Joint Multimodal Deep Learning-based Automatic Segmentation of Indocyanine Green Angiography and OCT Images for Assessment of Polypoidal Choroidal Vasculopathy Biomarkers.

Purpose: To develop a fully-automatic hybrid algorithm to jointly segment and quantify biomarkers of polypoidal choroidal vasculopathy (PCV) on indocyanine green angiography (ICGA) and spectral domain-OCT (SD-OCT) images. Design: Evaluation of diagnostic test or technology. Participants: Seventy-two participants with PCV enrolled in clinical studies at Singapore National Eye Center. Methods: The dataset consisted of 2-dimensional (2-D) ICGA and 3-dimensional (3-D) SD-OCT images which were spatially registered and manually segmented by clinicians. A deep learning-based hybrid algorithm called PCV-Net was developed for automatic joint segmentation of biomarkers. The PCV-Net consisted of a 2-D segmentation branch for ICGA and 3-D segmentation branch for SD-OCT. We developed fusion attention modules to connect the 2-D and 3-D branches for effective use of the spatial correspondence between the imaging modalities by sharing learned features. We also used self-supervised pretraining and ensembling to further enhance the performance of the algorithm without the need for additional datasets. We compared the proposed PCV-Net to several alternative model variants. Main Outcome Measures: The PCV-Net was evaluated based on the Dice similarity coefficient (DSC) of the segmentations and the Pearson's correlation and absolute difference of the clinical measurements obtained from the segmentations. Manual grading was used as the gold standard. Results: The PCV-Net showed good performance compared to manual grading and alternative model variants based on both quantitative and qualitative analyses. Compared to the baseline variant, PCV-Net improved the DSC by 0.04 to 0.43 across the different biomarkers, increased the correlations, and decreased the absolute differences of clinical measurements of interest. Specifically, the largest average (mean ± standard error) DSC improvement was for intraretinal fluid, from 0.02 ± 0.00 (baseline variant) to 0.45 ± 0.06 (PCV-Net). In general, improving trends were observed across the model variants as more technical specifications were added, demonstrating the importance of each aspect of the proposed method. Conclusion: The PCV-Net has the potential to aid clinicians in disease assessment and research to improve clinical understanding and management of PCV. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Novel volumetric imaging biomarkers for assessing disease activity in eyes with PCV.

The aim of this study was to evaluate influence of baseline imaging features on visual and anatomical outcomes in eyes with PCV treated with anti-VEGF monotherapy. In this prospective study we enrolled participants with treatment-naïve PCV who followed a treat-and-extend protocol using intravitreal aflibercept (IVA) monotherapy. Baseline clinical features evaluatedincluded best corrected visual acuity (BCVA), traditional features such as lesion size, fluid-related OCT parameters and novel parameters using automated software. This included quantitative and qualitative pigment epithelium detachment (PED) parameters [height, volume]; and choroidal parameters. [choroidal thickness (CT), choroidal volume (CV) and choroidal vascularity index (CVI). We evaluated the predictive value of each parameter on visual and anatomical outcome at month 12. We additionally evaluated initial treatment response after 3 monthly injections with respect to month 12 outcomes. Fifty-two eyes from 52 participants were included in the study. The BCVA increased from 61.1 ± 13.2 to 69.6 ± 13.2 early treatment diabetic retinopathy study (ETDRS) letters (p < 0.01) and CRT reduced from 455.7 ± 182.4 µm to 272.7 ± 86.2 (p < 0.01) from baseline to month 12. The proportion of eyes with PED decreased significant from 100% at baseline to 80% at month 12 (p < 0.01). Reduction in the mean maximum height of PED (from 381.3 ± 236.3 µm to 206.8 vs ± 146.4 µm) and PED volume (from 1322 ± 853 nl to 686 ± 593 nl) (p < 0.01) was also noted from baseline to month12. Baseline features associated with better month 12 BCVA included baseline BCVA (ß = - 0.98, 95%CI - 3.38 to - 1.61, p = 0.02) and baseline CRT (ß = - 0.98, 95%CI - 1.56 to - 0.40, p = 0.04) while the disease activity at month12 was significantly associated with lower baseline CRT (366.0 ± 129.5 vs 612.0 ± 188.0 , p < 0.001), lower baseline PED height (242.0 ± 150.0 vs 542.0 ± 298.0 µm, p < 0.01), lower baseline PED volume (0.6 ± 0.3 mm3 vs 2.2 ± 1.3 mm3 vs, p < 0.01), lower proportion with marked CVH (17.9% vs 46.2%, p = 0.02) and lower mean CVI (61.8 ± 1.4 vs 63.0 ± 1.4, p < 0.02). Additionally, a larger decrease in CRT (per 100 nm) and larger PED volume reduction (per 100 nl) at month 3 from baseline were associated with greater BCVA gain and inactive disease. PED-related volumetric parameters have an additional predictive value to traditional biomarkers of disease activity in eyes with PCV undergoing anti-VEGF monotherapy. With increasingly precise quantification, PEDs can be a crucial biomarker in addition to traditional parameters and may aid in retreatment decisions.

OPTICAL COHERENCE TOMOGRAPHY FEATURES OF POLYPOIDAL LESION CLOSURE IN POLYPOIDAL CHOROIDAL VASCULOPATHY TREATED WITH AFLIBERCEPT.

PURPOSE: To evaluate whether optical coherence tomography (OCT) can determine polypoidal lesion (PL) perfusion in polypoidal choroidal vasculopathy eyes after 12 months of aflibercept monotherapy. Polypoidal lesion perfusion status, assessed by indocyanine green angiography, is an important anatomical outcome in polypoidal choroidal vasculopathy management. METHODS: Post hoc data from a prospective randomized, open-label, study in eyes with polypoidal choroidal vasculopathy undergoing monotherapy with aflibercept evaluated PL perfusion status based on indocyanine green angiography (gold standard) and OCT features from baseline to 12 months. RESULTS: Individual PLs (110 in total) from 48 eyes (48 patients) showed at 12 months; 57/110 PLs (51.8%) were closed on indocyanine green angiography. At 12 months, eyes with closed PLs were more likely to have the following OCT features: 1) no subretinal fluid (67.1% vs. 32.9%), 2) smaller pigment epithelial detachment height (67.2 [±43.8] vs. 189.2 [±104.9] µm), 3) densely hyperreflective pigment epithelial detachment contents (84.0% vs. 16.0%), 4) an absence of a hyperreflective ring(64.0% vs. 36.0%), and a 5) indistinct overlying retinal pigment epithelial (71.4% vs. 28.6%) (all P < 0.05). The three highest performing OCT features that differentiated perfused from closed PLs were (1), (3), and (4) (area under the receiver operating characteristic curve 0.85, 0.73, and 0.70, respectively). A combination of these three features achieved an area under the receiver operating characteristic curve of 0.90. CONCLUSION: Polypoidal lesion closure, an important anatomical treatment outcome in polypoidal choroidal vasculopathy typically defined by indocyanine green angiography, can be accurately detected by specific OCT features.

Efficacy of a novel personalised aflibercept monotherapy regimen based on polypoidal lesion closure in participants with polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy of aflibercept using a personalised versus fixed regimen in treatment-naïve participants with polypoidal choroidal vasculopathy (PCV). DESIGN: A 52-week, randomised, open-label, non-inferiority, single-centre study that included participants with symptomatic PCV. Participants were randomised (3:1 ratio) to receive either personalised (n=40) or fixed 8-weekly treatment regimen (n=13). The personalised regimen allowed for either early treat and extend (T&E) after week 12 or late T&E with 3 additional 4-weekly aflibercept injections until week 24 in participants with residual polypoidal lesions (PL) on indocyanine green angiography (ICGA) at week 12. MAIN OUTCOMES AND MEASURES: Non-inferiority of personalised to fixed regimen for mean change in best-corrected visual acuity (BCVA) from baseline to week 52 (non-inferiority margin: -5 letters). The key secondary outcomes include reduction in central subfield thickness (CSFT) on optical coherence tomography and the anatomical closure of PL on ICGA. RESULTS: Of the 53 participants, the mean (SD) age was 69.2 (8.1) years, 19 (35.8 %) were male. Personalised group was non-inferior to fixed for the primary end point (+8.1 vs +7.9 letters at week 52, respectively; difference 0.16, 95% CI -2.8 to 2.4, p=0.79). There was greater reduction in mean CSFT (SD) in the personalised versus fixed group (-248.8 (169.9) vs -164.8 (148.9) µm, p=0.03). Closure of PL occurred in 21 (55.2%) and 5 (41.6%) of study eyes in personalised and fixed groups, respectively at week 52 (p=0.41). CONCLUSIONS: Personalised regimen achieved non-inferior BCVA gain and numerically higher PL closure compared with fixed regimen. TRIAL REGISTRATION NUMBER: NCT03117634.

Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV). METHODS AND ANALYSIS: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study. TRIAL REGISTRATION NUMBER: NCT03941587.

Diabetic Macular Ischemia: Influence of Optical Coherence Tomography Angiography Parameters on Changes in Functional Outcomes Over One Year.

Purpose: To prospectively evaluate whether diabetic macular ischemia detected with coherence tomography angiography (OCTA) is associated with change in functional outcomes over a period of one year. Methods: This is a one-year prospective, observational study that included 56 eyes with varying levels of diabetic retinopathy. All participants underwent best corrected visual acuity evaluation, swept-source OCTA and microperimetry at baseline and repeated at one year. Parafoveal vessel densities (VD) and foveal avascular zone (FAZ) areas were generated from OCTA in the superficial and deep vascular plexuses. The influence of baseline and change in OCTA parameters on change in visual acuity and retinal sensitivity over one year was evaluated. Results: Over the one-year follow-up period, 16% (9) of eyes had at least one line worsening in BCVA and 7% (4) of eyes had at least 5% decrease in retinal sensitivity compared to baseline. Diabetic retinopathy progressed in 12.5%. Mean superficial vascular plexus (SVP) FAZ area increased (0.32 ± 0.15 to 0.39 ± 0.18 mm2, P = 0.003) and parafoveal VD in deep vascular plexus (DVP) decreased (49.8 ± 3.7% to 48.8 ± 2.9%, P = 0.040) at one year compared to baseline. In the multivariate regression analysis, larger baseline DVP FAZ area was associated with worsening of BCVA over one year (ß = 0.16 logMAR per mm2, 95% CI 0.02 to 0.31, P = 0.032). In addition, larger decreases in SVP VD (ß = -4.18 db per 10% decrease, 95% CI -6.55 to -1.80, P = 0.002) was associated with worsening of retinal sensitivity over one year. Conclusions: Progression of parafoveal microvasculature changes over one year can be detected using OCTA. Larger baseline DVP FAZ area on OCTA is predictive of worsening in visual outcomes, and larger decreases in SVP VD were associated with worsening of retinal sensitivity over a course of one year in diabetic individuals.

T and genetic variations between Asian and Caucasian polypoidal choroidal vasculopathy.

PURPOSE: To compare phenotypic and genetic variations in polypoidal choroidal vasculopathy (PCV) between Caucasian and Asian patients. METHODS: We analysed phenotypic and genotypic data from two sites, Association for Innovation and Biomedical Research on Light and Image, Portugal and Singapore National Eye Centre, Singapore. Baseline fundus photography, spectral domain-optical coherence tomography, indocyanine green and fluorescein angiography scans were analysed by respective reading centres using a standardised grading protocol. Single nucleotide polymorphisms across 8 PCV loci were compared between cases and controls selected from each population. RESULTS: One hundred and forty treatment-naïve PCV participants (35 Portuguese and 105 Singaporean) were included. The Portuguese cohort were older (72.33±8.44 vs 68.71±9.40 years, p=0.043) and were comprised of a lower proportion of males (43% vs 71%, p=0.005) compared with the Singaporean cohort. Differences in imaging features include higher prevalence of soft drusen (66% vs 30%, p=0.004), lower prevalence of subretinal haemorrhage (14% vs 67%, p<0.001), smaller polypoidal lesion (PL) area (0.09±0.09 vs 0.76±0.93 mm2, p<0.001), lower ratio of PL to branching vascular network area (3% vs 38%, p<0.001) and lower central retinal thickness (346.48±93.74 vs 493.16±212.92 µm, p<0.001) in the Portuguese cohort. CETP rs3764261 (OR 2.467; 95% CI 1.282 to 4.745, p=0.006) in the Portuguese population was significantly associated with PCV and CFH rs800292 (OR 1.719; 95% CI 1.139 to 2.596, p=0.010) in the Singaporean population, respectively. CONCLUSION: Among Asian and Caucasian patients with PCV, there are significant differences in the expression of phenotype. We also identified different polymorphisms associated with PCV in the two populations.

Patterns and Determinants of Choroidal Thickness in a Multiethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To describe the distribution and determinants of choroidal thickness (CT) in participants in a population study based on spectral-domain (SD)-OCT measurements. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Ethnic Chinese, Indian, and Malay adults aged more than 50 years without any retinal diseases (e.g., diabetic retinopathy, macular edema, age-related macular degeneration, central serous chorioretinopathy) that might affect the CT were recruited from the Singapore Epidemiology of Eye Diseases Study. METHODS: Choroidal imaging was performed by SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany) in enhanced depth imaging (EDI) mode. Subfoveal choroidal thickness (SFCT) was measured on the foveal line scan by 2 retinal experts independently (YS and KT), and the average was used in the analyses. In Chinese and Indian cohorts in whom macular raster scans were captured, the manufacturer-supplied research software (Heyex SP-X version 6.4.8.116; Heidelberg Engineering) was used to obtain automated segmentation yielding mean choroidal thickness in each of the 9 ETDRS grid sectors. MAIN OUTCOME MEASURES: Subfoveal choroidal thickness and regional CT in the 9 ETDRS grid sectors. RESULTS: For the SFCT analysis, 2794 eyes of 1619 participants (Chinese, Indian, and Malay ) were included. The mean age was 60.9 years (standard deviation, 7.7), and 797 (49.2%) were male. Mean SFCT was 255.2 µm (standard deviation, 102.6). The normal range of SFCT was 106 to 447 µm (corresponding to 5th and 95th percentile limits of SFCT, respectively). In multivariable models, thinner SFCT was associated with older age, female gender, longer axial length, and Malay (vs. Chinese) ethnicity. In the subset of Chinese and Indian eyes (n = 1842) in whom regional variation was evaluated, the choroid was thickest at the superior and temporal sectors and thinner at the inferior and nasal sectors. CONCLUSIONS: Subfoveal choroidal thickness is influenced by age, gender, and ethnicity along with regional differences even within individual eyes. Subfoveal choroidal thickness also shows a wide range in physiologic limits. These data may be used as a reference in future studies.

POLYPOIDAL CHOROIDAL VASCULOPATHY FEATURES VARY ACCORDING TO SUBFOVEAL CHOROIDAL THICKNESS.

PURPOSE: To evaluate associations between choroidal thickness and features of polypoidal choroidal vasculopathy (PCV) lesions based on multimodal imaging. METHODS: This cross-sectional analysis included treatment-naive PCV eyes from a prospectively recruited observational cohort. Associations between of subfoveal choroidal thickness (SFCT) and qualitative and quantitative morphologic features of PCV lesions on color fundus photographs, indocyanine green and fluorescein angiography, and spectral-domain optical coherence tomography were evaluated. RESULTS: We included 100 eyes with indocyanine green angiography-proven PCV. Subfoveal choroidal thickness showed a bimodal distribution with peaks at 170 µm and 350 µm. There was a significant linear increase in the total lesion area (P-trend = 0.028) and the polypoidal lesion area (P-trend = 0.030 and P-continuous = 0.037) with increasing SFCT. Pairwise comparisons between quartiles showed that the total lesion area (4.20 ± 2.61 vs. 2.89 ± 1.43 mm2, P = 0.024) and the polypoidal lesion area (1.03 ± 1.01 vs. 0.59 ± 0.45 mm2, P = 0.042) are significantly larger in eyes in Q4 (SFCT ≥ 350 µm) than eyes in Q1 (SFCT ≤ 170 µm). Although there was no significant linear trend relating SFCT to best-corrected visual acuity, pairwise comparisons showed that eyes in Q4 (SFCT ≥ 350 µm) have significantly worse vision (0.85 ± 0.63 vs. 0.55 ± 0.27 logMAR, P = 0.030) than eyes in Q2 (SFCT 170-260 µm). CONCLUSION: Total lesion areas and polypoidal lesion areas tend to be larger in eyes with increasing SFCT. Choroidal background may influence the phenotype or progression pattern of PCV.

Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup.

PURPOSE: To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings. DESIGN: Evaluation of diagnostic test results. PARTICIPANTS: Panel of retina specialists. METHODS: As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. MAIN OUTCOME MEASURES: Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. RESULTS: The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%. CONCLUSIONS: We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

Prognosis of CT-derived Fractional Flow Reserve in the Prediction of Clinical Outcomes.

PURPOSE: To examine the prognostic implication of fractional flow reserve (FFR) derived from coronary CT (FFRCT) in routine clinical practice. MATERIALS AND METHODS: Patients referred for FFRCT analysis at a single center between October 2015 and June 2017 were retrospectively included and followed up for rates of invasive angiography and clinical events. Two hundred seven patients underwent successful FFRCT analysis with seven lost to follow-up, leaving 200 (mean age ± standard deviation, 62.4 years ± 10.0; 49 [24.5%] women) patients for analysis. At coronary CT angiography, patients were categorized as having significant stenosis (SS) in the presence of a diameter stenosis greater than or equal to 50% (hereafter, SS positive) and flow limitation in the presence of a postlesion (that is, FFRCT measured 2 cm to the distal aspect of the lesion) FFRCT less than 0.80 (hereafter, FFRCT positive). Vessel-oriented clinical events (VOCEs) were defined as vessel-related late revascularization (>90 days), myocardial infarction, and cardiac mortality. RESULTS: At CT angiography, 130 (65%) studies were SS positive and 63 (31.5%) were FFRCT positive. At median follow-up of 477 days (range, 252-859 days), there were 26 VOCE end points in 22 patients: 22 revascularizations and four nonfatal myocardial infarctions. VOCE end points occurred in zero of 58 (0%) of SS-negative and FFRCT negative patients, in eight of 79 (10.1%) of SS-positive and FFRCT-negative patients, in zero of 12 (0%) of SS-negative and FFRCT-positive patients, and in 18 of 51 (35.3%) of SS-positive and FFRCT-positive patients (log-rank χ2 = 30.1; P < .001). At multivariable Cox regression, both FFRCT (hazard ratio per 0.1 decrease, 1.54 [95% confidence interval: 1.1, 2.2] P = .013) and stenosis (hazard ratio per unit increase, 2.16 [95% confidence interval: 1.25, 3.72] P = .006) were independently associated with VOCE. CONCLUSION: Stenosis and FFRCT are independent predictors of intermediate-term outcomes. In the absence of a stenosis greater than 50%, a positive FFRCT result is not associated with an increased intermediate risk.© RSNA, 2019Supplemental material is available for this article.See also commentary by Fairbairn and Bull in this issue.

Infraclavicular and supraclavicular approaches to brachial plexus for ambulatory elbow surgery: A randomized controlled observer-blinded trial.

STUDY OBJECTIVE: To compare the effectiveness of supraclavicular and infraclavicular approaches to brachial plexus block for elbow surgery. DESIGN: Prospective, parallel arm, observer-blinded, randomized controlled trial. SETTING: This study occurred in a designated block room at St. Joseph's hospital, a large academic tertiary hospital in London, Canada. PATIENTS: 150 adult ASA class I-III patients undergoing elective ambulatory elbow surgery. INTERVENTIONS: Patients were randomized to receive either an ultrasound-guided infraclavicular or a supraclavicular block with ropivacaine. MEASUREMENTS: Both groups were assessed for performance and sensory block onset times. Motor block, effective surgical anesthesia, procedure-related pain, axillary nerve block and ulnar nerve sparing were additional outcomes. We analyzed continuous and non-continuous variables with the independent t-test and chi-square test respectively and considered statistical significance when type 1 error was under 0.05. MAIN RESULTS: We observed similar mean block procedure times at 285 (±128) seconds in infra and 307 (±138) seconds in supra group (p = 0.3). The mean time of sensory block onset in both groups was similar: Infra 20.4 (±7.9) and supra 18.9 (±7.1) min (p = 0.4). Conversion to general anesthesia (4.2 vs 5.5%; p = 0.73) and the need for local anesthetic supplement (4.2 vs 4.1%; p = 0.98) was similar in both groups. We observed an increased incidence of paresthesia in the supra group (8.3 vs 23.2%; p = 0.014). CONCLUSION: We found that both blocks were equally effective for elbow surgery with similar procedure and block onset times and failure rates. Lower incidence of paresthesia was associated with the infraclavicular block with no change in other complications compared to the supraclavicular technique.

The Stem Cell Club: a model for unrelated stem cell donor recruitment.

BACKGROUND: Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS: The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS: To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION: The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.

Improving Health System Efficiency: Perspectives of Decision-Makers.

While improving health system efficiency, or value for money, is a priority in Canada, there is little information about optimal approaches for improvement in the Canadian context. Through interviews with senior health system decision-makers from two provinces, this study conducted by the Canadian Institute for Health Information identified the following five main themes along with actions that can be taken to improve health system efficiency in Canada: performance monitoring for accountability and decision-making, system-level integration in governance and care delivery, partnerships outside the health sector to improve population health, physician engagement and remuneration and flexible funding. Future work could apply this framework to assess and compare progress towards health system efficiency in other jurisdictions.

A Fibroblast Growth Factor 21-Pregnane X Receptor Pathway Downregulates Hepatic CYP3A4 in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) alters drug response. We previously reported that NAFLD is associated with reduced in vivo CYP3A drug-metabolism activity and hepatic CYP3A4 expression in humans as well as mouse and human hepatoma models of the disease. Here, we investigated the role of the lipid- and glucose-modulating hormone fibroblast growth factor 21 (FGF21) in the molecular mechanism regulating CYP3A4 expression in NAFLD. In human subjects, mouse and cellular NAFLD models with lower CYP3A4 expression, circulating FGF21, or hepatic FGF21 mRNA levels were elevated. Administration of recombinant FGF21 or transient hepatic overexpression of FGF21 resulted in reduced liver CYP3A4 luciferase reporter activity in mice and decreased CYP3A4 mRNA expression and activity in cultured Huh7 hepatoma cells. Blocking canonical FGF21 signaling by pharmacological inhibition of MEK1 kinase in Huh7 cells caused de-repression of CYP3A4 mRNA expression with FGF21 treatment. Mice with high-fat diet-induced simple hepatic steatosis and lipid-loaded Huh7 cells had reduced nuclear localization of the pregnane X receptor (PXR), a key transcriptional regulator of CYP3A4 Furthermore, decreased nuclear PXR was observed in mouse liver and Huh7 cells after FGF21 treatment or FGF21 overexpression. Decreased PXR binding to the CYP3A4 proximal promoter was found in FGF21-treated Huh7 cells. An FGF21-PXR signaling pathway may be involved in decreased hepatic CYP3A4 metabolic activity in NAFLD.

Early Cerebral Infarction after Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a serious disease with high case fatality and morbidity. Early cerebral infarction has been suggested as a risk factor for poor outcome. We aimed to assess the pattern of early and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage. We prospectively enrolled consecutive aneurysmal subarachnoid hemorrhage (SAH) patients presenting to an academic neurosurgical referral center (Prince of Wales Hospital, the Chinese University of Hong Kong) in Hong Kong. Cerebral infarction occurred in 24 (48 %) patients, in which 14 (28 %) had early cerebral infarction and 14 (28 %) had delayed cerebral infarction. Early anterior cerebral infarction occurred in a similar proportion of anterior and posterior circulation aneurysms (24 % vs. 21 %), whereas posterior circulation aneurysm patients had a higher proportion of early posterior cerebral infarction compared with anterior circulation aneurysm patients (18 % vs. 2 %). In conclusion, early cerebral infarction was common and different from delayed cerebral infarction.

The effects of social capital and neighborhood characteristics on intimate partner violence: a consideration of social resources and risks.

Intimate partner violence (IPV) is a growing public health problem, and gaps exist in knowledge with respect to appropriate prevention and treatment strategies. A growing body of research evidence suggests that beyond individual factors (e.g., socio-economic status, psychological processes, substance abuse problems), neighborhood characteristics, such as neighborhood economic disadvantage, high crime rates, high unemployment and social disorder, are associated with increased risk for IPV. However, existing research in this area has focused primarily on risk factors inherent in neighborhoods, and has failed to adequately examine resources within social networks and neighborhoods that may buffer or prevent the occurrence of IPV. This study examines the effects of neighborhood characteristics, such as economic disadvantage and disorder, and individual and neighborhood resources, such as social capital, on IPV among a representative sample of 2412 residents of Toronto, Ontario, Canada. Using a population based sample of 2412 randomly selected Toronto adults with comprehensive neighborhood level data on a broad set of characteristics, we conducted multi-level modeling to examine the effects of individual- and neighborhood-level effects on IPV outcomes. We also examined protective factors through a comprehensive operationalization of the concept of social capital, involving neighborhood collective efficacy, community group participation, social network structure and social support. Findings show that residents who were involved in one or more community groups in the last 12 months and had high perceived neighborhood problems were more likely to have experienced physical IPV. Residents who had high perceived social support and low perceived neighborhood problems were less likely to experience non-physical IPV. These relationships did not differ by neighborhood income or gender. Findings suggest interesting contextual effects of social capital on IPV. Consistent with previous research, higher levels of perceived neighborhood problems can reflect disadvantaged environments that are more challenged in promoting health and regulating disorder, and can create stressors in which IPV is more likely to occur. Such analyses will be helpful to further understanding of the complex, multi-level pathways related to IPV and to inform the development of effective programs and policies with which to address and prevent this serious public health issue.

Initial radiographic features as outcome predictor of adult respiratory syncytial virus respiratory tract infection.

OBJECTIVE: The purposes of this study were to evaluate the chest radiographic features of adult patients hospitalized for respiratory syncytial virus respiratory tract infections and to assess whether initial chest radiographic findings help predict clinical outcome. MATERIALS AND METHODS: All adult patients hospitalized from January 2009 to December 2011 with laboratory-confirmed respiratory syncytial virus infection were included in the study. Patient clinical data and admission chest radiographs were retrospectively reviewed. Adverse outcomes included need for supplemental oxygen, need for assisted ventilation, and death. RESULTS: Of 285 patients (mean age, 74 ± 16 years) included, 199 (69.8%) had abnormal chest radiographic findings: 49.5% (141/285) had acute changes, and 47.7% (136/285) had chronic changes. Consolidation (68/141 [48.2%]) and ground-glass opacity (57/141 [40.4%]) were the predominant types of acute changes and were most common in unilateral single-lower-zone involvement. Consolidation, ground-glass opacity, and chronic changes occurred with significantly higher frequency in patients with adverse outcomes. The presence of acute (odds ratio, 3.6) and chronic (odds ratio, 2.2) changes were independent risk factors for mortality. CONCLUSIONS: A large proportion of adult patients hospitalized with respiratory syncytial virus respiratory tract infection had changes on initial chest radiographs. Consolidation or ground-glass opacity in a unilateral single-lower-zone distribution were the most common findings. The presence of acute and chronic radiographic lung changes was associated with adverse outcomes.