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.

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.

Efficacy of benralizumab for patients with severe eosinophilic asthma: a retrospective, real-life study.

BACKGROUND: Benralizumab, an anti-interleukin-5 (IL-5) receptor α monoclonal antibody, significantly reduces the number of annual exacerbations and oral corticosteroid (OCS) maintenance doses for patients with severe eosinophilic asthma (SEA). However, few studies on the efficacy of this biologic in real life are available. The aim was to elucidate the efficacy of benralizumab by evaluating changes in clinical parameters after benralizumab treatment in patients with SEA. METHODS: From July 2018 to December 2019, 24 Japanese patients with SEA received benralizumab at Jikei University Hospital. We retrospectively evaluated the patients' characteristics, parameters, numbers of exacerbations and maintenance OCS doses. RESULTS: Among the 24 patients, eleven patients had received mepolizumab treatment and were directly switched to benralizumab. The peripheral blood eosinophil and basophil counts significantly decreased after benralizumab treatment regardless of previous mepolizumab treatment. Pulmonary function, Asthma Control Test scores, the numbers of annual exacerbations and maintenance OCS doses in patients without previous mepolizumab treatment tended to improve without significant differences. Fourteen patients (58%) were responders according to the Global Evaluation of Treatment Effectiveness (GETE) score. The proportion of GETE responders among patients with aspirin-exacerbated respiratory disease (AERD) tended to be lower than that among patients without AERD (p = 0.085). After benralizumab treatment, the change in the forced expiratory volume in 1 s from baseline was 200 ml or greater in eight patients (33%), including three patients who were switched from mepolizumab. CONCLUSION: Benralizumab treatment improved and controlled asthma symptoms based on the GETE score.

Hydrophobicity of Residue 128 of the Stress-Inducible Sigma Factor RpoS Is Critical for Its Activity.

RpoS is a key stress-inducible sigma factor that regulates stress resistance genes in Escherichia coli, such as the katE gene encoding catalase HPII and the glg genes encoding glycogen synthesis proteins. Monitoring RpoS activity can provide information on the stress sensitivity of E. coli isolates in clinical settings because the RpoS in these isolates is often mutated. In the present study, we found a novel, missense point mutation at RpoS residue 128 in a clinical Shiga toxin-producing E. coli (STEC) isolate. This mutation caused RpoS dysfunction and increased stress sensitivity. A mutant rpoS was cloned from a clinical STEC that is vulnerable to cold temperature and oxidative stresses. Mutant RpoS protein expression was detected in the clinical isolate, and this RpoS was non-functional according to HPII activity and glycogen levels, which are positively regulated by RpoS and thus are used as indicators for RpoS function. A reporter assay with ß-galactosidase indicated that the dysfunction occurred at the transcriptional level of genes regulated by RpoS. Furthermore, substitution analysis indicated that the hydrophobicity of the amino acid at residue 128 was critical for RpoS activity; the simulation analysis indicated that the amino acids of RNA polymerase (RNAP) that interact with RpoS residue 128 are hydrophobic, suggesting that this hydrophobic interaction is critical for RpoS activity. In addition, substitution of Ile128 to Pro128 abolished RpoS activity, possibly as a result of disruption of the secondsary structure around residue 128, indicating that the structure is also a crucial factor for RpoS activity. These results indicate that only one point mutation at a hydrophobic residue of the complex formed during transcription leads to a critical change in RpoS regulation. Moreover, we found that Ile128 is widely conserved among various bacteria: several bacterial strains have Met128 or Leu128, which are hydrophobic residues, and these strains had similar or higher RpoS activity than that observed with Ile128 in this study. These data indicate that the hydrophobicity of the amino acid at residue 128 is critical for RpoS activity and is consequently important for bacterial survival. Taken together, these findings may contribute to a deeper understanding of protein functional mechanisms and bacterial stress responses.