Objective Although a relationship between post-challenge hyperglycemia and arterial stiffness has been reported, the relationship between the postprandial glucose levels and cardio-ankle vascular index (CAVI) in non-diabetic subjects is not clear. This study thus evaluated the association between the postprandial glucose levels after a composite meal and the degree of arterial stiffness measured according to CAVI in non-diabetic subjects.
Methods The subjects included 1,291 individuals (655 men and 636 women; mean age, 48.6 years; range, 23-85 years) who underwent medical examinations, including blood tests and CAVI assessments, between October 2005 and April 2012. The 1-hour postprandial glucose levels were determined after a 600-kcal traditional Japanese meal.
Results The CAVI values were significantly higher in the subjects with higher 1-hour postprandial glucose levels (≥140 mg/dL in men; ≥158 mg/dL in women). A simple regression analysis indicated that the CAVI values were significantly correlated with the 1-hour postprandial glucose levels in men (r=0.286, p<0.0001) and women (r=0.228, p<0.0001). After adjusting for age, BMI, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, 1-hour postprandial glucose, homeostatis model assessment of insulin resistance, estimated glemerular filtration rate, and high sensitive C-reactive protein, stepwise multiple regression analysis demonstrated that the 1-hour postprandial glucose level was an independent predictor associated with the CAVI in men (p=0.003) and older women 50 years of age or older (p=0.003).
Conclusion This study demonstrated that the 1-hour postprandial glucose levels are associated with increased CAVI values in non-diabetic men and older women 50 years of age or older.

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Objective Type 2 diabetes is a progressive disease characterized by insulin resistance and insulin secretory dysfunction. In this study, we assessed the factors contributing to an insulin secretory defect in type 2 diabetes patients.
Methods The subjects consisted of 382 patients with type 2 diabetes, aged 57±13 years. We estimated the β-cell function using 6-min post-glucagon increments in C-peptide (ΔCPR).
Results A significant inverse correlation was observed between the time since the diagnosis of diabetes and ΔCPR. A simple liner regression analysis showed that ΔCPR decreases at a rate of 0.056 ng/mL/year. According to a multiple regression model, body mass index (BMI) and log (triglyceride) were positively correlated with ΔCPR. Time since the diagnosis of diabetes, diabetes in 1st degree relatives, the presence of diabetic retinopathy, and HbA1c were inversely correlated with ΔCPR. In 50 patients who underwent the glucagon stimulation test twice, the ΔCPR decreased from 2.27±1.47 to 1.72±1.08 ng/mL over a period of 6.5±0.9 years. A multiple regression analysis revealed the BMI and fasting plasma glucose level to be significant contributing factors to the decline in ΔCPR.
Conclusion The duration of diabetes, a low BMI, genetic factors, and the presence of microangiopathy may be associated with β-cell dysfunction in diabetic patients. The observations in this study suggest that obese subjects showed a rapid decline in the β-cell function despite an initial high CPR response. Environmental factors causing insulin resistance and glucotoxicity may therefore be involved in progressive β-cell failure.

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Objective Analyses of tumor biopsy samples from non-small cell lung cancer patients with acquired epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance are expected to reveal the molecular mechanisms of resistance. However, due to limited tissue availability, performing such analyses can be challenging. We herein investigated the feasibility of tumor rebiopsy in this patient population.
Methods From April 2004 to March 2013, 53 consecutive patients were treated with EGFR-TKIs at our department. A retrospective medical chart review was conducted among patients with progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors criteria, as assessed radiographically. Sites of progression were evaluated at the time of PD.
Results Forty patients experienced PD at the following sites: isolated central nervous system (CNS) in 10 patients; isolated bone in five patients; isolated lymph nodes in two patients; the primary lesion in 10 patients; and systemic disease in 11 patients. Concerning the site of progression, 20 of the 40 patients had a lesion that could be accessed using endobronchial, transbronchial or percutaneous biopsy procedures. Among the 19 patients with oligoprogressive disease or CNS failure, the median overall survival was 24.1 months in eight patients who had received continuing treatment with EGFR-TKIs following radiotherapy and 16.8 months in 11 patients who received other therapies after PD.
Conclusion In this study, few patients had a site of progression capable of being accessed using relatively noninvasive biopsy procedures. Further investigations are warranted to develop more optimal treatment strategies after PD in patients with oligoprogressive disease or CNS failure.

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Objective To assess the outcomes in a large cohort of patients suffering from rheumatic diseases admitted to the ICU of a tertiary university medical center.
Methods A retrospective chart analysis was performed in 108 patients suffering from various rheumatic diseases and the outcomes, including morbidity and mortality, were assessed in relation to the underlying diseases, treatments and complications.
Results Overall, 48 patients with rheumatoid arthritis, five patients with spondyloarthritis, 14 patients with vasculitis, 30 patients with connective tissue diseases and 11 patients suffering from other rheumatologic conditions were admitted to the intensive care unit (ICU). The reasons for ICU admission included infection (30%), cardiovascular complications (22%), gastrointestinal problems (18%), endocrinological disorders (7%), neurological complications (2%) and others (3%). A total of 4% of the admitted patients required close monitoring and 14% suffered from acute exacerbation of the underlying rheumatic disease. The ICU mortality rate was 16%, whereas the overall hospital mortality rate was 20%. Fatal outcomes were related to exacerbation of the rheumatic disease in 14% of the patients, infectious complications in 46% of the patients and other reasons in 41% of the patients. An increased Apache II score, the need for mechanical ventilation, renal replacement therapy, treatment with vasopressor drugs and plasma exchange therapy were identified as risk factors for mortality.
Conclusion The overall outcomes of critically ill patients with rheumatic diseases are impaired compared to that observed in other patient groups. However, there were no significant differences in outcomes between the different rheumatic disease groups or based on the use of immunosuppressive therapy in this study. An increased Apache II score, the need for mechanical ventilation, renal replacement therapy, treatment with vasopressor drugs and plasma exchange therapy were identified as risk factors for mortality.

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Objective Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers.
Methods A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted.
Patients This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011.
Results The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000 /μL than for a WBC count of 4,000-8,000 /μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease.
Conclusion The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

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The diagnosis of NSAID-induced colon ulcers is difficult when the distribution or endoscopic findings are not typical. An 83-year-old woman was transferred to our hospital for hemorrhagic diarrhea. Colonoscopy showed multiple ulcers in the entire colon, particularly longitudinal ulcers in the transverse colon. These were unusual for NSAID-induced colopathy, although she had been on meloxicam. However, capsule endoscopy revealed multiple scars and erosions, characteristic of NSAIDs users. The final diagnosis was NSAID-induced enteropathy, and all lesions were in remission after meloxicam discontinuation. We herein emphasize the value of an endoscopic assessment of the entire digestive tract in the diagnosis of NSAID-induced mucosal lesions.

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Hepatic intracystic hemorrhage is a rare complication of polycystic liver diseases, such as autosomal dominant polycystic kidney disease (ADPKD). A hepatic cyst with mural nodules and septation may suggest the presence of a cystic malignancy, such as biliary cystadenocarcinoma. We herein report a case of hepatic intracystic hematoma with a mural nodule mimicking biliary cystadenocarcinoma in a patient with ADPKD. Hepatic intracystic hemorrhage with a mural nodule is a very rare occurrence. A fat-saturated T1-weighted magnetic resonance image may be useful for making an accurate diagnosis of intracystic hematoma.

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Castleman's disease of the pancreas is extremely rare. To the best of our knowledge, Castleman's disease arising around the main pancreatic duct has not been previously reported. The patient was a 74-year-old man. Abdominal ultrasonography performed at a health check-up revealed a dilated main pancreatic duct. Pancreatic cancer was strongly suspected on various imaging studies. However, the results of a cytological examination of the pancreatic juice were negative for malignancy. The patient did not want to undergo a histological diagnosis by endoscopic ultrasound-guided fine-needle aspiration, thus pylorus-preserving pancreatoduodenectomy was performed. Pancreatic Castleman's disease arising around the main pancreatic was diagnosed by the histopathological examination.

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A 54-year-old woman suffering from pruritus for five years was diagnosed to have Graves' disease and immune thrombocytopenia (ITP) associated with primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome, which was confirmed histologically after a prompt recovery in the platelet count number following steroid therapy. The association between PBC-AIH overlap syndrome and ITP has been rarely reported and the additional association with Graves' disease has not yet been reported. An underlying global derangement of autoimmunity or shared genetic susceptibility was suspected.

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We herein report the first case of Takotsubo cardiomyopathy triggered by influenza A virus. Myocardial involvement in influenza virus infection has been described in 10% of cases. The literature has principally reported cases of acute myocarditis ranging from asymptomatic to fulminant heart failure and cardiac tamponade. Takotsubo cardiomyopathy frequently occurs in the setting of significant emotional or physical stress or acute medical illness, with a predominance in postmenopausal women. We report the diagnosis, management and outcomes presented in this case, with the aim of describing a new cardiovascular complication of influenza virus infection.

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A 67-year-old man with a persistent high fever was diagnosed to have an infective aneurysm in his left internal iliac artery. A blood culture detected a gram-negative spiral rod that was first identified as Campylobacter fetus subsp. venerealis based on a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. However, the strain was finally confirmed to be Campylobacter fetus subsp. fetus based on a genetic analysis. The infection was successfully treated with emergency resection of the aneurysm, followed by 4 weeks of antibiotic therapy. Involvement of the peripheral artery is uncommon in cases of C. fetus-infective aneurysm. To figure out the epidemiology and pathogenicity of C. fetus infection, the accurate identification of the responsible organisms is essential.

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Diabetic ketoacidosis (DKA) is one of the most serious acute complications of diabetes mellitus. An arterial thrombotic tendency from DKA is relatively common; however, the occurrence of acute multiple arteriovenous thromboses is rare. We herein report the case of a 49-year-old man with DKA complicated by multiple thromboses. After transfer to our emergency room with DKA, the patient developed sudden abdominal pain. Contrast-enhanced computed tomography revealed near-complete occlusion of the superior mesenteric artery, superior mesenteric vein, splenic artery, and right femoral artery. This occurrence highlights the need for considering the risk of thrombosis during the initial treatment for DKA.

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Antiphospholipid syndrome (APS) is clinically characterized by arterial or venous thrombosis; however, non-thromboembolic lung manifestations, such as diffuse alveolar hemorrhage (DAH), have also been previously reported. DAH is relatively common in APS patients with systemic lupus erythematosus, although it is rare in primary APS. We encountered a 78-year-old man who presented with hemoptysis and dyspnea. Chest CT showed diffuse ground-glass opacity with pulmonary thromboembolism. He was successfully treated with corticosteroids and heparin; however, DAH recurred after the corticosteroid treatment was stopped. The treatment was intricate due to the concurrent bleeding and thrombotic manifestations.

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We herein present a case of pulmonary aluminosis diagnosed with in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis. The diagnosis of pulmonary aluminosis was supported by the occupational exposure to aluminum, ground glass opacity and ill-defined centrilobular nodular opacities seen in high resolution CT, and respiratory bronchioles accompanied by pigmented dust by histological examination by in-air micro-PIXE analysis of the lung tissues. The possibility of developing this rare condition should not be underestimated in workers at high-risk jobs. This is an important report showing the usefulness of an in-air micro-PIXE analysis for the early diagnosis of aluminosis.

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We herein report the case of a 93-year-old woman with breast cancer on the left side. Preoperative computed tomography of the chest showed irregularities and narrowing of the mid-trachea. Bronchoscopy was performed, and the results of a biopsy supported a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. The patient responded to treatment with prednisone alone, with a reduction in the size of the lesion. MALT lymphoma of the trachea is extremely rare, and there are only a few case reports of double cancer, i.e., MALT lymphoma of the trachea and breast cancer.

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A 49-year-old man was admitted to a hospital with chest pain and polyarthralgia. Chest radiography showed abnormal findings, and chest computed tomography showed a mass in the right lung. A transbronchial lung biopsy led to a diagnosis of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma. Bone scintigraphy revealed bilateral symmetrical accumulations of ^99mTechnetium complexes in the long bones, suggesting co-existing hypertrophic pulmonary osteoarthropathy (HPO). The patient underwent four courses of chemotherapy with cisplatin plus pemetrexed, which led to decreased ^99mTechnetium accumulations in the long bones. To the best of our knowledge, this is the first reported case of HPO associated with ALK-positive lung cancer.

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A 42-year-old woman presented with chest pain and breathlessness with a nodule measuring 2×2 cm in size at the base of the right lung. A bronchoscopic examination did not reveal any malignancy. However, the patient developed difficulty in breathing, enlargement of the nodule, and right pleural effusion 14 days later. A video-assisted thoracic surgical biopsy specimen revealed the presence of pleural synovial sarcoma. The patient was treated with doxorubicin-ifosfamide combination chemotherapy because of metastasis to the pelvis. However, after a transient partial clinical response, there was a relapse of refractory disease. Although treated with pazopanib as second-line chemotherapy, the patient died eight months after the initial presentation.

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Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.

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We report a 65-year-old woman with a chronic hepatitis C virus infection who developed pulmonary extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissues complicated with macroglobulinemia and mixed cryoglobulinemia. She was treated with immunochemotherapy which resulted in the reduction of both the tumors and the serum immunoglobulin (Ig) M level. This case exemplifies an extensive stimulation upon immune system with derangement in the production of immunoglobulines associated with EMZL, and suggests that it is necessary to consider the possibility of B-cell lymphoma when IgM paraprotein is detected.

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Varicella zoster virus (VZV) infection usually manifests with a skin rash. To the best of our knowledge, this is the first report of a case of VZV meningoencephalitis presenting with Elsberg syndrome without a rash in an immunocompetent patient. Clinicians should consider the potential for VZV infection as well as herpes simplex virus infection in cases of aseptic meningitis accompanied by bladder and rectal disturbances, even in patients without any rash symptoms.

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A 30-year-old woman had suffered from recurrent and self-limiting fevers since childhood. Although she had no mutations in the exons or introns of the tumor necrosis factor (TNF) receptor superfamily member 1A gene, her clinical characteristics were consistent with those of TNF receptor-associated periodic syndrome (TRAPS). She did not respond to treatment with etanercept, although tocilizumab therapy was successful, subsequently ameliorating her symptoms and preventing further inflammatory attacks. Interleukin-6 blocking therapy should be considered as a new alternative treatment in patients with TRAPS who do not respond to etanercept.

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Drug reaction eosinophilia with systemic symptoms (DRESS) syndrome is a potentially life threatening condition secondary to the usage of a wide type of drugs. A 38-year-old woman under allopurinol therapy for hyperuricemia was admitted in our department with fever and a diffuse cutaneous erythematous eruption. A few days after admission she developed rapidly progressive signs of acute liver and kidney failure. Subsequently, her clinical conditions shortly improved. The histologic findings obtained from skin and liver biopsies were consistent with a toxic drug reaction. The patient completely recovered and has been healthy for five years.

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