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Abstract Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.

Although there are a few case reports of patients with small cell lung cancer developing hypophosphatemia, detailed information on this condition is scarce. A 52-year-old patient with advanced stage small cell lung cancer developed hypophosphatemia (1.1 mg/dL) during chemotherapy. A reduced level of the tubular reabsorption of phosphate concomitant with an inappropriately elevated level of fibroblast growth factor (FGF) 23 (48.4 pg/mL) was noted, leading to the diagnosis of FGF23-related hypophosphatemia. Laboratory data also showed hypercortisolemia with an elevated ACTH level and hyponatremia with an inappropriately unsuppressed level of antidiuretic hormone (ADH). These data suggested the overproduction of FGF23 in addition to ACTH and ADH. Because the octreotide loading test did not present a suppressive effect on ACTH or FGF23 levels, the patient was treated with phosphate supplementation, active vitamin D and metyrapone, which partially improved the serum phosphate and cortisol levels. Even after two subsequent courses of chemotherapy, the small cell lung cancer progressed, and the FGF23 level was further elevated (83.7 pg/mL). Although it is very rare, FGF23-related hypophosphatemia is one of the hormonal disturbances that could be observed in patients with small cell lung cancer. This article reviews similar clinical conditions and revealed that advanced states of malignancy seemed to be associated with the development of renal wasting hypophosphatemia, especially in lung cancer and prostate cancer. Therefore, the parameters related to hypophosphatemia should be monitored in patients with advanced small cell lung cancer to prevent the development of hypophosphatemic osteomalacia.

Abstract Spirometry is a standard method for assessing lung function. However, its use is challenging in some patients, and it has limitations such as risk of infection and inability to assess regional chest wall motion. A three-dimensional motion capture system using the one-pitch phase analysis (MCO) method can facilitate high precision measurement of moving objects in real-time in a non-contacting manner. In this study, the MCO method was applied to examine thoraco-abdominal (TA) wall motion for assessing pulmonary function. We recruited 48 male participants, and all underwent spirometry and chest wall motion measurement with the MCO method. A significant positive correlation was observed between the vital capacity (Spearman’s ρ = 0.68, p

Abstract Background The incidence and prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) are reportedly increasing in many parts of the world. However, there are few published data on NTM-PD-related death. Using data from a national inpatient database in Japan, we aimed in this study to identify the characteristics of patients with NTM-PD and clinical deterioration and to identify risk factors for in-hospital mortality. Methods We examined data from the Diagnosis Procedure Combination (DPC) database in Japan from July 2010 to March 2014. We extracted data for HIV-negative NTM-PD patients who required unscheduled hospitalization. We evaluated these patients’ characteristics and performed multivariable logistic regression analysis to identify risk factors for all-cause in-hospital mortality. Results A total of 16,192 patients (median age: 78 years; women: 61.2%) were identified. The median body mass index (BMI) was 17.5 kg/m2 (IQR 15.4–20.0). All cause In-hospital death occurred in 3166 patients (19.6%). The median BMI of the patients who had died was 16.0 kg/m2 (IQR 14.2–18.4). Multivariable analysis revealed that increased mortality was associated with male sex, lower BMI, lower activities of daily living scores on the Barthel index, hemoptysis, and comorbidities, including pulmonary infection other than NTM, interstitial lung disease, pneumothorax, and malignant disease. Conclusions We found associations between being underweight and having several comorbidities and increased in-hospital mortality in patients with NTM-PD. Preventing weight loss and management of comorbidities may have a crucial role in improving this disease’s prognosis.

Summary: Background: Polypharmacy and its adverse drug events are a major healthcare challenge related to falls, hospitalisations and mortality. Comprehensive geriatric assessment (CGA) may contribute to polypharmacy improvement, however, there is no clear evidence so far. Methods: Using a national inpatient database in Japan from April 1, 2014 to March 31, 2018, we investigated the association between CGA and polypharmacy. We identified patients aged ≥65 years admitted for ischaemic stroke who could receive oral medications. Propensity score matching was conducted for patients with and without CGA during hospitalisation. The outcomes were polypharmacy (defined as use of five or more types of oral medications) at discharge, the number of medication types prescribed at discharge, and the difference between the numbers of medication types prescribed on admission and at discharge. Findings: A total of 162,443 patients were analysed, of whom 39,356 (24·2%) received CGA, and propensity score matching identified 39,349 pairs. Compared with non-CGA group, the CGA group had a significantly lower proportion of polypharmacy at discharge (34·3% vs. 32·9%, p

Lung hepatoid adenocarcinoma (HAC) is a rare primary lung carcinoma pathologically characterized by hepatocellular carcinoma-like tumor cells, the majority of which produce alpha-fetoprotein (AFP). The clinical prognosis of lung HAC is generally poor, and effective therapeutic regimens for inoperable or recurrent cases have not been established. Here, we report a case of AFP-producing lung HAC with brain metastasis with long-term disease control, treated with the 5-fluorouracil-derived regimen S-1. The patient was a 66-year-old male admitted to the hospital with alexia. Chest X-ray revealed a massive tumor in the left upper lobe, and a head CT scan revealed a metastasis in the left parietal lobe. The laboratory data showed a remarkably elevated AFP level (97,561 ng/mL). Pathological assessment of the resected brain tumor revealed HAC, which was compatible with the lung biopsies. Together with the absence of other metastatic lesions, a final diagnosis of primary lung HAC, stage IV T4N3M1b, was given. The patient first underwent non-small cell lung cancer chemotherapy regimens (carboplatin and paclitaxel as the first line, and pemetrexed as the second line), but had clinical progression. After third-line oral S-1 (tegafur/gimeracil/oteracil) administration, the serum AFP level significantly dropped and the patient achieved long-term disease control without relapse, surviving more than 19 months after disease presentation. The autopsy result was consistent with the diagnosis of primary lung HAC, and immunohistochemical staining was AFP+, glypican 3+, and spalt-like transcription factor 4+. Here, we report the case of a rare primary lung HAC with apparent disease control on S-1 therapy, together with a literature review.

Malignant tumors are often associated with eosinophilic pleural effusion. Here, we encountered a case of interleukin‐5 (IL‐5)‐producing malignant pleural mesothelioma with eosinophilic pleural effusion. The patient was a 50‐year‐old male. He had a history of a cough for several weeks and had visited a local doctor. Left pleural effusion was noted, and the patient was referred to our hospital. He was diagnosed with malignant pleural mesothelioma by pleural biopsy, with eosinophilic pleural effusion. IL‐5 in the pleural effusion increased, and tumor cells were IL‐5‐positive by immunostaining. There have been few reports of IL‐5‐producing tumors, and this is the first report of IL‐5‐producing malignant pleural mesothelioma. Host‐tumor cell interactions cause eosinophilic pleural effusion. In patients with eosinophilic pleural effusion, malignant pleural effusion should be considered. It is necessary to clarify the pathophysiology of malignant tumors and eosinophils.

Abstract Rearrangements of specific tyrosine kinases are associated with an elevated risk of venous thrombosis in lung adenocarcinoma, although their effects on arterial thrombosis have not been fully elucidated. Here, we report two cases of ROS proto‐oncogene 1 (ROS1)‐rearranged lung adenocarcinoma with cerebral infarction during the peri‐diagnostic period. Two cases took contrasting clinical courses: one patient could not receive targeted therapy because of a significant decline in performance status, whereas in the other patient, the performance status was maintained and targeted therapy drastically reduced the tumour size. Our cases suggest close monitoring could be considered in the selected cohort.

Transfusion-related acute lung injury (TRALI) is a severe condition characterised by noncardiogenic pulmonary oedema that develops within 6 h of blood transfusion. Patient factors and blood products have both been implicated in the development of TRALI; however, the role of pulmonary disease has not been investigated. We aimed to determine whether pulmonary disease is a risk factor for TRALI. We conducted a nested case-control study using data from the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan, between July 2010 and March 2015. Case patients who developed TRALI were 1:4-matched with control patients for sex, age and same hospital for receipt of blood transfusion. We conducted a multivariable conditional logistic regression analysis to evaluate the associations of TRALI with various factors including comorbidities, body mass index (BMI) and plasma-containing blood products. We identified 2 019 501 hospitalised patients who received a blood transfusion. Among these patients, 72 developed TRALI. The 72 case patients had higher proportions of haematological malignancy, trauma and interstitial lung disease (ILD) than the 288 matched control patients. The multivariable conditional logistic regression analysis showed that occurrence of TRALI was associated with ILD (odds ratio, 3.88; 95% confidence interval, 1.11–13.6), BMI ≥25.0 kg·m−2 (2.10; 1.05–4.24) and plasma-containing blood products (1.94; 1.10–3.42), but not with infectious lung disease or obstructive airway disease. In conclusion, ILD was an independent risk factor for the development of TRALI. Physicians should be aware of the increased risk of TRALI in patients with ILD.

Background: Comprehensive geriatric assessment (CGA) is a multidimensional and multidisciplinary method to identify geriatric conditions among older patients. The aim of the present study was to examine the associations between CGA and short-term outcomes among older adult inpatients with stroke. Methods: The study was a nationwide, retrospective cohort study. We used the Diagnosis Procedure Combination database, a national Japanese inpatient database, to identify older adult stroke patients from 2014 to 2017. The associations between CGA and in-hospital mortality, length of hospital stay, readmission rate, rehabilitation intervention, and introduction of home health care were evaluated using propensity score matching and instrumental variable analysis. Findings: We identified 338,720 patients, 21·3% of whom received CGA. A propensity score-matched analysis of 53,861 pairs showed that in-hospital mortality was significantly lower in the CGA group than in the non-CGA group (3·6% vs. 4·1%, p < 0·001). The rate of long-term hospitalization (> 60 days) was significantly lower in the CGA group than in the non-CGA group (8·7% vs. 10·1%, p < 0·001), and the rates of rehabilitation intervention (30·3% vs. 24·9%, p < 0·001) and home health care (8·3% vs. 7·6%, p = 0·001) were both higher in the CGA group than in the non-CGA group. Instrumental variable analysis showed similar results. Interpretation: CGA was significantly associated with the examined short-term outcomes. These findings from Japan, one of the most aged countries worldwide, highlight the possible benefits of CGA for short-term outcomes and can be of use for health policy in other international contexts. Funding: This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and H30-Policy-Designated-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141).

Preventing falls and bone fractures in hospital care is an important issue in geriatric medicine. Use of hypnotics is a potential risk factor for falls and bone fractures in older patients. However, data are lacking on the association between use of hypnotics and the occurrence of bone fracture.We used a national inpatient database including 1,057 hospitals in Japan and included dementia patients aged 50 years or older who were hospitalized during a period of 12 months between April 2012 and March 2013. The primary outcome was the occurrence of bone fracture during hospitalization. Use of hypnotics was compared between patients with and without bone fracture in this matched case-control study.Of 140,494 patients, 830 patients suffered from in-hospital fracture. A 1:4 matching with age, sex and hospital created 817 cases with fracture and 3,158 matched patients without fracture. With adjustment for the Charlson comorbidity index, emergent admission, activities of daily living, and scores for level walking, a higher occurrence of fractures were seen with short-acting benzodiazepine hypnotics (odds ratio, 1.43; 95% confidence interval, 1.19-1.73; P

Background: Proper artificial nutrition for patients who are unable to eat normally is an ongoing, unresolved concern in geriatric medicine and home medical care. Controversy surrounds prognostic differences between parenteral and enteral nutrition, 2 methods for artificial nutrition. Objectives: Short-term outcomes of parenteral and enteral nutrition for patients who are unable to eat normally were compared and analyzed. Design: Data were acquired from patients selected from a national inpatient database covering 1057 hospitals in Japan. Participants had received artificial nutrition between April 2012 and March 2013, were aged ≥20 y, and did not have cancer. They were separated into 2 groups: those who received parenteral nutrition and those who received enteral nutrition. We performed one-to-one propensity score matching between the groups. The primary outcome measurements were mortality rates at 30 and 90 d after the start of the procedure. The secondary outcomes were postprocedural complications, pneumonia, and sepsis. We analyzed survival length of stay after the procedure with the use of a Cox proportional hazards model. Results: There were 3750 patients in the parenteral group and 22,166 patients in the enteral group. Propensity score matching created 2912 pairs in the 2 groups. Patients with a similar propensity score (probability of being assigned to the enteral group) calculated from the baseline condition were matched. Mortality rates at 30 and 90 d after start of treatment were 7.6% and 5.7% (P = 0.003) and 12.3% and 9.9% (P = 0.002) in the parenteral and enteral groups, respectively. In Cox regression analysis, the HR for the enteral group relative to the parenteral group was 0.62 (95% CI: 0.54, 0.71; P < 0.001). The incidences of postprocedural pneumonia and sepsis were 11.9% and 15.5% (P > 0.001) and 4.4% and 3.7% (P = 0.164) for the parenteral and enteral groups, respectively. Conclusion: The present analysis showed the better survival rate with enteral compared with parenteral nutrition for adults who were not suffering from cancer. This trial was registered at clinicaltrials. gov as NCT02512224. [ABSTRACT FROM AUTHOR]