A Case of Tumor Lysis Syndrome during Palliative Radiotherapy for Breast Cancer Metastases.

Tumor lysis syndrome (TLS) is the rapid disintegration of a malignant tumor treated with anticancer drugs or radiation, causing electrolyte abnormalities such as elevated uric acid levels, elevated potassium and phosphorus levels, and decreased calcium levels. These abnormalities can lead to hypotension, renal dysfunction, consciousness disorders, and even death in some cases. The current patient was a 65-year-old woman who had breast cancer with local invasion, lung metastasis, and bone metastasis from the time of the initial disease onset. Despite the administration of various chemotherapy and hormone therapy regimens, the tumor increased gradually, and at 2 years and 5 months after the initial onset, pain and bleeding from metastatic infiltration of the cervical lymph nodes were noted. Therefore, radiotherapy was indicated for palliation of pain and bleeding caused by metastatic invasion of the cervical lymph nodes. Irradiation (30 Gy/10fr) was planned with a 3-field technique using 4MVX and 10MVX. Approximately 11 h after the initial irradiation, symptoms such as respiratory distress, tachycardia, and hypotension were observed. Blood tests revealed hyperuricemia and hyperkalemia, leading to a diagnosis of TLS. Dialysis and electrolyte correction were immediately initiated resulting in normalization of electrolytes and stabilization of the blood pressure. It is crucial to understand that TLS is relatively rare but can occur after radiation therapy or in solid tumors, and warrants a prompt response if suspected based on symptoms or blood findings.

Serum cystatin C and CRP are early predictive biomarkers for emergence of hypoxia in COVID-19.

BACKGROUND: In Japan, during the coronavirus disease 2019 (COVID-19) pandemic, patients with non-hypoxia are recommended to recuperate at home or in pre-hospital facilities. However, it was observed that unexpected hypoxia may occur and become severe subsequently in patients whose symptoms were initially expected to improve naturally. The aim of this study is to validate biomarkers that can predict at an early stage the emergence of hypoxia in COVID-19 patients without hypoxia. METHODS: We retrospectively enrolled 193 patients with COVID-19, excluding patients with hypoxia and severe disease from the onset. Participants were classified into two groups according to the emergence of hypoxia during the clinical course, and the laboratory data were compared to identify biomarkers that could predict early the emergence of hypoxia. RESULTS: The areas under the curve for serum cystatin C (CysC) and C-reactive protein (CRP) levels for the emergence of hypoxia during the clinical course were higher than those for other biomarkers (CysC, 0.84 and CRP, 0.83). Multivariate analysis showed that high serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course. CONCLUSIONS: Elevated serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course in COVID-19 patients without hypoxia. These findings may help determine the need for hospitalization in initially non-hypoxic COVID-19 patients.

Pathophysiological relevance of sputum MUC5AC and MUC5B levels in patients with mild asthma.

BACKGROUND: Airway mucus hypersecretion is an important pathophysiological feature of asthma. MUC5AC and MUC5B are the major secreted polymeric mucins in airways, and their compositions affect mucus properties. Despite the increasing appreciation of MUC5AC and MUC5B compositions in asthmatic airways, their pathophysiological relevance remains to be fully understood in humans. METHODS: In this cross-sectional study, we prospectively enrolled newly referred steroid-untreated patients with mild asthma and healthy controls. We compared induced sputum MUC5AC and MUC5B levels between patients and controls. Subsequently, we assessed the correlation between MUC5AC and MUC5B levels and clinical indices in patients. Sputum MUC5AC and MUC5B levels were measured using enzyme-linked immunosorbent assays. RESULTS: Sputum MUC5AC and MUC5B levels were significantly higher in patients (n = 87) than in controls (n = 22) (p = 0.0002 and p = 0.006, respectively). The ratio of sputum MUC5AC to MUC5B tended to be higher in patients than in controls (p = 0.07). Sputum MUC5AC levels significantly and positively correlated with fractional exhaled nitric oxide at expiratory flow of 50 mL/s (Spearman's rho = 0.29, p = 0.006), sputum eosinophil proportion (rho = 0.34, p = 0.0013), and airway sensitivity (rho = 0.39, p = 0.0005). By contrast, sputum MUC5B levels significantly and positively correlated with airway sensitivity (rho = 0.35, p = 0.002) and negatively correlated with airway reactivity (rho = -0.33, p = 0.004). CONCLUSIONS: Sputum MUC5AC is increased by protein levels and involved in airway type 2/eosinophilic inflammation and airway hyperresponsiveness in steroid-untreated patients with mild asthma.

Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products.

INTRODUCTION: Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. METHODS: This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. RESULTS: Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p<0.05). The logistic regression analysis model showed that a younger age and higher education level were associated with the use of HTP (age OR=0.83; higher education level OR=4.63; p<0.05). Many of the current smokers displayed smoking behaviors that are not guaranteed to be safe, such as reducing smoking or switching to lighter cigarettes or HTP. CONCLUSIONS: Patients with COPD who continue smoking tended to have low appetite as well as smoking behaviors that are not guaranteed to be safe. Physicians should provide appropriate guidance to these patients on smoking cessation.

Salt-Sensitive Hypertension of the Renal Tubular Cell-Specific NFAT5 (Nuclear Factor of Activated T-Cells 5) Knockout Mice.

[Figure: see text].

Guaiazulene derivative 1,2,3,4-tetrahydroazuleno[1,2-b] tropone reduces the production of ATP by inhibiting electron transfer complex II.

Molecularly targeted therapy has been used for treatment of various types of cancer. However, cancer cells often acquire resistance to molecularly targeted drugs that inhibit specific molecular abnormalities, such as constitutive activation of kinases. Even in cancer cells that have acquired resistance, enhanced anabolism, including the synthesis of nucleotides, amino acids and lipids, is common to normal cancer cells. Therefore, there is a renewed interest in effectively eliminating cancer cells by specifically targeting their abnormal energy metabolism. Multiple strategies are currently being developed for mitochondrial-targeted cancer therapy, with agents targeting oxidative phosphorylation, glycolysis, the tricarboxylic acid cycle and apoptosis. In this study, we found that one of the guaiazulene derivatives, namely, 1,2,3,4-tetrahydroazuleno[1,2-b] tropone (TAT), inhibited the proliferation of cancer cell lines stronger than that of normal cells. In addition, we showed that TAT inhibited energy production in cancer cell lines, resulting in apoptosis. Analyses done in cancer cell lines and in the animal model Caenorhabditis elegans suggested that TAT acts on the mitochondrial electron transfer complex II and suppresses cellular energy production by inhibiting oxidative phosphorylation across species. These results suggest that TAT could represent a novel anticancer agent that selectively targets mitochondria.

Multicentre Study on the Efficacy of Brachial Artery Transposition Among Haemodialysis Patients.

OBJECTIVE: Brachial artery transposition (BAT) is not a well known method for obtaining vascular access (VA) for maintenance haemodialysis. This study evaluated the outcomes of BAT. METHODS: This multicentre retrospective cohort study included 233 consecutive patients who underwent BAT between January 2012 and December 2013. The indications were inadequate vessels for obtaining VA, severe heart failure, hand ischaemia, central vein stenosis/occlusion, or a history of catheter/graft infection. The transposed brachial artery was used only for arterial inflow and other routes were used for outflow. RESULTS: BAT was successful in 227 patients, and adequate blood flow was achieved during dialysis sessions. The first successful cannulation was after a median of 18 days. BAT was performed using superficial veins as the return route in 127 patients and arteriovenous fistula (AVF) creation in 63 patients to prevent maturation failure. In 41 patients with central venous catheterisation, the transposed brachial artery was used for arterial inflow. The complications of BAT were impaired wound healing in 14 patients, including skin necrosis in two; large aneurysms in six, including a mycotic pseudo-aneurysm in one; arterial thrombosis in five; hand ischaemia in five; lymphorrhoea in four; and haematoma/bleeding in three. The transposed brachial artery was abandoned in four, three, three, and one case of arterial thrombosis/stenosis, haematoma/bleeding, skin necrosis, and large aneurysm, respectively. Access to the return routes failed in 48 cases because of vein damage caused by cannulation in 22, AVF thrombosis/stenosis in 14, catheter infection in six, and catheter occlusion in six. At two years, the primary patency rates of the transposed brachial artery and access circuit were 88% and 54%, respectively. CONCLUSION: BAT is a safe and effective technique. The patency was high for the transposed brachial artery but adequate for the access circuit. BAT can be considered for patients with an unobtainable standard arteriovenous access.

Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS: Sarcopenia is common in patients with chronic obstructive pulmonary disease (COPD). Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with COPD. Thus, the purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and clinical factors. METHODS: In this prospective observational study, we enrolled 234 male outpatients with COPD. We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers and prospectively investigated the relationship of Cr/CysC ratio with the annual exacerbation rate. RESULTS: Serum Cr/CysC was significantly correlated with handgrip strength (r = 0.53, P < 0.01) and muscle mass (r = 0.44, P < 0.01). The area under the curve for sarcopenia was significantly larger for serum Cr/CysC ratio than for other biomarkers (Cr/CysC: 0.87, CysC: 0.63, Cr: 0.61, albumin: 0.57). Multivariate analysis showed no significant difference in the frequency of acute exacerbations between patients in the low- and high-Cr/CysC group, defined by the cutoff value 0.71; however, the frequency of severe acute exacerbations was significantly higher in the low-Cr/CysC group. CONCLUSION: Serum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with COPD. Our study shows that patients with Cr/CysC below 0.71 have poor physical clinical factors and are at high risk of severe acute COPD exacerbations.

Airway Epithelial Dysfunction in Asthma: Relevant to Epidermal Growth Factor Receptors and Airway Epithelial Cells.

Airway epithelium plays an important role as the first barrier from external pathogens, including bacteria, viruses, chemical substances, and allergic components. Airway epithelial cells also have pivotal roles as immunological coordinators of defense mechanisms to transfer signals to immunologic cells to eliminate external pathogens from airways. Impaired airway epithelium allows the pathogens to remain in the airway epithelium, which induces aberrant immunological reactions. Dysregulated functions of asthmatic airway epithelium have been reported in terms of impaired wound repair, fragile tight junctions, and excessive proliferation, leading to airway remodeling, which contributes to aberrant airway responses caused by external pathogens. To maintain airway epithelium integrity, a family of epidermal growth factor receptors (EGFR) have pivotal roles in mechanisms of cell growth, proliferation, and differentiation. There are extensive studies focusing on the relation between EGFR and asthma pathophysiology, which describe airway remodeling, airway hypermucus secretion, as well as immunological responses of airway inflammation. Furthermore, the second EGFR family member, erythroblastosis oncogene B2 (ErbB2), has been recognized to be involved with impaired wound recovery and epithelial differentiation in asthmatic airway epithelium. In this review, the roles of the EGFR family in asthmatic airway epithelium are focused on to elucidate the pathogenesis of airway epithelial dysfunction in asthma.

Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide.

BACKGROUND: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD's usefulness if taken after a virus has already infected airway tissue. OBJECTIVE: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD's experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. CONCLUSION: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. CONCLUSION: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.

Sialylation of MUC4ß N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with type-2 inflammation.

Although type-2-induced (T2-induced) epithelial dysfunction is likely to profoundly alter epithelial differentiation and repair in asthma, the mechanisms for these effects are poorly understood. A role for specific mucins, heavily N-glycosylated epithelial glycoproteins, in orchestrating epithelial cell fate in response to T2 stimuli has not previously been investigated. Levels of a sialylated MUC4ß isoform were found to be increased in airway specimens from asthmatic patients in association with T2 inflammation. We hypothesized that IL-13 would increase sialylation of MUC4ß, thereby altering its function and that the ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) would regulate the sialylation. Using human biologic specimens and cultured primary human airway epithelial cells (HAECs),we demonstrated that IL-13 increases ST6GAL1-mediated sialylation of MUC4ß and that both were increased in asthma, particularly in sputum supernatant and/or fresh isolated HAECs with elevated T2 biomarkers. ST6GAL1-induced sialylation of MUC4ß altered its lectin binding and secretion. Both ST6GAL1 and MUC4ß inhibited epithelial cell proliferation while promoting goblet cell differentiation. These in vivo and in vitro data provide strong evidence for a critical role for ST6GAL1-induced sialylation of MUC4ß in epithelial dysfunction associated with T2-high asthma, thereby identifying specific sialylation pathways as potential targets in asthma.

Dysfunctional ErbB2, an EGF receptor family member, hinders repair of airway epithelial cells from asthmatic patients.

BACKGROUND: Genetic and genomic data increasingly point to the airway epithelium as critical to asthma pathogenesis. Epithelial growth factor (EGF) family members play a fundamental role in epithelial differentiation, proliferation, and repair. Although expression of erythroblastosis oncogene B2 (ErbB2) mRNA, an EGF family receptor, was reported to be lower in asthmatic patients, little is understood about its functional role. OBJECTIVE: We sought to determine whether decreased ErbB2 activation in freshly isolated human airway epithelial cells (HAECs) from asthmatic patients associated with impaired wound closure in vitro. METHODS: An in vitro scratch-wound model of air-liquid interface cultured and freshly isolated HAECs were compared between HAECs from healthy control subjects (HCs) and asthmatic patients in relation to ErbB2. RESULTS: Freshly brushed HAECs from asthmatic patients had impaired ErbB2 activation compared with those from HCs. In an in vitro scratch-wound model, HAECs from asthmatic patients showed delayed wound closure compared with HAECs from HCs. Cell proliferation, as assessed based on [3H] thymidine incorporation after wounding, and expression or activation of ErbB2 and cyclin D1 at the leading edge of the wound were lower in HAECs from asthmatic patients and HCs. A selective ErbB2 tyrosine kinase inhibitor, mubritinib, impaired wound closure and decreased cyclin D1 expression in healthy HAECs, with less effect on cells from asthmatic patients, supporting diminished activity in asthmatic patients. CONCLUSION: These results implicate a primary defect in the ErbB2 pathway as constraining epithelial repair processes in asthmatic patients. Restoration of homeostatic ErbB2 function should be considered a novel asthma therapeutic target.

Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury.

AIM: Metabolic acidosis occurs due to insufficient urinary ammonium excretion as chronic kidney disease (CKD) advances. Because obese subjects tend to have excessive consumption of protein and sodium chloride, they are prone to chronic acid loading and may therefore be predisposed to acid-induced kidney injury. We investigated the involvement of obesity in ammoniagenesis within damaged kidneys. METHODS: In the clinical study, urinary ammonium excretion was compared between 13 normal-weight and 15 overweight/obese CKD outpatients whose creatinine clearance was higher than 25 mL/min. For animal experiments, NH4 Cl was loaded to KKAy/TaJcl (KKAy), a metabolic syndrome model, and control BALB/c mice for 20 weeks. Kidney injury was evaluated through histological analysis and the expression of proinflammatory markers. RESULTS: Urinary ammonium excretion was lower in overweight/obese patients than in normal-weight patients, while intakes of protein and sodium chloride were higher in overweight/obese patients, implying that subclinical metabolic acidosis occurs in overweight/obese patients. The increase in urinary ammonium excretion induced by NH4 Cl loading was attenuated in KKAy mice after 16 weeks, whereas the increase was maintained in BALB/c mice throughout the study period. Histological study and real-time polymerase chain reaction analysis showed proximal tubular injury and enhanced expression levels of neutrophil gelatinase-associated lipocalin (NGAL) protein and messenger RNA, respectively, in KKAy mice but not in BALB/c mice. Finally, urinary NGAL concentration was higher in overweight/obese patients than in normal-weight patients in the early stage of CKD. CONCLUSION: Obesity could facilitate the induction of subclinical metabolic acidosis and acid accumulation in the kidney, which may potentially exacerbate kidney injury in CKD patients.

The collagen-derived compound collagen tripeptide induces collagen expression and extends lifespan via a conserved p38 mitogen-activated protein kinase cascade.

The skin consists mostly of extracellular matrix (ECM) composed mainly of collagen, which provides a protective barrier from the environment. The skin continuously experiences harmful stress and damage. As aging progresses, the expression of various genes declines, and physiological functional deterioration occurs. The reduction of collagen accompanying aging impairs the barrier function of the skin and weakens protection from stressors. In the nematode Caenorhabditis elegans, ECM proteins turn over during aging. Older worms of longevity mutants exhibit increased collagen expression, whereas knockdown of collagen genes shortens lifespan. However, it is unclear whether the progression of aging can be delayed by increasing collagen production via an external stimulus. In this study, we examined the effects of collagen tripeptide (CTP), a collagen-derived compound, on lifespan and aging. Our results showed that CTP upregulated collagen genes via the p38 mitogen-activated protein kinase (MAPK)/SKN-1 pathway. Moreover, CTP extended lifespan and delayed aging through p38 MAPK/SKN-1 pathway. In addition, CTP also induced collagen expression via the p38 MAPK pathway in mammals. Our findings supported that external stimuli such as CTP could promote ECM youthfulness using a conserved signaling pathway, thereby contributing to suppression of aging.

Sensitization to Staphylococcus aureus enterotoxins in smokers with asthma.

BACKGROUND: Sensitization to Staphylococcus aureus enterotoxins (SEs) augments eosinophilic inflammation in asthma. Recent epidemiologic studies demonstrate that sensitization to SEs is increased in healthy smokers; however, there is no evidence on the association between sensitization to SEs and eosinophilic inflammation in smokers with asthma. OBJECTIVE: To clarify the role of SEs on clinical indexes, including eosinophilic inflammation and lung function in smokers with asthma. METHODS: The frequency of atopic sensitization to SEs was examined in adult patients with asthma. In current or ex-smokers with asthma, the association of sensitization to SEs with eosinophilic inflammation, airflow limitation, or treatment steps was determined. Clinical indexes were examined at the first visit, and treatment steps were assessed 6 months after enrollment. RESULTS: Overall, 23 current smokers, 40 ex-smokers, and 118 never smokers with asthma were enrolled. The frequency of sensitization to SEs, but not to other aeroallergens, was significantly higher in current, ex-, and never smokers, in decreasing order. In current or ex-smokers with asthma, patients with sensitization to SEs exhibited higher serum levels of total and specific IgE to aeroallergens, higher blood eosinophil counts, greater airflow limitation, and more severe disease 6 months later than those without sensitization to SE. A longer smoking abstinence period was associated with serum specific IgE levels to SEs, and 3 years was the best cutoff of abstinence period to predict the absence of sensitization to SEs. CONCLUSION: Sensitization to SEs is increased in smokers with asthma, and it may be a marker of eosinophilic inflammation and severe asthma in smokers with asthma. TRIAL REGISTRATION: umin.ac.jp Identifier: UMIN000007818.

Staphylococcus aureus enterotoxin sensitization involvement and its association with the CysLTR1 variant in different asthma phenotypes.

BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. OBJECTIVE: To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. METHODS: We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. RESULTS: A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. CONCLUSION: SE sensitization contributes to TH2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.

Hypereosinophilic obliterative bronchiolitis clinically mimicking diffuse panbronchiolitis: four-year follow-up.

A 73-year-old man with a known history of asthma presented with dyspnea, worsening wheezing and a productive cough complicated by chronic sinusitis. Chest computed tomography showed bronchial wall thickening with centrilobular nodules and ground-glass opacity in the right lower lobe. Features meeting the diagnostic criteria for diffuse panbronchiolitis (DPB) were identified, and lobectomy confirmed the presence of lung cancer. Over the subsequent four years, the patient's symptoms worsened. We reevaluated a lung lobe specimen, which showed hypereosinophilic obliterative bronchiolitis (HOB). A transbronchial lung biopsy also indicated bronchitis with eosinophilic infiltration. Our initial diagnosis of DPB was subsequently changed to HOB after four years. We herein describe this case of HOB, which was initially diagnosed as DPB primarily based on high-resolution computed tomography, with a focus on the histopathology and long-term clinical course. This is the first report to document the long-term clinical course of HOB.

Massive haemoptysis following dabigatran administration in a patient with bronchiectasis.

We report a case of life-threatening haemoptysis after administration of dabigatran in a patient with bronchiectasis. A 72-year-old woman had received dabigatran at a dose of 110 mg twice daily for chronic atrial fibrillation. She was admitted to our hospital for cerebral infarction after a few days of self-interruption of dabigatran. After the diagnosis of cerebral infarction, administration of dabigatran was restarted. Seven days later, she suffered acute-onset massive haemoptysis and required mechanical ventilation. Dabigatran treatment was discontinued, and bronchial artery embolisation (BAE) was performed twice. The bleeding continued for 11 days, but she recovered and was discharged on day 58 after admission.

[A case of postoperative thymic carcinoma recurrence that was effectively treated with combination chemotherapy of nedaplatin and docetaxel].

We report a case of postoperative recurrence of thymic carcinoma that was effectively treated with combination chemotherapy of nedaplatin(NDP)and docetaxel(DOC). We performed thymectomy for thymoma in a 55-year-old man. The pathological diagnosis was squamous cell thymic carcinoma(pT3N0M0, Stage III). The patient was observed without postoperative radiotherapy being administered. Six months after the operation, the patient was admitted to our department with carcinomatous pericarditis. Whole-body examination revealed multiple lung and liver metastases and a left femoral metastasis. After pericardiocentesis, radiation therapy was administered for the left femoral metastasis. Combination chemotherapy (NDP[60mg/m2]/DOC[70mg/m2])was administered for the multiple lung and liver metastases. After 4 cycles of chemotherapy, the multiple lung metastases were completely resolved and the liver metastases were clearly reduced. Partial response and acceptable toxicity were identified. Thymic carcinoma is a rare epithelial neoplasm for which the optimal chemotherapy regimen has not yet been established. Combination chemotherapy with NDP/DOC was effective in the case of our patient with postoperative thymic squamous cell carcinoma recurrence, and it can be considered as a promising regimen for patients from the standpoint of clinical efficacy.

Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids.

BACKGROUND: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. OBJECTIVE: We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. METHODS: Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. RESULTS: High serum periostin levels (≥ 95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). CONCLUSIONS: Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.