IL-33 Reduces Saturated Fatty Acid Accumulation in Mouse Atherosclerotic Foci.

The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.

Effects of dapagliflozin on renal function in type 1 diabetes patients in the real world: A retrospective multicenter study of the KAMOGAWA-A cohort.

AIMS: This study aimed to investigate the effects of dapagliflozin on renal function of type 1 diabetes patients. METHODS: This retrospective multicenter cohort study enrolled 295 type 1 diabetes patients. The primary outcome was defined as the change in the estimated glomerular filtration rate (eGFR) after 24 months of dapagliflozin treatment. The secondary outcomes were defined as the changes in HbA1c, daily insulin dosage, and urinary albumin-to-creatinine ratio (UACR) after 24 months. RESULTS: Finally, 255 patients were included in the final analysis (dapagliflozin group; 76 patients, non-use group; 179 patients), with a median eGFR of 74.0 mL/min/1.73 m2. A 1:1 propensity score matching was performed, and 142 patients were analyzed in a linear mixed model. The least squares mean change in eGFR in the dapagliflozin group was -3.14 mL/min/1.73 m2 (95% CI: -5.62 to -0.66), a significantly smaller decrease than in the non-use group (-6.94 mL/min/1.73 m2 (95% CI: -9.39 to -4.50)) (p = 0.032). HbA1c level, total insulin dose, and UACR change were significantly lower in the dapagliflozin group than in the non-use group. CONCLUSIONS: At 24 months, the decline in eGFR was significantly lower in the dapagliflozin group than in the non-use group without increasing diabetic ketoacidosis and hypoglycemia.

Eating Behaviors and Incident Cardiovascular Disease in Japanese People: The Population-Based Panasonic Cohort Study 14.

Evidence on common eating behaviors to support the prevention of cardiovascular disease (CVD) in Japanese people is insufficient. This retrospective cohort study aimed to investigate the association of diet behaviors (eg, skipping breakfast, eating speed, snack after dinner, and alcohol consumption) with incident CVD in Japanese individuals. Employees of Panasonic Corporation who underwent the annual health checkups and without a history of CVD at baseline were enrolled. The main outcome was incident 3-point major adverse cardiovascular events (MACE). The secondary outcomes were incident coronary artery disease (CAD) and stroke. To assess the effect of BMI, the subgroup analysis was conducted. In total, 132,795 participants were included. Overall, 3115, 1982, and 1165 participants developed 3-point MACE, CAD, and stroke, respectively. Skipping breakfast (HR: 1.13, 95% CI: 1.03-1.23) and fast eating (HR: 1.23, 95% CI: 1.04-1.47) were associated with 3-point MACE in the participants overall. Skipping breakfast (HR: 1.23, 95% CI: 1.10-1.37) and fast eating (HR: 1.38, 95% CI: 1.12-1.71) were also associated with 3-point MACE in participants with BMI < 25 kg/m2. In contrast, in participants with BMI ≥ 25 kg/m2, these associations were not detectable (P value for the interaction between subgroups = 0.09 [skipping breakfast] and 0.03 [fast eating], respectively). The diet behavior is a potential risk factor of incident CVD in Japanese people, particularly in those with BMI < 25 kg/m2.

A Cortisol-Secreting Adrenal Adenoma Combined With a Micro-Pheochromocytoma: Case Report and Literature Review.

Cushing's syndrome and pheochromocytomas (PCCs) are associated with endocrine hypertension. Cortisol-producing adrenal adenomas are a major cause of Cushing's syndrome. Simultaneous occurrence of cortisol-producing adrenal adenomas and PCCs is rare. Additionally, a PCC generally produces catecholamines in proportion to its size; therefore, micro-PCCs are rarely found in clinical practice. It is unknown whether micro-PCCs produce excess catecholamines during the pre-biochemical phase. Herein, we report the case of a 53-year-old woman who was referred to our hospital for further evaluation of left adrenal incidentaloma. She had been suffering from hypertension for 7 years. Endocrine tests indicated autonomous cortisol secretion, and she was diagnosed with cortisol-producing adrenal adenoma. A laparoscopic left adrenalectomy was performed. The final pathological examination revealed an adrenocortical adenoma measuring 26 × 24 mm. In addition, a micro-PCC measuring 3 × 2 mm was incidentally found near the cortisol-secreting adrenal adenoma in the ipsilateral adrenal gland. All catecholamine biosynthetic enzymes, tyrosine hydroxylase, aromatic l-amino acid decarboxylase, dopamine ß-hydroxylase, and phenyl ethanolamine N-methyltransferase, were detected in this micro-PCC by immunohistochemical analyses. Although catecholamine levels were not biochemically elevated, the PCC expressed catecholamine biosynthetic enzymes. This is the first immunohistochemical report to show that a micro-PCC produces excess catecholamines in the pre-biochemical phase.

Refractory pneumothorax secondary to lung cancer in a patient with idiopathic pulmonary fibrosis.

An unusual case of refractory pneumothorax secondary to lung cancer in a 69-year-old man patient with idiopathic pulmonary fibrosis (IPF) is described. High-pressure suction applied through chest tube did not resolve the large right pneumothorax. Acute exacerbation of IPF has also appeared. Respiratory state worsened acutely, and the patient died on the fifth hospital day. In the present case, the large right pneumothorax was initially thought to be associated with IPF because pneumothorax is common in patients with IPF. However, postmortem microscopic examination revealed that the refractory pneumothorax was secondary to perforation of the pleura due to a necrotic peripheral lung cancer.

Docetaxel and cisplatin as second-line chemotherapy for advanced non-small cell lung cancer.

AIMS AND BACKGROUND: Docetaxel and cisplatin are both active against non-small cell lung cancer (NSCLC). This pilot study evaluated the efficacy and toxicity of docetaxel and cisplatin as second-line chemotherapy for patients with advanced NSCLC. PATIENTS AND METHODS: Eleven patients with advanced NSCLC who had no response to platinum-based treatment or had recurrence after a partial response were enrolled (2 stage III B, 9 stage IV; 8 men, 3 women). Median age was 58 years (range, 40 to 74 years). Seven patients had an Eastern Cooperative Oncology Group performance status of 0, and four had a performance status of 1. Four weeks or more after the end of previous therapy, all 11 patients received docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 every four weeks. RESULTS: Two patients (18.2%) achieved a partial response,five (45.4%) patients had stable disease, and four (36.4%) patients showed progressive disease after initiation of second-line therapy. Median survival was 277 days. Median time to disease progression was 101 days, and the one-year survival rate was 36.4%. Hematological toxicities were moderate. Grade 3 and 4 leukocytopenia and neutropenia were observed in five (45.4%) patients. Grade 3 anemia occurred in one (9 .1%) patient. No severe non-hematological toxicities were observed except grade 3 nausea in two (18.2%) patients. CONCLUSIONS: The regimen of docetaxel and cisplatin has reasonable efficacy with moderate toxicity as second-line chemotherapy for patients with previously treated, advanced NSCLC.

[Chronic necrotizing pulmonary aspergillosis in the surgically treated lung].

A 76-year-old man was admitted because of bloody sputum persisting for 3 months. Right upper lobectomy had been performed for non-small cell lung cancer (well-differentiated adenocarcinoma, pT1NOMO) 6 years prior, and the patient had uncontrolled diabetes. Chest computed tomography on admission showed a 1-cm nodule (fungus ball) in a cavitary lesion and consolidation with an air bronchogram were present in the right lung. Aspergillus flavus was detected in the patient's sputum, and laboratory tests were positive for Aspergillus antigen and antibody. Chronic necrotizing pulmonary aspergillosis (CNPA) was diagnosed in the surgically treated lung.

[Sjögren's syndrome with solitary nodular pulmonary amyloidosis].

We describe a case of limited pulmonary amyloidosis with Sjögren syndrome. A 58-yr-old woman was referred to our hospital because of an abnormal chest radiograph (solitary small nodule) that was examined to investigate the cause of a persistent cough. A chest CT revealed a solitary small nodule in the left lower lung field. The specimens obtained by thoracoscopic surgery showed AL (kappa) amyloid deposits with lymphoplasmacytic infiltrate. Immunofixation of the serum and concentrated urine failed to demonstrate monoclonal immunoglobulins, and no amyloid deposits in the stomach were detected. She was subsequently diagnosed as having primary Sjögren's syndrome. Nodular pulmonary amyloidosis with Sjögren syndrome is very rare condition, and most cases present multiple nodules. As far as is known, this is the first report of a solitary nodule in pulmonary amyloidosis with Sjögren syndrome.

[A case of pulmonary Langerhans' cell histiocytosis].

A 42-yr-old woman was referred to our hospital because of multiple small nodules in a chest radiograph. She had no symptoms such as dyspnea, cough or sputum. A chest CT revealed many centrilobular small nodules and thin-walled cysts with predominance in the peripheral area of the lungs. The specimens obtained by thoracoscopic surgery showed granulomas with scattered eosinophils and numerous Langerhans' cells. The Langerhans' cells were positive for both S-100 protein and CD1a. These findings are compatible with pulmonary Langerhans' cell histiocytosis (LCH). Since the granulomas showed no fibrotic changes, the LCH may have been in its early stages. However, there were clusters of lymphocytes and macrophages around the terminal and respiratory bronchioles, and cystic lesions without cellular infiltrates, in the specimens. The former histologic findings suggested respiratory bronchiolitis causing interstitial lung disease and the latter are indistinguishable from centrilobular emphysema. Therefore, these smoking-related diseases may have been superimposed on the LCH in this patient.

[A case of toxocariasis with eosinophil-rich pleural effusion].

A 68-yr-old man presented with fever, cough, and appetite loss. On admission, clinical examination revealed pleural effusion (with eosinophils accounting for 25% of the cellular component), eosinophilia, and mildly elevated liver enzymes. A diagnosis of toxocariasis was reached on the basis of a positive enzyme-linked immunosorbent assay for Toxocara canis, and the efficacy of steroid and tiabendazole. Typical thoracic involvement of toxocariasis causes cough, wheezing, transient infiltration shadows on the radiographs, and other symptoms of Löffler's syndrome. The infiltration shadows reflect the migration of the larvae through the lung, which involves their breaking through the alveolar walls. We report a rare case of toxocariasis with thoracic and pleural involvement without transient pulmonary infiltrates.

Production of eosinophilic chemokines by normal pleural mesothelial cells.

Eosinophilic pleural effusion occurs in many diseases. The mechanisms of eosinophil accumulation are not well understood. We showed previously that eotaxin was readily detectable in most pleural effusions, and its concentration significantly correlated with eosinophil number. To test the hypothesis that pleural eotaxin is produced by resident mesothelial cells, we examined its production by normal pleural mesothelial cells (NPMC). Eotaxin was induced by tumor necrosis factor (TNF)-alpha or interleukin (IL)-4 and was drastically increased by their combination. In contrast, interferon (IFN)-gamma inhibited eotaxin production. Regulated on activation, normal T cells expressed and secreted (RANTES) was also induced by TNF-alpha and was drastically increased by the addition of IFN-gamma. These effects were observed at both protein and mRNA levels. Stabilization of RANTES mRNA was observed with IFN-gamma but not IL-4; neither cytokine stabilized eotaxin mRNA. Eosinophil chemoattractant activity in culture supernatants of NPMC stimulated with TNF-alpha plus IL-4 was diminished by an anti-eotaxin antibody; that induced by TNF-alpha plus IFN-gamma was attenuated by an anti-RANTES antibody. Thus, NPMC can produce eotaxin, and different cytokines act on NPMC to induce different chemokines by different mechanisms. IFN-gamma, a Th1 cytokine, acts at least at the posttranscriptional level to induce RANTES production, but it inhibits eotaxin production. In contrast, IL-4, a Th2 cytokine, acts at the transcriptional level to induce eotaxin.