Clinical characteristics of allergic bronchopulmonary mycosis caused by Schizophyllum commune.

BACKGROUND: Allergic bronchopulmonary mycosis (ABPM) is an allergic disease caused by type I and type III hypersensitivity to environmental fungi. Schizophyllum commune, a basidiomycete fungus, is one of the most common fungi that causes non-Aspergillus ABPM. OBJECTIVE: Herein, we attempted to clarify the clinical characteristics of ABPM caused by S. commune (ABPM-Sc) compared with those of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Patients with ABPM-Sc or ABPA were recruited from a nationwide survey in Japan, a multicenter cohort, and a fungal database at the Medical Mycology Research Center of Chiba University. The definition of culture-positive ABPM-Sc/ABPA is as follows: (1) fulfills five or more of the 10 diagnostic criteria for ABPM proposed by Asano et al., and (2) positive culture of S. commune/Aspergillus spp. in sputum, bronchial lavage fluid, or mucus plugs in the bronchi. RESULTS: Thirty patients with ABPM-Sc and 46 with ABPA were recruited. Patients with ABPM-Sc exhibited less severe asthma and presented with better pulmonary function than those with ABPA (p = 0.008-0.03). Central bronchiectasis was more common in ABPM-Sc than that in ABPA, whereas peripheral lung lesions, including infiltrates/ground-glass opacities or fibrotic/cystic changes, were less frequent in ABPM-Sc. Aspergillus fumigatus-specific immunoglobulin (Ig)E was negative in 10 patients (34%) with ABPM-Sc, who demonstrated a lower prevalence of asthma and levels of total serum IgE than those with ABPM-Sc positive for A. fumigatus-specific IgE or ABPA. CONCLUSIONS: Clinical characteristics of ABPM-Sc, especially those negative for A. fumigatus-specific IgE, differed from those of ABPA.

An effective case of bronchoscopic balloon dilatation for tuberculous bronchial stenosis.

Endobronchial tuberculosis often causes bronchial stenosis. Balloon dilation is a minimally invasive and effective bronchoscopic intervention for bronchial stenosis; however, reports on balloon dilation in older individuals are limited. We present a case of a 77-year-old woman with endobronchial tuberculosis and clarify the efficacy and safety of balloon dilation. She presented with dyspnea, right lung atelectasis, and respiratory failure 55 days after initiation of antituberculosis therapy. We performed bronchoscopic balloon dilatation for the right main bronchial stenosis. Consequently, respiratory failure rapidly improved. Chest computed tomography (CT) showed improved lung atelectasis; however, severe bronchial stenosis and rhonchi persisted. Therefore, we performed a second balloon dilatation. CT 3 months after the first balloon dilation showed right upper bronchial stenosis and right lung middle lobe atelectasis. Restenosis was absent 21 months after third balloon dilatation. Bronchoscopic balloon dilation is effective for restenosis with repeated treatment and can be safely performed in older individuals.

Simultaneous occurrence of autoimmune pancreatitis and sclerosing cholangitis as immune-related adverse events of pembrolizumab.

A 57-year-old man with lung cancer, previously treated with the programmed death-1 inhibitor pembrolizumab, was evaluated for liver injury and acute pancreatitis. Serum IgG4 levels were not elevated. Contrast-enhanced CT showed pancreatic swelling, contrast unevenness in the liver and thickening of the common bile duct and gall bladder. Magnetic resonance cholangial pancreatography revealed beads in the left intrahepatic bile duct and localised narrowing of the head and body of the central pancreatic duct. Endoscopic ultrasound-guided fine-needle and liver needle biopsy showed CD8+ and CD4+ T lymphocyte aggregates, whereas immunostaining revealed greater infiltration by CD8+ cells than CD4+ cells. IgG4-related disease was ruled out based on serum and pathological findings. The patient simultaneously presented with immune-related adverse events, autoimmune pancreatitis-like features and sclerosing cholangitis, which were ameliorated by steroid therapy. CD8+ lymphocytes were the dominant infiltrating cells in autoimmune pancreatitis and sclerosing cholangitis.

Real-World Evidence of Safety and Efficacy of Carboplatin plus Nanoparticle Albumin-Bound Paclitaxel in Patients with Advanced Non-Small-Cell Lung Cancer and Preexisting Interstitial Lung Disease: A Retrospective Study.

Background: Standard chemotherapy for advanced non-small-cell lung cancer (NSCLC) with preexisting interstitial lung disease (ILD) has not yet been established. Although a combination of carboplatin and paclitaxel is most frequently used for patients with advanced NSCLC and ILD, the safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are yet to be elucidated. Objectives: This study aimed to evaluate the safety and efficacy of carboplatin plus nab-paclitaxel for advanced NSCLC with ILD. Methods: This retrospective study included nine patients with advanced NSCLC and ILD who received carboplatin plus nab-paclitaxel as first-line chemotherapy at the National Hospital Organization Kanazawa Medical Center between April 2013 and December 2017. The ILD-GAP index was used to evaluate mortality risk of baseline ILD. Results: A usual interstitial pneumonia (UIP) pattern of ILD was observed in five (55.6%) patients on their baseline high-resolution computed tomography (HRCT) scans. The median ILD-GAP index was 4 (range, 1-5), and six (66.7%) patients had ILD-GAP index ≥4. We observed no ILD exacerbations or chemotherapy-related deaths. The overall response and disease control rates were 77.8% (95% CI, 40.0-97.2) and 88.9% (95% CI, 51.8-97.2), respectively. The median progression-free survival and overall survival were 5.8 months (95% CI, 2.1-7.7) and 8.0 months (95% CI, 2.6-16.8), respectively. Conclusions: Carboplatin plus nab-paclitaxel showed favorable safety and efficacy in patients who had advanced NSCLC and ILD with a high risk of mortality. Prospective studies are required to further confirm these results.

Transformation to small-cell lung cancer following treatment with EGFR tyrosine kinase inhibitors in a patient with lung adenocarcinoma.

We report the case of a 52-year-old woman with lung adenocarcinoma treated with EGFR tyrosine kinase inhibitor (TKI) therapy. After disease progression, histological examination of a secondary biopsy specimen revealed small-cell lung cancer (SCLC) that was sensitive to standard SCLC treatment. Tumor markers, including ProGRP and NSE, were elevated. Transformation to SCLC is a mechanism for acquired resistance to EGFR-TKI therapy. Secondary biopsy is important for evaluation of genetic and histological changes and selection of appropriate treatment. Furthermore, ProGRP and NSE may be useful for early detection of SCLC transformation in cases resistant to EGFR-TKI therapy.

[The current status of nausea, vomiting and food intake in outpatients with cancer chemotherapy].

A survey on chemotherapy-induced nausea, vomiting and food intake was conducted on 126 outpatients receiving chemotherapy during a days from February 1 to February 12, 2010 in our hospital. Responses were obtained from 66 outpatients. In the acute phase, 11%of the patients developed nausea. In the late phase, 35%patients developed nausea. The development of nausea was significantly increased in the late phase, compared to the acute phase(p=0. 0008). Though nobody developed vomiting in the acute phase, 3% of the patients developed vomiting in the late phase. For food intake, in the acute phase, nobody showed a"reduced amount of diet", and 12% showed"not eating". In the late phase, 26% of the patients showed"reduced amount of food", and 8%"not eating". Food intake was significantly decreased in the late phase, compared in acute phase(p=0. 0001). Currently, in our hospital, steroids and/or 5-HT3 antagonists are given for antiemetic therapy, but the effect is not enough. We should add other antiemetics, which act in the late phase.

Injection of neural progenitor cells improved learning and memory dysfunction after cerebral ischemia.

Accumulating evidence indicates that stem cells have the ability to improve neurological deficits seen after cerebral ischemia. However, the effects of neural progenitor cells (NPCs) on cerebral ischemia-induced learning and memory dysfunction remain to be clarified. The purpose of the present study was to determine whether the injection of exogenous NPCs could prevent learning and memory dysfunction after cerebral ischemia. Sustained cerebral ischemia was produced by the injection of 700 microspheres into the right hemisphere of each rat. We demonstrated that injection of NPCs into the hippocampus at 10 min after the induction of cerebral ischemia reduced prolongation of the escape latency seen in acquisition and retention tests of the water maze task on Days 12-28 after cerebral ischemia. Injection of NPCs partially attenuated the decrease in viable areas of the ipsilateral hemisphere on Day 28 after the cerebral ischemia. We also demonstrated that injection of NPCs prevented the decrease in the level of BDNF seen at the early period after cerebral ischemia. These results suggest that the injection of exogenous NPCs into the hippocampus can prevent cerebral ischemia-induced learning and memory dysfunction, possibly through maintenance of the BDNF level.

Effect of NMDA receptor antagonist on proliferation of neurospheres from embryonic brain.

The N-methyl-D-aspartate (NMDA) receptor, a subtype of ionotropic glutamate receptors, plays an important role in the regulation of neuronal development, learning and memory, and neurodegenerative diseases. NMDA receptor blockade enhances neurogenesis in the hippocampal dentate gyrus in vivo. The effect of NMDA receptor antagonist on proliferation of neural progenitor cells, however, remains to be determined. We investigated changes in the diameter and number of neurospheres derived from the embryonic rat brain after NMDA receptor blockade. Cortical progenitor cells were isolated from gestational day 18 fetal rats according to the Percoll density gradient method. Cultured spheres expressed neural progenitor markers, musashi-1 and nestin. Immunohistochemical analysis demonstrated that cells in Dulbecco's modified Eagle medium/F12 containing 1% fetal bovine serum on day 8 differentiated to MAP-2-positive neurons and GFAP-positive astrocytes. The expression of NR1 and NR2B subunits of the NMDA receptor in neurospheres was detected. Neither brief nor sustained exposure to NMDA altered the diameter and number of neurospheres. Brief exposure to 30 microM MK-801, an NMDA receptor antagonist, decreased the diameter of neurospheres. Sustained exposure to 30 microM MK-801 decreased the diameter and number of neurospheres. Our results provide evidence that MK-801 directly decreased proliferation of neural progenitor cells.