Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients.

OBJECTIVE: Benralizumab is a promising drug for severe uncontrolled asthma. This study aimed to clarify the effectiveness of benralizumab in a real-life setting. METHODS: Subjects included 24 patients with severe type 2 asthma who received benralizumab between April 2018 and July 2019. Changes in parameters, exacerbation frequency, and oral corticosteroid (OCS) use after 4 and 24 weeks of administration were examined. The parameters included the Global Evaluation of Treatment Effectiveness (GETE) scale, Asthma Control Questionnaire (ACQ), Asthma Control Test (ACT), blood eosinophils, fractional exhaled nitric oxide (FeNO), and spirometry. The response to treatment was defined as follows: for patients with exacerbations or OCS use before treatment initiation, a reduction of ≥50% in exacerbation frequency or OCS use; and for patients without exacerbations or OCS use, an improvement of ≥0.5 in ACQ scores and ≥3 in ACT scores, or of ≥10.38% in FEV1. RESULTS: Twenty-one patients completed the treatment for 24 weeks. Excellent and good GETE scales and ACQ and ACT improvement were found in 67% of the patients at 4 weeks, and the effect continued until 24 weeks. The patients' rate with exacerbations was significantly reduced compared to the previous 24 weeks before administration. In 17 patients receiving OCS, the use could be reduced or quit in 14 patients. Overall, 16 patients (76.2%) met the responder definition and could be predicted by the baseline eosinophil count and FeNO levels with the best cutoff values of 100/µL and 40 ppb, respectively. CONCLUSIONS: Blood eosinophil and FeNO could predict benralizumab effectiveness.

Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung.

BACKGROUND: There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma. METHODS: Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis. RESULTS: Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p < 0.01) and undergo lobectomy (p < 0.01) and whose pro-gastrin-releasing peptide ≦ 72 pg/ml (p = 0.04) performed good prognosis after surgery. In multivariate analysis, surgery within 60 days and operative procedure were independent factors associated with OS. CONCLUSION: Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung should be performed as early as possible, and better outcome can be obtained with lobectomy than partial resection.

Clostridium perfringens α-Toxin Impairs Lipid Raft Integrity in Neutrophils.

Clostridium perfringens type A, a Gram-positive, anaerobic bacterium, causes gas gangrene. Recently, we reported that C. perfringens α-toxin blocked neutrophil differentiation in an enzyme activity-dependent manner to impair host innate immunity, which should be crucial for the pathogenesis of C. perfringens. However, the detailed mechanism remains unclear. Lipid rafts have been reported to be platforms for signaling molecules involved in the regulation of cell differentiation in many different cell types. In this study, we found that cell surface expression of a lipid raft marker, GM1 ganglioside, decreased in association with neutrophil differentiation by flow cytometry analysis and morphological observation. In vitro treatment of isolated mouse bone marrow cells with α-toxin or an α-toxin variant lacking phospholipase C and sphingomyelinase activities revealed that α-toxin increased the cell surface expression of GM1 ganglioside in an enzyme activity-dependent manner. C. perfringens infection also increased GM1 ganglioside levels in bone marrow myeloid cells. Moreover, treatment of bone marrow cells with methyl-ß-cyclodextrin, a lipid raft-disrupting agent, impaired neutrophil differentiation. Together, our results suggest that the integrity of lipid rafts should be properly maintained during granulopoiesis, and α-toxin might perturb lipid raft integrity leading to the impairment of neutrophil differentiation.

Transient leukocytopenia following combination therapy for COVID-19.

BACKGROUND: Combination therapy with dexamethasone, remdesivir, and baricitinib has become a promising treatment for moderate or severe COVID-19; however, we have observed transient leukocytopenia in COVID-19 patients who received combination therapy. METHODS: Twelve consecutive COVID-19 patients treated with combination therapy were included in this retrospective analysis. Blood cell counts collected at the following three time points were analyzed: before the start of therapy (period 1), within 24 h of starting therapy (period 2), and within 48 h of period 2 (period 3). RESULTS: The leukocyte count significantly decreased in period 2 compared to period 1 and then significantly increased in period 3 without withdrawal of baricitinib. The neutrophil count transiently decreased in period 2 and recovered in period 3. CONCLUSIONS: Clinicians should be aware of transient leukocytopenia in patients with COVID-19 during the early phase of combination therapy.

Sinobronchial allergic mycosis syndrome in an elderly male.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS) are characterized by hyper-responsiveness of the respiratory tract and the nasal cavity and paranasal sinuses, respectively to Aspergillus species and AFRS causes chronic rhinosinusitis. Herein, we report the first case of sinobronchial allergic mycosis (SAM) syndrome, defined as ABPA with concomitant AFRS, caused by Aspergillus fumigatus patient > 80 years. CASE PRESENTATION: An 82-year-old male with interstitial pneumonia who returned for follow-up exhibited high-attenuation mucus plug in the right intermediate bronchial trunk, infiltration in the right lung field, and right pleural effusion on regular chest computed tomography (CT). We found unilateral central bronchiectasis in the right upper lobe. Similarly, CT scan of the paranasal sinuses revealed high-attenuation mucus plugs in left ethmoid sinuses. Biopsy specimens from the plugs in the right intermediate bronchial trunk and the left ethmoid sinuses revealed allergic mucin with layers of mucus eosinophils, eosinophil-predominant mixed inflammatory cell infiltrate and Aspergillus hyphae. The patient fulfilled all the major criteria for ABPA and AFRS, and was diagnosed with SAM syndrome. CT scan of the lung and paranasal sinuses revealed apparent amelioration after oral steroid therapy. CONCLUSION: Despite mostly reported in relatively young patients, SAM syndrome can occur in elderly individuals as well.

Sarcoidosis with Pancreatic Mass, Endobronchial Nodules, and Miliary Opacities in the Lung.

Sarcoidosis affects multiple organs and rarely has unusual manifestations. A 78-year-old woman was referred to our hospital for coughing symptoms. A chest computed tomography (CT) scan revealed bilateral diffuse miliary patterns and right pleural effusion. Bronchoscopy showed multiple nodules in the carina and the bronchus intermedius. A CT scan of her abdomen revealed hypovascular lesions involving the pancreatic head and body. A transbronchial lung biopsy, bronchial mucosal biopsy, and endoscopic ultrasound-guided fine-needle aspiration of the pancreatic mass demonstrated non-caseating granulomas. We diagnosed the patient with sarcoidosis. She received no treatment for sarcoidosis and has been followed up for one year, during which no pulmonary disease progression had been observed and the pancreatic masses partially regressed.