Anti-Inflammatory Effects of Japanese Herbal Medicine Hochuekkito in a Mouse Model of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD. METHODS: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22-24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet. RESULTS: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF. CONCLUSION: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.

FGF23-related hypophosphatemia in a patient with small cell lung cancer: a case report and literature review.

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.

Association between Inhalation Instruction Method in Community Pharmacies and Inhaler Device Handling Error in Patients with Obstructive Lung Disease: An Evaluation of the Impact of Practical Demonstration by Pharmacists.

Inhaler devices play an important role in the management of obstructive lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Some of these patients show suboptimal inhaler techniques; however, time for inhaler instruction by pharmacists is limited in daily clinical practice. Therefore, sufficient education regarding inhaler device handling should be provided within a limited time frame. The current study aimed to investigate the instruction methods provided by community pharmacists and their influence on inhaler device handling techniques in outpatient clinical care settings. We retrospectively collected the data of outpatients with obstructive lung diseases who were referred to our hospital and who underwent inhalation technique assessments conducted by community pharmacists. The prevalence of handling errors, clinical characteristics of patients, and instruction methods were analyzed. In total, 138 patients (170 devices) were included in this study. Approximately 70.0% of patients received verbal explanations combined with leaflets about inhaler instructions. In a device-based analysis, 63 (37.1%) of 170 devices had at least one technical error and 18 (10.6%) of the devices had critical errors. Patients without critical errors received practical demonstration instructions from pharmacists combined with leaflets and verbal explanations more frequently than those with critical errors (22.8 vs. 0%, p < 0.01). This study revealed that patients with obstructive lung diseases commonly present with inhaler device handling errors and critical errors were observed with non-negligible frequency in daily practice in Japan. Combined instruction with leaflet, verbal explanation, and pharmacist demonstration may be effective in improving proper inhaler treatment.

Factors affecting in-hospital mortality of non-tuberculous mycobacterial pulmonary disease.

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.

The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema.

Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder. It often causes weight loss, which is considered a poor prognostic factor. A Japanese herbal Kampo medicine, Hochuekkito (TJ-41), has been reported to prevent systemic inflammation and weight loss in COPD patients, but the underlying biological mechanisms remain unknown. In the present study, we investigated the role of TJ-41 in vivo using a mouse model of lung emphysema. We used lung epithelium-specific Taz conditional knockout mice (Taz CKO mice) as the lung emphysema model mimicking the chronic pulmonary inflammation in COPD. Acute inflammation was induced by intratracheal lipopolysaccharide administration, simulating COPD exacerbation. Mice were fed a diet containing 2% TJ-41 or a control diet. Taz CKO mice showed increased numbers of inflammatory cells in the bronchoalveolar lavage fluid compared to control mice. This effect was reduced by TJ-41 treatment. In the acute exacerbation model, TJ-41 mitigated the increased numbers of inflammatory cells in the bronchoalveolar lavage fluid and attenuated lung inflammation in histopathological studies. Additional in vitro experiments using the human macrophage cell line U-937 demonstrated that lipopolysaccharide-induced tumor necrosis factor-alpha expression was significantly downregulated by TJ-41. These results suggest that TJ-41 has anti-inflammatory effects in lung emphysema both in the chronic phase and during an acute exacerbation. In conclusion, our study sheds light on the anti-inflammatory effects of TJ-41 in lung emphysema. This establishes its potential as a new anti-inflammatory therapy and a preventive medicine for exacerbations during the long-time maintenance of COPD patients.

Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.

Naftopidil, an α-1 adrenoceptor antagonist with few adverse effects, is prescribed for prostate hyperplasia. Naftopidil inhibits prostate fibroblast proliferation; however, its effects on lung fibroblasts and fibrosis remain largely unknown. Two normal and one idiopathic pulmonary fibrosis human lung fibroblast lines were cultured with various naftopidil concentrations with or without phenoxybenzamine, an irreversible α-1 adrenoceptor inhibitor. We examined the incorporation of 5-bromo-2'-deoxyuridine into DNA and lactic acid dehydrogenase release by enzyme-linked immunosorbent assay, cell cycle analysis by flow cytometry, scratch wound-healing assay, and mRNA expressions of type IV collagen and α-smooth muscle actin by polymerase chain reaction. Effects of naftopidil on bleomycin-induced lung fibrosis in mice were evaluated using histology, micro-computed tomography, and surfactant protein-D levels in serum. Naftopidil, dose-dependently but independently of phenoxybenzamine, inhibited 5-bromo-2'-deoxyuridine incorporation in lung fibroblasts. Naftopidil induced G1 cell cycle arrest, but lactic acid dehydrogenase release and migration ability of lung fibroblasts were unaffected. Naftopidil decreased mRNA expressions of type IV collagen and α-smooth muscle actin in one normal lung fibroblast line. Histological and micro-computed tomography examination revealed that naftopidil attenuated lung fibrosis and decreased serum surfactant protein-D levels in bleomycin-induced lung fibrosis in mice. In conclusion, naftopidil may have therapeutic effects on lung fibrosis.

Ultrasonographic evaluation of parathyroid hyperplasia in multiple endocrine neoplasia type 1: Positive correlation between parathyroid volume and circulating parathyroid hormone concentration.

There are few reports on parathyroid ultrasonography of multiple endocrine neoplasia type 1 (MEN1). This study investigated the ultrasonographic features of parathyroid glands in 10 patients with MEN1 who underwent preoperative neck ultrasonography and parathyroidectomy between 2006 and 2010 at Toranomon Hospital. We retrospectively analyzed clinical features, laboratory and ultrasonographic data, and pathological diagnosis. A total of 38 parathyroid glands were surgically removed (three to five glands from each patient). All removed parathyroids were pathologically diagnosed as hyperplasia. Seven cases (70.0 %) had adenomatous thyroid nodules. Twenty-five enlarged parathyroid glands (65.8 %) were detected by preoperative ultrasonography with a detection rate of 81.8 % (9/11) and 59.3 % (16/27) for patients without and with adenomatous nodules, respectively. Total parathyroid gland weight and potentially predictable total parathyroid volume by preoperative ultrasonography were significantly correlated with preoperative serum intact parathyroid hormone (iPTH) concentration (R = 0.97, P < 0.001 and R = 0.96, P < 0.001, respectively). The equation used for prediction of the total volume by ultrasonography was 15 × iPTH (pg/ml) - 1,000 and that for total weight was 20 × iPTH (pg/ml) - 1,400. Although adenomatous nodules often coexisted with MEN1 and made identification of enlarged parathyroid glands by ultrasonography difficult, the positive correlation between the predictable parathyroid volume by ultrasonography and serum iPTH suggests that their measurement is useful in the preoperative detection and localization of enlarged parathyroid glands in patients with MEN1. Furthermore, the presence of parathyroid glands that should be resected can be predicted before surgery using the equation proposed here.

Secondary metabolite profiles and antifungal drug susceptibility of Aspergillus fumigatus and closely related species, Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans.

The incidence of Aspergillus infection has been increasing in the past few years. Also, new Aspergillus fumigatus-related species, namely Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans, were shown to infect humans. These fungi exhibit marked morphological similarities to A. fumigatus, albeit with different clinical courses and antifungal drug susceptibilities. The present study used liquid chromatography/time-of-flight mass spectrometry to identify the secondary metabolites secreted as virulence factors by these Aspergillus species and compared their antifungal susceptibility. The metabolite profiles varied widely among A. fumigatus, A. lentulus, A. udagawae, and A. viridinutans, producing 27, 13, 8, and 11 substances, respectively. Among the mycotoxins, fumifungin, fumiquinazoline A/B and D, fumitremorgin B, gliotoxin, sphingofungins, pseurotins, and verruculogen were only found in A. fumigatus, whereas auranthine was only found in A. lentulus. The amount of gliotoxin, one of the most abundant mycotoxins in A. fumigatus, was negligible in these related species. In addition, they had decreased susceptibility to antifungal agents such as itraconazole and voriconazole, even though metabolites that were shared in the isolates showing higher minimum inhibitory concentrations than epidemiological cutoff values were not detected. These strikingly different secondary metabolite profiles may lead to the development of more discriminative identification protocols for such closely related Aspergillus species as well as improved treatment outcomes.

Alectinib-induced Hemolytic Anemia with Positive Direct Antiglobulin Test in a Patient with Lung Adenocarcinoma: A Possible Drug-drug Interaction Effect.

Recent studies have reported that direct antiglobulin test (DAT) results were negative in cases of alectinib-induced hemolytic anemia with abnormal red blood cell (RBC) morphology. We herein report the case of a 72-year-old female patient who was diagnosed with alectinib-induced hemolytic anemia who - in contrast to previous reports - showed a positive DAT result. After discontinuing famotidine and alectinib, the DAT results turned negative; however, when alectinib was resumed, hemolysis recurred. Although alectinib-induced hemolytic anemia has been previously thought to be associated with abnormal morphological changes of the RBCs, we suggest that alectinib-induced anemia may manifest as DAT-positive immune hemolytic anemia because of a complementary effect with other drugs.

Reduction in the need for surgery and mortality after early administration of fibrinolytics following empyema drainage.

OBJECTIVES: Although intrapleural administration of fibrinolytics is an important treatment option for the management of empyema, the addition of fibrinolytics failed to reduce the need for surgery and mortality in previous randomized controlled trials. This study aimed to investigate the effects of administrating fibrinolytics in the early phase (within 3 days of chest tube insertion) of empyema compared with late administration or no administration. METHODS: We used the Japanese Diagnosis Procedure Combination Inpatient Database to identify patients aged ≥16 years who were hospitalized and underwent chest tube drainage for empyema. A 1:2 propensity score matching and stabilized inverse probability of treatment weighting were conducted. RESULTS: Among the 16 265 eligible patients, 3082 and 13 183 patients were categorized into the early and control group, respectively. The proportion of patients who underwent surgery was significantly lower in the early fibrinolytics group than in the control group; the odds ratio (95% confidence interval) was 0.69 (0.54-0.88) in the propensity score matching (P = 0.003) and 0.64 (0.50-0.80) in the stabilized inverse probability of treatment weighting analysis (P < 0.001). All-cause 30-day in-hospital mortality, length of hospital stay, duration of chest tube drainage, and total hospitalization costs were also more favourable in the early fibrinolytics group. CONCLUSIONS: The early administration of fibrinolytics may reduce the need for surgery and death in adult patients with empyema.

A Japanese herbal medicine (kampo), hochuekkito (TJ-41), has anti-inflammatory effects on the chronic obstructive pulmonary disease mouse model.

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.

A large functioning parathyroid cyst in a patient with multiple endocrine neoplasia type 1.

A 62-year-old woman presented with a mass on the left side of the neck. Biochemical testing revealed primary hyperparathyroidism. Further, a prolactinoma was detected, and the patient's son and daughter also had primary hyperparathyroidism, indicating that the patient had multiple endocrine neoplasia type 1 (MEN1). Neck ultrasonography revealed several cystic nodules (≤ 30 mm) that appeared to be adenomatous. After parathyroidectomy with autotransplantation, the largest cystic mass, in the left lower thyroid lobe, was pathologically diagnosed as a functioning parathyroid cyst, and all laboratory data returned to normal. On genetic analysis of blood, we found a novel single base insertion (duplication) in exon 10 codon 552 of the MEN1 gene (c1659dupT) that creates an early stop codon. This is the first case report of a parathyroid cyst resulting from parathyroid hyperplasia in a MEN1 patient.

Putative Bidirectionality of Chronic Obstructive Pulmonary Disease and Periodontal Disease: A Review of the Literature.

The prevalence of chronic obstructive pulmonary disease (COPD) is increasing worldwide and is currently the third leading cause of death globally. The long-term inhalation of toxic substances, mainly cigarette smoke, deteriorates pulmonary function over time, resulting in the development of COPD in adulthood. Periodontal disease is an inflammatory condition that affects most adults and is caused by the bacteria within dental plaque. These bacteria dissolve the gums around the teeth and the bone that supports them, ultimately leading to tooth loss. Periodontal disease and COPD share common risk factors, such as aging and smoking. Other similarities include local chronic inflammation and links with the onset and progression of systemic diseases such as ischemic heart disease and diabetes mellitus. Understanding whether interventions for periodontal disease improve the disease trajectory of COPD (and vice versa) is important, given our rapidly aging society. This review focuses on the putative relationship between COPD and periodontal disease while exploring current evidence and future research directions.

The Link between Periodontal Disease and Asthma: How Do These Two Diseases Affect Each Other?

A growing body of evidence suggests that the effects of poor oral hygiene extend beyond the oral cavity and are associated with a variety of systemic diseases, including asthma. Asthma, which results in symptoms of cough, wheezing, and dyspnoea, and is characterized by airflow limitation with variability and (partial or complete) reversibility, is amongst the most prevalent respiratory diseases with approximately 262 million patients worldwide, and its prevalence and disease burden is on the increase. While asthma can occur at a young age, it can also develop later in life and affects a variety of age groups. Both of these diseases have a chronic course, and various researchers have suggested a link between the two. In this article, we aim to provide a literature review focusing on the association between the two diseases. The results demonstrate that medications (primarily, inhaler medicine), hypoxia induced by asthma, and the breathing behaviour of patients potentially trigger periodontal disease. In contrast, oral periodontopathogenic microorganisms and the inflammatory mediators produced by them may be involved in the onset and/or exacerbation of asthma. Common contributing factors, such as smoking, gastro-oesophageal reflux, and type-2 inflammation, should also be considered when evaluating the relationship between the two diseases.

Effectiveness and safety of the co-administration of Yokukan-San (Japanese herbal medicine) with antipsychotics in hospitalized older patients with pneumonia.

AIM: Behavioral and psychological symptoms and delirium frequently occur in hospitalized older patients with pneumonia and are associated with longer hospital stays. Yokukan-San (YKS, traditional Japanese [Kampo] medicine) and antipsychotics are often used to treat delirium and behavioral and psychological symptoms in Japan. Hence, this study aimed to assess the effectiveness and safety of the co-administration of YKS with atypical antipsychotics in older patients with pneumonia. METHODS: We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify older patients (≥65 years) hospitalized for pneumonia who received antipsychotics within 3 days of hospitalization. The patients were divided into two groups: those who received atypical antipsychotics alone (control group) and those who received both atypical antipsychotics and YKS (YKS group). We compared length of hospital stay, in-hospital mortality, bone fractures, and administration of potassium products between the two groups using propensity score overlap weighting. RESULT: We identified 4789 patients in the YKS group and 61 641 in the control group. After propensity score overlap weighting, length of hospital stay was statistically significantly shorter in the YKS group (percentage difference -3.0%; 95% confidence interval -5.8% to -0.3%). The proportion of patients who received potassium products was higher in the YKS group (odds ratio 1.34; 95% confidence interval 1.15-1.55). In-hospital death and bone fractures were not significantly different. CONCLUSION: Co-administration of YKS with atypical antipsychotics could be a reasonable treatment option for hospitalized older patients with pneumonia and aggressive psychiatric symptoms. Geriatr Gerontol Int 2023; 23: 849-854.

Association between the type of hypnotic drug and in-hospital fractures in older patients with neurocognitive disorders: A case-control study using a nationwide database.

AIM: Hypnotics might increase the risk of falls and fractures in older patients with neurocognitive disorders. Orexin receptor antagonists have recently been approved, but the relationship between the new drugs and fractures remains unclarified. This study aimed to evaluate the association between the type of hypnotic and in-hospital fractures in older patients with neurocognitive disorders using a nationwide inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we collected information on inpatients aged ≥65 years with neurocognitive disorders between April 2014 and March 2021. We examined trends in the prescription patterns of benzodiazepine drugs, Z-drugs, orexin receptor antagonists and melatonin receptor agonists. We also carried out a 1:4 matched case-control analysis of in-hospital fractures. The odds ratio of each hypnotic drug was estimated using a generalized estimating equation with adjustment for walking ability, comorbidities, osteoporosis, dialysis, selective serotonin reuptake inhibitor use and anti-dementia drug use. RESULTS: The prescription of benzodiazepine hypnotics decreased and that of orexin receptor antagonists increased. This case-control analysis included 6832 patients with fractures and 23 463 controls. Ultrashort-acting benzodiazepines, short-acting benzodiazepines and Z-drugs were associated with an increased risk of bone fracture (odds ratio [95% confidence interval] 1.38 [1.08-1.77], 1.38 [1.27-1.50], 1.49 [1.37-1.61], respectively). Orexin receptor antagonists were not associated with an increased risk of bone fracture (1.07 [0.95-1.19]). CONCLUSIONS: In contrast to other types of hypnotics, orexin receptor antagonists were not associated with in-hospital fractures in older patients with neurocognitive disorders. Geriatr Gerontol Int 2023; 23: 500-505.

Association between comprehensive geriatric assessment and polypharmacy at discharge in patients with ischaemic stroke: A nationwide, retrospective, cohort study.

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 < 0·001) and a smaller number of medication types prescribed at discharge (3·84 vs. 3·76, p < 0·001). Interpretation: This study shows the clear evidence that there is a positive relationship between CGA and a reduction in the number of medications in older inpatients with ischaemic stroke. Funding: The Ministry of Health, Labour and Welfare, Japan and the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Measurement of chest wall motion using a motion capture system with the one-pitch phase analysis method.

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 < 0.0001), forced vital capacity (Spearman's ρ = 0.62, p < 0.0001), and tidal volume (Spearman's ρ = 0.61, p < 0.0001) of spirometry and the counterpart parameters of MCO method. Moreover, the MCO method could detect regional rib cage and abdomen compartment contributions and could assess TA asynchrony, indicating almost complete synchronous movement (phase angle for each compartment: - 5.05° to 3.86°). These findings suggest that this technique could examine chest wall motion, and may be effective in analyzing chest wall volume changes and pulmonary function.

Pulmonary disease as a risk factor for transfusion-related acute lung injury.

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.

Multiple cerebral infarctions in ROS1-rearranged lung adenocarcinoma.

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.