Critically ill patients with COVID-19 in Tokyo,Japan: A single-center case series

IntroductionWe reported, in our previous study, a patient with coronavirus disease 2019 (COVID-19) who was successfully treated with extracorporeal membrane oxygenation. Data on clinical courses and outcomes of critically ill patients with COVID-19 in Japan are limited in the literature. This study aimed to describe the clinical courses and outcomes of critically ill patients with COVID-19 in Tokyo, Japan.MethodsThis is a single-center case series study. Patients with COVID-19 treated with mechanical ventilation (MV) were reviewed retrospectively. Data on baseline characteristics, in-hospital treatment, and outcomes were collected.ResultsBetween February 2, 2020, and June 30, 2020, 14 critically ill patients with COVID-19 were treated with MV. Most patients were male and had comorbidities, especially hypertension or diabetes; 35.7% were overweight and 21.4% were obese. The majority of the patients had dyspnea on admission. The median duration of MV was 10.5 days, and the 28-day mortality rate was 35.7%. In the four patients with COVID-19 who died, the cause of death was respiratory failure.ConclusionsAs in previous reports from other countries, the mortality rate of patients with COVID-19 requiring intensive care remains high in Tokyo. Further study on the appropriate timing of MV initiation and specific treatments for critically ill patients with COVID-19 is needed.     

Effectiveness of personal protective equipment in preventing severe acute respiratory syndrome coronavirus 2 infection among healthcare workers

IntroductionInformation on the effectiveness of personal protective equipment (PPE) for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs), especially among HCWs with frequent contact with patients with SARS-CoV-2, is limited.MethodsWe conducted a prospective cohort study on 49 HCWs who worked in close contact with patients with SARS-CoV-2 infection. HCWs had blood samples taken every 2 weeks to test for SARS-CoV-2 antibodies using two different types of assay.ResultsForty-nine participants (31 nurses, 15 doctors, 3 other workers) were enrolled. In total, 112 blood samples are obtained from participants. The median work days in 2 weeks was 9 (interquartile range (IQR): 5–10) days. In a single work day, 30 of the 49 participants (61.5%) had contact with patients with suspected or conformed SARS-CoV-2 at least 8 times, and approximately 60% of participants had more than 10 min of contact with a single patient. The median self-reported compliance to PPE was 90% (IQR: 80–100%). Seven participants tested positive for SARS-CoV-2 antibody using enzyme-linked immunosorbent assay (ELISA); however, none were seropositive for SARS-CoV-2 neutralizing antibody, so the positive ELISA results were assumed to be false-positive.ConclusionsThe study provides evidence that appropriate PPE is sufficient to prevent infection amongHCWs. It is necessary to establish a system that provides a stable supply of PPE for HCWs to perform their duties.     

Idiopathic left ventricular tachycardia originating from the mitral annulus

BACKGROUND: Radiofrequency catheter ablation (RFCA) can eliminate most idiopathic repetitive monomorphic ventricular tachycardias (RMVTs) originating from the right and left ventricular outflow tracts (RVOT, LVOT). Here, we describe the electrophysiological (EP) findings of a new variant of RMVT originating from the mitral annulus (MAVT). METHODS AND RESULTS: MAVT was identified in 35 patients out of 72 consecutive left ventricular RMVTs from May 2000 to June 2004. All patients underwent an EP study and RFCA. The sites of origin of the MAVT were grouped into four groups according to the successful ablation sites around the mitral annulus. Group I included the anterior sites (n = 11), group II the anterolateral sites (n = 9), group III the lateral sites (n = 6), and group IV the posterior sites (n = 9). The MAVTs were a wide QRS tachycardia with a delta wave-like beginning of the QRS complex. The transitional zone of the R wave occurred between V1-V2 in all cases. The 12-lead electrocardiogram (ECG) pattern might reflect the site of the origin of MAVTs around the mitral annulus. We proposed an algorithm for predicting the site of the focus and the tactics needed for successful RFCA of the MAVT. CONCLUSIONS: We described the EP findings of the new variant of RMVT, MAVT. Most MAVTs could be eliminated by RF applications to the endocardial mitral annulus using our proposed tactics.     

Importance of antitumor immunity for complete cure of highly drug-sensitive leukemia in mice

Summary Seven transplantable leukemia lines were established from spontaneous leukemias and screened for 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(chloroethyl)-1-nitrosourea hydrochloride (ACNU) sensitivity in DDD mice. Three of them were classified as highly sensitive, two as sensitive and two as resistant to ACNU. A highly sensitive line, DL812, was extensively characterized from a therapeutic point of view. DL812 cells were so invasive as to produced enlargement of spleens and lymph nodes but not local tumors when injected s.c., markedly sensitive to in vitro ACNU exposure and modrately immunogenic. The invasion process of DL812 cells differed with the status of host immunity. Advanced DL812 leukemias were macroscopically completely cured with normalization of spleen and lymph node sizes 3–7 days after an i.p. injection of 0.5 mg ACNU, but more ACNU-resistant leukemias with splenomegaly and enlarged lymph nodes recurred thereafter. Recurring DL812 cells were approximately four times more resistant to in vitro ACNU exposure but maintained similar immunogenicity as compared to the original ones. Permanent cures of advanced leukemias were achieved by ACNU treatment plus subsequent adoptive transfer of immune splenocytes in 15% of diseased mice. The results suggest the importance of host antitumor immunity for permanent cures of highly drug-sensitive leukemias, overcoming drug resistance and relapse.Abbreviations ACNU 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl[-1-(2-chloroethyl)-1-nitrosourea hydrochloride - FITC fluorescein-isothiocyanate-conjugated - Ig immunoglobulin - M199 medium 199 - PBS phosphate-buffered saline solution This work was supported in part by a grant-in-aid for cancer research from the Ministry of Education, Science and Culture, Japan     

Beneficial effect of candesartan treatment on cardiac autonomic nervous activity in patients with chronic heart failure: simultaneous recording of ambulatory electrocardiogram and posture

BACKGROUND: Reclining in the right lateral decubitus position in chronic heart failure (CHF) is a self-protective mechanism for normalizing impaired cardiac autonomic nervous activity (CANA). HYPOTHESIS: Candesartan, an angiotensin II receptor blocker, exerts beneficial effects on CANA and postural preferences in patients with CHF. METHODS: We studied 15 patients with CHF due to coronary artery disease. Cardiac autonomic nervous activity was assessed using spectral heart rate variability (HRV) analysis based on 24-h ambulatory electrocardiogram monitoring before and after an 8-week treatment with candesartan. The patients' posture was simultaneously recorded using a specially devised detector, as the right (R) or left (L) lateral decubitus or supine (S) positions, to evaluate postural modulations of CANA. Normalized high-frequency (0.15 to 0.40 Hz) power (nHF) and the low-frequency (0.04 to 0.15 Hz)/high-frequency power ratio (LF/HF) were used as indices of vagal activity and sympathovagal balance, respectively. RESULTS: When HRV was analyzed in each position, CANA was changed in L and S, but not in R, from sympathetic to parasympathetic prevalence by the treatment (R, nHF, 50 +/- 20 vs. 52 +/- 19 nu, p = 0.87; LF/HF, 1.39 +/- 1.11 vs. 1.32 +/- 1.32, p =0.93; L, nHF, 28 +/- 13 vs. 47 +/- 19 nu, p = 0.019; LF/HF, 3.34 +/- 2.48 vs. 1.56 +/- 1.39, p = 0.029; S, nHF, 38 +/- 17 vs. 53 +/- 16 nu, p = 0.0023; LF/HF, 2.43 +/- 2.21 vs. 1.03 +/- 0.59, p = 0.025). The fractions of the time in R and L were decreased and increased, respectively, by the treatment (R, 40 +/- 30 vs. 18 +/- 24%, p = 0.0018; L, 11 +/- 20 vs. 27 +/- 26%, p = 0.025). CONCLUSIONS: In patients with CHF, candesartan treatment improves cardiac autonomic balance, and the preference for the right lateral decubitus position disappears after the treatment.     

Molecular and electrophysiological differences in the L-type Ca2+ channel of the atrium and ventricle of rat hearts.

BACKGROUND: Many pathological conditions induce electrical remodeling, possibly through intracellular Ca2+ overload, but the currently available L-type Ca2+ channel blockers may be detrimental because of their global negative inotropic effects. METHODS AND RESULTS: To determine whether the L-type Ca2+ channel is identical throughout the heart, the distribution of the mRNAs and proteins comprising the L-type Ca2+ channel and its electrophysiological properties were analyzed in rat atria and ventricles. The mRNA of alpha2delta-2 (Cacna2d2) was more abundantly expressed in the atrium (approximately 5-fold) than in the ventricle. In contrast, alpha1C (Cacna1c) (Cav1.2) mRNA was significantly less abundant in the atrium. The level of the alpha1C (Cacna1c) (Cav1.2) protein was decreased (approximately 0.5-fold) and that of alpha2 delta-1 (Cacna2d1) was increased (approximately 2-fold) in the atrium compared with the ventricle. Although the peak ICa,L density showed no significant differences, voltage dependence of inactivation and activation of the current showed a more depolarized shift in the atrium than in the ventricle. CONCLUSION: These results indicate that in the rat heart the L-type Ca2+ channel differs between the atrium and ventricle with regard to gene expression and electrophysiological properties.     

Clinical characteristics of anti-glucose-6-phosphate isomerase antibody-positive Japanese patients with rheumatoid arthritis

Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are known to be arthritogenic in mice. These Abs are elevated in several forms of arthritic condition in humans, although their prevalence in rheumatoid arthritis (RA) patients is still in debate. Some RA patients have increased levels of anti-GPI Abs, but their clinical manifestation and relevance to other Abs are not clearly elucidated. The aims of this study were to explore the clinical and hematological characteristics of RA with anti-GPI Abs, and to compare their prevalence in RA patients, systemic lupus erythematosus (SLE) patients, and healthy subjects (HS) in a Japanese population. Anti-GPI Abs were positive in 16 patients with RA (12%, n = 137), in 10 patients with SLE (8%, n = 131), and in 6 HS (4%, n = 139). C-reactive protein (CRP), immunoglobulin G, and the antinuclear antibody titer were higher in anti-GPI-positive patients than in those who were negative (P = 0.049, P = 0.0003, and P = 0.002, respectively). Moreover, the positivity of anti-GPI Abs was correlated with CRP more than with rheumatoid factor in RA patients. It is unclear whether anti-GPI Abs can predict the progress of disease, but the prevalence of these Abs was higher in active RA patients with severe arthritis, suggesting that anti-GPI Abs may be related to the pathogenesis of severe forms of arthritis.