Thyroid hormone plays an important role in regulating the lipid and glucose metabolism. Previously, much attention has been drawn to define the pathophysiological relationship between thyroid dysfunction and the incidence of cardiovascular diseases (CVDs). While the conditions of overt hypothyroidism and subclinical hypothyroidism were both emphasized, the association between CVD risks and the deregulated circulating thyroid-stimulating hormone (TSH) level remains to be elucidated. Nevertheless, multiple TSH-mediated physiological adaptations, including alteration of the serum lipids, body mass index, blood pressure and insulin sensitivity, have led to the difficulty of clearly examining the association between the TSH level and CVD prevalence. The current review aims to 1) summarize the evidence for the role of thyroid dysfunction and TSH abnormality in CVD pathogenesis and 2) explore the possible underlying molecular mechanisms of TSH-mediated cardiovascular pathology in hopes of providing better therapeutic strategies for the patients with deregulated TSH.

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Objective Right-sided type colonic diverticulosis has been predominant in Japan, in contrast to European counties where the left-sided type is predominant. Considering the recent change in the dietary habits of Japanese people to a more Western diet in urban areas of Japan, the features of colonic diverticulosis may also change to reflect a more Western type. Therefore, we attempted to clarify the current situation.
Methods A total of 435 consecutive outpatients who agreed to a barium enema and complete examination were enrolled in this study.
Results 113 patients (26.0%) revealed colon diverticulosis; 50.4% of the patients had more than ten diverticula. The percentage of man with ten or more diverticula (67.4%) was significantly higher than that of women patients (40.0%, p<0.01). Among the 88 patients who had four or more diverticula, 39 patients (44.3%) were right-side dominant, 27 (30.7%) left-side dominant and 22 (25.0%) were both-sides. Thirteen (68.4%) of the 19 patients who had more than 30 diverticula were left-side dominant.
Conclusion The clinical features of colon diverticulosis in the patients living in Yokohama may be changing to reflect a more Western type, in particular decreased right-side dominance, increases in the left-side and both-sides dominant patients, and the emergence of patients with crowded diverticula in the left-side colon was observed.

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Objective This study evaluated the efficacy and safety of triple therapy with telaprevir (TVR), pegylated interferon α-2b (PegIFN-α-2b) and ribavirin (RBV) in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1b in real-world clinical practice.
Methods A total of 106 consecutive patients with HCV genotype 1b were treated with triple therapy for 12 weeks followed by dual therapy with PegIFN-α-2b and RBV for 12 weeks. The primary end point was sustained virological response (SVR), defined as undetectable serum HCV RNA at 24 weeks after the end of treatment.
Results The overall SVR rate was 87.7% (93/106 patients). Age and body weight (BW) differed significantly between patients with and patients without SVR. Multivariate analysis showed that age <67 years [odds ratio (OR) 5.03, p=0.014] and BW ≥55 kg (OR 5.87, p=0.008) were independent pretreatment factors predictive of SVR. When posttreatment factors were included, age <67 years (OR 7.30, p=0.041), rapid virological response (OR 10.60, p=0.019) and continuation of therapy (OR 14.45, p=0.012) were each independently associated with SVR. Body weight <55 kg (OR 5.96, p=0.015) and TVR initial dose ≥41 mg/kg/day (OR 5.19, p=0.017) were each independently associated with discontinuation of therapy. Discontinuation rates decreased in inverse proportion to the percentage of patients with an initial TVR dose of 1,500 mg/day.
Conclusion For TVR-based triple therapy, continuation of therapy is the most important predictor of SVR. Patients who are likely intolerant of standard-dose TVR should receive reduced initial doses of TVR to avoid discontinuation of therapy.

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Objective The purpose of this study was to determine the differences in emotional distress among three groups of inpatients with type 1, obese type 2, and non-obese type 2 diabetes during hospitalization.
Methods The 42 participating inpatients were divided into three groups: type 1 diabetes (n=11), obese type 2 diabetes [body mass index (BMI) ≥25 kg/m²; n=24], and non-obese type 2 diabetes (BMI <25 kg/m²; n=7). The Problem Areas in Diabetes (PAID) scale, which is a self-administered questionnaire to assess emotional distress in the patients with diabetes, was performed at admission and discharge.
Results The total PAID score was similar and tended to improve during hospitalization in all three groups, although there were differences among the groups in the scores of particular questions. At admission, the score of the question "worrying about low blood sugar reactions?" was significantly different among the three groups and highest in the patients with type 1 diabetes. At discharge, the score of "not accepting diabetes?" was significantly different among the three groups and highest in the patients with non-obese type 2 diabetes, while that of "feeling unsatisfied with your diabetes physician?" was significantly different among the three groups and highest in the patients with obese type 2 diabetes. The score of "feelings of deprivation regarding food and meals?" significantly worsened in the patients with obese type 2 diabetes during hospitalization compared with the patients in with non-obese type 2 diabetes.
Conclusion The characteristics of emotional distress during hospitalization varied among the patients with the three types of diabetes, thus emphasizing the importance of tailoring support according to the type of diabetes.

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Objective Chronic obstructive pulmonary disease (COPD) is often associated with concomitant systemic manifestations and comorbidities, such as cardiovascular disease. There are limited data regarding airflow limitation (AL) and atherosclerosis in Japanese patients, and the potential association between AL and arterial stiffness has not yet been investigated in Japanese patients. Therefore, the purpose of this study was to investigate the association between AL severity and arterial stiffness using the brachial-ankle pulse wave velocity (baPWV).
Methods This cross-sectional study included 1,356 subjects aged 40-79 years without clinical cardiovascular diseases who underwent a comprehensive health screening that included spirometry, the baPWV measurement, and blood sampling during medical check-ups in 2009 at the Japanese Red Cross Kumamoto Health Care Center. AL was defined in accordance with the Global Initiative for COPD criteria (forced expiratory volume in one second / forced vital capacity of < 0.7). A cut-off baPWV value of >1,400 cm/s was used for risk prediction and screening.
Results The average baPWV (SD) results were 1,578.0 (317.9), 1,647.3 (374.4), and 1,747.3 (320.1) cm/s in the patients with a normal pulmonary function, mild AL, and moderate-to-severe AL, respectively (p< 0.001). Using logistic regression models adjusted for the age, body mass index, smoking status, hypersensitive C-reactive protein levels, hypertension, hyperglycemia, and dyslipidemia, an increased baPWV (>1,400 cm/s) was significantly associated with moderate-to-severe AL compared with a normal pulmonary function (odds ratio=2.76; 95% confidence intervals, 1.37-5.55; p=0.004).
Conclusion Our results indicated an association between AL and increased arterial stiffness. Arterial stiffness may therefore worsen with an increase in the severity of AL.

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Objective We examined the prevalence and clinical features of primary exercise headache (PEH) in middle-aged Japanese population.
Methods A headache specialist interviewed middle-aged subjects serially on health check-up. The primary headaches were diagnosed according to the International Classification of Headache Disorders (ICHD-III beta). Cardiovascular disease (CVD) risk and radiological findings were analyzed. Prevalence of PEH and clinical features were assessed.
Results Among 2,546 subjects (1,588 men and 958 women), thirty subjects (13 men and 17 women) were diagnosed with PEH. The prevalence of PEH was 1.19%, 0.82% in men and 1.77% in women. The mean age [standard deviation (SD)] of the subjects was 44.3 (8.8) years and their mean duration (SD) of PEH was 4.5 (7.0) months. Headache occurred bilaterally (23 patients) or unilaterally (7 patients), and in the occipital (16 patients), frontal (10 patients) or diffuse region (4 patients). The persistent headache time ranged from 5 minutes to 12 hours. The degree of headache severity was classified as mild (13 patients), moderate (5 patients) or severe degree (12 patients). PEH was triggered by gym training (16 patients), swimming (6 patients), running (6 patient) and skiing (2 patients). All patients were exercise beginners or played a sport occasionally. No patients visited physicians for headache consultation. Other primary headaches coexisted in 20 patients (67%). Twenty patients had migraine without aura (MO). Seven patients had headache associated with sexual activity. Five patients had cough headache. Two patients had CVD risk factors.
Conclusion The present study of PEH indicated the prevalence of 1.2% and the female/male ratio of 2.1 in middle-aged Japanese. The comorbidity rate of MO was high. PEH may not be an uncommon headache in middle-aged MO sufferers and sport beginners.

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Objective There appears to be differences in the clinical presentation of hereditary angioedema (HAE) and angiotensin-converting enzyme inhibitor-induced (ACE-I) angioedema (AE). The aim of this study was to compare the clinical characteristics of these two AE forms.
Methods We conducted a retrospective study of consecutive patients with HAE or ACE-I AE. The attack characteristics experienced by the patients were compared by a logistic regression analysis using generalized estimating equations.
Results A total of 56 patients were included in this study (ACE-I AE, n=25; HAE, n=31). A total of 534 attacks were documented. Severe attacks were more common in the patients who had an acute episode of ACE-I AE than HAE. Swelling of the tongue, lips and larynx were significantly associated with ACE-I AE [OR: 8.70 (95% CI, 1.04-73.70), OR: 20.4 (95% CI, 4.9-84.2) and OR: 7.50 (95% CI, 1.20-48.30), respectively].
Conclusion Swelling of the tongue, lips and larynx are significantly more frequent in drug-induced AE than HAE.

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Objective Patients diagnosed with psoas abscess have a high mortality rate. The major cause of its poor prognosis is delayed treatment. Therefore, making a correct diagnosis rapidly is important. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered to be the gold standards as imaging modalities that have a high sensitivity for detecting psoas abscess. There have been few reports regarding the limitations of these methods, but psoas abscess in its early stage may go undetected by CT and MRI.
Methods Detection of psoas abscess by CT and MRI was investigated in the present study through a retrospective review of 15 patients in whom psoas abscess was diagnosed during a course of ten years at our hospital.
Results In all patients, psoas abscess was diagnosed by at least a plain CT, enhanced CT, and/or plain MRI. The interval between the onset of symptoms and diagnosis was 20.9±17.9 days (mean ± standard deviation). In three patients, repeat imaging identified a psoas abscess, whereas initial imaging failed to detect it. The overall sensitivity of plain CT, enhanced CT, and plain MRI for psoas abscess was 78%, 86%, and 88%, respectively. From six days after the onset of symptoms, the sensitivity of each modality was 100%, while the sensitivity from day one to five days was only 33%, 50%, and 50%, respectively.
Conclusion Although CT and MRI are considered to be gold standard modalities for diagnosing psoas abscess, both methods can fail to notice this condition in its early stage.

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A 50-year-old woman who presented with a one-month history of abdominal fullness and dyspnoea was admitted to our hospital. Esophagogastroduodenoscopy showed the scirrhous-type gastric cancer on the greater curvature of the gastric body. Computed tomography revealed bilateral large ovarian tumours with massive right pleural effusion and ascites. A repeated cytological examination of pleural effusion and ascites revealed no malignant cells. The definitive diagnosis of pseudo-Meigs' syndrome was made by confirming the fact that pleural effusion and ascites disappeared after bilateral oophorectomy. Resection of ovarian tumours may also lead to long-term survival, even in the patients with pseudo-Meigs' syndrome caused by gastric cancer.

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As numerous reports were published regarding the so-called seatbelt syndrome involved in car crashes, most of them were mentioned about small intestine, duodenum and colon perforations and solid organ bleeding. No reports have been published regarding multiple gastric mucosal tears with intra-gastric wall air leakage with massive bleeding. A 65-year-old woman was admitted after a motor vehicle crash. She vomited massive fresh blood. Gastric mucosal breaks, approximately 5 cm in length, were observed. Computed tomography imaging revealed multiple gastric mucosal breaks. We report a rare case wherein a traffic accident caused a serious condition associated with massive digestive bleeding.

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Crohn's disease (CD) is characterized by transmural inflammation of the gastrointestinal tract, which predisposes patients to the formation of a fistula. The efficacy of adalimumab (ADA) for an enterocutaneous fistula remains unclear. In this report, we present a case series of 3 patients with enterocutaneous fistulizing CD treated with ADA. ADA treatment achieved sustained complete fistula closure in one patient. The other two cases, which failed to achieve fistula closure, had intestinal stenosis and were not receiving concomitant azathioprine. Combination therapy with ADA and azathioprine may be a useful option and an alternative to surgery for enterocutaneous fistulizing CD.

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A 72-year-old man with advanced hepatocellular carcinoma and decompensated hepatitis C virus-related cirrhosis suffered from a metastatic femoral fracture. After undergoing radiotherapy, he was only treated with supportive care, except for the administration of zoledronic acid (ZA). Thereafter, the initially elevated serum α-fetoprotein and des-gamma carboxyprothrombin levels declined to within the normal ranges. Hepatic and metastatic adrenal tumors, distant from the radiation field, exhibited a surprising regression. ZA is known to inhibit the activity of osteoclasts, bone-residential macrophages, and has been reported to have a direct anti-tumor effect. ZA may adjust the immunological milieu in tumor microenvironments by inhibiting the tumor-associated macrophages. Because radiotherapy can enhance the presentation of tumor-associated antigens, ZA and radiotherapy may exert synergistic anti-tumor effects.

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An 80-year-old female with a history of hypertension and atrial fibrillation had been receiving warfarin anticoagulant therapy and had stably maintained an international normalized ratio (INR) within the 2.0-3.0 range. Due to dental extractions, she was prescribed aspirin (100 mg/day) as an alternative therapy to warfarin. Three days later, the patient complained of hemoptysis without obvious inducement and the INR was 3.51. The aspirin was immediately discontinued and intravenous vitamin K was administered. Hemoptysis did not reappear and the INR returned to the normal limits. According to the Drug Interaction Probability Scale, a causal relationship between aspirin and warfarin and an increased INR value is possible.

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We herein report the case of a 60-year-old man who presented with chest discomfort. Coronary angiography demonstrated that the short left anterior descending artery (LAD) arose from the left main coronary artery and the long LAD from the right coronary sinus of Valsalva, which was confirmed by 64-slice multidetector computed tomography coronary angiography. Single-photon emission computed tomography revealed a significant, almost irreversible degree of hypoperfusion in the anterior wall of the left ventricle, thus indicating that the short LAD was associated with myocardial ischemia and severe atherosclerotic lesions. Therefore, SPECT showed that the myocardium was largely necrotic, and we did not perform angioplasty for the short LAD.

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A 67-year-old man with non-valvular atrial fibrillation (AF) and previous myocardial and cerebral infarctions had uncontrollable bleeding after undergoing dental extraction because of an exacerbation of chronic disseminated intravascular coagulation (DIC) due to an abdominal aortic aneurysm. After successful treatment of the bleeding with the transfusion of fresh frozen plasma and platelets, nafamostat mesilate was used to treat the chronic DIC. Finally, rivaroxaban (an oral direct Factor Xa inhibitor) was prescribed for chronic DIC, as well as non-valvular AF. Following the initiation of rivaroxaban, the chronic DIC gradually improved, and the patient was discharged.

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A 67-year-old woman developed isolated adrenocorticotropin deficiency (IAD), which manifested as lethargy, a 20-kg body weight loss, hypoglycemia, and parkinsonism, and began corticosteroid replacement. Her symptoms resolved rapidly, and her weight returned to normal within six months. However, she then developed slowly progressive type 1 diabetes mellitus (T1D) with co-existing Hashimoto thyroiditis, and commenced insulin therapy. To our knowledge, this is the first reported case of parkinsonism associated with IAD. In addition, because diabetes mellitus, including T1D, could be latent in patients with untreated IAD, careful assessment of glucose metabolism is needed after commencing corticosteroid replacement until weight regain is achieved.

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We herein present the case of a patient with myeloma and chronic kidney disease (CKD) who developed rapidly progressive vascular and soft tissue calcification during the course of treatment for severe hypocalcemia induced by the administration of denosumab for myeloma and hypercalcemia. Because a large amount of supplementation with active vitamin D and calcium was required to correct the severe hypocalcemia, rapidly progressive vascular calcification developed. Seeing that patients with CKD are prone to developing severe and prolonged hypocalcemia after denosumab treatment, physicians should closely monitor the patients' serum calcium levels and manage their hypocalcemia appropriately so as to avoid the development of significant ectopic calcification.

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A 37-year-old man was admitted to our hospital for an evaluation of renal dysfunction and hypertension. The C-reactive protein level was 6.0 mg/dL, and the serum renin activity was extremely high. A renal biopsy showed malignant nephrosclerosis-like lesions with an onion skin pattern. He had a history of recurrent abdominal pain associated with periodic fevers above 38 degrees that resolved within three days. A MEditerranean FeVer (MEFV) gene analysis revealed that he was homozygous for the E148Q polymorphism (exon 2) and heterozygous for the L110P polymorphism (exon 2). The present case demonstrates that persistent subclinical inflammation can lead to malignant nephrosclerosis in familial Mediterranean fever patients with this genotype.

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A 75-year-old man with interstitial pneumonia and enlarged mediastinal lymph nodes underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). He developed a high-grade fever seven days after EBUS-TBNA was performed; laboratory and radiologic findings showed intense inflammatory reactions, with swelling of the mediastinal lymph nodes on chest computed tomography. Mediastinal lymph node abscess was diagnosed, and it worsened in spite of systemic antibacterial treatment. Surgical treatment using a median sternotomy was performed, and the cultivation of surgically obtained mediastinal lymph node abscess fluid revealed Streptococcus intermedius. Combined treatment with antibiotics and surgical treatment was effective, leading to remission.

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We herein report the case of an 80-year-old Japanese man with multiple lymph node metastases of lymphoepithelioma-like carcinoma (LELC) from an unknown primary site. The patient was admitted to our hospital due to hoarseness and left supraclavicular lymphadenopathy. Contrast-enhanced whole-body computed tomography revealed mediastinal, left supraclavicular, and left axillary lymphadenopathy. A left supraclavicular lymph node biopsy was performed and the specimen was consequently diagnosed as exhibting LELC. The patient's Eastern Cooperative Oncology Group performance status was 0, therefore he was started on chemotherapy with carboplatin and pemetrexed. His lymph nodes responded well to four cycles of chemotherapy without any intolerable adverse effect.

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Primary renal lymphoma (PRL) is a rare disease which is often mistaken for renal cell carcinoma. In the present study, a 56-year-old man visited a clinic complaining of an intermittent fever and right flank pain. A computerized tomography examination revealed a hypoenhancing mass in his right kidney. Radical nephrectomy was conducted, and a diagnosis of diffuse large B-cell lymphoma was confirmed. The present case was determined to be a true PRL according to the results of a positron emission tomography examination and a bone marrow biopsy to rule out any lymphoma invasions apart from the right kidney.

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The relatively rare entity pyothorax-associated lymphoma (PAL) is an aggressive disease with a poor prognosis. Therefore, PAL should be diagnosed as soon as possible with minimal invasion. We herein report the case of an 81-year-old man with PAL that was successfully treated with chemotherapy. A computed tomography-guided tumor biopsy could not provide adequate specimens for pathological investigation, whereas a diffusion-weighted magnetic resonance imaging-guided tumor biopsy led to a diagnosis. Our findings suggest that diffusion-weighted image guidance for planning the biopsy of an intrathoracic mass, especially in cases of suspected PAL, is a highly accurate method because it provides information about cellularity and does not create calcification-related artifacts.

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A 66-year-old man presented with a disturbed consciousness and seizure-like movements, followed by the initial symptoms of herpes zoster. Immunoglobulin (Ig) M antibodies to varicella zoster virus (VZV) as well as herpes simplex virus (HSV) were positive in the cerebrospinal fluid (CSF), whereas polymerase chain reaction of the CSF was positive for VZV-DNA but negative for HSV-DNA. The serum/CSF IgM ratio for VZV and HSV increased in association with a clinical improvement. This is a case report of a rare case of VZV encephalitis demonstrating false-positive results for IgM to HSV in the CSF. The increase in the serum/CSF IgM ratio possibly reflects a recovery from blood-brain barrier breakdown.

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Orbital inflammation has been rarely associated with adult-onset Still's disease (AOSD). We herein describe two AOSD patients who developed lacrimal gland enlargement with inflammation spreading to the contiguous tissues in the orbit. Case 1 was a 26-year-old woman who developed bilateral eyelid swelling while taking prednisolone (22.5 mg/day) for AOSD. The swelling of the eyelid worsened after other symptoms emerged, such as a fever, a rash, and arthritis. The laboratory findings, including leukocytosis, liver dysfunction, and ferritin elevation, also suggested an AOSD flare-up. Case 2 was a 62-year-old woman who presented with left eyelid swelling. She was diagnosed with AOSD at 45 years of age but sustained remission. During admission, she subsequently developed a fever, a rash, arthritis, lymphadenopathy, and ocular hyperemia. AOSD was suspected from the clinical course. We speculate that dacryoadenitis and orbital inflammation are manifestations of AOSD.

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There have been many previously reported cases of adult-onset Still's disease (AOSD) which were successfully treated with tocilizumab (TCZ). However, the efficacy and safety of TCZ therapy for AOSD-associated macrophage activation syndrome (MAS), and the optimal duration of TCZ therapy, remain unclear. We herein report two cases of refractory AOSD, one of which was associated with MAS. These two patients were treated with TCZ, and the withdrawal of TCZ was planned according to the serum interleukin-6 level, which resulted in TCZ-free remission.

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A 69-year-old man was diagnosed with granulomatosis with polyangiitis (GPA) based on the presence of skin granuloma, refractory otitis media, renal insufficiency and myeloperoxidase-antineutrophil cytoplasmic antibody positivity and slight lung opacity. He was treated with high-dose corticosteroid therapy. Despite the initial improvement of his renal function and a decrease in his C-reactive protein level, he suffered from an alveolar hemorrhage one week after the start of corticosteroid therapy. An anti-dsDNA antibody test was positive and the patient had hypocomplementemia. Elements of both GPA and systemic lupus erythematosus were thought to have affected his clinical course.

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We herein report a case of female eosinophilic granulomatosis with polyangiitis (EGPA) in which polyethylene glycol (PEG) precipitation was used to evaluate the patient's levels IgE-immune complexes (IC). Her serum IgE (7,110 IU/mL) and IgE-IC (1,880 IU/mL) levels were observed with an IgE PEG precipitated index of 26.4%. We speculate that the circulating IgE-IC were formed by anti-neutrophil IgE autoantibodies. Therefore, the large amount of IgE autoantibodies in the patient's serum appears to have induced a constant allergic pathology. This pathology may have resulted in a marked infiltration of eosinophils into the tissues, as well as intensified the EGPA pathology.

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A 51-year-old Japanese woman developed candidemia as an outpatient secondary to a Candida albicans upper urinary tract infection complicated by previously undiagnosed type 2 diabetes mellitus with poor glycemic control and ureterolithiasis. The patient did not have any risk factors typically associated with candidemia, such as an indwelling vascular catheter, parenteral nutrition or broad-spectrum antibiotic use. During the clinical course, her condition was complicated by unilateral candida endophthalmitis, which progressed despite the administration of systemic antifungal agents and ultimately required vitreous surgery. The etiology of candidemia in this patient and the reason she developed progressive ocular symptoms after starting antifungal treatment are reviewed.

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A 75-year-old Japanese man underwent thoracic surgery to treat a large lung cancer lesion in the left upper lobe with calcified pleural thickening. Postoperatively, viable Mycobacterium tuberculosis was detected in the margin of the resected thickened calcified pleural lesion. Therefore, an infection control investigation of medical staff who had come in contact with the patient was conducted. Consequently, two of the 14 healthcare professionals who had been in the operating room were diagnosed with latent tuberculous infections. Therefore, strict precautions against airborne infections are required to prevent the in-hospital transmission of M. tuberculosis in such cases.

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