Diagnostic yields and safety of thoracoscopic cryobiopsies in Japan: A single-center retrospective observational study.

BACKGROUND: Thoracoscopy is useful for diagnosing unexplained pleural effusions. A sufficient specimen volume is often difficult to obtain using forceps biopsies (FBs) but can be obtained with pleural cryobiopsies (CBs). This study aimed to assess the utility and safety of CB during thoracoscopy in the Japanese population. METHODS: Patients who underwent thoracoscopic CBs at the Japanese Red Cross Medical Center between January 2017 and August 2023 were included in the study. Data were retrospectively analyzed, including clinical data, thoracoscopic findings, specimen size, diagnostic yield, and complications. The number of collected specimens and the freezing time were left to the discretion of the attending physician. RESULTS: Twenty-six patients underwent thoracoscopic CB. Specimens obtained by CB were larger than those obtained by FB. Primary lung cancer was the most common cause of pleural effusion, followed by malignant pleural mesothelioma. CB contributed to the diagnosis in 24 of 26 cases (92.3%) and FB contributed to the diagnosis in 11 of 18 cases (61.1%). Severe fibrosis could be diagnosed in all 3 cases by CB, but not by FB. The common complications of CB included bleeding at the biopsy site and atelectasis, but no severe complications occurred. CONCLUSIONS: The utility and safety of thoracoscopic CB for diagnosing pleural effusions in Japan were verified. The diagnostic yield, specimen size, and safety profile of CB support the diagnostic utility of this method.

A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib.

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

Polymyxin B-immobilised fibre column treatment for acute exacerbation of idiopathic pulmonary fibrosis patients with mechanical ventilation: a nationwide observational study.

BACKGROUND: The prognosis for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is poor, and there is no established treatment. Hence, we aimed to investigate the effectiveness of a polymyxin B-immobilised fibre column (PMX) for the treatment of AE-IPF. METHODS: Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from 1 July 2010 to 31 March 2018. We identified adult patients with idiopathic pulmonary fibrosis who received high-dose methylprednisolone (mPSL) therapy and mechanical ventilation upon admission. Eligible patients (n = 5616) were divided into those receiving PMX treatment combined with high-dose mPSL (PMX group, n = 199) and high-dose mPSL alone (mPSL alone group, n = 5417). To compare outcomes between the two groups, we applied a stabilised inverse probability of treatment weighting (IPTW) using propensity scores. The primary outcome was in-hospital mortality, and the secondary outcomes were 14- and 28-day mortality and length of hospital stay. RESULTS: The in-hospital mortality rates of the PMX and mPSL alone groups were 79.9% and 76.4%, respectively. The results did not significantly differ between the two groups after performing a stabilised IPTW. The odds ratio of the PMX group compared with the mPSL alone group was 1.56 (95% confidence interval 0.80-3.06; p = 0.19). The 14- and 28-day mortality and length of hospital stay (secondary outcomes) also did not significantly differ between the two groups. CONCLUSIONS: In AE-IPF patients using mechanical ventilation, the treatment outcome was not significantly better for PMX combined with high-dose mPSL than for high-dose mPSL alone.

Hospital volume and outcomes following bronchoscopy in patients with interstitial lung disease: A retrospective observational study using a national inpatient database in Japan.

BACKGROUND: Interstitial lung diseases (ILDs) are a group of diffuse parenchymal lung disorders that cause inflammation and fibrosis in the interstitium of the lungs. Histopathological examination is pivotal to accurately diagnose the type of ILD, and bronchoscopy (BS) is often performed to collect lung tissue. This study aimed to determine the relationship between hospital volume and outcomes following BS in patients with ILD. METHODS: Inpatient data on patients with ILD who underwent BS between July 1, 2010 and March 31, 2021 were extracted from the Japanese Diagnosis Procedure Combination database. The annual hospital volume of BS was categorized into four (very low- [≤15 cases/year], low- [16-29 cases/year], high- [30-54 cases/year], and very high- [≥55 cases/year] volume) groups. The primary outcome was all-cause 14-day mortality after BS. Multiple imputation methods followed by multivariable logistic regression analyses fitted with generalized estimating equations were used to estimate the association between hospital volume and 14-day mortality after BS. RESULTS: A total of 89,454 patients with ILD from 1002 hospitals underwent BS. The all-cause mortality within 14 days after BS was 0.77%. An inverse trend was observed between mortality and hospital volume. Compared with the very low-hospital volume group, the very high-hospital volume group was significantly associated with a lower mortality (adjusted odds ratio = 0.63, 95% confidence interval: 0.48-0.85, p = 0.002). CONCLUSIONS: Hospital volume was inversely associated with all-cause mortality within 14 days after BS for hospitalized patients with ILD.

Propensity-Score Matched Analysis of the Effectiveness of Baricitinib in Patients With Coronavirus Disease 2019 (COVID-19) Using Nationwide Real-World Data: An Observational Matched Cohort Study From the Japan COVID-19 Task Force.

Background: To determine the effectiveness of baricitinib in patients with coronavirus disease 2019 (COVID-19), investigate whether baricitinib prevents the need for invasive mechanical ventilation and identify patient subgroups that would benefit from baricitinib. Methods: This observational matched-cohort study was conducted by the Japan COVID-19 Task Force, a nationwide multicenter consortium. Patients with COVID-19 aged ≥18 years were identified from 70 hospitals in Japan. Among patients with confirmed COVID-19 from February 2020 to September 2021, those receiving baricitinib were propensity-score matched with controls. Results: Among 3309 patients, 144 propensity score-matched pairs were identified. Thirteen (9.0%) patients in the baricitinib group and 27 (18.8%) in the control group required invasive mechanical ventilation during the disease course (odds ratio, 0.43). Although the baricitinib group had more severe disease, there were no significant differences in the intensive care unit admission rates (odds ratio, 1.16) and mortality rates (odds ratio, 0.74) between groups. In subgroup analyses, baricitinib was associated with a significant reduction in the need for invasive mechanical ventilation in patients requiring oxygen support (odds ratio, 0.28), with rapid shadow spread on chest radiography (odds ratio, 0.11), or treated with remdesivir (odds ratio, 0.27), systemic corticosteroids (odds ratio, 0.31), or anticoagulants (odds ratio, 0.17). Conclusions: Baricitinib is effective at preventing the need for invasive mechanical ventilation in patients with COVID-19.

Skeletal muscle atrophy and short-term mortality in patients with acute exacerbation of idiopathic pulmonary fibrosis: an observational cohort study.

BACKGROUND: Skeletal muscle atrophy, a common complication of idiopathic pulmonary fibrosis (IPF), and its presence upon diagnosis can indicate a poor prognosis. Patients with IPF frequently experience acute exacerbations (AE), which is associated with a high mortality rate. However, the association between skeletal muscle atrophy and short-term mortality remains unknown. METHODS: We performed a retrospective, multicenter cohort study of patients admitted for AE-IPF in Japan. The cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) were analyzed via single-slice computed tomography (CT). The primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. RESULTS: Of the 212 patients included, 94 (44%) died during the observation period. The low ESMCSA group (<25.6 cm2) had a significantly worse prognosis than that of the high ESMCSA group (≥25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00-2.33], P = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98-2.60]; model 2, 1.55 [0.95-2.56], and model 3, 1.67 [1.00-2.78], respectively). The adjusted HR of low PMCSA (<20.4 cm2) vs. high PMCSA (≥20.4 cm2) was 1.39 (95% CI: 0.88-2.20). CONCLUSIONS: Low ESMCSA on CT images is associated with a high 90-day mortality rate in patients with AE-IPF.

Validity of diagnoses of respiratory diseases recorded in a Japanese administrative database.

BACKGROUND: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. METHODS: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. RESULTS: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. CONCLUSIONS: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.

Adult T-cell leukemia/lymphoma complicated by Pneumocystis pneumonia in a non-endemic area.

Adult T-cell leukemia/lymphoma (ATLL) is a human T-cell leukemia virus type 1-inducing unevenly-distributed T-cell malignancy, which is often complicated by opportunistic infections. Here, we discuss the case of a 75-year-old woman presenting with Pneumocystis pneumonia (PCP) who was subsequently diagnosed with ATLL in Tokyo, a non-endemic area of ATLL. In addition to the elevated soluble interleukin-2 receptor and the detection of flower cells in the screening blood test, the high-resolution computed tomography findings, atypical of PCP, were clues to the diagnosis of ATLL. ATLL should be considered as an underlying disease when patients present with PCP, even in non-endemic areas.

Efficacy of initial high- versus low-dose intravenous corticosteroid therapy in patients with acute exacerbation of idiopathic interstitial pneumonia: A nationwide observational study.

BACKGROUND: Acute exacerbation of idiopathic interstitial pneumonias (AE-IIPs) has a high mortality. However, there is no established treatment for AE-IIPs. Therefore, we aimed to compare the efficacy of high- and low-dose corticosteroid therapies in AE-IIPs patients. METHODS: Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from July 2010 to March 2018. Adult patients with AE-IIPs who received high-dose (methylprednisolone at a dose of 500-1000 mg/day for 3 days starting within 4 days after admission) or low-dose (methylprednisolone at a dose of 100-200 mg/day for at least 5 days starting within 4 days after admission) corticosteroid therapy were identified. Eligible patients (n = 17,317) were divided into the high-dose (n = 16,998) and low-dose (n = 319) groups. A stabilized inverse probability of treatment weighting using propensity scores was performed to compare outcomes between the groups. RESULTS: The primary outcome was in-hospital mortality, and the secondary outcomes were 28-day mortality, infections during hospitalization, length of hospitalization, duration of steroid use, and discharge to home. The in-hospital mortality rates of the high- and low-dose corticosteroid groups were 50.6% and 47.0%, respectively. In-hospital mortality did not significantly differ between the two groups after stabilized inverse probability of treatment weighting, and the odds ratio in the low-dose corticosteroid group was 0.86 (95% confidence interval: 0.64-1.16; p = 0.33). The secondary outcomes also did not significantly differ between the groups. CONCLUSIONS: There was no significant difference in outcomes between patients with AE-IIPs who received high- and low-dose corticosteroid therapies.

Early corticosteroid dose tapering in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF. METHODS: In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering. RESULTS: The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22-0.76] and 0.65 [0.36-1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14-0.99] and 0.27 [0.094-0.83] in the multi-center and administrative cohorts, respectively). CONCLUSION: Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

Comparison of Mental Health among Japanese Healthcare Workers at Two Points during the COVID-19 Pandemic.

BACKGROUND: The prolonged pandemic of coronavirus disease 2019 (COVID-19) has resulted in mental burden among healthcare workers (HCWs). This study aimed to conduct a repeated study to assess changes in psychological concerns among Japanese HCWs. METHODS: This study is the second survey involving HCWs at the Japanese Red Cross Medical Center conducted between November 20, 2020 and December 4, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale, Center for Epidemiologic Studies Depression Scale, and 10-item Connor-Davidson Resilience Scale, respectively. RESULTS: The survey included 594 HCWs, comprising 95 physicians, 261 nurses, 150 other co-medical staff, and 88 office workers. Among them, 46 (7.7%) and 152 (25.6%) developed moderate-to-severe symptoms of anxiety and depression, respectively. Compared with those in the initial survey conducted 6 months earlier, the resilience score did not change, whereas the anxiety and depression scores improved significantly (P < 0.001, P = 0.033, respectively). However, the frequency of HCWs developing moderate-to-severe symptoms of anxiety or depression did not significantly improve. Multivariable logistic regression analysis showed that having higher anxiety symptoms was a risk factor for depression symptoms, while older HCWs and those with higher resilience were less likely to develop depression symptoms. CONCLUSIONS: Many HCWs still suffer from psychological concerns during the COVID-19 pandemic.

Pulmonary amyloidosis diagnosed via transbronchial lung cryobiopsy without surgical lung biopsy: A case series.

Pulmonary amyloidosis is a rare disease characterized by abnormal extracellular deposition of amyloid fibril in the lung tissue, and the identification of amyloid deposits is essential for its diagnosis. Surgical lung biopsy (SLB) is a standard diagnostic method for pulmonary amyloidosis. However, it has a relatively high post-procedural mortality rate. Recently, transbronchial lung cryobiopsy (TBLC) has been gradually used for diagnosing interstitial lung disease. However, its diagnostic efficacy for pulmonary amyloidosis has not yet been validated. Here, we describe two cases of pulmonary amyloidosis with deposition of amyloid light chain detected via TBLC. Since SLB is a high-risk procedure for the patients due to age and complications, TBLC was performed. Both patients presented with Congo red-positive amyloid deposits. One patient with localized pulmonary amyloidosis had a good clinical course without therapeutic intervention and was followed up. The other with systemic amyloidosis received chemotherapy and presented with a stable clinical course. TBLC can collect a larger pulmonary specimen for pulmonary amyloidosis than forceps biopsy and has fewer complications and a lower mortality rate than SLB. Thus, it can be a diagnostic method for pulmonary amyloidosis.

Efficacy and safety of sotrovimab for vaccinated or unvaccinated patients with mild-to-moderate COVID-19 in the omicron era.

Although sotrovimab, one of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies has been shown to be effective in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) with risk factors, their efficacy in mRNA COVID-19 vaccinated patients in omicron era is unknown. To evaluate the effectiveness of sotrovimab clinical data from both COVID-19 vaccinated and unvaccinated patients who were hospitalized and receiving sotrovimab at the Japanese Red Cross Medical Center were compared. The efficacy and adverse events were evaluated. Of the total 60 patients enrolled in this study, 45 had received the mRNA COVID-19 vaccine and 15 were unvaccinated. The clinical progression with low nasal cannula or face mask was not significantly different between groups (occurring in one patient in each group; p = 0.44), with no further progression in both groups. The duration of hospitalization was eight days for both groups (p = 0.90). Two patients in each group experienced adverse events (7%, p = 0.26). The results suggested that the efficacy and safety of sotrovimab against mild-to-moderate COVID-19 with risk factors in the omicron era might not be different regardless of the vaccination status. The results of the present study are encouraging; however, further randomized clinical studies are needed.

Recombinant human soluble thrombomodulin for acute exacerbation of idiopathic pulmonary fibrosis: a nationwide observational study.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the leading cause of death among patients with IPF. However, there is no established treatment for this condition. Hence, we aimed to investigate the effectiveness and safety of recombinant human soluble thrombomodulin (rTM) for the treatment of AE-IPF. METHODS: Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from 1 January 2014 to 31 March 2018. We identified adult patients with IPF who received high-dose methylprednisolone (mPSL) therapy and mechanical ventilation upon admission. Eligible patients (n = 2814) were divided into those receiving high-dose mPSL alone (mPSL alone group, n = 2602) and rTM combined with high-dose mPSL (rTM group, n = 212). A stabilised inverse probability of treatment weighting (IPTW) using propensity scores was performed to compare outcomes between the two groups. The primary outcome was in-hospital mortality, and the secondary outcomes were 14- and 28-day mortality, bleeding events and length of hospital stay. RESULTS: The in-hospital mortality rates of the mPSL alone and rTM groups were 75.9% and 76.9%, respectively. The results did not significantly differ between the two groups after performing a stabilised IPTW. The odds ratio of the rTM group compared to the mPSL alone group was 1.15 (95% confidence interval: 0.71-1.84; p = 0.57). Moreover, the secondary outcomes did not differ significantly between the two groups. CONCLUSIONS: In patients with AE-IPF who developed severe respiratory failure, rTM in addition to high-dose mPSL was not associated with a better outcome.

An autopsy case of idiopathic pulmonary fibrosis with remarkable honeycomb cyst expansion.

Herein, we report an autopsy case of idiopathic pulmonary fibrosis (IPF) in which remarkable honeycomb cyst expansion appeared in the clinical course. Radiological findings initially showed subpleural predominant reticulation that had progressed to usual interstitial pneumonia with honeycomb cysts, along with a restrictive pattern in the pulmonary function tests. The diameter of honeycomb cysts had gradually increased, and some cysts had abruptly expanded at the end stage. Based on pathological findings of autopsy specimens, bronchiectasis, alveolar collapse due to inflammation, and check-valve mechanism caused by a slit-like orifice of the cysts could have contributed to honeycomb cyst expansion.

The Accuracy of Japanese Administrative Data in Identifying Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

BACKGROUND: This study aimed to develop criteria for identifying patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) from Japanese administrative data and validate the pre-existing criteria. METHODS: This retrospective, multi-center validation study was conducted at eight institutes in Japan to verify the diagnostic accuracy of the disease name for AE-IPF. We used the Japanese Diagnosis Procedure Combination data to identify patients with a disease name that could meet the diagnostic criteria for AE-IPF, who were admitted to the eight institutes from January 2016 to February 2019. As a reference standard, two respiratory physicians performed a chart review to determine whether the patients had a disease that met the diagnostic criteria for AE-IPF. Furthermore, two radiologists interpreted the chest computed tomography findings of cases considered AE-IPF and confirmed the diagnosis. We calculated the positive predictive value (PPV) for each disease name and its combination. RESULTS: We included 830 patients; among them, 216 were diagnosed with AE-IPF through the chart review. We combined the groups of disease names and yielded two criteria: the criteria with a high PPV (0.72 [95% confidence interval 0.62 to 0.81]) and that with a slightly less PPV (0.61 [0.53 to 0.68]) but more true positives. Pre-existing criteria showed a PPV of 0.40 (0.31 to 0.49). CONCLUSION: The criteria derived in this study for identifying AE-IPF from Japanese administrative data show a fair PPV. Although these criteria should be carefully interpreted according to the target population, our findings could be utilized in future database studies on AE-IPF.

Drug-induced hypersensitivity syndrome caused by minodronic acid hydrate.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings. CASE PRESENTATION: An 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test. CONCLUSIONS: We described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

Predictive model for the development of critical coronavirus disease 2019 and its risk factors among patients in Japan.

BACKGROUND: This study aimed to examine risk factors associated with critical coronavirus disease 19 (COVID-19) and to establish a risk predictive model for Japanese patients. METHODS: We retrospectively assessed adult Japanese patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center, Tokyo, Japan between February 1, 2020 and March 10, 2021. The patients were divided into critical and non-critical groups based on their condition during the clinical courses. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between clinical characteristics and critical illness. Based on the results, we established a predictive model for the development of critical COVID-19. RESULTS: In total, 300 patients were enrolled in this study. Among them, 86 were included in the critical group. Analyses revealed that age ≥65 y, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL were independently associated with the development of critical COVID-19. Next, a predictive model for the development of critical COVID-19 was created, and this included the following variables: age ≥65 y, male sex, diabetes, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL. The area under the receiver operating characteristic curve of the model was 0.86 (95% confidence interval, 0.81-0.90). Using a cutoff score of 12, the positive and negative predictive values of 74.0% and 80.4% were obtained, respectively. CONCLUSIONS: Upon diagnosis, the predictive model can be used to identify adult Japanese patients with COVID-19 who will require intensive treatment.

Clinical impact of combination therapy with baricitinib, remdesivir, and dexamethasone in patients with severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib-a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown. METHODS: Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated. RESULTS: In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3% (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90%, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34%). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11%, 11%, 2%, 2%, 2%, 2%, and 2% of patients, respectively. CONCLUSIONS: Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.