Predictors of in-hospital mortality in elderly unvaccinated patients during SARS-CoV-2 Alpha variants epidemic.

Background: COVID-19, caused by SARS-CoV-2, has caused a global pandemic. This study aimed to identify predictors of in-hospital mortality in unvaccinated elderly patients with COVID-19 by comparing various predictive factors between the survivors and non-survivors. Methods: We retrospectively selected 132 unvaccinated patients aged over 65 years with COVID-19 at a hospital in Kanagawa, Japan, during SARS-CoV-2 Alpha variants epidemic. We compared the clinical characteristics, laboratory and radiological findings, treatment, and complications of the survivors and non-survivors. In logistic regression analysis, variables that were significant in the univariate analysis were subjected to multivariate analysis using the variable increase method. Results: There were 119 and 13 patients in the survivor and non-survivor groups, respectively. Multivariate regression revealed increasing odds with the presence of ARDS and DIC (odd ratio (OR) = 16.35, 34.36; P=0.002, 0.001, respectively) and prolonged hospital stay (OR = 1.17; P=0.004). Conclusions: We found the complications of ARDS and DIC and hospital length of stay to be independent predictors of in-hospital mortality in elderly unvaccinated patients with COVID-19. Establishing treatments and prevention methods for ARDS and DIC could result in lower mortality rates.

Usefulness of High-resolution Computed Tomography for Macrolide Therapy of Idiopathic Bronchiectasis.

Background: High-resolution computed tomography (HRCT) correlates with clinical symptoms, respiratory function, and quality of life in bronchiectasis. Objective: We aimed to investigate the relationship between macrolide and acute exacerbation (AE) in idiopathic bronchiectasis classified by the Bronchiectasis Radiologically Indexed CT Score (BRICS). Methods: We retrospectively reviewed the medical records of patients diagnosed with idiopathic bronchiectasis between April 2014 and December 2020 at a single hospital. Overall, 115 patients with idiopathic bronchiectasis were selected and divided into three groups, according to the BRICS. Each group was divided into subgroups with and without macrolide therapy, and the number of patients with AE in each group was retrospectively compared. Results: About 45, 48, and 22 patients were included in the mild, moderate, and severe groups, respectively. In the mild group, the subgroup with macrolide therapy had significantly fewer patients with single AE than those without macrolide ( P = 0.029). There was no significant difference in the moderate and severe groups ( P = 1.00 and 0.64, respectively). In the multiple AE, the subgroup with macrolide therapy had significantly fewer patients than those without macrolide therapy in the mild, moderate, and severe groups ( P = 0.024, 0.029, and 0.026, respectively). Conclusion: HRCT severity assessment might be useful in predicting treatment efficacy in patients with idiopathic bronchiectasis without previous AEs. Further large-scale clinical trials are required on the usefulness of HRCT in the future.

Impact of inhaled ciclesonide on asymptomatic or mild COVID-19: A randomized trial.

The aim of this study was to determine the efficacy and safety of ciclesonide in the treatment of novel coronavirus disease 2019 (COVID-19) as gauged by pneumonia progression. This multi-center, open-label randomized trial was conducted with patients recruited from 22 hospitals across Japan. Participants were patients admitted with mild or asymptomatic COVID-19 without signs of pneumonia on chest X-rays. Asymptomatic participants were diagnosed after identification through contact tracing. Trial participants were randomized to either the ciclesonide or control arm. Participants in the treatment arm were administered 400 µg of ciclesonide three times a day over seven consecutive days. The primary endpoint was exacerbated pneumonia within seven days. Secondary outcomes were changes in clinical findings, laboratory findings, and changes over time in the amount of the viral genome. In the treatment group, 16 patients (39.0%) were classified as having exacerbated pneumonia compared to 9 (18.8%) in the control group. The risk ratio (RR) was 2.08 (95% confidence interval (CI): 1.15-3.75), indicating a worsening of pneumonia in the ciclesonide group. Significant differences were noted in participants with a fever on admission (RR: 2.62, 90% CI: 1.17-5.85, 95% CI: 1.00-6.82) and individuals 60 years of age or older (RR: 8.80, 90% CI: 1.76-44.06, 95% CI: 1.29-59.99). The current results indicated that ciclesonide exacerbates signs of pneumonia on images in individuals with mild or asymptomatic symptoms of COVID-19 without worsening clinical symptoms.

A Convenient Risk Prediction Score for COVID-19 for Determining Whether or Not Hospitalization Is Recommended: Kanagawa Admission Priority Assessment Score.

Objective Coronavirus disease 2019 (COVID-19) has caused a collapse of the medical care system, with effective triage proving vital. The Kanagawa admission priority assessment score, version-1 (KAPAS-1) and version-2 (KAPAS-2), was developed to determine the need for hospitalization. Patients with a high KAPAS (≥5) are recommended for hospitalization. We retrospectively investigated the correlation between the KAPAS and oxygen requirement during hospitalization. Methods We collected the clinical data of COVID-19 patients admitted between February 5 and December 6, 2020. Patients were divided into two groups: those who required oxygen therapy during hospitalization (OXY) and those who did not (NOXY). We assessed the correlations between the groups and KAPAS-1 and KAPAS-2. Results Overall, 117 COVID-19 patients were analyzed, including 20 OXY and 97 NOXY and 54 high KAPAS-1 and 63 high KAPAS-2. The median KAPAS-1 and KAPAS-2 were significantly higher in OXY than in NOXY (6.5 vs. 3, and 9 vs. 4, respectively). The areas under the receiver operating characteristic curves of KAPAS-1 and KAPAS-2 for oxygen requirement were 0.777 and 0.825, respectively, and the maximum values of Youden's index were 4 and 6, respectively. The proportions of high KAPAS-1 and high KAPAS-2 were significantly higher in OXY than in NOXY (90.0% vs. 37.1%, and 90.0% vs. 46.4%, respectively). Conclusion The KAPAS was significantly correlated with oxygen requirement. Furthermore, the KAPAS may be useful for deciding which patients are most likely to require hospitalization and for selecting non-hospitalized patients who should be carefully monitored.

Localized pleural metastasis without other organ metastases after nephrectomy for renal cell carcinoma.

We present a case of a 69-year-old man who had localized pleural metastasis without other organ metastases after nephrectomy for right renal cell carcinoma (RCC). He complained of respiratory symptoms for more than two years after the operation and was confirmed to have right pleural effusion and multiple pleural masses on computed tomography (CT). There were no abnormal findings in the other organs, but the pleural mass gradually increased in size on CT. We suspected malignant tumors such as malignant pleural mesothelioma and synovial sarcoma in addition to RCC metastasis. Finally, we performed surgical resection of the pleural mass under general anesthesia, and we diagnosed pathologically as metastasis from RCC. Distant metastases of RCC are common in the lungs, bones, brain, and liver. To our knowledge, localized pleural metastases from RCC is rare.

Successful treatment with methyl-prednisolone pulses for the late phase of COVID-19 with respiratory failure: A single-center case series.

Although some prospective studies provided the evidence of corticosteroids for critically ill patients with COVID-19, the optimal dosage or timing of corticosteroids is still unknown. This is a case series of four patients on methyl-prednisolone pulses for the late phase of Coronavirus disease 2019 (COVID-19) with respiratory failure in our hospital. All patients needed invasive mechanical ventilation and had bimodal worseness of their respiratory status with consolidation and volume loss after intubation. All cases could successfully discontinue oxygen therapy without any severe adverse events after this pulse therapy in the late phase of COVID-19. This therapy is believed to be effective on some optimal patients. Hence, further studies to explore this efficacy and safety were needed.

Benefits and Risks of Inhaled Corticosteroid Treatment in Patients with Chronic Obstructive Pulmonary Disease Classified by Blood Eosinophil Counts.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) typically includes neutrophilic airway inflammation and eosinophilic inflammation in some cases. Inhaled corticosteroid (ICS) suppresses eosinophilic inflammation of the airway and reduces acute exacerbation (AE). The present study investigated the relationship between ICS and AE in patients with COPD classified by blood eosinophil counts. METHODS: Overall, 244 patients with COPD were retrospectively evaluated between 2014 and 2017 and classified into two groups based on blood eosinophil counts (≥ 300/µL and < 300/µL). These patients were then reclassified into subgroups of those with and without ICS. Differences in the characteristics and incidence of AE and pneumonia with AE in each subgroup were evaluated retrospectively. RESULTS: All patients with ICS used 320 µg budesonide twice daily. In the group with blood eosinophil counts ≥ 300/µL, patients with ICS had a significantly lower incidence of AE than those without ICS (P = 0.023). Meanwhile, no significant differences were observed in incidence of AE in the group with blood eosinophil counts < 300/µL. In the group with blood eosinophil counts < 300/µL, patients with ICS had a higher incidence of pneumonia with AE (P = 0.009). Conversely, no significant differences were observed in the group with blood eosinophil counts ≥ 300/µL. CONCLUSIONS: ICS significantly reduced AE in COPD patients with blood eosinophil counts ≥ 300/µL. Meanwhile, ICS significantly increased pneumonia rate in patients with blood eosinophil count < 300/µL. Blood eosinophil count may be a useful indicator to identify the benefits and risks of ICS in COPD.

Characteristics of pleural effusion in IgG4-related pleuritis.

Here we describe the case of a 78-year-old man with respiratory failure and right pleural effusion. Computed tomography showed right pleural effusion with pleural calcification, tumor-like shadows induced by passive atelectasis, and enlarged mediastinal lymph nodes. Positron emission tomography showed right pleural thickening, rounded atelectasis, and enlarged mediastinal lymph nodes, without fluid accumulation in other organs. The pleural effusion showed lymphocyte-dominated exudates with elevated adenosine deaminase (ADA) levels. Tuberculous pleuritis was suspected, but thoracoscopic pleural biopsy revealed lymphoplasmacytic infiltration and fibrosis, with 10 immunoglobulin G4 (IgG4)-positive plasma cells/high-power field, and IgG4/IgG ratio of 40%. IgG4 concentrations in serum and right pleural effusion were 929 and 1120 mg/dL, respectively. The patient was diagnosed with IgG4-related pleuritis without other systemic manifestations, and reduction in right pleural effusion was confirmed by corticosteroid therapy. IgG4-related disease is typically a systemic disease causing lymphoplasmacytic inflammation in multiple organs. We describe a rare form of IgG4-related pleuritis showing pleural effusion with no other systemic manifestation.

Impact of renal function-based anti-tuberculosis drug dosage adjustment on efficacy and safety outcomes in pulmonary tuberculosis complicated with chronic kidney disease.

BACKGROUND: Dosages of anti-tuberculosis (TB) drugs are recommended to be adjusted according to renal function for patients complicated with chronic kidney disease (CKD). However, the efficacy and safety outcomes of such renal function-based dosage adjustments are not fully elucidated. METHODS: We retrospectively reviewed cases of pulmonary TB susceptible to first-line drugs that were treated at Jikei University Daisan Hospital between 2005 and 2014 with standard regimens based on dosage adjustments according to renal function recommended by international guidelines. Patients were divided into four groups, those with no, mild, moderate or severe CKD. In-hospital TB-related mortality, the rate of sputum culture conversion at 2 months, the frequency of adverse events (AEs), for which at least the temporal discontinuation of the suspect drug was required for patient improvement, and the rate of regimen change due to AEs were assessed. RESULTS: In the 241 enrolled patients (mean age, 64.1 years; 143 men), fourteen patients (5.8%) died due to TB during their hospitalization. The rate of sputum culture conversion at 2 months was 78.0%. The frequency of in-hospital TB-related death and the conversion rate in the groups did not vary significantly according to CKD severity including those in the non-CKD group (P = 0.310 and P = 0.864). Meanwhile, a total of 70 AEs were observed in 60 patients (24.9%) and the difference between the groups in the overall frequency of AEs was almost significant (P = 0.051). Moreover, for the 154 patients with CKD, severe CKD stage was a significant risk factor for regimen change (OR = 5.92, 95% CI = 1.08-32.5, P = 0.041), as were drug-induced hepatitis and cutaneous reaction (OR = 35.6, 95% CI = 8.70-145, P < 0.001; OR = 17.4, 95% CI = 3.16-95.5, P = 0.001; respectively). CONCLUSIONS: Adjusting the dosage of TB treatment for CKD patients according to the guidelines was efficient in terms of similar therapeutic outcome to that of the non-CKD group. However, AEs warrant attention to avoid regimen change in patients with severe CKD, even if the renal function-based dosage adjustment is performed.

Predictive factors for relapse of cryptogenic organizing pneumonia.

BACKGROUND: Relapse of cryptogenic organizing pneumonia (COP) may lead to poor long-term prognosis and necessitates multiple rounds of steroid treatment with potential adverse effects. The objective of this study is to identify predictive factors of COP relapse by comparing demographic and clinical variables between relapse and non-relapse groups. METHODS: During 2008-2013, 33 COP patients were treated, of which 23 (69.7%) and 10 patients (30.3%) were assigned to the non-relapse and relapse group, respectively. From medical records, we compared the following variables at initial episode: clinical characteristics, serum parameters, chest CT scan findings, and steroid treatment. RESULTS: Clinical characteristics, cumulative prednisone dose, and steroid treatment duration were similar between groups. In univariate analysis, alternatively, the proportion of patients with bilateral shadow pattern, traction bronchiectasis, and partial remission after steroid treatment was significantly higher in the relapse group. These differences were not significant by multivariate Cox regression analysis. CONCLUSIONS: We identified radiographic findings, such as bilateral shadow pattern, traction bronchiectasis, and partial remission, may have possibility of predictive factors for COP relapse. Larger-scale studies are required to confirm if any are independent predictors of COP relapse.

Neutropenia related to an azathioprine metabolic disorder induced by an inosine triphosphate pyrophosphohydrolase (ITPA) gene mutation in a patient with PR3-ANCA-positive microscopic polyangiitis
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A 68-year-old Japanese man was monitored for chronic kidney disease (CKD), with unknown primary disease starting in 2014. His serum creatinine (sCr) was stable at ~ 2.5 mg/dL for ~ 2 years. Two weeks before admission, he had bloody sputum, and sCr increased to 4.63 mg/dL. Soon after admission, the patient developed a high fever with pigment spots on the legs. A kidney biopsy was performed. The kidney specimens showed necrotizing and crescentic glomerulonephritis without granuloma formation. An additional blood-sampling test revealed high titers of PR3-ANCA, and we diagnosed PR3-ANCA-positive microscopic polyangiitis (MPA). Treatment with intravenous steroid pulse therapy and intermittent pulse intravenous cyclophosphamide therapy was started for remission induction. With these treatments, sCr improved to ~ 3.0 mg/dL. Azathioprine (AZA) was added for remission-maintenance therapy. Three days later, the dose of AZA was increased from 50 to 100 mg/day, and the number of neutrophils decreased to 30/µL. After withdrawal of AZA, neutrophil levels gradually recovered. We suspected that an abnormal metabolism of AZA was responsible for the neutropenia. Therefore, we analyzed three AZA metabolism-associated genes for mutations: thiopurine S-methyltransferase (TPMT), inosine triphosphate pyrophosphohydrolase (ITPA), and nucleoside diphosphate linked moiety X-type motif 15 (NUDT15), and we identified ITPA 94C>A mutation. This was a rare case of PR3-positive MPA with AZA-induced severe neutropenia that was possibly due to an ITPA gene mutation. This case suggests that ITPA gene mutation is related to the adverse reactions of AZA in Japanese patients. We have to pay attention to severe neutropenia when we use AZA, especially in Asian patients with CKD.
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Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis.

BACKGROUND: The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity) during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. METHODS: During 2006-2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of more than twice the upper limit of normal (ULN). We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN), moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN), and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN). We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin). RESULTS: In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97). In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046). CONCLUSION: Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

Medical thoracoscopy performed under local anesthesia is useful for diagnosing pleural metastasis of renal cell carcinoma.

A patient with a past history of renal cell carcinoma (RCC) presented to us with an exudative pleural effusion. Because pleural effusion cytology was inconclusive, we performed medical thoracoscopy under local anesthesia. Multiple white tumors measuring approximately 2 cm in diameter were observed on the parietal pleura. Metastatic carcinoma from RCC was diagnosed histologically. Although malignant effusions are rare in cases of RCC metastasis, clinicians should be aware of this possibility. When pleural effusion cytology is inconclusive in a patient with a past history of RCC, medical thoracoscopy can be useful for making the diagnosis of pleural metastasis.