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Influenza remains a clinically heavy burden worldwide. It is well known that some populations are at high risk of complications from influenza, whereas, even previously healthy people might suffer from severe influenza. The objective of this study was to clarify clinical manifestations of hospitalized patients without risk factors infected with influenza.The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2020 (6 influenza seasons) using an internet-surveillance system. Among them, the patients who had no risk factors of complications from influenza were extracted.Finally, a total of 91 patients (9.0% of all influenza-related hospitalizations) without risk factors were analyzed. The no risk group was younger than the risk group, though other significant differences of clinical characteristics were not recognized between the groups. Pneumonia was the most common cause of hospitalization in the no risk group, and primary influenza viral pneumonia was the most common pneumonia. Antiviral drugs were administered in 96.7% of the no-risk group, and artificial ventilation was performed in 18.7%. In-hospital death was recorded for 3 patients without risk factors.Severe complications of influenza which required hospitalization may occur in a certain degree of patients with no risk factors. Efforts are needed to diagnose and treat influenza appropriately even in previously healthy younger patients. Continuous nationwide surveillance will be required to clarify risk factors for severe influenza even in previously healthy younger patients. (UMIN000015989).

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. Methods COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. Results A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. Conclusions The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. Trial registration Clinicaltrials.jp number: JapicCTI-205238. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00517-4.

The clinical characteristics and prognostic factors of aspiration pneumonia remain poorly defined. Geriatric nutrition risk index (GNRI) has recently been reported to exhibit a prognostic value for several diseases in older adults. We investigated the clinical characteristics and prognostic significance of GNRI for aspiration pneumonia in older adult patients. In this retrospective observational cohort study, conducted in a single-institute acute-phase community hospital, patients with aspiration pneumonia diagnosed at our institute between April 2014 and March 2016 were enrolled. Data on patient characteristics, microbiological findings, and clinical course were collected. The outcome was in-hospital mortality. Receiver operating characteristic curve (ROC) analysis was conducted to compare the predictive value of each parameter. Logistic regression analysis was performed to identify independent prognostic factors. Overall, 587 aspiration pneumonia patients aged ≥ 65 years were enrolled. Their mean age was 86 years. Among them, 97 (16.5%) died. In ROC analysis for in-hospital mortality, as compared to albumin, body mass index, and A-DROP score, GNRI had a greater area under the curve value, with a significant difference between GNRI and albumin (p = 0.0058). Male sex (p = 0.028), chronic heart failure (p = 0.023), history of malignancy (p = 0.0025), lower GNRI (p

Introduction Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza. Methods The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system. Results A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67–84), and the patients in the 2015–2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality. Conclusions Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989).

"The aim of this study was to develop a cross-cultural competency scale based on perspectives from the experiential model of cross-cultural learning skills for successful adaptation of international assignees. The study involved 134 participants from 41 countries who studied at a graduate school in Japan, specializing in international relations and international management. Maximum likelihood exploratory factor analysis was conducted with varimax rotation, extracting three latent components of cross-cultural competency: building relationships, translation of complex information, and conflict management. To validate those components, confirmatory factor analysis was conducted with the same group of participants. Results showed acceptable levels of model fit, and the reliability of the three components ranged from 0.83 to 0.87. Accordingly, the cross-cultural competency scale developed in this study seems to be an effective measurement model to analyze cross-cultural competencies."

Introduction Risk factors for seriously ill coronavirus disease 19 (COVID-19) patients have been reported in several studies. However, to date, few studies have reported simple risk assessment tools for distinguishing patients becoming severely ill after initial diagnosis. Hence, this study aimed to develop a simple clinical risk nomogram predicting oxygenation risk in patients with COVID-19 at the first triage. Methods This retrospective study involved a chart review of the medical records of 84 patients diagnosed with COVID-19 between February 2020 and March 2021 at ten medical facilities. The patients were divided into requiring no oxygen therapy (non-severe group) and requiring oxygen therapy (severe group). Patient characteristics were compared between the two groups. We utilized univariate logistic regression analysis to confirm determinants of high risks of requiring oxygen therapy in patients with moderate COVID-19. Results Thirty-five patients ware in severe group and forty-nine patients were in non-severe group. In comparison with patients in the non-severe group, patients in the severe group were significantly older with higher body mass index (BMI), and had a history of hypertension and diabetes. Serum blood urea nitrogen (BUN), lactic acid dehydrogenase (LDH), and C-reactive protein (CRP) levels were significantly higher in the severe group. Multivariate analysis showed that older age, higher BMI, and higher BUN levels were significantly associated with oxygen requirements. Conclusions This study demonstrated that age, BMI, and BUN were independent risk factors in the moderate-to-severe COVID-19 group. Elderly patients with higher BMI and BUN require close monitoring and early treatment initiation.

This study examined the effect of anxiety reduction sessions conducted in English as a foreign language (EFL) classrooms. EFL anxiety reduction sessions were developed based on two assumpti...

A 70-year-old woman was admitted to our hospital due to difficulty in moving her limbs. She had trismus and a necrotic and contaminated wound in her left lower leg. A diagnosis of tetanus was confirmed and intensive care was started. On the second day, her blood pressure fell and a ST segment elevation on electrocardiography (ECG) was detected. She was diagnosed with takotsubo cardiomyopathy by echocardiogram and improved undergoing conservative therapy.

Purpose. This study aimed to explore whether a match between learning style and teaching style in English as a foreign language (EFL) class affects two student variables: proficiency and motivation...

This studyempirically explored how learning style relates to intercultural sensitivity and international attitudes in the context of a Japanese university. Atotal of 109 undergraduate students completed three questionnaires: Kolb’s Learning Style Inventory, Chen and Starosta’s Intercultural Sensitivity Scale, and Yashima’s International Posture as a measurefor international attitudes. Because the factor structure with constituent items of the Intercultural Sensitivity Scale was unresolved, we first examined the configuration of its latent constructs and then identified four underlying components. In terms of intercultural sensitivity, results of regression analysis illustrated that a learning style with a focus on acting over reflecting significantlynegativelyrelated to Anxious Interactionand marginallyrelated to Affirmative andEnjoyment Interaction. Results for international attitudes revealed that the samelearning variable wassignificantlyassociated with Intercultural Approach Tendency,Interest in International Vocation, andWillingness to Communicate to the World, whereas the learning variable of thinking versus feeling was marginally negatively related to Intercultural Approach Tendency. In conclusion, the study suggests that the learning styledimension of actionversus reflection has a strongerinfluence on intercultural sensitivity and international attitudesthan the learning dimension of thinking versus feeling.

Background: Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease.Methods: This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15.Results: Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388–0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323–2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841–2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347–5.950; p = 0.006).Conclusions: Corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Background This open-label, single-arm, phase 3 study evaluated safety and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in pneumococcal vaccine-naive Japanese individuals aged 6–64 years at increased risk of pneumococcal disease (PD). Methods Participants received 1 PCV13 dose. Reactogenicity events were recorded for 7 days (individuals aged 6- to 17-year-old) or 14 days (individuals aged 18 to 64 years old) postvaccination. Adverse events (AEs) were collected for 1 month postvaccination. Opsonophagocytic activity (OPA) and anticapsular immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured for vaccine serotypes before and 1 month postvaccination. Post hoc analyses compared immunogenicity in participants categorized as at-risk (immunocompetent but having chronic medical conditions associated with increased PD risk) or high-risk (immunocompromised due to diseases/conditions and/or medications). Results 206 participants aged 6- to 17-year-old (n = 53) and 18 to 64 years old (n = 153) completed the study. Reactogenicity events were generally mild to moderate in severity. AEs were reported in 16% (33/206) of participants; 1.0% (2/206) were severe. Six AEs were vaccine-related; most were associated with local reactions. No serious AEs occurred. Circulating antibody levels for all 13 serotypes increased postvaccination. OPA geometric mean fold rises (GMFRs) from prevaccination to 1 month postvaccination were 5.5–61.7; lower limits of the 2-sided, 95% CI were > 1 for all serotypes. IgG GMFRs were consistent with OPA analyses. In post hoc analyses, 55.8% (115/206) and 44.2% (91/206) of participants were categorized as at risk and at high risk of PD, respectively; OPA GMFRs from prevaccination to 1 month postvaccination were 3.9–635.1, with lower limits of the 2-sided 95% CIs > 1 for all 13 serotypes across these risk groups; IgG GMFRs were consistent with OPA analyses. Conclusions PCV13 was well tolerated and immunogenic in Japanese individuals aged 6–64 years considered at increased risk of PD. Results were broadly comparable with past PCV13 studies in other Japanese and non-Japanese populations. Registration number: NCT03571607; JapicCTI-184024.

Experimental studies have developed, conducted, and evaluated classroom interventions for foreign language anxiety (FLA) reduction. However, various characteristics of those classroom interventions make it difficult to synthesize the findings and apply them to practice. We conducted what is, to the best of our knowledge, the first systematic review on educational interventions for FLA. Six criteria were established for inclusion of studies. Using English keywords, we identified 854 potentially eligible studies through ProQuest and Scopus, 40 of which were finally included. All included studies were published from 2007 to 2020. The studies differed in type of intervention, duration of intervention, and scale to measure FLA. Our systematic review resulted in seven features of classroom interventions, categorized as student–student interactions, student-teacher interactions, self-management, and mood boosters; we also categorized interventions as either individual or interactional.

An 81-year-old man was admitted to our medical center for dyspnea. He underwent right upper lobectomy due to squamous cell lung cancer 5 years ago. Chest computed tomography(CT)revealed stenosis ofthe right main bronchus, and pathological diagnosis ofthe lesion was squamous cell carcinoma and PD-L1 expression was low(tumor proportion score [TPS]: 1%). Because his performance status(PS)was 1, he underwent 4 courses ofnab -paclitaxel(nab-PTX)plus carboplatin( CBDCA)plus pembrolizumab chemotherapy and pembrolizumab maintenance chemotherapy. The stenosis ofthe right main bronchus was clear after chemotherapy, and his dyspnea was improved. Chemotherapy using nab-PTX plus CBDCA plus pembrolizumab may become one of the therapeutic choices for the recurrence after operation of an elderly person with squamous cell lung carcinoma and low PD-L1 expression.

The effect of systemic corticosteroids on clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains controversial. While the use of corticosteroids raises concerns regarding delayed viral clearance, secondary infections, and long-term complications that can lead to increased mortality, corticosteroids have the potential to reduce mortality if used appropriately. Herein, we report good outcomes in two patients with COVID-19 who received systemic corticosteroids as adjunctive therapy. An 83-year-old man with hypertension and smoking history and a 62-year-old man with a drinking habit were transferred to our hospital with a diagnosis of COVID-19. The patients developed general malaise and loss of appetite with persistent high fever. Despite the prescription of antiviral drugs, their hypoxemia progressed rapidly. However, after the introduction of systemic corticosteroids, their symptoms improved as the fever decreased, and their hypoxemia gradually improved. These results suggest that some patients with COVID-19 may benefit from the appropriate use of systemic corticosteroids as adjunctive therapy.

We report the case of a patient with pneumonia caused by the new coronavirus (COVID-19 pneumonia), who contracted the novel coronavirus (SARS-CoV-2) infection on a large cruise ship, and was hospitalized due to fever and cough The fever resolved immediately after admission, however, a mild cough persisted Chest CT showed multiple ground-glass opacities in the upper and lower lobes of both lungs However, we judged that the patient was at a low risk of exacerbation of the disease as he was young, and did not administer any antiviral drugs Since the subjective symptoms improved, we repeated the SARS-CoV-2 PCR test on day 9 after the onset of the illness, but the result was still positive As the patient was observed to have sinus stenosis in the left nasal cavity at the time of collection of the nasopharyngeal swab for testing, sinus CT was performed The findings were suggestive of inflammation of the left nasal mucosa, ethmoid sinusitis, and maxillary sinusitis It took a long 41 days before we could finally confirm two consecutive negative results of the nasopharyngeal swab PCR test for the novel virus It has not yet been clarified whether the SARS-CoV2-19 virus can cause rhinitis and/or sinusitis, but from our experience of this case, we believe that SARS-CoV2-19 can colonize already infected nasal mucosa and sinuses for a prolonged period of time It is necessary to pay attention to this aspect, as it may prolong the disease duration and/or increase the risk of relapse

This study examined how learning style relates to self-efficacy beliefs in a managerial context. To make a theoretical frame, the study relied on Kolb’s experiential learning theory and a model of ...

Purpose The purpose of this study is to empirically explore how managers differ from non-managers with regard to learning skills as competencies and learning style in a public-sector work setting. The paper also examined how learning style affects competency development. Design/methodology/approach This study applied Kolb’s experiential learning theory concomitant with its instruments to analyze 12 skills and 4 learning styles. A total of 457 government officers from the Indonesian Ministry of Finance and Ministry of Internal Affairs participated in this study, including 112 managers and 345 non-managers. Findings The study had four major findings. Although the two groups were similar in technology skills, managers had stronger skills than non-managers in leadership, relationship, helping, sense making, information gathering, information analysis, theory building, quantitative analysis, goal setting, action and initiative. Relationship skills were important for both managers and non-managers. Managers were more abstract and less concrete learners than non-managers. The learning style with more thinking over feeling affected learning skills development much more than the learning style with more acting over reflecting. Originality/value Using experiential learning theory, this study has clarified what competencies of managers are more developed than those of non-managers and how the two groups learn differently.

Background Japan has an aging population and an increasing number of patients who reside in long-term care and mental health facilities. Both pneumococcal pneumonia and influenza B infection outbreaks have been observed in these populations, although no reports have described concurrent outbreaks of pneumococcal pneumonia and influenza B infection in these facilities. Case presentation Six patients and two staffs were initially diagnosed with influenza B infection at a mental health facility on March 14, 2015. By March 21, influenza B infection was diagnosed in 26 patients and 10 staff; all individuals received anti-influenza drugs. On March 19, two patients were diagnosed with pneumococcal pneumonia, and seven patients had developed pneumococcal pneumonia by March 24. Six of these seven patients also had influenza B infection. All individuals who developed pneumococcal pneumonia were hospitalized and treated using ampicillin/sulbactam at our hospital, and their symptoms subsequently subsided. Among the seven pneumococcal strains that were frozen and stored, two strains were type 3 and five strains were type 11A/E. Pulsed-field gel electrophoresis testing revealed that each of the serum types were from the same clone. Conclusion It appears that an outbreak of influenza B infection was followed by the spread of multi-clone pneumococcal pneumonia among elderly patients at a mental health facility. Therefore, it may be prudent to use vaccinations to prevent the spread of pneumococcal pneumonia among elderly patients and this diagnosis should be actively considered during outbreaks of influenza infection at elder care facilities.

Anti-HER2 antibody is molecular targeted antibody for cancer therapy. Approximately 20% of breast cancers are characterized by overexpression of HER2 protein. However, the recurrence rate was 30% and the metastasis rate was 18% one year after treatment of Anti-HER2 antibody for HER2 positive breast cancer. The resistance to antibody treatment is a major problem for patients. We previously reported that Anti-HER2 antibody and Gamma Interferon (IFN-γ) combined therapy showed higher anti-tumor effect than usual therapy in vitro and in vivo mouse experiments.In this study, we evaluated whether anti-HER2 antibody and IFN-γ combined therapy shows good synergistic effect against drug resistant HER2 positive breast cancer cells and higher antitumor effect than conventional clinical treatment. The resistant cell lines were made under the continuous presence of antibody until cell growth was not affected by the drug. We divided the resistant cells into the appropriate number of groups, which we and treated with anti-cancer therapy. We evaluated the antitumor effect for both in vitro study and in vivo mouse xenograft model prepared with the same immunogenicity. And we investigated the differences of immunofluorescence staining of CD8, Gr-1 and PDL-1 in tissues, especially related to immunity system.The combined therapy showed significantly higher anti-tumor effect than other groups in vitro and in vivo experiments. The combined therapy affects anti-tumor immunity in this immunofluorescence experiment. Taken together, we showed the possibility that combined therapy could be an effective treatment option for anti-HER2 antibody resistant breast cancer, helping patients suffering from cancer progression after developing treatment resistance.

This chapter aimed to understand how learning style and learning skills differ among three countries—Japan, Thailand, and the United States—as viewed through Kolb's experiential learning theory. The study consisted of 300 undergraduates, with 100 freshmen from each country. Results indicated that Japanese students depended the most on a feeling mode rather than a thinking mode, followed by Thai students; Americans, in contrast, strongly preferred to learn from a thinking mode. Of the 12 learning skills analyzed, nine differed by both learning style (converging or diverging) and country, while three were affected only by country. Thais showed the highest level of most learning skills, Americans were in the middle, and Japanese exhibited the lowest level of all 12 skills. A converging learning style influenced learning skill development more than a diverging learning style. This study offers theoretical and practical implications.

This study explored how managers' fairness perceptions of performance evaluation systems differ across countries and relate to their job satisfaction. Lack-of-group bias and transparency were the constructs used to assess fairness perceptions. The data sample consisted of 903 Asian managers from the subsidiaries of a leading multinational corporation ( MNC) strategically expanding its retail markets in Japan, China, Hong Kong, Malaysia, and Thailand. Results showed that the fairness perceptions of lack-of-group bias and transparency concerning the common performance evaluation system varied within these Asian countries. Furthermore, those fairness perceptions were significantly related to job satisfaction among Asian managers overall, as well as in each of the five geographical subgroups with the exception of Hong Kong, where the perception of a lack-of-group bias was only marginally related to job satisfaction. These findings offer theoretical implications regarding organizational justice, cross-national management, and performance evaluation, as well as practical implications for leveraging organizational justice perceptions of performance evaluation systems for the effectiveness of MNCs. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This is a rare case of tuberculosis (TB) complicated with pseudogout of the wrist joint in a non-immunocompromised 84-year-old female with a history of pulmonary tuberculosis. She was diagnosed with extrapulmonary tuberculosis of the wrist based on a polymerase chain reaction (PCR) study and synovial fluid aspiration in which the cytology was positive for acid-fast bacilli. Calcium pyrophosphate was also positive. We must be careful not to miss articular tuberculosis as it may mimic common inflammatory arthritis, such as pseudogout of the wrist. Even if the patient is positive for calcium pyrophosphate, this does not exclude the possibility of articular tuberculosis.

This study empirically explored host-country nationals (HCNs) in multinational enterprises (MNEs) using a competency approach. Participants consisted of 500 managers working for a leading Japanese retail MNE, with 100 each from Japan, China, Hong Kong, Malaysia and Thailand. The study highlighted three competency variables for 12 skills of those managers: (1) the level of competency demands, (2) the level of developed competencies and (3) the level of competency improvement needs as assessed by the difference between the levels of developed competencies and the levels of corresponding competency demands. Three conclusions were drawn: First, relationship skills are the most demanded and developed competency of HCN managers in Asia, while their levels tend to vary with Asian countries. Second, goal-setting skills are also very important competency demands but are insufficiently developed by HCN managers. Therefore, HCN managers need to improve their goal-setting skills to a great degree as a top priority. T...

Background Patients with slowly progressive idiopathic interstitial pneumonia, including idiopathic pulmonary fibrosis, often deteriorate, thus suggesting that the clinical course may be unpredictable. Such episodes are termed acute exacerbation of idiopathic interstitial pneumonia. The etiology of an acute exacerbation of idiopathic interstitial pneumonia is unknown. In this study, we tested the hypothesis that an acute exacerbation of idiopathic interstitial pneumonia is induced by respiratory viral infections. Methods Bronchoalveolar lavage fluid obtained from patients with an acute exacerbation of idiopathic interstitial pneumonia was tested for viral nucleic acid using polymerase chain reaction. Results Only 1 of the 14 patients with an acute exacerbation of idiopathic interstitial pneumonia exhibited evidence of respiratory syncytial virus B, and 2 patients exhibited evidence of cytomegalovirus. Seven patients fulfilled the diagnostic criteria of idiopathic pulmonary fibrosis. Conclusions Most cases with an acute exacerbation of idiopathic interstitial pneumonia are not caused by a viral infection.

A 14- year- old girl underwent a medical checkup for Mycobacterium tuberculosis infection because her grandmother had been diagnosed with pulmonary tuberculosis three months earlier. The interferon- gamma release assay (IGRA) showed a positive result. The patient's chest X- ray findings were normal. Chest computed tomography (CT) showed a single mass lesion in the right lower lobe of the lung. A sputum smear of acid- fast bacilli was positive; however, the polymerase chain reaction results for tuberculosis were negative. We diagnosed the patient with pulmonary tuberculosis based on the fact that she had come in contact with a tuberculosis patient. Six weeks later, a liquid culture examination for acid- fast bacilli was found to be positive and the acid- fast bacillus was identified as M. tuberculosis. The use of chest CT is not routinely recommended in all children suspected of having M. tuberculosis infection. However, IGRA- positive children who report frequent contact with infected individuals should undergo CT tomography if chest X- rays do not show any abnormal shadows., Article, INTERNAL MEDICINE. 53(8):913-916 (2014)

Acute otitis media (AOM) is the most common upper respiratory tract infection in childhood. Children with AOM were enrolled at Tohoku Rosai Hospital between July 2006 and June 2011 if their middle ear fluid cultures after tympanocentesis yielded only Haemophilus influenzae . The susceptibilities of the isolates to ampicillin were determined, and microtiter biofilm assays and invasion assays using BEAS-2B cells were performed. The association between these bacterial characteristics and clinical relapses of AOM and treatment failures was evaluated. Seventy-four children (39 boys and 35 girls) with a median age of 1 year (interquartile range [IQR], 0.25 to 2 years) were enrolled. Among 74 H. influenzae isolates, 37 showed intermediate resistance or resistance to ampicillin (MIC, ≥2 μg/ml). In the microtiter biofilm assay, the median optical density at 600 nm (OD 600 ) was 0.68 (IQR, 0.24 to 1.02), and 70 isolates formed biofilms. The median invasion rate was 15% (IQR, 0 to 10%), and 46 isolates invaded BEAS-2B cells. Relapses and treatment failures occurred in 19 and 6 children, respectively. There was no significant difference in the invasion rates between patients with and those without relapses or treatment failures. Also, there was no significant association between biofilm formation and relapse or treatment failure. The improvements in the severity scores after 1 week were significantly associated with the recovery time ( P < 0.0001). We did not identify any significant association between relapse or treatment failure and bacterial factors. AOM has a multifactorial etiology, and this may explain why we could not find a significant association. An improvement in the severity score after 1 week of treatment may be a useful predictor of the outcome of AOM.

A 72-year-old Japanese woman who had been suffering from rheumatoid arthritis for five years started treatment with infliximab. The screening of a chest X-ray before initiating infliximab treatment showed no abnormal shadows. After a month of infliximab, she was admitted to the emergency hospital with a half-month history of a fever, fatigue, dyspnea, and cough. She was diagnosed with tuberculosis from a culture smear and referred to our hospital. The chest images showed a bilateral massive cavity and infiltration. Despite the administration of an anti-tuberculous agent, the cavity and infiltration were enlarged on a chest X-ray and the patient died due to respiratory failure. Cases of tuberculosis resulting in death after a short duration of infliximab treatment have been rarely reported. We speculate that chest CT and the interferon-gamma release assay (IGRA) for tuberculosis screening should be evaluated before starting infliximab treatment, and preventive administration of isoniazid should be considered with consultation with a pulmonologist.

The present study was designed to evaluate inflammatory changes in collapsed lungs during one-lung ventilation using the assistance of a bronchoscopic microsampling probe. Serial albumin and interleukin (IL)-8 concentrations in epithelial lining fluid (ELF) were measured in seven patients undergoing resection of lung tumors. The samples were taken after induction of anesthesia (baseline), 30 min after one-lung ventilation was started (point 2), just before resuming two-lung ventilation (point 3), and 30 min after two-lung ventilation was restarted (point 4). The albumin and IL-8 concentrations in ELF were significantly increased at point 2 and point 3, respectively, and remained to be high, compared to the baseline. The increase in IL-8 at point 3 was correlated with the interval of one-lung ventilation; however, none developed specific acute lung injury. These findings suggest that inflammatory changes can occur on the epithelium of a collapsed lung even in patients who underwent successful and standard thoracic surgery., Article, INFLAMMATION. 35(6):1844-1850 (2012)

IL-13 is a T-helper class 2 cytokine that induces goblet cell hyperplasia and mucus production in airway epithelial cells. Because macrolide antibiotics are known to have immunomodulatory and mucoregulatory properties, the aim of this study was to examine the effect of clarithromycin on IL-13-induced goblet cell hyperplasia and mucin hypersecretion in normal human bronchial epithelial (NHBE) cells. NHBE cells were cultured to differentiation at an air-liquid interface with IL-13 plus clarithromycin or vehicle. Histochemical analysis was performed using H&E staining, periodic acid-Schiff (PAS) staining, and MUC5AC immunostaining. MUC5AC synthesis was assayed using RT-PCR and ELISA. Western blotting was used to evaluate signaling pathways. IL-13 significantly increased the number of PAS-positive, MUC5AC-positive goblet cells, and this was significantly attenuated by clarithromycin at concentrations greater than 8 μg/ml (P < 0.01). Clarithromycin also dose-dependently decreased MUC5AC mRNA expression induced by IL-13 (P < 0.001), and, at 24 μg/ml, clarithromycin significantly attenuated the amount of MUC5AC protein in cell supernatants (P < 0.01). Western blotting showed that clarithromycin affected IL-13 receptor janus kinase signal transducers, activators of transcription6 (STAT6), and epidermal growth factor receptor mitogen-activated protein kinase signaling and that inhibition of these pathways by clarithromycin decreased goblet cell hyperplasia via nuclear factor-κB inactivation. We conclude that clarithromycin inhibits goblet cell hyperplasia and may directly regulate mucus secretion by IL-13 in NHBE cells.

信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第891号)・牛木淳人, Objective The incidence of pulmonary Mycobacterium avium complex (MAC) infections with nodular/bronchiectasis lesions is increasing. However, factors determining deterioration are unknown. In the present study, we investigated quantitative MAC cultures obtained through bronchoscopic microsampling (BMS) from patients with pulmonary MAC infection and analyzed the relationship between MAC culture and the short-term natural history. We also assessed chest computed tomography (CT) findings for the deteriorating factors. Design For this prospective study, MAC was collected from peripheral lung lesions by BMS through endobronchial ultrasonography. MAC colonies were counted on Middlebrook 7H11 agar. We compared the number of MAC colonies with laboratory data and chest CT findings. Patients We studied 26 patients with pulmonary MAC infection. Results The patients were divided into 2 groups: 11 patients in the non-deteriorated group and 15 patients in the deteriorated group. The number of MAC colonies was significantly correlated with deterioration of MAC infection (p, Article, INTERNAL MEDICINE. 50(12):1287-1292 (2011)