Neutralizing Activity against BQ.1.1, BN.1, and XBB.1 in Bivalent COVID-19 Vaccine Recipients: Comparison by the Types of Prior Infection and Vaccine Formulations.

Bivalent COVID-19 vaccines that contain BA.1 or BA.4/BA.5 have been introduced worldwide in response to pandemic waves of Omicron subvariants. This prospective cohort study was aimed to compare neutralizing antibodies (Nabs) against Omicron subvariants (BA.1, BA.5, BQ.1.1, BN.1, and XBB.1) before and 3-4 weeks after bivalent booster by the types of SARS-CoV-2 variants in prior infections and bivalent vaccine formulations. A total of 21 participants were included. Prior BA.1/BA.2-infected, and BA.5-infected participants showed significantly higher geometric mean titers of Nab compared to SARS-CoV-2-non-infected participants after bivalent booster (BA.1, 8156 vs. 4861 vs. 1636; BA.5, 6515 vs. 4861 vs. 915; BQ.1.1, 697 vs. 628 vs. 115; BN.1, 1402 vs. 1289 vs. 490; XBB.1, 434 vs. 355 vs. 144). When compared by bivalent vaccine formulations, Nab titers against studied subvariants after bivalent booster did not differ between BA.1 and BA.4/BA.5 bivalent vaccine (BA.1, 4886 vs. 5285; BA.5, 3320 vs. 4118; BQ.1.1, 311 vs. 572; BN.1, 1028 vs. 1095; XBB.1, 262 vs. 362). Both BA.1 and BA.4/BA.5 bivalent vaccines are immunogenic and provide enhanced neutralizing activities against Omicron subvariants. However, even after the bivalent booster, neutralizing activities against the later Omicron strains (BQ.1.1, BN.1, and XBB.1) would be insufficient to provide protection.

Targeted Literature Review of the Burden of Respiratory Syncytial Infection among High-Risk and Elderly Patients in Asia Pacific Region.

INTRODUCTION: The burden of respiratory syncytial virus (RSV), which causes acute respiratory illness, is well recognized among the pediatric population but also imposes a significant risk to the elderly (age ≥ 60) and those with underlying comorbidities. The study aimed to review the most recent data on epidemiology and burden (clinical and economic) of RSV in the elderly/high-risk populations in China, Japan, South Korea, Taiwan, and Australia. METHODS: A targeted review was conducted of English, Japanese, Korean, and Chinese language articles published from 1 January 2010 to 7 October 2020 relevant for the purpose. RESULTS: A total of 881 studies were identified, and 41 were included. The median proportion of elderly patients with RSV in all adult patients with acute respiratory infection (ARI) or community acquired pneumonia was 79.78% (71.43-88.12%) in Japan, 48.00% (3.64-80.00%) in China, 41.67% (33.33-50.00%) in Taiwan, 38.61% in Australia, and 28.57% (22.76-33.33%) in South Korea. RSV was associated with a high clinical burden on those patients with comorbidities such as asthma and chronic obstructive pulmonary disease. In China, inpatients with ARI showed a significantly higher rate of RSV-related hospitalization than outpatients (13.22% versus 4.08%, p < 0.01). The median length of hospital stay among elderly patients with RSV was longest in Japan (30 days) and shortest in China (7 days). Mortality data varied by region with some studies reporting rates as high as 12.00% (9/75) in hospitalized elderly patients. Finally, data on the economic burden was only available for South Korea, with the median cost of a medical admission for an elderly patient with RSV being US dollar (USD) 2933. CONCLUSION: RSV infection is a major source of disease burden among elderly patients, especially in regions with aging populations. It also complicates the management of those with underlying diseases. Appropriate prevention strategies are required to reduce the burden among the adult, especially the elderly, population. Data gaps regarding economic burden of RSV infection in the Asia Pacific region indicates the need for further research to increase our understanding on the burden of this disease in this region.

Wavelet subband discriminator for efficient unsupervised chest X-ray image restoration.

BACKGROUND: Chest X-ray (CXR) images are commonly used to show the internal structure of the human body without invasive intervention. The quality of CXR is an important factor as it affects the accuracy of a clinical diagnosis. Unfortunately, it is difficult to always get good quality CXR scans due to noises and scatters. PURPOSE: Recently, wavelet directional CycleGAN (WavCycleGAN) has shown promising results in image restoration tasks by removing noise and artifacts without sacrificing high-frequency components of the input image. Unfortunately, WavCycleGAN directly reconstructs wavelet directional images that require a wavelet transform in both the training and test phases, resulting in additional processing steps and unnatural artifacts originating from the wavelet domain image. In addition, WavCycleGAN can only process artifact-related subbands, so it is difficult to apply WavCycleGAN when different levels of artifacts are present in all subbands. To address this, here we present a novel unsupervised CXR image restoration scheme with similar or even better artifact removal performance than WavCycleGAN in spite of wavelet transform being only applied in the training phase. METHODS: We introduce a novel wavelet subband discriminator which can be combined with CycleGAN or switchable CycleGAN, where wavelet transform is applied only in the training phase for discriminators to match the distribution of wavelet subband components. In our framework, the image restoration network can be still applied in the image domain to prevent unnatural artifacts of the wavelet domain image with the help of the image-domain cycle-consistency loss. In addition, using wavelet subband discriminator makes it possible to remove artifacts in all subbands by utilizing frequency-specific wavelet subband discriminators. RESULTS: Through extensive experiments for noise and scatter removal in CXRs, we confirm that our method provides competitive performance compared to existing approaches without additional processing steps in the test phase. Furthermore, we show that our wavelet subband discriminator combined with the switchable CycleGAN can provide the flexibility by generating different levels of artifact removal. CONCLUSIONS: The proposed wavelet subband discriminator can be combined with the existing CycleGAN or switchable CycleGAN structures to construct an efficient unsupervised CXR image reconstruction. The advantage of our wavelet subband discriminator-based CXR image restoration is that, unlike traditional WavCycleGAN, it does not require any additional processing steps in the testing phase and does not generate unnatural artifacts originating from the wavelet domain image. We believe that our wavelet subband discriminator can be applied to various CXR image applications.

Effects of Residual Arch Tears on Late Outcomes After Hemiarch Replacement for DeBakey I Dissection.

BACKGROUND: This study evaluated the effect of residual arch tears on late reinterventions and arch dilatation after hemiarch replacement for patients with acute DeBakey type I aortic dissection. METHODS: Between January 1995 and October 2018, 160 consecutive patients who underwent hemiarch replacement for DeBakey type I dissection were retrospectively enrolled. They were divided into patients with (n = 73) and without (n = 87) residual arch tears. The arch tears group was subdivided into the proximal/middle arch (n = 26) and distal arch (n = 47) groups to evaluate arch growth rates according to the locations of residual arch tears. The endpoints were arch growth rate and late arch and composite events. RESULTS: The arch diameter increased significantly over time in patients with residual arch tears (1.620 mm/y, P < .001). The increase occurred more rapidly when residual tears occurred at the distal arch than at the proximal/middle arch level (2.101 vs 1.001 mm/y). In the adjusted linear mixed model, residual arch tears or luminal communications at the distal arch level were significant factors associated with increases in the arch diameter over time. The 10-year freedom from late arch and composite event rate was significantly lower for patients with residual arch tears than for those without (82.4% vs 95.5%, P = .001; and 68.0% vs 89.3%, P = .002, respectively). CONCLUSIONS: Residual arch tears are significant factors associated with late arch dilatation and reinterventions, especially for patients with distal arch tears. Extensive arch replacement during the initial surgery to avoid residual arch tears may improve long-term outcomes.

Human Tissue Analysis of Left Atrial Adipose Tissue and Atrial Fibrillation after Cox Maze Procedure.

Cardiac adipose tissue is a well-known risk factor for the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation, but its correlation with maze surgery remains unknown. The aim of this study was to investigate the correlation between the recurrence of AF and the adipose component of the left atrium (LA) in patients who underwent a modified Cox maze (CM) III procedure. We reviewed the pathology data of resected LA tissues from 115 patients, including the adipose tissue from CM-III procedures. The mean follow-up duration was 30.05 ± 23.96 months. The mean adipose tissue component in the AF recurrence group was 16.17% ± 14.32%, while in the non-recurrence group, it was 9.48% ± 10.79% (p = 0.021), and the cut-off value for the adipose component for AF recurrence was 10% (p = 0.010). The rates of freedom from AF recurrence at 1, 3, and 5 years were 84.8%, 68.8%, and 38.6%, respectively, in the high-adipose group (≥10%), and 96.3%, 89.7%, and 80.3%, respectively, in the low-adipose group (<10%; p = 0.002). A high adipose component (≥10%) in the LA is a significant risk factor for AF recurrence after CM-III procedures. Thus, it may be necessary to attempt to reduce the perioperative adipose portion of the cardiac tissue using a statin in a randomized study.

Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by sequential PPSV23 vaccination in healthy adults aged ≥50 years: A randomized phase III trial (PNEU-PATH).

BACKGROUND: Streptococcus pneumoniae causes pneumococcal disease, and older adults are at an increased risk. Sequential vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for broad protection against pneumococcal disease in some countries. METHODS: This phase III trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 12 months later by PPSV23, in healthy adults aged ≥50 years (NCT03480763). A total of 652 participants were randomized 1:1 to receive either V114 or PCV13, followed by PPSV23. RESULTS: The most common solicited adverse events (AEs) following PCV vaccination included injection-site pain and fatigue. Higher proportions of participants with these events were observed in the V114 group following PCV; however, these differences were not clinically significant. Following PPSV23 vaccination, the most common solicited AEs were injection-site pain and injection-site swelling; the proportions of participants with these events were comparable between both groups. Incidence of serious AEs was low in both groups following PCV and PPSV23, and none were related to study vaccines. No deaths occurred during the study. Serum opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations were comparable between both groups for all 15 serotypes in V114 following PPSV23. Immune responses elicited by V114 persisted for at least 12 months. Immune responses at 30 days and 12 months post-vaccination with PCV were comparable between both groups for the 13 shared serotypes and higher in the V114 group for the V114-unique serotypes (22F and 33F). CONCLUSION: Administration of V114 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged ≥50 years.

Correlation between the Level of Social Distancing and Activity of Influenza Epidemic or COVID-19 Pandemic: A Subway Use-Based Assessment.

Social distancing is an effective measure to mitigate the spread of novel viral infections in the absence of antiviral agents and insufficient vaccine supplies. Subway utilization density may reflect social activity and the degree of social distancing in the general population.; This study aimed to evaluate the correlations between subway use density and the activity of the influenza epidemic or coronavirus disease 2019 (COVID-19) pandemic using a time-series regression method. The subway use-based social distancing score (S-SDS) was calculated using the weekly ridership of 11 major subway stations. The temporal association of S-SDS with influenza-like illness (ILI) rates or the COVID-19 pandemic activity was analyzed using structural vector autoregressive modeling and the Granger causality (GC) test. During three influenza seasons (2017-2020), the time-series regression presented a significant causality from S-SDS to ILI (p = 0.0484). During the COVID-19 pandemic in January 2020, S-SDS had been suppressed at a level similar to or below the average of the previous four years. In contrast to the ILI rate, there was a negative correlation between COVID-19 activity and S-SDS. GC analysis revealed a negative causal relationship between COVID-19 and S-SDS (p = 0.0098).; S-SDS showed a significant time-series association with the ILI rate but not with COVID-19 activity. When public transportation use is sufficiently suppressed, additional social mobility restrictions are unlikely to significantly affect COVID-19 pandemic activity. It would be more important to strengthen universal mask-wearing and detailed public health measures focused on risk activities, particularly in enclosed spaces.

Ciclesonide Inhaler Treatment for Mild-to-Moderate COVID-19: A Randomized, Open-Label, Phase 2 Trial.

Although some intravenous drugs have been used to treat coronavirus disease 2019 (COVID-19), no effective antiviral agents are currently available in the outpatient setting. We aimed to evaluate the efficacy and adverse events of 14-day ciclesonide treatment vs. standard care for patients with mild-to-moderate COVID-19. A randomized, open-label, multicenter clinical trial of ciclesonide inhalers was conducted in patients with mild-to-moderate COVID-19. Patients were enrolled within 3 days of diagnosis or within 7 days from symptom onset and randomly assigned to receive either ciclesonide (320 µg inhalation twice per day for 14 days) or standard care. The primary endpoint was the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication rate on day 14 from study enrollment. Clinical status was assessed once daily, and serial nasopharyngeal viral load was evaluated by quantitative reverse transcription polymerase chain reaction. There were 35 and 26 patients in the ciclesonide and standard care groups, respectively. The SARS-CoV-2 eradication rate at day 14 was significantly higher in the ciclesonide group (p = 0.021). In multivariate analysis, SARS-CoV-2 negative conversion within 14 days was 12 times more likely in the ciclesonide group (95% confidence interval, 1.187-125.240). Additionally, the clinical failure rate (high-flow nasal oxygen therapy or mechanical ventilation) was significantly lower in the ciclesonide group (p = 0.034). In conclusion, ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and it may inhibit the progression to acute respiratory failure in patients with mild-to-moderate COVID-19. Clinical Trial Registration NCT04330586.

Development and Validation of Enzyme-Linked Immunosorbent Assay for Group B Streptococcal Polysaccharide Vaccine.

Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of neonatal sepsis and meningitis in infants. Limitations of prenatal GBS screening and intrapartum antibiotic prophylaxis render developing GBS vaccines a high priority. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) for the practical and large-scale evaluation of GBS capsular polysaccharide (PS) vaccine immunogenicity against three main serotypes, Ia, III, and V. GBS-ELISA was developed and subsequently validated using a standardized curve-fitting four-parameter logistic method. Specificity was measured using adsorption of serum with homologous and heterologous PS. Homologous adsorption showed a ≥75% inhibition of all three serotypes, whereas with heterologous PS, IgG GBS-ELISA inhibited only ≤25% of serotypes III and V. However, with serotype Ia, IgG antibody levels decreased by >50%, even after adsorption with heterologous PS (III or V). In comparison, the inhibition opsonophagocytic killing assay (OPA) of serotypes Ia GBS exhibited a reduction in opsonophagocytic activity of only 20% and 1.1% for serotypes III and V GBS, respectively. The precision of the GBS-ELISA was assessed in five independent experiments using four serum samples. The coefficient of variation was <5% for all three serotypes. This standardized GBS-ELISA would be useful for GBS vaccine development and its evaluation.

How lessons learned from the 2015 Middle East respiratory syndrome outbreak affected the response to coronavirus disease 2019 in the Republic of Korea.

The Republic of Korea (ROK) experienced a public health crisis due to Middle East respiratory syndrome (MERS) in 2015 and is currently going through the coronavirus disease 2019 (COVID-19) pandemic. Lessons learned from the disastrous MERS outbreak were ref lected in the preparedness system, and the readiness capabilities that were subsequently developed enabled the country to successfully flatten the epidemic curve of COVID-19 in late February and March 2020. In this review, we summarize and compare the epidemiology and response of the ROK to the 2015 MERS outbreak and the COVID-19 epidemic in early 2020. We emphasize that, because further COVID-19 waves seem inevitable, it is urgent to develop comprehensive preparedness and response plans for the worst-case scenarios of the COVID-19 pandemic. Simultaneously strengthening healthcare capacity to endure the peak demand and implementing smart strategies to sustain social distancing and public hygiene are necessary until safe and effective therapeutics and vaccines against COVID-19 are available.

Evaluation of Functional Decline in Alzheimer's Dementia Using 3D Deep Learning and Group ICA for rs-fMRI Measurements.

Purpose: To perform automatic assessment of dementia severity using a deep learning framework applied to resting-state functional magnetic resonance imaging (rs-fMRI) data. Method: We divided 133 Alzheimer's disease (AD) patients with clinical dementia rating (CDR) scores from 0.5 to 3 into two groups based on dementia severity; the groups with very mild/mild (CDR: 0.5-1) and moderate to severe (CDR: 2-3) dementia consisted of 77 and 56 subjects, respectively. We used rs-fMRI to extract functional connectivity features, calculated using independent component analysis (ICA), and performed automated severity classification with three-dimensional convolutional neural networks (3D-CNNs) based on deep learning. Results: The mean balanced classification accuracy was 0.923 ± 0.042 (p < 0.001) with a specificity of 0.946 ± 0.019 and sensitivity of 0.896 ± 0.077. The rs-fMRI data indicated that the medial frontal, sensorimotor, executive control, dorsal attention, and visual related networks mainly correlated with dementia severity. Conclusions: Our CDR-based novel classification using rs-fMRI is an acceptable objective severity indicator. In the absence of trained neuropsychologists, dementia severity can be objectively and accurately classified using a 3D-deep learning framework with rs-fMRI independent components.

Opportunistic diseases among HIV-infected patients: a multicenter-nationwide Korean HIV/AIDS cohort study, 2006 to 2013.

BACKGROUND/AIMS: The frequencies of opportunistic diseases (ODs) vary across countries based on genetic, environmental, and social differences. The Korean HIV/AIDS cohort study was initiated in 2006 to promote research on human immunodeficiency virus (HIV) infection in Korea, and to provide a logistical network to support multicenter projects on epidemiological, clinical, and laboratory aspects of HIV infection. This study evaluated the prevalence of ODs among HIV-infected patients in the era of highly active antiretroviral therapy, and the risk factors associated with ODs. METHODS: The study enrolled 1,086 HIV-infected patients from 19 hospitals. This study examined the baseline data of the HIV/AIDS Korean cohort study at the time of enrollment from December 2006 to July 2013. RESULTS: Candidiasis was the most prevalent opportunistic infection (n = 176, 16.2%), followed by Mycobacterium tuberculosis infection (n = 120, 10.9%), Pneumocystis jirovecii pneumonia (n = 121, 11.0%), cytomegalovirus infection (n = 52, 4.7%), and herpes zoster (n = 44, 4.0%). The prevalence rates of Kaposi's sarcoma (n = 8, 0.7%) and toxoplasmosis (n = 4, 0.4%) were very low compared with other countries. The risk factors for ODs were a low CD4 T cell count at the time of HIV diagnosis (odds ratio [OR], 1.01; p < 0.01), current smoking (OR, 2.27; p = 0.01), current alcohol use (OR, 2.57; p = 0.04), and a history of tuberculosis (OR, 5.23; p < 0.01). CONCLUSIONS: Using recent Korean nationwide data, this study demonstrated that an important predictor of ODs was a low CD4 T cell count at the time of HIV diagnosis. Tuberculosis remains one of the most important ODs in HIV-infected patients in Korea.

Humoral and cellular immune responses to influenza vaccine in patients with advanced cirrhosis.

Influenza vaccine has been shown to successfully reduce influenza- and pneumonia-associated hospitalizations and deaths. Yet in liver cirrhosis, influenza vaccines have received little attention in determining the potential benefits. Thus, we undertook this study to evaluate the humoral and cellular immune responses to vaccination against influenza in patients with advanced cirrhosis. We measured interferon (IFN)-gamma secretion response and hemagglutinin inhibition (HI) of antibody titer from pre- and post-vaccination blood samples in 80 cirrhotic patients (Child-Pugh class B or C) and 80 healthy, age-matched subjects. Although the patients with advanced cirrhosis showed similar humoral immune response against influenza vaccination compared to the healthy controls, cell-mediated immunity showed different results according to the remnant liver function.