Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study.

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Single-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases.

CD4+ T cells are key mediators of various autoimmune diseases; however, their role in disease progression remains unclear due to cellular heterogeneity. Here, we evaluated CD4+ T cell subpopulations using decomposition-based transcriptome characterization and canonical clustering strategies. This approach identified 12 independent gene programs governing whole CD4+ T cell heterogeneity, which can explain the ambiguity of canonical clustering. In addition, we performed a meta-analysis using public single-cell datasets of over 1.8 million peripheral CD4+ T cells from 953 individuals by projecting cells onto the reference and cataloging cell frequency and qualitative alterations of the populations in 20 diseases. The analyses revealed that the 12 transcriptional programs were useful in characterizing each autoimmune disease and predicting its clinical status. Moreover, genetic variants associated with autoimmune diseases showed disease-specific enrichment within the 12 gene programs. The results collectively provide a landscape of single-cell transcriptomes of CD4+ T cell subpopulations involved in autoimmune disease.

Association of HFA-PEFF score with clinical outcomes after catheter ablation for atrial fibrillation.

BACKGROUND: The Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing and final aetiology (HFA-PEFF) score has been developed for diagnosing heart failure with preserved ejection fraction (HFpEF), which is frequently associated with atrial fibrillation (AF). We aimed to investigate whether preprocedural HFA-PEFF score could be used to predict clinical outcomes in patients with AF who underwent catheter ablation (CA). METHODS: Overall, 1679 patients with AF who underwent primary CA (71±10 years, 1218 males (72.5%), median follow-up duration 3.3 years) from July 2011 to December 2019 were included in this retrospective study. HFpEF was defined as an HFA-PEFF score ≥5. The primary study outcome was 5-year major adverse cardiovascular and cerebrovascular events (MACCE), which is a composite of all-cause death, hospitalisation for heart failure (HF) and hospitalisation for stroke. RESULTS: The prevalence of HFpEF was 32.3%, but only 7.7% were diagnosed with HF at the time of CHADS2 scoring. Five-year MACCE occurred in 77 patients (4.6%). The cumulative 5-year incidence of MACCE was significantly higher in the HFpEF group than in the non-HFpEF group (11.2% vs 4.8% at 5 years, p<0.001). In the multivariable analysis, HFpEF by the HFA-PEFF score was associated with MACCE (adjusted HR 1.65, 95% CI 1.02 to 2.65, p=0.041). CONCLUSIONS: Early detection of HFpEF using the HFA-PEFF score may have clinical applications in guiding therapeutic decision-making and improving prognosis by preventing HF and stroke in patients with AF undergoing CA.

Analysis of postural stability using foam posturography in patients with persistent postural-perceptual dizziness.

BACKGROUND/OBJECTIVE: Persistent postural-perceptual dizziness (PPPD) is worsened in a standing posture, or by body movement, or visual stimulation. We aimed to evaluate postural stability in PPPD patients using foam posturography and to investigate the dependence on visual and somatosensory input in the standing posture. METHODS: Foam posturography was performed on 53 PPPD patients, and data from the PPPD patients were compared with the data from an age- and sex-matched healthy controls. The PPPD patients were divided into four groups based on the findings of vestibular function tests and the effect of vestibular function on posturographic data was examined. RESULTS: Romberg's ratios were significantly higher in PPPD patients than in controls. The median Romberg's ratios in PPPD patients with normal vestibular function were also higher than those in controls. However, foam ratio was significantly lower in PPPD patients than in controls. The median foam ratios in PPPD patients with vestibular dysfunction were also lower than those in controls. CONCLUSIONS: In a standing posture, PPPD patients may be more dependent on visual input and less dependent on somatosensory input than healthy subjects. Higher dependence on visual and lower dependence on somatosensory input in PPPD may be a feature unaffected by vestibular function.

RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS.

Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone-collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients with ALS and transgenic mice overexpressing the mutant human superoxide dismutase1 (mSOD1 mice). Treatment with humanized anti-RGMa monoclonal antibody ameliorated the clinical symptoms in mSOD1 mice. Histochemical analysis revealed that the anti-RGMa antibody significantly decreased mutant SOD1 protein accumulation in the motor neurons of mSOD1 mice via inhibition of actin depolymerization. In vitro analysis revealed that the anti-RGMa antibody inhibited the cellular uptake of the mutant SOD1 protein, presumably by reinforcing the neuronal actin barrier. Collectively, these data suggest that RGMa leads to the collapse of the neuronal actin barrier and promotes aberrant protein deposition, resulting in exacerbation of the ALS pathology.

Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population.

Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7ß-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population.

Inter-day and intra-day variations in effective intensity of noisy galvanic vestibular stimulation to improve postural stability in bilateral vestibulopathy.

BACKGROUND: The reproducibility of the effective intensity of noisy galvanic vestibular stimulation (nGVS) to improve postural stability is not well known. OBJECTIVE: We aimed to investigate inter-day and intra-day variations in effective intensity in patients with bilateral vestibulopathy (BVP). METHODS: Thirteen BVP patients were measured for center-of-pressure movements in the standing posture at five time points: morning of the first test day, morning and evening of the second test day, and morning and evening of the third test day. The mean velocity, the envelopment area, and the root mean square were measured in the eyes-closed condition for 30 s during nGVS application ranging from 0 to 1000µA. The effective intensity was defined as the intensity at which all the three parameters measured during the stimulation were simultaneously smaller than the values at baseline (0µA). RESULTS: Seven of the 13 patients had a common effective intensity throughout the three test days. Six patients on the second test day and five patients on the third test day had no common effective intensity between morning and evening. CONCLUSIONS: The effective intensity of nGVS changes depending on the time during the day as well as between the days.

The effect of self-management vestibular rehabilitation on persistent postural-perceptual dizziness.

Objective: To investigate the effects of self-management vestibular rehabilitation (VR) on the subjective symptoms of dizziness and postural stability in persistent postural-perceptual dizziness (PPPD). Study design: Retrospective case review. Methods: The medical records of 30 patients newly diagnosed with PPPD based on the Bárány Society's diagnostic criteria were reviewed. Nineteen patients (4 males and 15 females; age range 27-84 years, mean age ± standard deviation 57.4 ± 14.2 years) who was newly instructed to self-management VR were included and instructed to perform self-management VR for 2 months. Results: One patient did not visit the outpatient clinic again, and in the remaining 18 patients, 4 (22%) discontinued VR at their own discretion. In the 12 patients who completed 2 months of VR (67%), there was a significant improvement in Niigata PPPD Questionnaire (NPQ) and Dizziness Handicap Inventory (DHI) scores after VR compared to those before VR (p < .05). However, the mean velocity of center of pressure (COP) movement (velocity) and the envelopment area traced by COP movement (area), as well as the Romberg ratio and foam ratio of velocity and area, did not differ significantly after VR when compared to those before VR (p > .05). Conclusions: For PPPD, self-management VR improved subjective symptoms of dizziness, but not stability of standing posture. It is necessary to improve patients' adherence to the treatment. Level of evidence: 4.

Autoimmune-mediated astrocytopathy.

Recently accumulating evidence identified the disease entity where astrocytes residing within the central nervous system (CNS) are the target of autoantibody-mediated autoimmunity. Aquaporin4 (AQP4) is the most common antigen to serve as astrocyte-targeted autoimmune responses. Here, in this review, the clinical and pathological aspects of AQP4-mediated astrocyte disease are discussed together with the pathogenic role of anti-AQP4 antibody. More recently, the mechanism of immune dysregulation resulting in the production of astrocyte-targeted autoantibody is also revealed, and the postulated hypothesis is discussed.

Reconstruction of the personal information from human genome reads in gut metagenome sequencing data.

Human DNA present in faecal samples can result in a small number of human reads in gut shotgun metagenomic sequencing data. However, it is presently unclear how much personal information can be reconstructed from such reads, and this has not been quantitatively evaluated. Such a quantitative evaluation is necessary to clarify the ethical concerns related to data sharing and to enable efficient use of human genetic information in stool samples, such as for research and forensics. Here we used genomic approaches to reconstruct personal information from the faecal metagenomes of 343 Japanese individuals with associated human genotype data. Genetic sex could be accurately predicted based on the sequencing depth of sex chromosomes for 97.3% of the samples. Individuals could be re-identified from the matched genotype data based on human reads recovered from the faecal metagenomic data with 93.3% sensitivity using a likelihood score-based method. This method also enabled us to predict the ancestries of 98.3% of the samples. Finally, we performed ultra-deep shotgun metagenomic sequencing of five faecal samples as well as whole-genome sequencing of blood samples. Using genotype-calling approaches, we demonstrated that the genotypes of both common and rare variants could be reconstructed from faecal samples. This included clinically relevant variants. Our approach can be used to quantify personal information contained within gut metagenome data.

Preceding Balance Disorders Affect Vestibular Function in Persistent Postural-Perceptual Dizziness.

Persistent postural-perceptual dizziness (PPPD) is induced by preceding conditions that cause balance disorders. To investigate the association between vestibular function and preceding balance disorders in PPPD patients, a retrospective chart review was performed. Vestibular function in 55 PPPD patients was measured using the caloric test, cervical vestibular evoked myogenic potential testing to air-conducted sound (ACS cVEMP), ocular vestibular evoked myogenic potential testing to bone-conducted vibration (BCV oVEMP), and video head impulse testing (vHIT). Patients were classified according to the type of preceding balance disorder. The age-stratified Cochran-Mantel-Haenszel (CMH) test and the exact test for the common odds ratio were conducted to evaluate the association between preceding n ≥ 4 balance disorders and present peripheral vestibular dysfunction. PPPD patients with preceding vestibular neuritis presented a significant positive association with abnormal caloric responses (p = 0.013), while those with preceding benign paroxysmal positional vertigo (BPPV) had significantly lower rates of abnormal BCV oVEMP (p = 0.003). Furthermore, patients with preceding vestibular neuritis showed lateral semicircular canal dysfunction, while those with preceding BPPV presented normal utricular functions. These results present the influence of preceding balance disorders on the vestibular function in PPPD.

Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination.

Recently accumulating evidence has highlighted the rare occurrence of COVID-19 vaccination-induced inflammation in the central nervous system. However, the precise information on immune dysregulation related to the COVID-19 vaccination-associated autoimmunity remains elusive. Here we report a case of encephalitis temporally associated with COVID-19 vaccination, where single-cell RNA sequencing (scRNA-seq) analysis was applied to elucidate the distinct immune signature in the peripheral immune system. Peripheral blood mononuclear cells (PBMCs) were analyzed using scRNA-seq to clarify the cellular components of the patients in the acute and remission phases of the disease. The data obtained were compared to those acquired from a healthy cohort. The scRNA-seq analysis identified a distinct myeloid cell population in PBMCs during the acute phase of encephalitis. This specific myeloid population was detected neither in the remission phase of the disease nor in the healthy cohort. Our findings illustrate induction of a unique myeloid subset in encephalitis temporally associated with COVID-19 vaccination. Further research into the dysregulated immune signature of COVID-19 vaccination-associated autoimmunity including the cerebrospinal fluid (CSF) cells of central nervous system (CNS) is warranted to clarify the pathogenic role of the myeloid subset observed in our study.

The Safety and Strategies for Reinitiating Electroconvulsive Therapy After ECT-Induced Takotsubo Cardiomyopathy: A Case Report and Systematic Review.

OBJECTIVES: Takotsubo cardiomyopathy (TCM) is a life-threatening complication of electroconvulsive therapy (ECT). We report the case of a 66-year-old woman who was rechallenged with ECT after ECT-induced TCM. Moreover, we have made a systematic review to assess the safety of and strategies for reinitiating ECT after TCM. METHODS: We searched for published reports on ECT-induced TCM since 1990 in MEDLINE (PubMed), Scopus, Cochrane Library, ICHUSHI, and CiNii Research. RESULTS: A total of 24 ECT-induced TCM cases were identified. Patients who developed ECT-induced TCM were predominantly middle-aged and older women. There was no specific trend in anesthetic agents used. Seventeen (70.8%) cases developed TCM by the third session in the acute ECT course. Eight (33.3%) cases developed ECT-induced TCM despite the use of ß-blockers. Ten (41.7%) cases developed cardiogenic shock or abnormal vital signs related to cardiogenic shock. All cases recovered from TCM. Eight (33.3%) cases tried to receive ECT retrial. The duration until ECT retrial was between 3 weeks and 9 months. The most common preventive measures during ECT retrial were related to ß-blockers; however, the type, dose, and route of administration of ß-blockers varied. In all cases, ECT could be reperformed without TCM recurrence. CONCLUSIONS: Electroconvulsive therapy-induced TCM is more likely to cause cardiogenic shock than nonperioperative cases; nevertheless, it has good prognosis. Cautious reinitiation of ECT after TCM recovery is possible. Further studies are required to determine preventive measures for ECT-induced TCM.

[Staged Hybrid Repair of Extensive Thoracic Aortic Aneurysm with Right Aortic Arch and Isolated Left Subclavian Artery:Report of a Case].

A 69-year-old male was referred to our hospital due to extensive thoracic aortic aneurysm with right aortic arch and isolated left subclavian artery. We chose staged hybrid repair to avoid the risk of spinal cord injury and bilateral recurrent nerve paralysis. First, ascending aorta replacement with elephant trunk and reconstruction of the cervical branches were underwent. Second, we performed the thoracic endovascular aortic repair for aortic arch and descending aortic aneurysm. The postoperative course was satisfactory and, computed tomography (CT) showed successful aortic repair without any type of endoleak. He was discharged on the ninth day after the second operation. To our knowledge, this is the first report of surgical repair for an aortic aneurysm with right aortic arch and isolated subclavian artery.

Oral Administration of TrkB Agonist, 7, 8-Dihydroxyflavone Regenerates Hair Cells and Restores Function after Gentamicin-Induced Vestibular Injury in Guinea Pig.

The causes of vestibular dysfunction include the loss of hair cells (HCs), synapses beneath the HCs, and nerve fibers. 7, 8-dihydroxyflavone (DHF) mimics the physiological functions of brain-derived neurotrophic factor. We investigated the effects of the orally-administered DHF in the guinea pig crista ampullaris after gentamicin (GM)-induced injury. Twenty animals treated with GM received daily administration of DHF or saline for 14 or 28 days (DHF (+) or DHF (-) group; N = 5, each). At 14 days after GM treatment, almost all of the HCs had disappeared in both groups. At 28 days, the HCs number in DHF (+) and DHF (-) groups was 74% and 49%, respectively, compared to GM-untreated control. In the ampullary nerves, neurofilament 200 positive rate in the DHF (+) group was 91% at 28 days, which was significantly higher than 42% in DHF (-). On day 28, the synaptic connections observed between C-terminal-binding protein 2-positive and postsynaptic density protein-95-positive puncta were restored, and caloric response was significantly improved in DHF (+) group (canal paresis: 57.4% in DHF (+) and 100% in DHF (-)). Taken together, the oral administration of DHF may be a novel therapeutic approach for treating vestibular dysfunction in humans.

Importance of the relative epicardial connection locations and right-sided pulmonary vein isolation line for successful pulmonary vein isolation.

INTRODUCTION: The presence of an epicardial connection (EC) decreases the success rate of pulmonary vein isolation (PVI); however, the effect of designing isolation lines has not been evaluated. We sought to clarify the effects of designing an anterior line for right-sided PVI considering the presence and location of the EC. METHODS: Seventy-four consecutive patients who underwent initial catheter ablation for atrial fibrillation were retrospectively included in this study. The presence of the EC was determined by the left atrial (LA) activation map during right atrial pacing, and patients were divided into EC-positive (n = 23, 31%) and EC-negative (n = 51, 69%) groups. EC-positive patients were further subdivided based on the EC location: on-the-line group, (EC on the PVI line, n = 11); inside-line group (EC on the pulmonary vein [PV] side, n = 10); and outside-line group (EC on the LA side, n = 2). The PVI parameters were compared among the three groups. RESULTS: The success rates of the first-pass isolation were comparable between the EC-negative and EC-positive groups (70.6% vs. 60.9%, ns), but the success rate was significantly higher in the on-the-line group than in the inside-line group (91% vs. 20%, p = 0.002). First-pass isolation was successful in both patients in the outside-line group. Additional carina ablation was required only in the inside-line group. CONCLUSIONS: The association between the EC site and the right-sided PV anterior isolation line affected the success rate of first-pass isolation. For successful right-sided PVI, it is important to consider the EC site when designing the PVI line.