Clinical features of adult patients with avoidant/restrictive food intake disorder presenting for medical stabilization: A descriptive study.

OBJECTIVE: The purpose of this study is to describe the clinical features of adult patients with avoidant/restrictive food intake disorder (ARFID) to better understand the medical findings, psychological comorbidities, and laboratory abnormalities in this population. METHOD: We completed a retrospective chart review of all adult patients with a diagnosis of ARFID, admitted for medical stabilization, between April 2016 and June 2021, to an inpatient hospital unit, which specializes in severe eating disorders. Information collected included anthropomorphic data, laboratory assessments, and medical history at time of admission. RESULTS: One hundred and twenty-two adult patients with ARFID were identified as meeting inclusion criteria for the study. The most common ARFID presentation was "fear of adverse consequences." The majority were female (70%), with an average age of 32.7 ± 13.7 years and mean percent of ideal body weight (m%IBW) of 68.2 ± 10.9. The most common laboratory abnormalities were low serum prealbumin and vitamin D, hypokalemia, leukopenia, and elevated serum bicarbonate. The most common psychiatric diagnoses were anxiety and depressive disorders, and the most common medical diagnoses were disorders of gut-brain interaction (DGBI). DISCUSSION: This is the largest study to the authors' knowledge of medical presentations in adult patients with ARFID. Our results reflect that the adult patient with ARFID may, in some aspects, present differently than pediatric and adolescent patients with ARFID, or from ARFID patients requiring less intensive care. This study highlights the need for further investigation of adult patients with ARFID. PUBLIC SIGNIFICANCE: ARFID is a restrictive eating disorder first defined in 2013. This study explores the medical presentations of adult patients (>18 years old) with ARFID presenting for specialized eating disorder treatment and identifies unique features of the adult presentation for treatment, compared to pediatric and adolescent peers.

OUTCOMES IN PRIMARY UNCOMPLICATED RHEGMATOGENOUS RETINAL DETACHMENT REPAIR USING PARS PLANA VITRECTOMY WITH OR WITHOUT SCLERAL BUCKLE.

PURPOSE: To compare outcomes after primary uncomplicated rhegmatogenous retinal detachment repair using pars plana vitrectomy (PPV) or PPV with scleral buckle (PPV-SB). METHODS: This is a retrospective cohort study with propensity score analysis in a single tertiary care center between 2014 and 2018 comparing patients with primary uncomplicated rhegmatogenous retinal detachment repaired using PPV only or PPV-SB (full cohort: n = 1,516, propensity-matched cohort: n = 908). The primary outcome was single surgery anatomic success, whereas secondary outcomes were 3-month and final pinhole visual acuity in logarithm of the minimum angle of resolution and final retina status. RESULTS: In the full cohort, single surgery anatomic success was achieved in 745 (91%) PPV patients versus 623 (89%) PPV-SB patients (P = 0.13). This was 390 (92%) versus 314 (88%) in phakic patients (P = 0.06) compared with 353 (91%) versus 301 (90%) in pseudophakic patients (P = 0.79), respectively. After matching, single surgery anatomic success was achieved in 424 (93%) PPV patients versus 412 (91%) PPV-SB patients (P = 0.14). Median pinhole visual acuity after PPV was better at 3 months (PPV: 20/40 vs. PPV-SB: 20/50; both cohorts: P < 0.001) and final follow-up (PPV: 20/29 vs. PPV-SB: 20/38; full cohort: P < 0.001 and PPV: 20/29 vs. PPV-SB: 20/36; matched cohort: P < 0.001). CONCLUSION: Addition of scleral buckle does not significantly change the rate of single surgery anatomic success compared with PPV only in primary uncomplicated rhegmatogenous retinal detachment. It is also associated with worse pinhole visual acuity at follow-up.

DELAYED FOLLOW-UP IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED UNDER UNIVERSAL HEALTH COVERAGE: Risk Factors and Visual Outcomes.

BACKGROUND/PURPOSE: To report the rate of delayed follow-up visits (DFU), to identify risk factors of DFU, and to assess the impact of DFU on outcomes in neovascular age-related macular degeneration. METHODS: This retrospective study included all patients with neovascular age-related macular degeneration (n = 1,291) treated with antivascular endothelial growth factor injections between January 2013 and December 2020 in 2 centers in Quebec, Canada. A DFU was defined as a delay of ≥4 weeks than scheduled. Visual outcomes, especially ≥15 letters loss, were reported. RESULTS: A total of 351 patients (27.2%) experienced ≥1 DFU. Odds were greater among older patients ( P = 0.005), patients treated at the hospital rather than the clinic ( P < 0.001), and patients with worse initial visual acuity ( P = 0.024). A DFU was associated with a mean visual acuity loss of 4.2 ± 13.4 letters ( P < 0.001) and an increased incidence of intraretinal fluid and subretinal fluid ( P = 0.001, P = 0.005) at 6 months despite resumption of injections. Central foveal thickness increased after DFU but returned to pre-DFU visit at 6 months. CONCLUSION: The DFU rate in patients with neovascular age-related macular degeneration treated under a universal health care system was around 27%. Delayed follow-up visits caused significant decreases in visual acuity and increases in intraretinal fluid and subretinal fluid on optical coherence tomography that did not recover after injections resumption despite normalization of central foveal thickness.

Outcomes of surgical repair of Retinoschisis-associated retinal detachment compared to Rhegmatogenous retinal detachment.

BACKGROUND: The aim of this study is to compare outcomes of primary retinal detachment (RD) repair in retinoschisis-associated RD (RSRD) and rhegmatogenous RD (RRD). METHODS: This is a retrospective observational cohort study. Charts of 2247 consecutive patients operated for RD repair at the Centre hospitalier universitaire de Québec - Université Laval between 2014 and 2018 were reviewed. Patients with RSRD and RRD were included to compare the visual and anatomical outcomes of both groups. RESULTS: There were 41 patients (1.8%) with RSRD and 1661 patients (74%) with RRD. RSRD patients had more primary repair failures (n = 9, 22%, vs. n = 166, 10%; p = 0.013). The primary anatomical success rates for pars plana vitrectomy with and without scleral buckle (PPV-SB vs. PPV) as primary repair method were similar in both RSRD patients (n = 11/14, 79% vs. n = 20/25, 80%; p = 0.92) and RRD patients (n = 751/827, 91% vs. n = 641/721, 89%; p = 0.21). At final follow-up, best corrected visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) was 0.30 [0.10, 0.88] and 0.18 [0.10, 0.40] (p = 0.03) in RSRD patients and RRD patients, respectively. Presence of retinoschisis was associated with worse final VA (ß 0.082, p < 0.001). Other predictive variables included female sex, macula-off presentation, number of RD quadrants involved, longer symptoms duration, worse baseline VA, and primary repair failure. The greatest predictors were worse baseline VA, primary repair failure, and macula-off status at presentation. Presence of retinoschisis did not significantly increase risk of primary repair failure in multivariable analysis (OR 1.45, 95% CI: 0.50-4.17; p = 0.49). Symptoms duration was the greatest effect factor associated with for primary repair failure (OR 1.37, 95% CI: 1.12-1.69; p = 0.003). CONCLUSIONS: RSRD is associated with more primary repair failure in univariate analysis, but not in multivariate analysis after adjusting for symptoms duration. It is however associated with worse final VA even after adjusting for primary repair failure. Both PPV and PPV-SB are valid repair methods for RSRD. However, RSRD remains a challenge to treat.

Intravoxel incoherent motion diffusion-weighted MRI for the characterization of inflammation in chronic liver disease.

OBJECTIVE: To evaluate the diagnostic performance of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for grading hepatic inflammation. METHODS: In this retrospective cross-sectional dual-center study, 91 patients with chronic liver disease were recruited between September 2014 and September 2018. Patients underwent 3.0-T MRI examinations within 6 weeks from a liver biopsy. IVIM parameters, perfusion fraction (f), diffusion coefficient (D), and pseudo-diffusion coefficient (D*), were estimated using a voxel-wise nonlinear regression on DWI series (10 b-values from 0 to 800 s/mm2). The reference standard was histopathological analysis of hepatic inflammation grade, steatosis grade, and fibrosis stage. Intraclass correlation coefficients (ICC), univariate and multivariate correlation analyses, and areas under receiver operating characteristic curves (AUC) were assessed. RESULTS: Parameters f, D, and D* had ICCs of 0.860, 0.839, and 0.916, respectively. Correlations of f, D, and D* with inflammation grade were ρ = - 0.70, p < 0.0001; ρ = 0.10, p = 0.35; and ρ = - 0.27, p = 0.010, respectively. When adjusting for fibrosis and steatosis, the correlation between f and inflammation (p < 0.0001) remained, and that between f and fibrosis was also significant to a lesser extent (p = 0.002). AUCs of f, D, and D* for distinguishing inflammation grades 0 vs. ≥ 1 were 0.84, 0.53, and 0.70; ≤ 1 vs. ≥ 2 were 0.88, 0.57, and 0.60; and ≤ 2 vs. 3 were 0.86, 0.54, and 0.65, respectively. CONCLUSION: Perfusion fraction f strongly correlated, D very weakly correlated, and D* weakly correlated with inflammation. Among all IVIM parameters, f accurately graded inflammation and showed promise as a biomarker of hepatic inflammation. KEY POINTS: • IVIM parameters derived from DWI series with 10 b-values are reproducible for liver tissue characterization. • This retrospective two-center study showed that perfusion fraction provided good diagnostic performance for distinguishing dichotomized grades of inflammation. • Fibrosis is a significant confounder on the association between inflammation and perfusion fraction.

Early and Long-Term Outcomes after Direct Bridge-to-Transplantation with Extracorporeal Membrane Oxygenation.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as direct bridge-to-transplantation (dBTT) remains controversial. We compared the short- and long-term outcomes of adult patients undergoing urgent heart transplantation (HT) with (dBTT) and without (non-BTT) VA-ECMO support at the time of HT. METHODS: Adults who underwent urgent HT in two institutions were assessed (N = 133; dBTT: N = 34 and non-BTT: N = 99). Patient characteristics, donor characteristics, in-hospital outcomes, and overall survival were compared. Mean follow up was 77±38 months and was 100% complete. Mortality predictors were identified using univariate and multivariate analyses. RESULTS: Before HT, patients with dBTT had higher rates of ischemic cardiomyopathy, acute kidney injury, liver failure, respiratory failure, and longer graft ischemia times. More patients in the dBTT group had complications, such as requiring VA-ECMO postoperatively (dBTT=50% vs. non-BTT=20%, P < 0.01). Hospital deaths (dBTT=23% vs. non-BTT=19%, P = 0.58), one-year (74% vs. 80%) and five-year survival (62% vs. 75%, P = 0.74 for overall survival) were not significantly different. The MELD-XI score and previous cardiac surgery were independent predictors of hospital mortality. CONCLUSION: Direct bridge-to-transplantation in patients on VA-ECMO support was not associated with worse long-term outcomes compared with non-VA-ECMO urgent HT, especially in recipients without any associated organ failure and a low MELD-XI score before HT.

Use of extracorporeal membrane oxygenation for heart graft dysfunction in adults: incidence, risk factors and outcomes in a multicentric study.

BACKGROUND: The decision about whether to use venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiac graft dysfunction (GD) is usually made on a case-by-case basis and is guided by the team's experience. We aimed to determine the incidence of VA-ECMO use after heart transplantation (HT), to assess early- and long-term outcomes and to assess risk factors for the need for VA-ECMO and early mortality in these patients. METHODS: We included adults who underwent heart transplantation at 3 cardiac centres who met the most recent International Society for Heart and Lung Transplantation definition of graft dysfunction (GD) over a 10-year period. Pre-transplant, intraoperative and posttransplant characteristics of the heart recipients as well as donor characteristics were analyzed and compared among recipients with GD treated with and without VA-ECMO. RESULTS: There were 135 patients with GD in this study, of whom 66 were treated with VA-ECMO and 69 were not. The mean follow-up averaged 81.2 months (standard deviation 36 mo, range 0-184 mo); follow-up was complete in 100% of patients. The overall incidence of GD (30%) and of VA-ECMO use increased over the study period. We did not identify any predictive pre-transplantation factors for VA-ECMO use, but patients who required VA-ECMO had higher serum lactate levels and higher inotropes doses after HT. The overall survival rates were 83% and 42% at 1 year and 78% and 40% at 5 years among patients who received only medical treatment and those who received VA-ECMO, respectively. Delayed initiation of VA-ECMO and postoperative bleeding were strongly associated with increased in-hospital mortality. CONCLUSION: The incidence of GD increased over the study period, and the need for VA-ECMO among patients with GD remains difficult to predict. In-hospital mortality decreased over time but remained high among patients who required VA-ECMO, especially among patients with delayed initiation of VA-ECMO.

MRI cine-tagging of cardiac-induced motion for noninvasive staging of liver fibrosis.

BACKGROUND: MR elastography is a noninvasive technique that provides high diagnostic accuracy for the staging of liver fibrosis; however, it requires external hardware and mainly assesses the right lobe. PURPOSE: To evaluate the diagnostic performance of MRI cine-tagging for staging fibrosis in the left liver lobe, using biopsy as the reference standard. STUDY TYPE: Institutional Review Board (IRB)-approved two-center prospective study. POPULATION: Seventy-six patients with chronic liver disease who underwent an MRI cine-tagging examination and a liver biopsy within a 6-week interval. FIELD STRENGTH/SEQUENCE: 2D-GRE multislice sequence at 3.0T with spatial modulation of the magnetization preparation sequence and peripheral pulse-wave triggering on two coronal slices chosen underneath the heart apex to capture maximal deformation with consecutive breath-holds adapted to patient cardiac frequency. ASSESSMENT: A region of interest was selected in the liver close to the heart apex. Maximal strain was evaluated with the harmonic phase (HARP) technique. STATISTICAL TESTS: Spearman's correlation, Kruskal-Wallis test, Mann-Whitney U-test, and receiver operating characteristic (ROC) analysis were performed. RESULTS: Liver strain measured on tagged images decreased with higher histological fibrosis stage (ρ = -0.68, P < 0.0001). Strain values were significantly different between all fibrosis stages (P < 0.0001), and between groups of fibrosis stages ≤F3 vs. F4 (P < 0.05). Areas under the ROC curves were 0.95 (95% confidence interval: 0.89-1.00) to distinguish fibrosis stages F0 vs. F4, 0.81 (0.70-0.92) for stages F0 vs. ≥F1, 0.84 (0.76-0.93) for stages ≤F1 vs. ≥F2, 0.86 (0.78-0.94) for stages ≤F2 vs. ≥F3, and 0.87 (0.77-0.96) for stages ≤F3 vs. F4. DATA CONCLUSION: MRI cine-tagging is a promising technique for measuring liver strain without additional elastography hardware. It could be used to assess the left liver lobe as a complement to current techniques assessing the right lobe. LEVEL OF EVIDENCE: 1 Technical Efficacy: 3 J. Magn. Reson. Imaging 2020;51:1570-1580.

Reassessment of kidney function equations in predicting long-term survival in cardiac surgery.

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) is a risk factor for long-term survival in cardiac surgery. The Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) study, CKD Epidemiology Collaboration (CKD-EPI), revised Lund-Malmö (LM), and full age spectrum equations are used to estimate glomerular filtration rates (eGFR), but each have advantages and disadvantages. Our objective was to determine which equation better predicts long-term survival. METHODS: Data on 1492 consecutive patients who underwent isolated off-pump coronary artery bypass surgery between September 1996 and December 2008 were prospectively collected. Preoperative and postoperative eGFR were calculated using the five equations and compared using Cox regression analyses and time-dependent receiver operating characteristic (ROC) curves at 10 years. RESULTS: In a Cox regression model after correction for significant predictors of long-term mortality, adjusted hazard ratios (HR) for one standard deviation increase in preoperative eGFR were 0.661 (P < .0001), 0.844 (P = .0166), 0.787 (P = .0002), 0.746 (P < .0001), and 0.717 (P < .0001) for the CG, MDRD, CKD-EPI, LM, and FAS equations, respectively. The areas under the time-dependent ROC curve at 10 years also showed that the CG formula has a better predictive value. Postoperative eGFR at discharge were also significant predictors of long-term mortality (HR = 0.603, P < .0001; HR = 0.725, P < .0001; HR = 0.688, P < .0001; HR = 0.673, P < .0001; HR = 0.632, P < .0001 for the CG, MDRD, CKD-EPI, LM, and FAS equations, respectively). CONCLUSIONS: The CG formula was shown to better predict survival in cardiac surgery, though the FAS equation has a comparable prognostic value. Additionally, postoperative eGFR at discharge also predicted long-term survival.

Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS.

The molecular and cellular basis of selective motor neuron (MN) vulnerability in amyotrophic lateral sclerosis (ALS) is not known. In genetically distinct mouse models of familial ALS expressing mutant superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS), we demonstrate selective degeneration of alpha MNs (α-MNs) and complete sparing of gamma MNs (γ-MNs), which selectively innervate muscle spindles. Resistant γ-MNs are distinct from vulnerable α-MNs in that they lack synaptic contacts from primary afferent (IA) fibers. Elimination of these synapses protects α-MNs in the SOD1 mutant, implicating this excitatory input in MN degeneration. Moreover, reduced IA activation by targeted reduction of γ-MNs in SOD1G93A mutants delays symptom onset and prolongs lifespan, demonstrating a pathogenic role of surviving γ-MNs in ALS. This study establishes the resistance of γ-MNs as a general feature of ALS mouse models and demonstrates that synaptic excitation of MNs within a complex circuit is an important determinant of relative vulnerability in ALS.

Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia.

BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury. METHODS: To visualize effects of neuroinflammation on neurogenesis/gliogenesis, we created a transgenic model bearing the dual reporter system luciferase and GFP under transcriptional control of the murine nestin promoter. In this model, transcriptional activation of nestin was visualized from the brains of living animals using biophotonic/bioluminescence molecular imaging and a high resolution charged coupled device camera. Nestin induction profiles in vivo and in tissue sections were analyzed in two different experimental paradigms: middle cerebral artery occlusion and lipopolysaccharide-induced innate immune stimuli. RESULTS: We report here a context- and injury-dependent induction and cellular expression profile of nestin. While in the baseline conditions the nestin signal and/or GFP expression was restricted to neuronal progenitors, the cellular expression patterns of nestin following innate immune challenge and after stroke markedly differed shifting the cellular expression patterns towards activated microglia/macrophages and astrocytes. CONCLUSIONS: Our results suggest that nestin may serve as a context-dependent biomarker of inflammatory response in glial cells including activated microglia/macrophages.

Live imaging of the innate immune response in neonates reveals differential TLR2 dependent activation patterns in sterile inflammation and infection.

Activation of microglial cells in response to brain injury and/or immune stimuli is associated with a marked induction of Toll-like receptors (TLRs). While in adult brain, the contribution of individual TLRs, including TLR2, in pathophysiological cascades has been well established, their role and spatial and temporal induction patterns in immature brain are far less understood. To examine whether infectious stimuli and sterile inflammatory stimuli trigger distinct TLR2-mediated innate immune responses, we used three models in postnatal day 9 (P9) mice, a model of infection induced by systemic endotoxin injection and two models of sterile inflammation, intra-cortical IL-1ß injection and transient middle cerebral artery occlusion (tMCAO). We took advantage of a transgenic mouse model bearing the dual reporter system luciferase/GFP under transcriptional control of a murine TLR2 promoter (TLR2-luc-GFP) to visualize the TLR2 response in the living neonatal brain and then determined neuroinflammation, microglial activation and leukocyte infiltration. We show that in physiological postnatal brain development the in vivo TLR2-luc signal undergoes a marked ∼30-fold decline and temporal-spatial changes during the second and third postnatal weeks. We then show that while endotoxin robustly induces the in vivo TLR2-luc signal in the living brain and increases levels of several inflammatory cytokines and chemokines, the in vivo TLR2-luc signal is reduced after both IL-1ß and tMCAO and the inflammatory response is muted. Immunofluorescence revealed that microglial cells are the predominant source of TLR2 production during postnatal brain development and in all three neonatal models studied. Flow cytometry revealed developmental changes in CD11b+/CD45+ and CD11b+/Ly6C+ cell populations, involvement of cells of the monocyte lineage, but lack of Ly6G+ neutrophils or CD3+ cells in acutely injured neonatal brains. Cumulatively, our results suggest distinct TLR2 induction patterns following PAMP and DAMP - mediated inflammation in immature brain.

Medications for Alcohol Use Disorder.

The U.S. Preventive Services Task Force recommends that clinicians screen adults for alcohol misuse and provide persons engaged in risky or hazardous drinking behaviors with brief behavioral counseling to reduce alcohol misuse. However, only a minority of American adults with high-risk alcohol use receive treatment. Three medications are approved by the U.S. Food and Drug Administration to treat alcohol use disorder: acamprosate, disulfiram, and naltrexone. Acamprosate and naltrexone reduce alcohol consumption and increase abstinence rates, although the effects appear to be modest. Disulfiram has been used for years, but evidence supporting its effectiveness is inconsistent. Other medications may be beneficial to reduce heavy alcohol use. The anticonvulsants topiramate and gabapentin may reduce alcohol ingestion, although long-term studies are lacking. Antidepressants do not decrease alcohol use in patients without mood disorders, but sertraline and fluoxetine may help depressed patients decrease alcohol ingestion. Ondansetron may reduce alcohol use, particularly in selected subpopulations. Further study is needed for genetically targeted or as-needed medications to reduce alcohol use.

Diagnostic Accuracy of Conjunctival Rt-Pcr in Sars-Cov-2: A Systematic Review and Diagnostic Accuracy Meta-Analysis.

PURPOSE: To study the positivity rate of conjunctival realtime polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN: Systematic review and diagnostic accuracy meta-analysis. METHODS: MEDLINE and EMBASE were queried using medical subject headings terms. Diagnostic accuracy meta-analyses and forest plots were obtained using the RevMan software. RESULTS: After deduplication, appraisal of abstract titles and full-text analysis of 1441 articles, 42 articles with 3351 COVID-19 patients were included in this review. Of these, 412 conjunctival swabs/Schirmer paper strips tested positive for SARS-CoV-2 by RT-PCR. The pooled sensitivity of the RT-PCR tests across the 24 studies with laboratory-confirmed COVID-19 patients was 10.3%. CONCLUSIONS: Only 1 in 10 RT-PCR tests performed on conjunctival swabs were positive for SARS-CoV-2. Although this suggests that SARS-CoV-2 is likely present and detectable in the conjunctiva, this detection method has low diagnostic potential.

Wnt7A identifies embryonic γ-motor neurons and reveals early postnatal dependence of γ-motor neurons on a muscle spindle-derived signal.

Motor pools comprise a heterogeneous population of motor neurons that innervate distinct intramuscular targets. While the organization of motor neurons into motor pools has been well described, the time course and mechanism of motor pool diversification into functionally distinct classes remains unclear. γ-Motor neurons (γ-MNs) and α-motor neurons (α-MNs) differ in size, molecular identity, synaptic input and peripheral target. While α-MNs innervate extrafusal skeletal muscle fibers to mediate muscle contraction, γ-MNs innervate intrafusal fibers of the muscle spindle, and regulate sensitivity of the muscle spindle in response to stretch. In this study, we find that the secreted signaling molecule Wnt7a is selectively expressed in γ-MNs in the mouse spinal cord by embryonic day 17.5 and continues to molecularly distinguish γ-from α-MNs into the third postnatal week. Our data demonstrate that Wnt7a is the earliest known γ-MN marker, supporting a model of developmental divergence between α- and γ-MNs at embryonic stages. Furthermore, using Wnt7a expression as an early marker of γ-MN identity, we demonstrate a previously unknown dependence of γ-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week.

Galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury.

Growing evidence suggests that galectin-3 is involved in fine tuning of the inflammatory responses at the periphery, however, its role in injured brain is far less clear. Our previous work demonstrated upregulation and coexpression of galectin-3 and IGF-1 in a subset of activated/proliferating microglial cells after stroke. Here, we tested the hypothesis that galectin-3 plays a pivotal role in mediating injury-induced microglial activation and proliferation. By using a galectin-3 knock-out mouse (Gal-3KO), we demonstrated that targeted disruption of the galectin-3 gene significantly alters microglia activation and induces ∼4-fold decrease in microglia proliferation. Defective microglia activation/proliferation was further associated with significant increase in the size of ischemic lesion, ∼2-fold increase in the number of apoptotic neurons, and a marked deregulation of the IGF-1 levels. Next, our results revealed that contrary to WT cells, the Gal3-KO microglia failed to proliferate in response to IGF-1. Moreover, the IGF-1-mediated mitogenic microglia response was reduced by N-glycosylation inhibitor tunicamycine while coimmunoprecipitation experiments revealed galectin-3 binding to IGF-receptor 1 (R1), thus suggesting that interaction of galectin-3 with the N-linked glycans of receptors for growth factors is involved in IGF-R1 signaling. While the canonical IGF-1 signaling pathways were not affected, we observed an overexpression of IL-6 and SOCS3, suggesting an overactivation of JAK/STAT3, a shared signaling pathway for IGF-1/IL-6. Together, our findings suggest that galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury.

The endocannabinoid 2-arachidonoyl-glycerol activates human neutrophils: critical role of its hydrolysis and de novo leukotriene B4 biosynthesis.

Although endocannabinoids are important players in nociception and obesity, their roles as immunomodulators remain elusive. The main endocannabinoids described to date, namely 2-arachidonoyl-glycerol (2-AG) and arachidonyl-ethanolamide (AEA), induce an intriguing profile of pro- and anti-inflammatory effects. This could relate to cell-specific cannabinoid receptor expression and/or the action of endocannabinoid-derived metabolites. Importantly, 2-AG and AEA comprise a molecule of arachidonic acid (AA) in their structure and are hydrolyzed rapidly. We postulated the following: 1) the released AA from endocannabinoid hydrolysis would be metabolized into eicosanoids; and 2) these eicosanoids would mediate some of the effects of endocannabinoids. To confirm these hypotheses, experiments were performed in which freshly isolated human neutrophils were treated with endocannabinoids. Unlike AEA, 2-AG stimulated myeloperoxidase release, kinase activation, and calcium mobilization by neutrophils. Although 2-AG did not induce the migration of neutrophils, it induced the release of a migrating activity for neutrophils. 2-AG also rapidly (1 min) induced a robust biosynthesis of leukotrienes, similar to that observed with AA. The effects of 2-AG were not mimicked nor prevented by cannabinoid receptor agonists or antagonists, respectively. Finally, the blockade of either 2-AG hydrolysis, leukotriene (LT) B(4) biosynthesis, or LTB(4) receptor 1 activation prevented all the effects of 2-AG on neutrophil functions. In conclusion, we demonstrated that 2-AG potently activates human neutrophils. This is the consequence of 2-AG hydrolysis, de novo LTB(4) biosynthesis, and an autocrine activation loop involving LTB(4) receptor 1.

Bilateral Panuveitis with Occlusive Vasculitis following Coronavirus Disease 2019 Vaccination.

PURPOSE: To report a case of bilateral panuveitis and occlusive vasculitis following COVID-19 vaccination. STUDY DESIGN: Case report. RESULTS: A 41-year-old otherwise healthy male presented with progressive vision loss and floaters starting 48 hours after a first dose of COVID-19 vaccine. Examination initially showed bilateral anterior uveitis, but this evolved into bilateral panuveitis with occlusive vasculitis despite topical corticosteroids over two weeks. The patient underwent extensive testing for other etiologies which were excluded. He was successfully treated with a gradual taper of topical and systemic corticosteroids leading to improvement of signs and symptoms. Follow-up is maintained for observation of avascular zones with possible neovascularization which could require laser as needed. CONCLUSIONS: The temporal association between vaccine and presentation makes this a plausible etiology. This remains a rare adverse event, but clinicians should be aware of this possibility to include it in their differential diagnosis when confronted with idiosyncratic ocular presentations.

Indications and pathologic diagnoses of diagnostic chorioretinal biopsies in the province of Quebec, Canada.

OBJECTIVE: To review the clinical usefulness of chorioretinal biopsies in diagnostically undefined cases of intraocular inflammation or chorioretinal lesions. DESIGN: Retrospective case series. PARTICIPANTS: Seven patients who underwent chorioretinal biopsies. METHODS: This case series included all consecutive patients who underwent chorioretinal biopsies in 2 academic tertiary care centres in the province of Quebec between 2014 and 2020. RESULTS: A total of 7 patients were included in the study. Five patients with intraocular inflammation underwent chorioretinal biopsies to rule out an infectious or neoplastic etiology, whereas 2 patients underwent biopsies for suspicion of neoplastic chorioretinal masses. Final diagnoses included primary chorioretinal lymphoma (n = 2), toxoplasmosis (n = 1), benign choroidal mass (n = 1), nonnecrotizing granuloma (n = 1), and peripheral exudative hemorrhagic chorioretinopathy (n = 1). No specific diagnosis was defined in 1 case of panuveitis with scleritis. No postoperative complications were reported. CONCLUSIONS: Chorioretinal biopsies clarified the diagnosis in 6 of 7 patients, including a definitive diagnosis of lymphoma in 2 patients. This is a high rate of diagnosis that also represents clinically meaningful results that influence management. Future directions include identifying patients in whom adjuvant chorioretinal biopsy would yield a high rate of diagnosis.