Long-term clinical and ultrasound follow-up after transient perivascular inflammation of the carotid artery (TIPIC) syndrome: a multicenter study.

BACKGROUND: The present study aimed to describe the clinical and ultrasound (US) long-term follow-up of patients with transient perivascular inflammation of the carotid artery (TIPIC) syndrome and the risk of recurrence. METHODS: We enrolled patients with a definitive diagnosis of TIPIC syndrome who were included in a retrospective multicenter study. These patients were recontacted at least six months after the first TIPIC episode for a clinical and imaging follow-up. Each patient underwent a clinical evaluation through a tailored questionnaire as well as US imaging. RESULTS: Twenty-eight patients were enrolled with a median follow-up of 58.7 months (interquartile range = 8-121). Nineteen out of the 28 patients (67.8%) had residual pain, eight (28.6%) had experienced a clinical recurrence and 12 (42.9%) had a thickening of the carotid wall on US. No patients had neurological complication or other associated diseases. CONCLUSIONS: Patients with TIPIC syndrome have often residual pain and recurrence in about one quarter of cases but the long-term follow-up is in favor a benign self-limited pathology.Trial registration: ClinicalTrials.gov (identifier NCT03804112).

First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

OBJECTIVE: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. METHODS: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. RESULTS: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. INTERPRETATION: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Reproducibility and accuracy of vessel wall MRI in diagnosing giant cell arteritis: a study with readers of varying expertise.

OBJECTIVE: To evaluate the reproducibility of vessel wall magnetic resonance imaging (VW-MRI) in diagnosing giant cell arteritis (GCA) among groups of radiologists with varying levels of expertise. METHODS: This institutional review board-approved retrospective single-center study recruited patients with suspected GCA between December 2014 and September 2021. Patients underwent 3 -T VW-MRI before temporal artery biopsy. Ten radiologists with varying levels of expertise, blinded to all data, evaluated several intracranial and extracranial arteries to assess GCA diagnosis. Interobserver reproducibility and diagnostic performance were evaluated. RESULTS: Fifty patients (27 women and 23 men) with a mean age of 75.9 ± 9 years were included. Thirty-one of 50 (62%) had a final diagnosis of GCA.VW-MRI had an almost perfect reproducibility among expert readers (kappa = 0.93; 95% CI 0.77-1) and substantial reproducibility among all readers, junior and non-expert senior readers (kappa = 0.7; 95% CI 0.66-0.73; kappa = 0.67 95% CI 0.59-0.74; kappa = 0.65; 95% CI 0.43-0.88 respectively) when diagnosing GCA. Substantial interobserver agreement was observed for the frontal branch of superficial temporal artery. Moderate interobserver agreement was observed for the superficial temporal artery and its parietal branch, as well as ophthalmic arteries in all groups of readers. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy varied depending on the group of readers. CONCLUSION: VW-MRI is a reproducible and accurate imaging modality for detecting GCA, even among less-experienced readers. This study advocates for the use of VW-MRI when diagnosing GCA even in less-experienced centers. CLINICAL RELEVANCE STATEMENT: VW-MRI is a reproducible and accurate imaging modality for detecting GCA, even among less-experienced readers, and it could be used as a first-line diagnostic tool for GCA in centers with limited expertise in GCA diagnosis. KEY POINTS: • Vessel wall magnetic resonance imaging (VW-MRI) is a reproducible and accurate imaging modality for detecting giant cell arteritis (GCA) in both extracranial and intracranial arteries. • The reproducibility of vessel wall magnetic resonance imaging for giant cell arteritis diagnosis was high among expert readers and moderate among less-experienced readers. • The use of vessel wall magnetic resonance imaging for giant cell arteritis diagnosis can be recommended even in centers with less-experienced readers.

Incidence and risk factors for secondary extralaryngeal dystonia in patients with laryngeal dystonia.

BACKGROUND AND OBJECTIVES: Laryngeal dystonia (LD) is a focal dystonia affecting adductor and/or abductor muscles of the larynx. It can be isolated or may spread to extra laryngeal muscles. The aim of this study was to report the characteristics of LD over time in a large single-center study with a long follow-up. METHODS: Retrospective review of patients with LD referred to our institution between 1991 and 2021. Demographic data, time to diagnosis, type of LD, follow-up and spread of dystonia [SD] were recorded. Risk factors for spread of dystonia during follow-up were analyzed. RESULTS: Over the 30-year period, 516 patients (77.3 % female, median age 50 years, range 5-87 years) were analyzed. Three hundred and fifteen patients (61 %) had adduction laryngeal dystonia, 136 patients (26.4 %) had abduction laryngeal dystonia, 46 patients (8.9 %) had adductor respiratory laryngeal dystonia, 12 patients (2.3 %) had mixed laryngeal dystonia, and seven patients (1.4 %) had singer's laryngeal dystonia. A previous history of dystonia was found in 47 patients (9.1 %). A laryngeal tremor was found in 68 patients (13.2 %). Since the onset of symptoms, LD was diagnosed after a median of 3 years (IQR: 1.0, 7.0). SD occurred in 55 patients (10.7 %) after a median time of 4 year (IQR: 1.5, 13.0). Patients with mixed laryngeal dystonia had higher probability of SD (p = 0.018). DISCUSSION: This study reports a large European study of LD, with a long follow-up. SD occurred in 10.5 % of patients. Patients with mixed laryngeal dystonia had a higher probability of SD. A close follow-up may be recommended for patients with mixed laryngeal dystonia.

Local budesonide therapy in the management of persistent hyposmia in suspected non-severe COVID-19 patients: Results of a randomized controlled trial.

OBJECTIVES: Consequences of COVID-19 on olfactory functions remained unclear during the pandemic. We assessed the efficacy of local budesonide in addition to olfactory rehabilitation when managing non-severe COVID-19 patients with persistent hyposmia. METHODS: A multicentric, randomized, superiority trial was conducted (ClinicalTrials.gov NCT04361474). The experimental group (EG) received budesonide and physiological saline nasal irrigations administered via three syringes of 20 ml in each nasal cavity in the morning and evening for 30 days. The control group (CG) received a similar protocol without budesonide. Patients were included if they were >18 years old, with a SARS-CoV-2 infection and presenting an isolated hyposmia persisting 30 days after symptom onset. The primary endpoint was the percentage of patients with improvement of more than two points on the ODORATEST score after 30 days of treatment. RESULTS: In total, 123 patients were included and randomized (EG: 62 vs CG: 61). Two patients from the EG met the primary endpoint with no statistical difference between the two groups (P = 0.5). CONCLUSION: To our knowledge, this is the first study evaluating local budesonide for COVID-19 related hyposmia treatment even though previous trials were performed with other local corticosteroids. Local budesonide efficacy was not demonstrated for persistent hyposmia related to COVID-19.

Quality of life and depression in Wilson's disease: a large prospective cross-sectional study.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive genetic disorder due to a mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and accumulation in various tissues. Lifelong decoppering treatments are the keystone of the treatment. These treatments can prevent, stabilize, or reverse the symptoms making WD a chronic disease. Quality of life (QoL) is one of the best outcome measures of any therapeutic intervention in chronic diseases but has not been evaluated in large cohorts of WD patients. METHOD: To better evaluate the QoL in WD and the correlation with different clinical or demographic factors we have performed a prospective cross-sectional study. RESULTS: Two hundred fifty-seven patients (53.3% men, mean age of 39.3 years and median disease duration of 18.8 years) were included between 1st January 2021 and 31st December 2021. Hepatoneurological form of the disease and depression were significantly correlated with low QoL (p < 0.001 for both). However, the patients' quality of life was similar to that of the general population, and only 29 patients (11.3%) had moderate to severe depression. CONCLUSIONS: Neurological patients should be closely monitored to prevent and treat symptoms of depression that impact their quality of life.

Acute optic neuritis: What are the clues to the aetiological diagnosis in real life?

BACKGROUND: Previous cross-sectional studies have reported distinct clinical and radiological features among the different acute optic neuritis (ON) aetiologies. Nevertheless, these reports often included the same number of patients in each group, not taking into account the disparity in frequencies of ON aetiologies in a real-life setting and thus, it remains unclear what are the truly useful features for distinguishing the different ON causes. To determine whether clinical evaluation, ophthalmological assessment including the optical coherence tomography (OCT), CSF analysis, and MRI imaging may help to discriminate the different causes of acute ON in a real-life cohort. METHODS: In this prospective monocentric study, adult patients with recent acute ON (<1 month) underwent evaluation at baseline and 1 and 12 months, including, high- and low-contrast visual acuity, visual field assessment and OCT measurements, baseline CSF analysis and MRI. RESULTS: Among 108 patients, 71 (65.7%) had multiple sclerosis (MS), 19 (17.6%) had idiopathic ON, 13 (12.0%) and 5 (4.6%) had myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, at last follow up respectively.At baseline, the distribution of bilateral ON, CSF-restricted oligoclonal bands, optic perineuritis, optic nerve length lesions and positive dissemination in space and dissemination in time criteria on MRI were significantly different between the four groups (p <0.001). No significant difference in visual acuity nor inner retinal layer thickness was found between the different ON aetiologies. CONCLUSIONS: In this large prospective study, bilateral visual involvement, CSF and MRI results are the most useful clues in distinguishing the different aetiologies of acute ON, whereas ophthalmological assessments including OCT measurements revealed no significant difference between the aetiologies.

Outcome of Patients Treated by Intravitreal Injections During the COVID-19 Lockdown: An Institutional Experience.

PURPOSE: To determine the loss of follow-up ratio and reasons during the COVID-19 lockdown in patients with retinal diseases treated by anti-vascular endothelial growth factor intravitreal injections and to report the visual outcome and rate of complications of these patients 1 year after the end of the lockdown. METHODS: This is a prospective descriptive cohort study (NCT04395859) conducted at the Rothschild Foundation Hospital - Paris between April 2020 and May 2021. Patients with retinal diseases treated by repeated intravitreal anti-VEGF injections (IVI) since before October 2019 were included. They filled-out a questionnaire and were followed up during a period of 1 year. RESULTS: During the COVID-19 lockdown 198 eyes (82.5%) of 157 patients (82.6%) received their injections in a timely manner (group 1) while 42 eyes (17.5%) of 33 patients (17.4%) had their injections delayed or missed (group 2). No statistically significant difference was found between group 1 and group 2 when comparing the change of mean best corrected distance visual acuity (BCVA) between month 12 and inclusion (p = 0.6) and the rate of ocular complications. The most frequent reasons for missing scheduled injections are appointments cancellation by the hospital (12 patients, 36%), fear of virus exposure during transportation (7 patients, 21%) or at the hospital (5 patients, 15%). Eighty-four percent (130/157 patients) of patients who attended their appointment were satisfied by the protective measures used in the hospital. CONCLUSION: COVID-19 lockdown did not seem to negatively affect the 1-year outcome of patients with retinal diseases treated by anti-VEGF IVIs who missed their scheduled injections. The BCVA and rate of complications at 1 year did not differ whether patients missed their scheduled injections or not. Maintaining IVIs during lockdown periods and educating patients about the risks of missing injections are pivotal in improving prognosis of retinal diseases.

Atypical Foveal Hypoplasia in Best Disease.

PURPOSE: To determine the prevalence and characteristics of foveal hypoplasia (also called fovea plana) in patients with Best disease using spectral-domain (SD) optical coherence tomography (OCT) and OCT-angiography (OCT-A). DESIGN: A retrospective observational study including patients diagnosed with Best disease. SUBJECTS AND PARTICIPANTS: Fifty-nine eyes of thirty-two patients (fifteen females (46.9%) and seventeen males (53.1%), p = 0.9) diagnosed with Best disease were included. Patients' eyes were categorized into two groups: Eyes with a fovea plana appearance ('FP group') and eyes without fovea plana appearance ('no FP group'), based on the foveal appearance on B-scan SD-OCT. METHODS AND MAIN OUTCOME MEASURES: Cross-sectional OCT images were assessed for the persistence of inner retinal layers (IRL) and OCT-A was analyzed for the presence of a foveal avascular zone (FAZ), the size of which was determined when applicable. RESULTS: Overall, 16 eyes (27.1%) of 9 patients had a fovea plana appearance ('FP group') with the persistence of IRL, and 43 eyes (72.9%) of 23 patients did not have fovea plana appearance ('no FP group'). Among FP eyes, OCT-A performed in 13 eyes showed bridging vessels through the FAZ in 100% of eyes with OCT-A. Using Thomas classification, 14 out of the 16 eyes with fovea plana (87.5%) had atypical foveal hypoplasia, and the 2 others (12.5%) had a grade 1b fovea plana. CONCLUSION: In our series, foveal hypoplasia was present in 27.1% of patients with Best disease. OCT-A showed bridging vessels through the FAZ in all eyes. These findings highlight the microvascular changes associated with Best disease, which can be an early sign of the disease in patients with a family history.

"En Face" Spectral-Domain Optical Coherence Tomography versus Multifocal Electroretinogram in Hydroxychloroquine Retinopathy Screening.

INTRODUCTION: The performance of "en face" optical coherence tomography (OCT) in screening for chloroquine (CQ) or hydroxychloroquine (HCQ) retinopathy has not been largely explored. The aim of this study was to determine the concordance of "en face" OCT with multifocal electroretinography (mfERG) in screening for CQ/HCQ retinopathy. METHODS: This is a prospective cohort study conducted at the Rothschild Foundation Hospital, Paris, between August 2016 and February 2021. Patients taking HCQ were followed up over 2 consecutive years and received an "en face" OCT and a mfERG on each visit. RESULTS: A total of 91 patients (182 eyes) were analyzed. mfERG and "en face" OCT were concordant in 147 eyes (86.3%). Cohen's kappa coefficient for concordance between mfERG and "en face" OCT was considered weak with a value 0.61 (95% CI: 0.50-0.72). The sensitivity and specificity of "en face" OCT were 70% (95% CI: 59-79%) and 91% (95% CI: 83-96%), respectively, relatively to mfERG. Proportion of abnormal R2/R5 and R3/R5 ratios did not differ between patients with normal and abnormal "en face" OCT (p = 0.2). DISCUSSION: "En face" OCT and mfERG have low concordance and cannot be used interchangeably as each investigation evaluates a different facet of CQ/HCQ retinopathy. "En face" OCT could be used as a complement in screening for CQ/HCQ retinal toxicity if the anomalies detected on "en face" OCT are confirmed by B-scan OCT sections.

A signature of structural MRI features at 3 Tesla allows an accurate characterization of orbital cavernous venous malformation.

OBJECTIVES: To differentiate OCVM from other orbital lesions using structural MRI. METHODS: This IRB-approved a historical-prospective cohort single-center analysis of a prospective cohort that included consecutive adult patients presenting with an orbital lesion undergoing a 3T MRI before surgery from December 2015 to May 2021. Two readers blinded to all data read all MRIs assessing structural MRI characteristics. A univariate analysis followed by a stepwise multivariate analysis identified structural MRI features showing the highest sensitivity and specificity when diagnosing OCVM. RESULTS: One hundred ninety-one patients with 30/191 (16%) OCVM and 161/191 (84%) other orbital lesions were included. OCVM were significantly more likely to present with a higher signal intensity than that of the cortex on T2WI: 26/29 (89.7%) versus 28/160 (17.5%), p < 0.001, or with a chemical shift artifact (CSA): 26/29 (89.7%) versus 16/155 (10.3%), p < 0.001, or to present with a single starting point of enhancement, as compared to other orbital lesions: 18/29 (62.1%) versus 4/159 (2.5%), p = 0.001. The step-wise analysis identified 2 signatures increasing performances. Signature 1 combined a higher signal intensity than that of the cortex on T2WI and a CSA. Signature 2 included these two features and the presence of a single starting point of enhancement. Sensitivity, specificity, and accuracy were 0.83, 0.94, and 0.92 for signature 1 and 0.97, 0.93, and 0.93 for signature 2, respectively. CONCLUSION: Structural MRI yields high sensitivity and specificity when diagnosing OCVM. KEY POINTS: • Structural MRI shows high sensitivity and specificity when diagnosing orbital cavernous venous malformation. • We identified two signatures combining structural MRI features which might be used easily in routine clinical practice. • The combination of higher signal intensity of the lesion as compared to the cortex on T2WI and of a chemical shift artifact yields a sensitivity and specificity of 0.83 and 0.94 for the diagnosis of orbital cavernous venous malformation, respectively.

Attachment patterns, self-compassion, and coping strategies in patients with chronic pain.

Introduction: In the recent year's literature, attachment insecurity is described as a vulnerability factor among patients with chronic pain, associated with poor pain coping, anxiety, depression, catastrophizing, greater pain intensity, and disability. Self-compassion, on the other hand, is described as a protective factor, associated with lower levels of negative affect, catastrophizing, depression, and anxiety in patients with chronic pain. Methods: In this study, we aim to explore the association between attachment, self-compassion quality, and coping strategies, in patients with chronic pain. Thus, 134 eligible patients with chronic pain were recruited at the certified Evaluation and Treatment Pain Center of the A. de Rothschild Foundation in Paris. We used a sociodemographic questionnaire, the Relationship Scale Questionnaire (RSQ-RC), the Self-Compassion Scale, and the Brief COPE. Results: Results supported our principal hypothesis; securely attached participants reported a significantly higher global self-compassion score compared with insecurely attached ones. Secure attachment and higher self-compassion levels were positively correlated with functional coping strategies and negatively correlated with dysfunctional ones. Discussion: Attachment patterns may be the basis of someone's ability to be compassionate to himself and to cope adequately with a difficult situation, such as a chronic pain condition. An attachment-informed approach to pain management could offer a better understanding of the complexity of this clinical condition and potentially provide appropriate support for both patients and health professionals, aiming to improve the effectiveness of interventions.

Prospective longitudinal study on prognostic factors of visual recovery and structural change after a first episode of optic neuritis.

BACKGROUND AND PURPOSE: This study was undertaken to determine the role of optical coherence tomography (OCT) in predicting the final visual and structural outcome, and to evaluate the correlation between functional eye outcome and retinal changes, in patients with a first episode of optic neuritis (ON). METHODS: In this prospective study, consecutive adult patients with acute ON underwent ophthalmological evaluation at baseline and at 1 and 12 months, including OCT measurements of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell and inner plexiform layer, and inner nuclear layer thicknesses; high- and low-contrast visual acuity; visual field assessment; and baseline brain magnetic resonance imaging. Univariate and multivariate linear regressions were used to assess predictive factors of outcome. Correlations between 12-month visual function and retinal structure were estimated by Spearman coefficients. Two groups of patients were analyzed, with or without multiple sclerosis (MS). RESULTS: Among 116 patients, 79 (68.1%) had MS, and 37 (31.9%) had ON not related to MS (including 19 idiopathic [i.e., isolated] ON, and 13 and five with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, respectively). We found no independent predictive factor of visual and retinal outcome. Analysis of the relationship between the visual field test (mean deviation) and pRNFL thickness demonstrated a threshold of 75.4 µm and 66.4 µm, below which the mean deviation was worse, for patients with MS (p = 0.007) and without MS (p < 0.001), respectively. CONCLUSIONS: We found that inner retinal layer measurements during the first month are not predictive of final outcome. The critical threshold of axonal integrity, below which visual function is damaged, is different between patients with and without MS.

Early diffusion-weighted MRI at 3 Tesla detects ischemic changes of the optic nerve in anterior ischemic optic neuropathy.

OBJECTIVES: To assess the impact of timing from visual symptoms' onset to diffusion-weighted (DW) 3 T MRI completion to detect ischemic changes of the optic disc and optic nerve in AION patients. METHODS: This IRB-approved retrospective single-center study included 3 T MRI data from 126 patients with AION and 111 controls with optic neuritis treated between January 2015 and May 2020. Two radiologists blinded to all data individually analyzed imaging. A senior neuroradiologist resolved any discrepancies by consensus. The primary judgment criterion was the restricted diffusion of the optic disc and/or the optic nerve assessed subjectively on the ADC maps. ADC values were also measured. Spearman rank correlations were used to examine the relationships between timing from visual symptoms' onset to MRI completion and both the restricted diffusion and the ADC values. RESULTS: One hundred twenty-six patients (47/126 [37.3%] women and 79/126 [62.7%] men, mean age 69.1 ± 13.7 years) with AION were included. Restricted diffusion of the optic disc in AION eyes was more frequent in the early MRI group than in the late MRI group: 35/49 (71.4%) eyes versus 3/83 (3.6%) eyes, p < 0.001. ADC values of the pathological optic discs and optic nerves were lower in the early MRI group than in the late MRI group: 0.61 [0.52-0.94] × 10-3 mm2/s versus 1.28 [1.01-1.44] × 10-3 mm2/s, p < 0.001, and 0.74 [0.61-0.88] × 10-3 mm2/s versus 0.89 [0.72-1.10] × 10-3 mm2/s, p < 0.001, respectively. CONCLUSIONS: DWI MRI showed good diagnostic performance to detect AION when performed early after the onset of visual symptoms. KEY POINTS: • Restricted diffusion of the optic disc in eyes affected by AION was significantly more likely to be observed in patients who had undergone MRI within 5 days after onset of visual symptoms. • ADC values of the pathological optic discs and optic nerves were significantly lower in patients who had undergone MRI within 5 days after onset of visual symptoms of AION: 0.61 × 10-3 mm2/s versus 1.28 × 10-3 mm2/s, p < 0.001, and 0.74 × 10-3 mm2/s versus 0.89 × 10-3 mm2/s, p < 0.001, respectively. • The optimal threshold for timing from visual symptoms' onset to MRI completion to detect restricted diffusion of the optic disc and/or optic nerve was 5 days, with an AUC of 0.88 (CI95%: 0.82-0.94).

Auricular Neuromodulation for Mass Vagus Nerve Stimulation: Insights From SOS COVID-19 a Multicentric, Randomized, Controlled, Double-Blind French Pilot Study.

Importance: An exacerbated inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is believed to be one of the major causes of the morbidity and mortality of the coronavirus disease 2019 (COVID-19). Neuromodulation therapy, based on vagus nerve stimulation, was recently hypothesized to control both the SARS-CoV-2 replication and the ensuing inflammation likely through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway and could improve the clinical outcomes as an adjunct treatment. We proposed to test it by the stimulation of the auricular branch of the vagus nerve, i.e., auricular neuromodulation (AN), a non-invasive procedure through the insertion of semipermanent needles on the ears. Objective: The aim of this study was to assess the effect of AN on the clinical outcomes in patients affected by COVID-19. Design, Setting, and Participants: A multicenter, randomized, placebo-controlled, double-blind clinical trial included 31 patients with respiratory failure due to COVID-19 requiring hospitalization. Within 72 h after admission, patients received either AN (n = 14) or sham neuromodulation (SN, n = 15) in addition to the conventional treatments. Main Outcome and Measures: The primary endpoint of the study was the rate of a clinical benefit conferred by AN at Day 14 (D14) as assessed by a 7-point Clinical Progression Scale. The secondary endpoint of the study was the impact of AN on the rate of transfer to the intensive care unit (ICU) and on the survival rate at D14. Results: The AN procedure was well-tolerated without any reported side effects but with no significant improvement for the measures of both primary (p > 0.3) and secondary (p > 0.05) endpoints at the interim analysis. None of the AN-treated patients died but one in the SN group did (81 years). Two AN-treated patients (73 and 79 years, respectively) and one SN-treated patient (59 years) were transferred to ICU. Remarkably, AN-treated patients were older with more representation by males than in the SN arm (i.e., the median age of 75 vs. 65 years, 79% male vs. 47%). Conclusion: The AN procedure, which was used within 72 h after the admission of patients with COVID-19, was safe and could be successfully implemented during the first two waves of COVID-19 in France. Nevertheless, AN did not significantly improve the outcome of the patients in our small preliminary study. It is pertinent to explore further to validate AN as the non-invasive mass vagal stimulation solution for the forthcoming pandemics. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT04341415].

COVID-19-Related Food Insecurity Among Households with Dietary Restrictions: A National Survey.

BACKGROUND: Food insecurity dramatically increased because of the COVID-19 pandemic; however, little is known about pandemic-related food insecurity in households with dietary restrictions. OBJECTIVE: To examine pre-pandemic rates of and pandemic-related change in food insecurity among households with and without dietary restrictions. METHODS: A cross-sectional, panel-based survey of 3200 U.S. women was conducted in April 2020. Pre-pandemic food insecurity and early pandemic-related change in food insecurity were assessed using the adapted Hunger Vital Sign. Weighted, multivariate logistic regression was used to model the odds of pre-pandemic food insecurity and the odds of incident or worsening pandemic-related food insecurity among households with and without dietary restrictions. In models predicting pandemic-related outcomes, interaction effects between race/ethnicity and dietary restrictions were examined. RESULTS: Before the COVID-19 pandemic, households with self-reported food allergy (adjusted odds ratio [aOR]: 1.5, 95% confidence interval [CI]: 1.2-1.9), celiac disease (aOR: 2.3, 95% CI: 1.4-3.5), or both (aOR: 2.1, 95% CI: 1.2-3.6) were significantly more likely to be food insecure than households without restrictions. Households with dietary restrictions were also significantly more likely to experience incident or worsening food insecurity during the early pandemic (food allergy: aOR: 1.6, 95% CI: 1.3-2.1) (celiac disease: aOR: 2.3, 95% CI: 1.5-3.5) (both: aOR: 2.0, 95% CI: 1.2-3.4). Race/ethnicity was not a significant moderator of the relationship between dietary restrictions and pandemic-related food insecurity. CONCLUSION: Households with dietary restrictions were more likely to experience both pre-pandemic and pandemic-related incident or worsening food insecurity than households without restrictions. Clinical care for patients with dietary restrictions requires attention to food insecurity.

Determining the Impact of Metabolic Nutrients on Autophagy.

Tumorigenesis relies on the ability of cancer cells to obtain necessary nutrients and fulfill increased energy demands associated with rapid proliferation. However, as a result of increased metabolite consumption and poor vascularization, most cancer cells must survive in a nutrient poor and high cellular stress microenvironment. Cancer cells undergo metabolic reprogramming to evade cell death and ensure proliferation; in particular, cancer cells utilize the catabolic process of autophagy. Autophagy creates an intracellular pool of metabolites by sequestering cytosolic macromolecules in double-membrane vesicles targeted for lysosomal degradation. During times of environmental stress and nutrient starvation, autophagy is upregulated through the dynamic interactions between two nutrient sensing proteins, AMP activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR), in cooperation with Unc-51 like autophagy activating kinase 1 (ULK1). In this way, a lack of metabolic nutrients plays a critical role in inducing autophagy, while the products of autophagy also serve as readily available fuel for the cell. In this chapter, we describe methods to visualize and quantify autophagy using a fluorescent sensor of autophagic membranes. Thus, the impact of specific nutrients on autophagy can be measured using live-cell fluorescent microscopy.