Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells.

Cholesterol is a major constituent of myelin membranes, which insulate axons and allow saltatory conduction. Therefore, Schwann cells, the myelinating glia of the peripheral nervous system, need to produce large amounts of cholesterol. Here, we define a crucial role of the transcription factor Maf in myelination and cholesterol biosynthesis and show that Maf acts downstream from Neuregulin1 (Nrg1). Maf expression is induced when Schwann cells begin myelination. Genetic ablation of Maf resulted in hypomyelination that resembled mice with defective Nrg1 signaling. Importantly, loss of Maf or Nrg1 signaling resulted in a down-regulation of the cholesterol synthesis program, and Maf directly binds to enhancers of cholesterol synthesis genes. Furthermore, we identified the molecular mechanisms by which Nrg1 signaling regulates Maf levels. Transcription of Maf depends on calmodulin-dependent kinases downstream from Nrg1, whereas Nrg1-MAPK signaling stabilizes Maf protein. Our results delineate a novel signaling cascade regulating cholesterol synthesis in myelinating Schwann cells.

White matter tract density index is associated with disability in multiple sclerosis.

BACKGROUND: The association between common neuroradiological markers of multiple sclerosis (MS) and clinical disability is weak. Given that the disability in patients with MS may depend on the underlying structural connectivity of the brain, our study aimed to examine the association between white matter tracts affected by MS and the patients' disability using a new tract density index (TDI). METHOD: This study included 53 patients diagnosed with MS, examined between 2019 and 2020. Manual lesion segmentation was performed on fluid-attenuated inversion recovery (FLAIR) images, and the density of white matter tracts encompassing the lesion (i.e., TDI) was calculated. Correlation analysis was employed to assess the association between TDI and disability. Additionally, the relationship between disability, TDI, and lesion-derived network metrics was examined by computing a partial correlation network. RESULTS: The TDI significantly correlated with the expanded disability status scale (EDSS) (r = 0.30, p = 0.03). Furthermore, the patient's disability is linked solely through TDI to lesion-derived network metrics -a key metric that 'bridges' the gap between the brain lesion and disability. CONCLUSIONS: In this study, MS lesions encompassing regions with high white matter tract density were associated and linked with severe physical disability. These findings indicate that TDI may be an outcome predictor that may connect radiologic findings to clinical practice.

Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging.

OBJECTIVE: The glymphatic system is a glial-based perivascular network that promotes brain metabolic waste clearance. Glymphatic system dysfunction has been observed in both multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), indicating the role of neuroinflammation in the glymphatic system. However, little is known about how the two diseases differently affect the human glymphatic system. The present study aims to evaluate the diffusion MRI-based measures of the glymphatic system by contrasting MS and NMOSD. METHODS: This prospective study included 63 patients with NMOSD (n = 21) and MS (n = 42) who underwent DTI. The fractional volume of extracellular-free water (FW) and an index of diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Age and EDSS scores were adjusted. RESULTS: Using Bayesian hypothesis testing, we show that the present data substantially favor the null model of no differences between MS and NMOSD for the diffusion MRI-based measures of the glymphatic system. The inclusion Bayes factor (BF10) of model-averaged probabilities of the group (MS, NMOSD) was 0.280 for FW and 0.236 for the ALPS index. CONCLUSION: Together, these findings suggest that glymphatic alteration associated with MS and NMOSD might be similar and common as an eventual result, albeit the disease etiologies differ. PRACTITIONER POINTS: Previous literature indicates important glymphatic system alteration in MS and NMOSD. We explore the difference between MS and NMOSD using diffusion MRI-based measures of the glymphatic system. We show support for the null hypothesis of no difference between MS and NMOSD. This suggests that glymphatic alteration associated with MS and NMOSD might be similar and common etiology.

Nanosized DNA Hydrogel Functionalized with a DNAzyme Tetrahedron for Highly Efficient Gene Silencing.

DNAzymes are DNA oligonucleotides that have catalytic activity without the assistance of protein enzymes. In particular, RNA-cleaving DNAzymes were considered as ideal candidates for gene therapy due to their unique characteristics. Nevertheless, efforts to use DNAzyme as a gene therapeutic agent are limited by issues such as their low physiological stability in serum and intracellular delivery efficiency. In this study, we developed a nanosized synthetic DNA hydrogel functionalized with a DNAzyme tetrahedron (TDz Dgel) to overcome these limitations. We observed remarkable improvement in the gene-silencing effect as well as intracellular uptake without the support of gene transfection reagents using TDz Dgel. The improved catalytic activity of the DNAzyme resulted from the combination of the cell-penetrating DNA tetrahedron structure and high stability of DNA hydrogel. We envision that this approach will become a convenient and efficient strategy for gene-silencing therapy using DNAzyme in the future.

Factors associated with the development of exudation in treatment-naive eyes with nonexudative macular neovascularization.

PURPOSE: To identify the predictive factors for development of exudation in patients with treatment-naïve nonexudative macular neovascularization (MNV). METHODS: We retrospectively analyzed 61 treatment-naïve patients with nonexudative MNV who had not received treatment for nonexudative MNV before the exudation developed. Baseline characteristics and changes in MNV were evaluated using multivariate modeling to determine the potential risk factors for exudative conversion. RESULTS: Exudation development was identified in 31.1% (19/61 eyes) of the study eyes during the 46.2 ± 8.2-month mean follow-up period. The mean period of development of exudation from the baseline was 21.5 ± 6.7 months. Multivariate Cox regression analysis identified that older age (hazard ratio [HR] of 1.380, 95% confidence interval [CI] 1.129-1.688, P = 0.008), larger MNV area at baseline (HR of 1.715, CI 1.288-2.308; P = 0.006), increase of MNV area by doubling (HR of 4.992, CI 1.932-9.246; P = 0.002), and retinal pigment epithelium (RPE) elevation more than 100 µm (HR of 1.017, CI 1.006-1.233; P = 0.015) were associated with increased risk of the development of exudation. CONCLUSION: Older age, larger MNV area, increasing MNV area, and higher RPE elevation were associated with an increased risk of exudative conversion in patients with treatment-naïve nonexudative MNV. Identifying these risk factors may be helpful in establishing treatment strategies and monitoring patients.

Sophie de Grouchy's Political Thought in the Letters on Sympathy (1798).

This article proposes a reading of Sophie de Grouchy's moral, political, and economic thought as embedded in the tradition of natural jurisprudence, adapted to the context of the French First Republic. A close reading of her French translation of Adam Smith's Theory of Moral Sentiment and her eight Letters on Sympathy confirms that there are points to be made by reading her works in the context of the language of early modern natural law. This sheds light on the important question of how to read revolutionary republicanism emanating from multiple traditions other than the neo-Roman discourse of non-domination.

Impaired physical function in patients with idiopathic inflammatory myopathies: results from the multicentre COVAD patient-reported e-survey.

OBJECTIVES: The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs. METHODS: Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease. RESULTS: A total of 1057 IIM patients, 3635 non-IIM AIRD patients and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs [36.3 (95% CI 35.5, 37.1) vs 41.3 (95% CI 40.2, 42.5) vs 46.2 (95% CI 45.8, 46.6), P < 0.001], irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis. CONCLUSION: Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.

High fatigue scores in patients with idiopathic inflammatory myopathies: a multigroup comparative study from the COVAD e-survey.

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0-10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1-6). Patients with IIMs had similar fatigue scores (5, IQR 3-7) to non-IIM SAIDs [5 (IQR 2-7)], but higher compared to HCs (2, IQR 1-5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient -0.17; 95%CI -0.21 to -13; P < 0.001) and Caucasians (reference Caucasians; coefficient -0.22; 95%CI -0.30 to -0.14; P < 0.001 for Asians and coefficient -0.08; 95%CI -0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life.

COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls: a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey.

OBJECTIVES: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs). METHODS: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis. RESULTS: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7). CONCLUSIONS: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.

Immune Responses After Vaccination With Primary 2-Dose ChAdOx1 Plus a Booster of BNT162b2 or Vaccination With Primary 2-Dose BNT162b2 Plus a Booster of BNT162b2 and the Occurrence of Omicron Breakthrough Infection.

BACKGROUND: Before the omicron era, health care workers were usually vaccinated with either the primary 2-dose ChAdOx1 nCoV-19 (Oxford-AstraZeneca) series plus a booster dose of BNT162b2 (Pfizer-BioNTech) (CCB group) or the primary 2-dose BNT162b2 series plus a booster dose of BNT162b2 (BBB group) in Korea. METHODS: The two groups were compared using quantification of the surrogate virus neutralization test for wild type severe acute respiratory syndrome coronavirus 2 (SVNT-WT), the omicron variant (SVNT-O), spike-specific IgG, and interferon-gamma (IFN-γ), as well as the omicron breakthrough infection cases. RESULTS: There were 113 participants enrolled in the CCB group and 51 enrolled in the BBB group. Before and after booster vaccination, the median SVNT-WT and SVNT-O values were lower in the CCB (SVNT-WT [before-after]: 72.02-97.61%, SVNT-O: 15.18-42.29%) group than in the BBB group (SVNT-WT: 89.19-98.11%, SVNT-O: 23.58-68.56%; all P < 0.001). Although the median IgG concentrations were different between the CCB and BBB groups after the primary series (2.677 vs. 4.700 AU/mL, respectively, P < 0.001), they were not different between the two groups after the booster vaccination (7.246 vs. 7.979 AU/mL, respectively, P = 0.108). In addition, the median IFN-γ concentration was higher in the BBB group than in the CCB group (550.5 and 387.5 mIU/mL, respectively, P = 0.014). There was also a difference in the cumulative incidence curves over time (CCB group 50.0% vs. BBB group 41.8%; P = 0.045), indicating that breakthrough infection occurred faster in the CCB group. CONCLUSION: The cellular and humoral immune responses were low in the CCB group so that the breakthrough infection occurred faster in the CCB group than in the BBB group.

Gender differences in patient experience in idiopathic inflammatory myopathies: Sub analysis from the COVAD dataset.

OBJECTIVES: We aimed to investigate gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing data obtained through the international COVID-19 vaccination in autoimmune disease (COVAD) e-survey. METHODS: Patient-reported outcomes including fatigue, pain, and physical function were extracted from the COVAD database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of substantial differences in outcomes. RESULTS: 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [IQR], p < 0.001) and more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, p < 0.001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3-7] vs. 4 [2-6], median [IQR], p = 0.004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue. CONCLUSIONS: Women with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men.

COVID-19 vaccination-related adverse events among autoimmune disease patients: results from the COVAD study.

OBJECTIVES: COVID-19 vaccines have been proven to be safe in the healthy population. However, gaps remain in the evidence of their safety in patients with systemic autoimmune and inflammatory disorders (SAIDs). COVID-19 vaccination-related adverse events (AEs) in patients with SAIDs and healthy controls (HC) seven days post-vaccination were assessed in the COVAD study, a patient self-reported cross-sectional survey. METHODS: The survey was circulated in early 2021 by >110 collaborators (94 countries) to collect SAID details, COVID-19 vaccination details and 7-day vaccine AEs, irrespective of respondent vaccination status. Analysis was performed based on data distribution and variable type. RESULTS: Ten thousand nine hundred respondents [median (interquartile range) age 42 (30-55) years, 74% females and 45% Caucasians] were analysed; 5867 patients (54%) with SAIDs were compared with 5033 HCs. Seventy-nine percent had minor and only 3% had major vaccine AEs requiring urgent medical attention (but not hospital admission) overall. Headache [SAIDs = 26%, HCs = 24%; odds ratio (OR) = 1.1 (95% CI: 1.03, 1.3); P = 0.014], abdominal pain [SAIDs = 2.6%, HCs = 1.4%; OR = 1.5 (95% CI: 1.1, 2.3); P = 0.011], and dizziness [SAIDs = 6%, HCs = 4%; OR = 1.3 (95% CI: 1.07, 1.6); P = 0.011], were slightly more frequent in SAIDs. Overall, major AEs [SAIDs = 4%, HCs = 2%; OR = 1.9 (95% CI: 1.6, 2.2); P < 0.001] and, specifically, throat closure [SAIDs = 0.5%, HCs = 0.3%; OR = 5.7 (95% CI: 2.9, 11); P = 0.010] were more frequent in SAIDs though absolute risk was small (0-4%). Major AEs and hospitalizations (<2%) were comparable across vaccine types in SAIDs. CONCLUSION: Vaccination against COVID-19 is safe in SAID patients. SAIDs were at a higher risk of major AEs than HCs, though absolute risk was small. There are small differences in minor AEs between vaccine types in SAID patients.

COVID-19 Vaccination in Autoimmune Diseases (COVAD) study: Vaccine safety in idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: In this study we investigated COVID-19 vaccination-related adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs). METHODS: Seven-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics were obtained and multivariable regression was performed. RESULTS: Ten thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30-455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquartile range [IQR], 1.04-7.3) and minor (OR, 1.5; IQR, 1.1-2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2-4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1-3.3; and OR, 2.2; IQR, 1.1-4.3, respectively). Overall, ADEs were less frequent in inclusion-body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients. DISCUSSION: Seven-day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyositis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs. Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines.

Prevalence of anterolateral ligament injuries and lateral meniscus tear on MR imaging in patients with both-bundle tear vs. selective bundle incomplete tear of the anterior cruciate ligament.

OBJECTIVES: We investigated the prevalence of anterolateral ligament (ALL) injury and lateral meniscus (LM) tear in cases with both-bundle tear and selective bundle incomplete tear of the anterior cruciate ligament (ACL). METHODS: A total of 174 cases of magnetic resonance (MR) images that had an ACL tear and underwent arthroscopic ACL reconstruction were retrospectively reviewed. ACL injury was classified into both bundle, anteromedial bundle, and posterolateral bundle (PL) on arthroscopic finding. The ALL was divided into three portions: femoral, meniscal, and tibial. ALL injury was scored into three groups: grade 0 is intact; grade 1 is stranding and edema surrounds the expected location of the ALL; grade 2 is clear discontinuity of the ALL consistent with rupture. Traumatic LM tear was also assessed on MR images. RESULTS: The total prevalence of ALL injury was 36.2% (reader 1) and 42.0% (reader 2). ALL injury was statistically related to the selective bundle tear (p = 0.002 and 0.004, readers 1 and 2). PL bundle tear was significantly correlated with the ALL injury (p value < 0.001, readers 1 and 2, both). The location and grade of ALL injury were not significantly correlated with the type of ACL injury. LM tear was not significantly related to the types of ACL tear (p = 0.208 and 0.907, readers 1 and 2) and ALL injury (p value = 0.096 and 0.383, readers 1 and 2). CONCLUSIONS: ALL injury was significantly related to the PL bundle tear of the ACL. LM tear was not significantly correlated with the types of ACL injury and ALL injury. KEY POINTS: • Anterolateral ligament (ALL) injury was significantly related to the posterolateral bundle (PL) tear of the anterior cruciate ligament (ACL). • Lateral meniscus (LM) tear was not significantly correlated with the types of ACL injury and ALL injury. • Clinicians and radiologists should be aware of these relationships and scrutinize ALL injury in cases with PL bundle tears, even with an incomplete ACL injury.

A Longer Route to the PICU Can Lead to a Longer Stay in the PICU: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Admission to the pediatric ICU versus general pediatric floor for patients is a significant triage decision for emergency department physicians. Escalation of care within 24 hours of hospital admission is considered as a quality metric for pediatric E.R. There exists, however, a lack of data to show that such escalation leads to a poor outcome. METHODS: A retrospective cohort study was conducted to compare outcomes of patients who required escalation of care within 24 hours of hospital admission to the pediatric ICU (cases) from 01/01 2015 to 02/28 2019 with those who were directly admitted from emergency department to the PICU (controls). A total of 327 cases were compared to 931 controls. Univariate and multivariable regression analysis was done to compare the length of stay and mortality data. RESULTS: Patients who required escalation of care were significantly younger (median age 1.9 years compared to 4.6 years for controls) and had lower severity of illness score (PIM 3). Cases had a much higher proportion of respiratory diagnosis. ICU length of stay, hospital length of stay and the direct cost was significantly higher for cases compared to controls. This difference persisted for all age groups and respiratory diagnosis. The cost of care, however, was only different for 1-5 years and >5 years age groups. The difference in ICU length of stay (Δ11.1%) and hospital length of stay (Δ7.8%) persisted on multivariate regression analysis after controlling for age, sex, PIM3 score, and diagnostic variables. There was no difference in mortality on the univariate or multivariate analysis between the 2 groups. CONCLUSIONS: Patients who required escalation of care within 24 hours of hospital admissions have more prolonged ICU and hospital stay and potentially increased cost of care. This measure should be considered while making patient disposition decisions in the emergency department.

COVAD survey 2 long-term outcomes: unmet need and protocol.

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups.

Cardiovascular Disease Risk Factors in US Adults With Vision Impairment.

INTRODUCTION: Adults with vision impairment (VI) have a higher prevalence of cardiovascular disease (CVD) compared with those without VI. We estimated the prevalence of CVD and CVD risk factors by VI status in US adults. METHODS: We used nationally representative data from the 2018 National Health Interview Survey (N = 22,890 adults aged ≥18 years). We estimated the prevalence of self-reported diagnosis of CVD (coronary heart disease [including angina and myocardial infarction], stroke, or other heart disease) by VI status. We used separate logistic regression models to generate adjusted prevalence ratios (aPRs), controlling for sociodemographic covariates, for those with VI (reference group, no VI) for CVD and CVD risk factors: current smoking, physical inactivity, excessive alcohol intake, obesity, hypertension, high cholesterol, and diabetes. RESULTS: Overall, 12.9% (95% CI, 12.3-13.5) of the sample had VI. The prevalence of CVD was 26.6% (95% CI, 24.7-28.6) in people with VI versus 12.2% (95% CI, 11.7-12.8) in those without VI (aPR = 1.65 [95% CI, 1.51-1.80]). Compared with adults without VI, those with VI had a higher prevalence of all risk factors examined: current smoking (aPR = 1.40 [95% CI, 1.27-1.53]), physical inactivity (aPR = 1.14 [95% CI, 1.06-1.22]), excessive alcohol intake (aPR = 1.29 [95% CI, 1.08-1.53]), obesity (aPR = 1.28 [95% CI, 1.21-1.36]), hypertension (aPR = 1.29 [95% CI, 1.22-1.36]), high cholesterol (aPR = 1.21 [95% CI, 1.14-1.29]), and diabetes (aPR = 1.54 [95% CI, 1.38-1.72]). CONCLUSION: Adults with VI had a higher prevalence of CVD and CVD risk factors compared with those without VI. Effective clinical and lifestyle interventions, adapted to accommodate VI-related challenges, may help reduce CVD risk in adults with VI.

Rhinovirus Incidence Rates Indicate We Are Tired of Non-pharmacological Interventions Against Coronavirus Disease 2019.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of rhinovirus (RV) is inversely related to the intensity of non-pharmacological interventions (NPIs), such as universal mask wearing and physical distancing. METHODS: Using RV surveillance data, changes in the effect of NPIs were investigated in South Korea during the pandemic. The time to the first visible effect of NPIs after the onset of NPIs (T1), time to the maximum effect (T2), and duration of the maximum effect (T3) were measured for each surge. For each week, the RVdiff [(RV incidence during the pandemic) - (RV incidence within 5 years before the pandemic)] was calculated, and number of weeks for RVdiff to be below zero after NPIs (time to RVdiff ≤ 0) and number of weeks RVdiff remains below zero after NPIs (duration of RVdiff ≤ 0) were measured for each surge. RESULTS: During the study period, four surges of COVID-19 were reported. As the pandemic progressed, T1 and T2 increased, but T3 decreased. Additionally, the "time to RVdiff of ≤ 0" increased and "duration of RVdiff of ≤ 0" decreased. These changes became more pronounced during the third surge (mid-November 2020), before the introduction of the COVID-19 vaccine, and from the emergence of the delta variant. CONCLUSION: The effect of NPIs appears slower, the duration of the effect becomes shorter, and the intensity also decreases less than a year after the onset of the pandemic owing to people's exhaustion in implementing NPIs. These findings suggest that the COVID-19 response strategy must be completely overhauled.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. METHODS: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. RESULTS: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03-13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26-14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). CONCLUSION: Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Association of transcutaneous CO2 with respiratory support: a prospective double blind observational study in children with bronchiolitis and reactive airway disease.

The use of clinical scoring to assess for severity of respiratory distress and respiratory failure is challenging due to subjectivity and interrater variability. Transcutaneous Capnography (TcpCO2) can be used as an objective tool to assess a patient's ventilatory status. This study was designed to assess for any correlation of continuous monitoring of TcpCO2 with the respiratory clinical scores and deterioration in children admitted for acute respiratory distress. A prospective observational study over one year on children aged 2 weeks to 5 years admitted with acute respiratory distress or failure secondary to Bronchiolitis and Reactive airway disease was performed. Continuous TcpCO2 monitoring for upto 48 h was recorded. Investigators, bedside physicians, respiratory therapists, and nurses were blinded from the transcutaneous trends at the time of data collection. Total of 813 TcpCO2 measurements at standard intervals of 30 min were obtained on 38 subjects. Subjects with abnormal TcpCO2 (> 45 mmHg) were younger (6.9 ± 5.2 vs. 23.05 ± 17.7 months,) and were more likely to be on higher oxygen flow rate (0.52 L/min/kg vs 0.46 lier/min/kg, p = 0.004) and higher FiO2 (38.4 vs 33.6, p < 0.001 using heated high flow nasal cannula. No difference was found in bronchiolitis score or PEW score in subjects with normal and abnormal TcpCO2. A small but statistically significant increase in TcpCO2 was observed at the escalation of care. Even though odds of escalation of care are higher with abnormal TcpCO2 (OR 1.92), this difference did not reach statistical significance. pCO2 can provide additive information for non-invasive clinical monitoring of children requiring varying respiratory support; however, it does not provide predictive value for escalation or de-escalation of care.