Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

Specific IgE Response and Omalizumab Responsiveness in Severe Allergic Asthma.

Objective: Omalizumab has demonstrated clinical efficacy in patients with severe allergic asthma sensitized to perennial allergens and/or severe pollinosis through inhibition of IgE-dependent allergic response. When considering the "one airway, one disease" concept, sensitization to pollen could predict responsiveness to omalizumab. This study aimed to assess whether the pretreatment specific IgE response could be a predictor of responsiveness to omalizumab in severe allergic asthma sensitized to perennial allergens. Methods: In this retrospective study, 41 adult patients with severe allergic asthma sensitized to perennial allergens (27 females; mean age 59 years) who had completed 52-week omalizumab treatment were enrolled. The Global Evaluation of Treatment Effectiveness was performed, and demographic characteristics and the positive ratios of specific IgE responses classified into five subgroups (pollen, dust mite, house dust, mold, and animal dander) were compared between responders and non-responders. Multivariate logistic regression analyses were performed to identify predictors of responsiveness to omalizumab. Results: Thirty-one patients (76%) were identified as responders. The number of sensitized aeroallergen subgroups and sensitization to pollens were significantly higher in responders than in non-responders (both p<0.05). Multivariate logistic regression analysis showed that sensitization to pollen (OR = 8.41, p = 0.02) was independently associated with the effectiveness of omalizumab. Conclusion: Pretreatment serum pollen-specific IgE could be a predictor of responsiveness to omalizumab.

[Change of the patient characteristics among adult asthmatics hospitalized due to acute exacerbation].

BACKGROUND: We analysed the patient characteristics among adult asthmatics hospitalized to our hospital to clearfy the residual problems in the prevention and treatment of asthma. METHODS: We identified the adult asthmatics hospitalized to our hospital during the period A: Jan 2004-Dec 2005 and the period B: Jan 2009-Dec2010 and analysed retrospectively around age, smoking history, and the use of ICS (including combination medicine) and so on. RESULTS: The total patient numbers were A: 161 and B: 88, decreasing to almost half. The rates of the patients older than 65 years were equivalent between the 2 groups. Categorized according to age, in the group <65 years old, the rates of ICS use were A: 22.9% and B: 35.8% and the current smoking rates were A: 42.7% and B: 49.1% respectively. In the group 65≤ years old, the rates of ICS use were A: 46.2% and B: 48.6%, and the current smoking rates were A: 19.7% and B: 22.9%. CONCLUSION: In the group <65 years old, ICS has become more popular but smoking rate has increased among hospitalized adult asthmatics. It is estimated that smoking leads to reduce the effect of ICS and the strategy of smoking cessation will be needed to reduce acute exacerbations. In the group 65≤ years old, ICS is relatively more popular than youth and smoking rate is limited. Asthma among elder people may be refractory and more efficient strategies must be required.

[Two cases of recurrent non-small cell lung cancer successfully treated with S-1 as fifth-line chemotherapy].

There is at present no defined role for S-1 chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who previously failed chemotherapy. Two cases of multidrug-resistant, NSCLC that were successfully treated with S-1 as fifth-line chemotherapy are reported. A 75-year-old man was diagnosed as having pulmonary adenocarcinoma, cT1N3M0, stage III B. He was treated with S-1 as fifth-line chemotherapy after treatment with cisplatin(CDDP)and vinorelbine(VNR), docetaxel (DOC), gemcitabine (GEM) and VNR, and amrubicin (AMR). After completing two courses, chest computed tomography(CT)showed a partial response( PR)of the recurrent tumors, and the serum carcinoembryonic antigen level decreased. Currently, seven courses have been completed, and this treatment will be continued due to the tumor response of stable disease. A 65-year-old woman was referred for treatment of recurrent pulmonary adenocarcinoma after right upper lobe resection. She was treated with S-1 as fifth-line chemotherapy after treatment with GEM and VNR, carboplatin(CBDCA) and paclitaxel ( PTX), DOC, and gefitinib. After completing five courses, chest CT showed PR of the intrapulmonary metastases. Though grade 3 toxicity-anemia in the first case and an elevated serum amylase level in the second case were observed in both cases, the patients' quality of life was preserved. S-1 could therefore be a treatment option for patients with advanced NSCLC who previously underwent chemotherapy unsuccessfully.

Small-cell lung cancer arising after chemotherapy for a patient with lymphoma of pulmonary mucosa-associated lymphoid tissue-a case report.

A 76-year-old woman was admitted to our hospital with infiltrations evident in the right lower lobe on chest computed tomography. Bronchoscopic biopsy showed lymphoma of mucosa-associated lymphoid tissue (MALT). Lymphoma of the pulmonary MALT became enlarged at 8 months after diagnosis and dyspnea developed. Four courses of chemotherapy(rituximab+ cladribine)resulted in a partial response. However, 14 months after the chemotherapy, she developed multiple lung and liver tumors accompanied by disseminated intravascular coagulation syndrome. A histological examination of bone marrow aspiration showed small cell carcinoma. We administered one course of carboplatin and etoposide, but bone marrow suppression was so severe that further chemotherapy was precluded. To our knowledge, this is a rare case of small cell lung cancer arising from the treatment of lymphoma of pulmonary MALT.

Endobronchial metastasis from primary papillary serous carcinoma of the peritoneum.

A 59-year-old woman was admitted to our hospital with a left lower lobe opacity and mediastinal shift on the chest X-ray. She had been complaining of intermittent nonproductive cough and exertional dyspnea. Chest computed tomography (CT) showed an endobronchial tumor of the left main to the lower bronchus, atelectasis of the left lower lobe, and mediastinal shift. Bronchoscopy revealed a polypoid tumor at the distal portion of the left main bronchus that occluded the bronchus. Biopsy specimens from the endobronchial tumor were shown to be serous papillary adenocarcinoma. Since the patient had been treated surgically for primary papillary serous carcinoma of the peritoneum (PSCP) 10 years earlier, immunohistochemical examinations were performed. The diagnosis of endobronchial metastasis of PSCP was confirmed by immunohistochemical staining with cancer antigen 125 (CA125), vimentin, and Wilms tumor-1 (WT-1). This is a rare case of endobronchial metastasis from PSCP.

Pharmacokinetic study of pleural fluid penetration of carbapenem antibiotic agents in chemical pleurisy.

STUDY OBJECTIVES: We investigated pleural fluid penetration of carbapenem antibiotic agents [imipenem (IPM), panipenem (PAPM), meropenem (MEPM), and biapenem (BIPM)] using an experimental rabbit pleuritis model to clarify the usefulness of the carbapenem agents for the treatment of bacterial pleurisy or pyothorax. MEASUREMENTS AND RESULTS: Serum and pleural fluid specimens were serially collected at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min after antibiotic administration for measurement of antibiotic levels. We investigated each agent alone as well as drug solutions containing each agent and a dehydropeptidase-I-specific inhibitor, cilastatin (CS), to remove the influence of dehydropeptidase-I-related hydrolysis. Groups of animals (n=3) received each carbapenem agent with or without CS. Serum and pleural fluid antibiotic levels were measured by high-performance liquid chromatography (HPLC). Because Cmax is not useful for evaluating the antimicrobial effects of carbapenem antibiotic agents due to their dose-dependent antimicrobial activity, we also investigated the AUC, which is correlated with the total drug levels in vivo. Among the drug solutions containing CS, MEPM/CS had the highest pleural fluid AUC0-360 (1594.8+/-510.3 microg min/ml), and the highest pleural fluid AUC0-360/plasma AUC0-360 ratio (0.79+/-0.04). BIPM/CS had the highest plasma AUC0-360 (3040.1+/-1525.9 microg min/ml). In pleural fluid AUC0-360/plasma AUC0-360 ratio MEPM/CS was significantly higher than those for the remaining agents. In pleural fluid AUC0-360 and plasma AUC0-360 there were no significant differences among these mixed solutions. CONCLUSIONS: MEPM had the most favorable pleural fluid penetration. Pleural fluid penetration should be examined in infection models and in clinical trials.

Combined effects of panipenem and aminoglycosides on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in vitro.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the main causes of refractory infections that are often resistant to antimicrobial agents. In these cases, combination of agents with antimicrobial activity is being examined. However, few studies have investigated combined effects with antimicrobial agents including carbapenem and aminoglycosides. METHODS: We evaluated the effects of panipenem (PAPM) combined with 3 aminoglycosides, arbekacin, amikacin, and netilmicin, and vancomicin (VCM) with an agar dilution checkerboard technique and the fractional inhibitory concentration index against 47 strains of MRSA and 56 strains of P. aeruginosa. RESULTS: PAPM combined with VCM achieved a synergic effect against MRSA in 80.9%. PAPM combined with aminoglycosides showed only additive effects against MRSA and P. aeruginosa. When comparing the activity of Mueller-Hinton agar (MHA) medium with MHA medium diluted 40-fold (1/40 MHA) against P. aeruginosa, the mean minimum inhibitory concentration of PAPM was decreased to 1/16. CONCLUSIONS: Combination of PAPM and VCM is effective against MRSA. Combinations of PAPM and aminoglycosides showed additive effects against MRSA and P. aeruginosa.

Bronchoscopic intralesional injection of triamcinolone acetonide treated against bronchial obstruction caused by peanut aspiration.

We encountered a case of obstructive pneumonia 1 month after peanut aspiration. Bronchoscopic examination revealed obstruction of the right basal bronchus with immature granulation tissue due to the peanut aspiration. Despite antibiotic treatment, the obstruction had not been resolved. To relieve the bronchial obstruction, bronchoscopic intralesional injection of triamcinolone acetonide was performed without any complications. Seven days after injection, the bronchial obstruction had resolve. In conclusion, intralesional injection of triamcinolone acetonide may play a role in one of the non-surgical repairs against obstruction due to foreign body aspiration.

Isolation of nontuberculous mycobacteria from patients with pneumoconiosis.

This study aimed to confirm the isolation of nontuberculous mycobacteria (NTM) from patients with pneumoconiosis. Monthly sputum examinations in 155 patients were performed from April 1998 to December 2002. When NTM were isolated, species were identified and the frequency of isolation was reviewed. We then identified the patients who satisfied the bacteriologic criteria for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM pulmonary disease) recommended by the American Thoracic Society (ATS). Symptoms and findings on computed tomography (CT) scans were evaluated. NTM were isolated from 60 patients (39%): common etiologic species defined by the ATS, i.e., Mycobacterium avium, M. intracellulare, M. abscessus, and M. kansasii, were identified in 21 patients; unusual etiologic species, i.e., M. fortuitum, M. simiae, and M. szulgai, were identified in 11 patients; and undefined species, which appeared to be nonpathogenic, were identified in 41 patients. The bacteriologic criteria were satisfied in 8 patients. NTM species isolated in conformity with the bacteriologic criteria were: M. avium in 4 patients, M. intracellulare in 2, a combination of M. intracellulare and M. kansasii in 1, and M. gordonae in 1 patient. Two patients, from whom M. avium were repeatedly isolated, satisfied the ATS diagnostic criteria for NTM pulmonary disease. It is important to note that NTM, including both pathogenic species and nonpathogenic species, were isolated from patients with pneumoconiosis.

[A case of chronic necrotizing pulmonary aspergillosis diagnosed using percutaneous intracavitary endoscopy].

A 65-year-old man with pneumoconiosis visited our hospital for dyspnea on effort. Chest radiography and computed tomography on admission showed cavities with an air-fluid level, consolidation in the right lower lung, and right pleural effusion. The thoracic cavity and an infected cyst were drained, and antibiotics were administered. On detection of molds like Aspergillus species and of aspergillus antigen from the sputum, aspergillosis was suspected and amphotericin B was administered intravenously. Renal dysfunction caused by amphotericin B led to its withdrawal. Abnormal shadows in the chest radiographs and computed tomograms did not improve. To aid in diagnosis, percutaneous intracavitary endoscopy was performed. Yellow-white mural nodules resembling cauliflower were found on endoscopic examination, and a biopsy specimen of the nodules showed hyphae of Aspergillus. Aspergillus fumigatus was cultured from the intracavity fluid. Pulmonary aspergillosis was diagnosed and amphotericin B was administered via the drainage catheter in order to protect renal function. The abnormal shadows then disappeared and the subsequent clinical course was good. In this case, percutaneous intracavitary endoscopy was useful in diagnosing pulmonary aspergillosis.

Analysis of epitope recognition of antibodies induced by DNA immunization against hemagglutinin protein of influenza A virus.

In an effort to find efficient DNA vaccine candidates, cDNA of influenza A virus hemagglutinin (HA) gene and several derived mutants were injected into mice using a gene gun. Mice immunized with HA1 DNA, with or without a membrane domain, showed a humoral immune response and the survival rate against homologous virus challenge was comparable to that of mice injected with HA DNA. In order to analyze epitopes recognized by antibodies induced by gene gun immunization, we used a binding assay employing the chimeric HA protein method. Serum antibodies of mice immunized with HA DNA recognized the HA1 domain but not the HA2 domain. In addition, antisera obtained from mice immunized with HA1 DNA reacted with each of the known antigenic sites on the HA1 domain, similar to the results obtained with HA DNA immunization.

An adult case of Bochdalek hernia complicated with hemothorax.

A 53-year-old female with mild shock due to vomiting and abdominal pain visited the emergency room of our hospital. Chest X-ray on admission showed a large amount of left pleural effusion. Thoracentesis revealed hemorrhagic pleural effusion. An upper gastrointestinal series showed interruption of the upper gastric body, but the anal side was not visualized. Contrast X-ray examination of the thoracic cavity via the drainage tube demonstrated intrathoracic herniation through the diaphragm. These findings suggested gastric impaction in the foramen of Bochdalek, and thoracotomy was immediately performed. A black-colored stomach and greater omentum, suggesting necrotic changes, were observed in the thoracic cavity, and there was bleeding from the greater omentum. Resection of the necrotic organs and closure of the hernial orifice were followed by good recovery.