Monocytes predict prognosis and successful treatment in older patients with miliary tuberculosis.

Background: The increasing number of patients with miliary tuberculosis (MTB) is a concern in an aging society because of its high mortality rate. Several prognostic biomarkers for MTB have been identified; however, the predictive ability of monocytes as biomarkers remains unknown. This study demonstrates the usefulness of monocytes as prognostic biomarkers for MTB. Materials and methods: We retrospectively compared the clinical findings of 52 patients with MTB hospitalized between April 2013 and October 2021. The predictive ability of biomarkers for 3-month prognosis and their cutoff values were calculated. Survival times and longitudinal changes in monocytes after initiating treatment were compared. Results: A smaller number of monocytes (#M), higher lymphocyte-monocyte ratio (LMR), higher neutrophil-monocyte ratio, and poorer performance status were associated with death within 3 months. #M was an independent prognostic factor. #M and LMR exhibited the highest predictive performance compared to others using receiver operating characteristic curve analysis (area under the curve = 0.86 and 0.85, respectively). Survival time was shorter in patients with #M ≤ 200 cells/µL and LMR > 2.5. Rapidly increasing #M after treatment was related to better prognosis in patients with #M ≤ 200 cells/µL at diagnosis. Conclusions: #M at diagnosis and longitudinal changes in monocytes are related to MTB prognosis.

Mechanism of action of adapalene for treating EGFR-TKI-induced skin disorder.

BACKGROUND: Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. It is important to manage skin lesions. Adapalene has been used to treat skin lesions caused by EGFR-TKIs in some cases. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib-induced skin disorder. METHODS: To analyze the effect of adapalene on skin rash, afatinib and adapalene were administered to mice. The relationship between the concentration of adapalene and skin disorders was also examined by analyzing AQP3 expression. A skin lesion model was experimentally established in human skin keratinocytes (HaCaT) by using erlotinib with TNF-α and IL-1ß. We used qRT-PCR to analyze chemokine-induced inflammation and western blotting to analyze the effects of adapalene on the NF-κB signaling pathway. Antimicrobial peptides and adhesion factors were also examined using qRT-PCR. RESULTS: Mice administered 0.01% adapalene had less skin inflammation than mice treated with afatinib alone. The expression level of AQP3 decreased in an adapalene concentration-dependent manner. The mRNA levels of proinflammatory cytokines such as CCL2 and CCL27 in HaCaT cells were significantly reduced by adapalene. The expression of an antimicrobial peptide, hBD3, was upregulated after adapalene treatment. Adhesion factors, such as E-cadherin, were significantly downregulated by EGFR-TKI and significantly upregulated by adapalene treatment. Western blot analysis suggested that erlotinib-induced phosphorylation of p65 was decreased by adapalene. CONCLUSION: We suggest that adapalene may be a possible treatment option for skin disorders induced by EGFR-TKIs.

Retrospective analysis of the effect of inhaler education on improvements in inhaler usage.

INTRODUCTION: Various types of inhalation devices have been released, and it is necessary to acquire the skills for using each of them. The factors that have been previously associated with poor inhalator usage include gender, duration of disease, age, and the type of device. However, it is unclear whether these factors also apply to the Japanese population. The number of education sessions needed to acquire inhaler usage skills is also not established. PATIENTS AND METHODS: We performed a retrospective review of the medical records of selected patients and their subjective assessments of their inhaler usage skills between January 2016 and March 2018. The primary outcome was the effect of inhaler education for each inhaler device. The secondary outcomes were the factors affecting the effectiveness of inhaler education, the effects of inhalation education stratified by age, and the number of inhaler education sessions needed to improve inhaler usage skills. RESULTS: Data from 399 patients were analyzed. Age and the type of delivery device affected the mastery of inhaler usage skills. Approximately half of the patients had acquired inhaler usage skills during baseline evaluation. Approximately 90% of patients acquired inhalation usage skills after two education sessions, regardless of the type of inhalation device. Among the older patients, 35.0% had acquired inhaler usage skills during the baseline evaluation, and 86.8% acquired them after two education sessions. CONCLUSIONS: Inhaler usage skills significantly improved, regardless of the device, after inhalation education, and this was also observed in elderly patients after two education sessions.

Caspase Recruitment Domain-Containing Protein 9 Expression is a Novel Prognostic Factor for Lung Adenocarcinoma.

PURPOSE: Caspase recruitment domain-containing protein 9 (CARD9) is expressed at high levels in bone marrow cells and has a crucial role in innate immunity. Current studies indicate that CARD9 also plays a key role in tumor progression, but there are few reports on the role of CARD9 in lung cancer. The aim of this study was to clarify the role of CARD9 in lung adenocarcinoma. PATIENTS AND METHODS: Lung adenocarcinoma tumor samples from 74 patients who underwent complete resection at Kobe University Hospital from January 2014 to December 2014 were analyzed by immunohistochemistry. The role of CARD9 in cancer cells was analyzed using lung cancer cell lines treated with CARD9 siRNA. RESULTS: High expression of CARD9 was observed in 32.4% of tumors, and compared to low expression of CARD9, high expression was associated with poorer overall survival (P = 0.0365). Univariate and multivariate analyses showed that high expression of CARD9 was an independent prognostic factor. Knockdown of CARD9 in lung adenocarcinoma cells inhibited proliferation but did not increase apoptosis. In addition, CARD9 activated the NF-κB pathway in a lung adenocarcinoma cell line. CONCLUSION: CARD9 was shown to be an independent prognostic factor of poor outcome for lung cancer and may represent a molecular target for treatment.

An Open-Label, Multi-Institutional, Randomized Study to Evaluate the Additive Effect of a Leukotriene Receptor Antagonist on Cough Score in Patients with Cough-Variant Asthma Being Treated with Inhaled Corticosteroids.

Cough-variant asthma is one of the most common reasons for chronic cough. It is important to treat appropriately cough-variant asthma because 30% to 40% of cough-variant asthma becomes a typical asthma. However, little is known about the treatment of cough-variant asthma except for inhaled corticosteroid (ICS). The aim of this study was to validate the additive efficacy of a leukotriene receptor antagonist (LTRA) on cough score and respiratory function in patients with cough-variant asthma being treated with ICS. A total 28 patients were randomly assigned to either an ICS + LTRA group or an ICS group. There were statistically significant improvements in cough scores in the ICS + LTRA group from 0 weeks (6.7 ± 4.4) to 2 weeks (2.9 ± 3.2) (P < 0.05), 4 weeks (0.7 ± 1.1) (P < 0.001), and 8 weeks (0.8 ± 1.2) (P < 0.001). However similar improvements were not evident in the ICS group from 0 weeks (6.7 ± 4.4) to 2 weeks (5.6 ± 10.0) (P = 0.59), 4 weeks (4.6 ± 7.6) (P = 0.32), and 8 weeks (2.9 ± 5.2) (P = 0.08). On the other hand, no significant changes were evident in the forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC). In conclusion, the LTRA was useful in improving cough in patients with cough-variant asthma, even though it appeared to be ineffective in improving respiratory function.