The κ, sensitivity, specificity, and PPV for all hysterectomies were 0.92 (95% CI 0.90-0.95), 95.1% (95% CI 93.2-96.7), 97.9% (95% CI 96.6-99.3), and 98.5% (95% CI 97.6-99.5), respectively. The κ coefficients for vaginal, laparoscopic, and abdominal hysterectomy were 0.91 (95% CI 0.88-0.94), 0.92 (95% CI 0.89-0.95), and 0.92 (95% CI 0.89-0.95), respectively. Agreement for sub-total hysterectomy and bilateral salpingectomy with oophorectomy was excellent, with κ exceeding 0.80. The level of agreement for salpingectomy alone was poor, though specificity and PPV were high. CONCLUSIONS: Our study suggests that hysterectomy-associated CCI codes in CIHI's DAD have a high level of validity for clinical research purposes.

Diagnosis of Endometriosis at Laparoscopy: A Validation Study Comparing Surgeon Visualization with Histologic Findings.

OBJECTIVE: This study aimed to evaluate the validity of laparoscopic visualization for the diagnosis of endometriosis compared with histopathology. METHODS: We conducted a retrospective chart review at a tertiary care hospital in Canada for the period of April 1, 2016 to March 31, 2017. Of 1069 women, 96 were selected for having undergone laparoscopic visualization and concurrent histopathological biopsy for suspected endometriosis. Standard measures of validity for diagnostic tests (sensitivity, specificity, positive predictive and negative predictive values, accuracy) were used. RESULTS: Mean age of the 96 women included was 40 ± 7.2 years, and median gravidity and parity were 1 (IQR 0-3) and 0 (IQR 0-2), respectively. Common symptoms were abdominal and pelvic pain (41.7%), menstrual bleeding concerns (34.4%), dysmenorrhea (29.2%), and infertility (8.3%). Approximately one-third of women had endometriomas (31.3%), while more than half had deep infiltrating endometriosis (59.4%). The diagnosis of endometriosis was made by surgeons at laparoscopic visualization in 82.3% of women and by histopathology in 74.0%. Using histopathology as the gold standard, sensitivity for laparoscopic visualization was 90.1% (95% CI 81.0-95.1), while specificity was 40.0% (95% CI 23.4-59.3). Positive and negative predictive values were 81.0% (95% CI 71.0-88.1) and 58.8% (95% CI 36.0-78.4), respectively; and the accuracy was 77.1% (95% CI 67.7-84.4). CONCLUSION: Although laparoscopic visualization had relatively high sensitivity and positive predictive value, its specificity and negative predictive value were relatively low. These findings support the use of laparoscopic visualization with histopathological analysis for accurate diagnosis of endometriosis.

Down-regulation of FZD3 receptor suppresses growth and metastasis of human melanoma independently of canonical WNT signaling.

Frizzled 3 receptor (FZD3) plays an important role in the homeostasis of the neural crest and its derivatives, which give rise to pigment-synthesizing cells, melanocytes. While the role for FZD3 in specification of the melanocytic lineage from neural crest is well established, its significance in the formation of melanoma, its associated malignancy, is less understood. In this study we identified FZD3 as a critical regulator of human melanoma tumorigenesis. Down-regulation of FZD3 abrogated growth, colony-forming potential, and invasive capacity of patient-derived melanoma cells. Xenotransplantation of tumor cells with down-regulated FZD3 levels originating from melanomas carrying the BRAF(V600) mutation uniformly suppressed their capacity for tumor and metastasis formation. FZD3 knockdown leads to the down-regulation of the core cell cycle protein components (cyclins D1, E2, B1, and CDKs 1, 2, and 4) in melanomas with a hyperactive BRAF oncogene, indicating a dominant role of this receptor during melanoma pathogenesis. Enriched pathway analysis revealed that FZD3 inhibits transcriptional networks controlled by CREB5, FOXD1, and ATF3, which suppress the activity of MAPK-mediated signaling. Thus, FZD3 establishes a positive-feedback mechanism that activates MAPK signal transduction network, critical to melanoma carcinogenesis. Importantly, high levels of FZD3 mRNA were found to be correlated with melanoma advancement to metastatic stages and limited patient survival. Changes in gene-expression patterns mediated by FZD3 activity occur in the absence of nuclear ß-catenin function, thus representing an important therapeutic target for the melanoma patients whose disease progresses independent of canonical WNT signaling.

Yield of ASPECTS and Collateral CTA Selection for Mechanical Thrombectomy within 6-24 hours from Symptom Onset in a Hub and Spoke System.

BACKGROUND: Recent extended window trials support the benefit of mechanical thrombectomy in anterior circulation large vessel occlusions with clinical-radiographic dissociation. Using trial imaging criteria, 6% were found eligible for MT in the EW in a hub-and-spoke system. We examined the eligibility and outcomes in consecutive extended window-mechanical thrombectomy patients using more pragmatic selection criteria. METHODS: We retrospectively analyzed single-institution data of anterior circulation large vessel occlusions patients presenting between 6-24 h who underwent mechanical thrombectomy based on a priori determined criteria including non-contrast CT head ASPECTS ≥ 6 and/or CTA collateral scores ASITN/SIR 2-4. Primary outcomes consisted of post-mechanical thrombectomy TICI 2b-3 and 3-month modified Rankin scores; safety outcomes consisted of in-hospital mortality and symptomatic intracerebral hemorrhage. RESULTS: 767 consecutive acute ischemic strokes patients presented within the 6-24 hour window, and of these 48 (6%) anterior circulation large vessel occlusions patients underwent mechanical thrombectomy. In this cohort the mean age was 63±17 years, 56% were male, the median NIHSS was 16 [IQR 10-19], the median ASPECTS was 9 (IQR 8-10), and 79% (n=38) had good CTA collaterals. Occlusions were primarily M1 MCA (46%), with 29% tandem occlusions. Successful recanalization (mTICI 2b or 3) was achieved in 73% (n=35), while 6% (n=3) of patients developed symptomatic intracerebral hemorrhage. In-hospital mortality was 25% (n=12) while 40% (n=19) achieved 3-month modified Rankin Scores 0-2. CONCLUSIONS: Our data suggest the use of pragmatic imaging approach of ASPECTS ≥6 with CTA collateral grade in extended time window which is already established in most hospitals.

ACUTE RETINAL NECROSIS: Difference in Outcome by Viral Type and Options for Antiviral Therapy.

PURPOSE: To investigate differences in outcomes of acute retinal necrosis with confirmed viral polymerase chain reaction between viral types and highlight different treatment options. METHODS: The study evaluated 22 eyes in 18 patients of polymerase chain reaction-positive acute retinal necrosis at the University of Pittsburgh Medical Center from 2007 to 2018. Outcome measures included final visual acuity, treatment paradigms, and retinal detachment rate. RESULTS: Eight eyes were polymerase chain reaction-positive for varicella zoster virus, two eyes for herpes simplex virus Type 1 (HSV-1), and 12 eyes for herpes simplex virus Type 2 (HSV-2). Final Snellen best-corrected visual acuity averaged 20/51 for varicella zoster virus, 20/25 for HSV-1, and 20/814 for HSV-2. Retinal detachment occurred in 2 (25%) of varicella zoster virus eyes and 8 (75%) of HSV-2 eyes. One eye with HSV-1 and three eyes with HSV-2 received cidofovir for treatment of refractory retinitis. CONCLUSION: Acute retinal necrosis secondary to HSV-2 tended to have persistent active retinitis with a higher rate of retinal detachment despite similar treatment protocols, suggesting that in some cases combination intravenous acyclovir and adjuvant intravitreal foscarnet injections are not sufficient. Despite the risk of renal toxicity, intravenous cidofovir may be a consideration in select patients.