Clinical trends among patients with asthma hospitalized for COVID-19 based on data from a nationwide database: an observational study.

BACKGROUND: While the prevalence of severe cases and mortality rate of coronavirus disease 2019 (COVID-19) appear to be reducing, the clinical characteristics and severity of hospitalized patients with asthma and COVID-19 remain largely unknown. This study aimed to examine the association of asthma with COVID-19 severity and mortality risk. METHODS: Data from the Japanese COVID-19 Registry Database were used to investigate the association between COVID-19 and asthma. This study focused on patients hospitalized for COVID-19 in 690 facilities from January 31, 2020, to December 31, 2022. Multivariate analysis using logistic regression was conducted to assess whether asthma, compared with other conditions, represents a risk factor for mortality and invasive mechanical ventilation after COVID-19. RESULTS: In total, 72,582 patients with COVID-19 were included in the analysis, of whom, 3731 were diagnosed with asthma. From January 2020 to June 2021, asthma showed no significant association with an increase in mortality (OR 0.837, 95% CI 0.639-1.080, p = 0.184) or invasive mechanical ventilation events (OR 1.084, 95% CI 0.878-1.326, p = 0.440). An analysis conducted after July 2021 yielded similar results. For patients with asthma, factors such as age, body-mass index, sex, and chronic kidney disease increased the risk of mechanical ventilation. However, non-vaccination status and high blood pressure increased the risk of mechanical ventilation during the second half of the study. CONCLUSION: Patients with asthma did not have an increased risk of mortality or mechanical ventilation due to COVID-19. However, patients with asthma had a higher risk of more severe COVID-19 due to factors such as advancing age, elevated body-mass index, chronic kidney disease, and non-vaccination.

Amikacin liposome inhalation suspension for Mycobacterium avium complex pulmonary disease: A subgroup analysis of Japanese patients in the randomized, phase 3, CONVERT study.

BACKGROUND: CONVERT, a randomized, active-controlled, global, Phase 3 trial demonstrated that patients with treatment-refractory Mycobacterium avium complex (MAC) pulmonary disease were more likely to achieve culture conversion with amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) versus those continuing on GBT alone. This subgroup analysis reports the efficacy and safety of ALIS in Japanese patients enrolled in CONVERT. METHODS: Japanese patients aged ≥20 years with treatment-refractory MAC pulmonary disease from Japanese sites were included. Patients were randomized to receive once-daily 590 mg ALIS + GBT or GBT alone; patients converting by Month 6 remained in the study to complete 12-month treatment followed by a 12-month off-treatment period. Nonconverters exited the study at Month 8. The primary endpoint was the proportion of patients achieving culture conversion by Month 6. RESULTS: Of the 59 Japanese patients screened, 48 were randomized to receive ALIS + GBT (n = 34) or GBT alone (n = 14), and 41/48 (85.4 %) were women. The mean (standard deviation) age of patients was 64.5 (8.6) years, and 83.3 % of patients had bronchiectasis at baseline. By Month 6, sputum culture conversion was cumulatively achieved in 9/34 (26.5 %) patients receiving ALIS + GBT versus none receiving GBT alone. Treatment-emergent adverse events were reported in 94.1 % and 100.0 % of patients receiving ALIS + GBT and GBT alone, respectively. No deaths were reported. CONCLUSIONS: The efficacy observed in the Japanese subpopulation was largely consistent with that in the overall CONVERT study population, with more patients achieving culture conversion with ALIS + GBT versus GBT alone. Safety profiles were similar between the overall population and the Japanese subpopulation. CLINICAL TRIAL REGISTRATION: NCT02344004.

A Case of Spinal Echinococcosis in a Japanese Woman Living in Tokyo: Diagnostic Challenges in Non-endemic Areas and Public Health Implications.

Echinococcosis, caused by Echinococcus spp., often affects the lungs and liver, and spinal involvement is rare. Echinococcus multilocularis is prevalent in Japan, particularly in Hokkaido. We herein report a rare case of spinal echinococcosis in a 31-year-old woman who was diagnosed in Tokyo. Spinal echinococcosis is uncommon and often leads to misdiagnoses. The patient likely contracted the disease via contaminated fresh produce transported from an endemic region. This study emphasizes the diagnostic challenges of spinal echinococcosis in non-endemic regions and highlights the public health concerns related to the spread of infections in non-endemic areas.

Efficacy of first-line immune checkpoint inhibitor and anti-angiogenic agent combination therapy for Kirsten rat sarcoma viral antigen-mutant advanced non-small-cell lung cancer: a systematic review and network meta-analysis.

BACKGROUND: Recent advancements in advanced non-small-cell lung cancer (NSCLC) treatment have significantly improved primary therapy outcomes owing to the emergence of various molecular targeted therapies and immune checkpoint inhibitors (ICIs). However, for Kirsten rat sarcoma viral antigen (KRAS) mutations, molecular targeted drugs, such as sotorasib, are not applicable as first-line treatments, and the optimal primary treatment remains unclear. Therefore, we aimed to investigate the efficacy of ICI combination therapy as first-line treatment for KRAS-mutant NSCLC. METHODS: We conducted a systematic search for phase 3 randomized controlled trials (RCTs) that presented data on KRAS mutation status in advanced NSCLC. The primary endpoints were progression-free survival (PFS) and overall survival (OS). A random-effects network meta-analysis was conducted to perform direct and indirect comparisons among treatment groups. RESULTS: Six RCTs were eligible for inclusion. In the network meta-analysis for KRAS-mutant NSCLC, Chemo + bevacizumab (Bev) + ICI was associated with improved PFS (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.22-0.64), followed by Chemo + ICI + ICI (HR 0.66, 95% CI 0.47-0.93) and Chemo + ICI (HR 0.67, 95% CI 0.49-0.91). The most beneficial effect on OS was observed with Chemo + Bev + ICI (HR 0.50, 95% CI 0.34-0.73), followed by Chemo + ICI + ICI (HR 0.64, 95% CI 0.48-0.87) and Chemo + ICI (HR 0.72, 95% CI 0.56-0.92). Regarding OS in wild-type KRAS, ICI + ICI (HR 0.73, 95% CI 0.50-1.07) produced the most favorable effects, followed by Chemo + ICI (HR 0.79, 95% CI 0.63-0.99). CONCLUSION: The efficacy of Chemo + Bev + ICI is potentially high for improving PFS and OS in KRAS-mutant NSCLC. In advanced NSCLC, the presence or absence of KRAS mutations may need to be considered when administering first-line treatment.

Blood perfusion with polymyxin B immobilized columns in patients with COVID-19 requiring oxygen therapy.

Extracorporeal blood purification with polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP), is reported to be effective in treating COVID-19 pneumonitis with oxygen demand. This multicenter prospective study evaluated the efficacy and safety of PMX-DHP in oxygen-requiring patients with COVID-19 admitted between September 28, 2020, and March 31, 2022. The primary endpoint was the percentage of clinical improvement 15 days after treatment. The secondary endpoint was the percentage of worsened disease status. Data from the COVID-19 patient registry were used for the synthetic control group. The improvement rate on Day 15 did not differ between PMX-treated patients and controls; however, the deterioration rate was 0.38 times lower in the PMX-treated group, and the death rates on Day 29 were 0 and 11.1% in the PMX-treated and control groups, respectively. The PMX group showed a 0.73 times higher likelihood for reduced intensive care demand, as 16.7% of PMX-treated patients and 22.8% of controls worsened. After treatment blood oxygenation improved, urinary ß2-microglobulin and liver-type fatty acid-binding protein showed significant decreases, and IL-6 decreased once during treatment but did not persist. In this study, PMX treatment effectively prevented the worsening of COVID-19 pathology, accompanied by improved oxygenation. PMX treatment to remove activated cells may effectively improve patient outcomes.

Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan.

AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Diagnostic accuracy of direct reverse transcription-polymerase chain reaction using guanidine-based and guanidine-free inactivators for SARS-CoV-2 detection in saliva samples.

This study aimed to evaluate diagnostic accuracy of SARS-CoV-2 RNA detection in saliva samples treated with a guanidine-based or guanidine-free inactivator, using nasopharyngeal swab samples (NPS) as referents. Based on the NPS reverse transcription-polymerase chain reaction (RT-PCR) results, participants were classified as with or without COVID-19. Fifty sets of samples comprising NPS, self-collected raw saliva, and saliva with a guanidine-based, and guanidine-free inactivator were collected from each group. In patients with COVID-19, the sensitivity of direct RT-PCR using raw saliva and saliva treated with a guanidine-based and guanidine-free inactivator was 100.0%, 65.9%, and 82.9%, respectively, with corresponding concordance rates of 94.3% (κ=88.5), 82.8% (κ=64.8), and 92.0% (κ=83.7). Among patients with a PCR Ct value of <30 in the NPS sample, the positive predictive value for the three samples was 100.0%, 80.0%, and 96.0%, respectively. The sensitivity of SARS-CoV-2 RNA detection was lower in inactivated saliva than in raw saliva and lower in samples treated with a guanidine-based than with a guanidine-free inactivator. However, in individuals contributing to infection spread, inactivated saliva showed adequate accuracy regardless of the inactivator used. Inactivators can be added to saliva samples collected for RT-PCR to reduce viral transmission risk while maintaining adequate diagnostic accuracy.