An Increase in Aspartate Aminotransferase Can Predict Worsening Disease Severity in Japanese Patients with COVID-19.

BACKGROUND: The prognostic significance of liver dysfunction in COVID-19 patients remains unclear. In this study, we investigated the association between liver function test results and severe disease progression in COVID-19 patients. METHODS: This retrospective study included consecutive Japanese COVID-19 patients admitted between February 2020 and July 2021. Predictive variables for severe disease progression were identified by multivariate logistic regression analysis. Severe disease-free survival was estimated with the Kaplan-Meier method and Cox regression analysis. Aspartate aminotransferase (AST) was divided into three grades: grade 1, AST < 30 U/L; grade 2, 30 U/L ≤ AST < 60 U/L; and grade 3, AST > 60 U/L. RESULTS: Among 604 symptomatic patients, 141 (23.3%) developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were the significant predictive variables. Severe disease-free survival time was significantly different between the different AST grades (hazard ratio (HR): grade 2 vs. grade 1, 4.07 (95% confidential interval (CI): 2.06-8.03); grade 3 vs. grade 1, 7.66 (95% CI: 3.89-15.1)). CONCLUSIONS: The AST level at admission was an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.

Glucose control in the early phase of hospitalization is associated with severe prognosis in coronavirus disease 2019 (COVID-19) patients with diabetes in Japan.

We investigated the association of glycemic control in the early phase of hospitalization with the prognosis of COVID-19 in patients with diabetes. We analyzed the relationship between various clinical indices, including preprandial blood glucose levels measured by self-monitoring devices in the early phase after admission, and severe prognosis in 189 patients with complicated diabetes who were admitted to our hospital between February 22, 2020 and June 20, 2021. Enrolled patients had a median age of 72 years, median body mass index of 24.7, median HbA1c of 7.1%, and median mean preprandial capillary glucose (PPCG) of 179.1 mg/dL. Sixty-six patients progressed to severe disease, and the mean PPCG in severe cases was significantly higher than that in non-severe cases, 195.2 vs 167.8 mg/dL (p = 0.005). Analysis of the receiver operating characteristic curve showed that 179 mg/dL was the cut-off value, and the risk of severity was significantly higher in patients with a mean PPCG of 180 mg/dL or higher (odds ratio (OR) 3.210, p = 0.017) in multiple regression analysis. In this study, we found that the risk of severe COVID-19 increased in patients with a high mean PPCG in the early phase of hospitalization, suggesting that good glucose control in the early phase of COVID-19 with diabetes may be effective in preventing disease severity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00656-8.

A randomized phase 2 study on demeclocycline in patients with mild-to-moderate COVID-19.

Tetracyclines exhibit anti-viral, anti-inflammatory, and immunomodulatory activities via various mechanisms. The present study investigated the efficacy and safety of demeclocycline in patients hospitalized with mild-to-moderate COVID-19 via an open-label, multicenter, parallel-group, randomized controlled phase 2 trial. Primary and secondary outcomes included changes from baseline (day 1, before the study treatment) in lymphocytes, cytokines, and SARS-CoV-2 RNA on day 8. Seven, seven, and six patients in the control, demeclocycline 150 mg daily, and demeclocycline 300 mg daily groups, respectively, were included in the modified intention-to-treat population that was followed until day 29. A significant change of 191.3/µL in the number of CD4+ T cells from day 1 to day 8 was observed in the demeclocycline 150 mg group (95% CI 5.1/µL-377.6/µL) (p = 0.023), whereas that in the control group was 47.8/µL (95% CI - 151.2/µL to 246.8/µL), which was not significant (p = 0.271). The change rates of CD4+ T cells negatively correlated with those of IL-6 in the demeclocycline-treated groups (R = - 0.807, p = 0.009). All treatment-emergent adverse events were of mild-to-moderate severity. The present results indicate that the treatment of mild-to-moderate COVID-19 patients with demeclocycline elicits immune responses conducive to recovery from COVID-19 with good tolerability.Trial registration: This study was registered with the Japan Registry of Clinical Trials (Trial registration number: jRCTs051200049; Date of the first registration: 26/08/2020).

Gastrointestinal symptoms in 609 Japanese patients with COVID-19: a single-center retrospective study.

BACKGROUND: GI symptoms are common in acute COVID-19 patients. This study aimed to characterize the GI symptoms occurring in Japanese COVID-19 patients. METHODS: This retrospective single-center cohort study included 751 hospitalized acute COVID-19 patients. The primary outcomes were the frequency and severity of GI symptoms. The secondary outcomes included the association between COVID-19 severity and GI symptoms and the timing of GI symptom onset. RESULTS: After exclusion, the data of 609 patients were analyzed. The median age was 62 years, and 55% were male. The median time from initial symptom onset to admission was five days. On admission, 92% of the patients had fever, 35.1% had fatigue, 75% had respiratory symptoms, and 75% had pneumonia. The sample included patients with mild (19%), moderate (59%), and severe COVID-19 (22%). A total of 218 patients (36%) had GI symptoms, of which 93% were classified as grade 1/2; 170 patients had both respiratory and GI symptoms. Diarrhea was the most frequent GI symptom, occurring in 170 patients, followed by anorexia in 73 patients and nausea/vomiting in 36 patients, and abdominal pain in 8 patients. There was no significant relationship between COVID-19 severity and GI symptoms. Among COVID-19 patients with both GI and respiratory symptoms, 48% had respiratory symptoms preceding GI symptoms, 25% had GI symptoms preceding respiratory symptoms and 27% had a simultaneous onset of respiratory and GI symptoms. CONCLUSION: Thirty-six percent of the Japanese COVID-19 patients had GI symptoms; diarrhea was the most frequent GI symptom but did not predict severe COVID-19.

Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification: clinical features with a progressive phenotype.

BACKGROUND: Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO. METHODS: We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO. RESULTS: Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. CONCLUSIONS: IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

Seroprevalence of SARS-CoV-2 antibodies among 925 staff members in an urban hospital accepting COVID-19 patients in Osaka prefecture, Japan: A cross-sectional study.

ABSTRACT: The subclinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rate in hospitals during the pandemic remains unclear. To evaluate the effectiveness of our hospital's current nosocomial infection control measures, we conducted a serological survey of anti-SARS-CoV-2 antibodies (immunoglobulin [Ig] G) among the staff of our hospital, which is treating coronavirus disease 2019 (COVID-19) patients.The study design was cross-sectional. We measured anti-SARS-CoV-2 IgG in the participants using a laboratory-based quantitative test (Abbott immunoassay), which has a sensitivity and specificity of 100% and 99.6%, respectively. To investigate the factors associated with seropositivity, we also obtained some information from the participants with an anonymous questionnaire. We invited 1133 staff members in our hospital, and 925 (82%) participated. The mean age of the participants was 40.0 ±â€Š11.8 years, and most were women (80.0%). According to job title, there were 149 medical doctors or dentists (16.0%), 489 nurses (52.9%), 140 medical technologists (14.2%), 49 healthcare providers (5.3%), and 98 administrative staff (10.5%). The overall prevalence of seropositivity for anti-SARS-CoV-2 IgG was 0.43% (4/925), which was similar to the control seroprevalence of 0.54% (16/2970) in the general population in Osaka during the same period according to a government survey conducted with the same assay. Seropositive rates did not significantly differ according to job title, exposure to suspected or confirmed COVID-19 patients, or any other investigated factors.The subclinical SARS-CoV-2 infection rate in our hospital was not higher than that in the general population under our nosocomial infection control measures.

Obesity, glucose intolerance, advanced age, and lymphocytopenia are independent risk factors for oxygen requirement in Japanese patients with Coronavirus disease 2019 (COVID-19).

At the current time of rising demand for hospital beds, it is important to triage COVID-19 patients according to the treatment needed during hospitalization. The need for oxygen therapy is an important factor determining hospital admission of these patients. Our retrospective study was designed to identify risk factors associated with the progression to oxygen requirement in COVID-19 patients. A total of 133 patients with laboratory-confirmed COVID-19 were admitted to our hospital from February 22, 2020, to August 23. After excluding asymptomatic, non-Japanese, pediatric, pregnant patients and also those who needed oxygen immediately at admission, data of the remaining 84 patients were analyzed. The patients were separated into those who required oxygen after admission and those who did not, and their characteristics were compared. Age, body mass index (BMI), lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase, estimated glomerular filtration rate, glucose intolerance, hypertension, and dyslipidemia were significantly different between the two groups. Multivariate analysis identified four significant and independent risk factors of oxygen requirement, including advanced age, obesity, glucose intolerance and lymphocytopenia. Dividing the patients into subgroups according to the number of these risk factors found in each patient indicated that the need for oxygen increased with higher number of these risk factors in the same individual. Our results suggest that the presence of higher number of these risk factors in COVID-19 patients is associated with future oxygen requirement and that this index can be potentially useful in triaging COVID-19 patients staying home in the context of need for hospitalization.

Early clinical factors predicting the development of critical disease in Japanese patients with COVID-19: A single-center, retrospective, observational study.

The factors predicting the progression of coronavirus disease-2019 (COVID-19) from mild to moderate to critical are unclear. We retrospectively evaluated risk factors for disease progression in Japanese patients with COVID-19. Seventy-four patients with laboratory-confirmed COVID-19 were hospitalized in our hospital between February 20, 2020, and June 10, 2020. We excluded asymptomatic, non-Japanese, and pediatric patients. We divided patients into the stable group and the progression group (PG; requiring mechanical ventilation). We compared the clinical factors. We established the cutoff values (COVs) for significantly different factors via receiver operating characteristic curve analysis and identified risk factors by univariate regression. We enrolled 57 patients with COVID-19 (median age 52 years, 56.1% male). The median time from symptom onset to admission was 8 days. Seven patients developed critical disease (PG: 12.2%), two (3.5%) of whom died; 50 had stable disease. Univariate logistic analysis identified an elevated lactate dehydrogenase (LDH) level (COV: 309 U/l), a decreased estimated glomerular filtration rate (eGFR; COV: 68 ml/min), lymphocytopenia (COV: 980/µl), and statin use as significantly associated with disease progression. However, in the Cox proportional hazards analysis, lymphocytopenia at admission was not significant. We identified three candidate risk factors for progression to critical COVID-19 in adult Japanese patients: statin use, elevated LDH level, and decreased eGFR.

Anti-proteinase 3-positive Eosinophilic Granulomatosis with Polyangiitis Revealed by Cardiac Tamponade.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by asthma, eosinophilia, and diffuse eosinophilic infiltration. Although cardiovascular involvement is common and a leading cause of EGPA-related mortality, severe pericarditis-led cardiac tamponade occurs rarely. We herein report a 72-year-old man with anti-proteinase 3 (anti-PR3) anti-neutrophil cytoplasmic antibody (ANCA)-positive EGPA diagnosed by the presence of cardiac tamponade, which responded quickly to pericardiocentesis and a single administration of prednisolone. This is the first case of anti-PR3 ANCA-positive EGPA with cardiac tamponade; the patient displayed clinical features of both ANCA-positive and ANCA-negative cases.

Tubular nephrotoxicity induced by docetaxel in non-small-cell lung cancer patients.

Renal dysfunction is a characteristic of many patients with cancer; however, a standard therapy has not been established for stage III or IV non-small-cell lung cancer (NSCLC) complicated with chronic renal failure. Docetaxel has a proven significant activity against NSCLC. This agent is predominantly eliminated by hepatobiliary extraction and is safe in patients with renal failure, including dialysis patients. Docetaxel is, thus, a therapeutic option in that patient population. Here, we report acute tubular nephrotoxicity secondary to docetaxel in NSCLC patients, even in patients with normal renal function. Little is known about tubular nephrotoxicity induced by docetaxel; however, oncologists should be aware of its possibility.

[A case of locally advanced non-small-cell lung cancer complicated with chronic renal failure and gastric cancer, successfully treated with weekly docetaxel and concurrent thoracic radiotherapy].

A standard therapy is not established for locally advanced non-small-cell lung cancer(NSCLC)complicated with chronic renal failure, although some cases of the disease have been reported. We report a case of a locally advanced squamous cell carcinoma of the lung, complicated with chronic renal failure. He was successfully treated with weekly docetaxel(DOC)and concurrent thoracic radiotherapy, and no deterioration of renal function was observed. In locally advanced NSCLC complicated with renal dysfunction, treatment with weekly DOC and concurrent thoracic radiotherapy is considered to be a therapeutic option. Since radiation pneumonitis occurred in the present case, the accumulation and precise analysis of applicable cases is an important subject for future consideration.

[A radical resection of non-small cell lung cancer invading chest wall with ipsilateral axillary lymph node metastases].

A 41-year-old man who had non-small cell lung cancer invading his right 3rd, 4th and 5th ribs with hilum lymph node swelling(cT3N1M0, cStage III A), received chemoradiation therapy, cisplatin(CDDP)/docetaxel, and 2 Gy/Fr of irradiation prior to surgery. But the therapy was discontinued due to interstitial pneumonitis on day 24, during 28 Gy of radiation. At that time, a PET-CT scan revealed the accumulation of FDG in the primary tumor, hilar lymph node, and one of the ipsilateral axillar lymph nodes, in which cancer cell presence was proven by aspiration needle cytology. We organized a radical operation even though the node status was classified to cStage IV, because ipsilateral axillary lymph nodes may be regarded as regional nodes for tumors invading the chest wall. Right upper lobectomy and chest wall resection were performed, and the ipsilateral hilar, mediastinal, and axillary lymphnode were dissected. Pathological findings showed no active cancer cell in the primary lesion and hilar lymph nodes(Ef. 3), but obvious metastasis in one of the axillary lymph nodes(pT0N0M1b, pStage IV). The patient received adjuvant chemotherapy(CDDP/vinorelbine), and is alive and tumor-free 10months after the resection.

Increased level of soluble E-selectin in the serum from patients with idiopathic pulmonary fibrosis.

To elucidate the biological significance of selectin for idiopathic pulmonary fibrosis, we titrated the serum soluble E-selectin. From 31 cases of idiopathic pulmonary fibrosis patients without signs or symptoms of infection, the serum was obtained and the concentration was titrated by enzyme-linked immunosorbent assay. The serum soluble E-selectin titer was significantly higher than that of healthy controls. However, significant elevation was not observed in the sera from the patients with other pulmonary diseases, such as pulmonary emphysema, sarcoidosis, or bronchiectasis. In the patients with idiopathic pulmonary fibrosis, the number of white blood cells, C-reactive protein or lactate dehydrogenase activity did not show a significant relationship with the soluble E-selectin titer. About 16 out of the 31 idiopathic fibrosis patients, the serum surfactant apoprotein-A titer, which is a parameter of the disease activity of idiopathic pulmonary fibrosis, was also tested. The surfactant apoprotein-A titer was loosely correlated with the soluble E-selectin titer. These observations suggest that E-selectin may be relevant to the pathogenesis of idiopathic pulmonary fibrosis, and it may be a novel clinical parameter for idiopathic pulmonary fibrosis.