Objective This study was designed to compare the association between the body mass index (BMI) and symptoms of gastroesophageal reflux disease (GERD) in allegedly normal subjects undergoing regular medical checkups and subjects diagnosed with non-alcoholic fatty liver disease (NAFLD). Additionally, the correlation between the BMI and GERD symptoms was evaluated in subjects with NAFLD.
Methods This study included 50 patients with NAFLD and 228 normal subjects evaluated during regular medical checkups. The height, weight, BMI, frequency scale for the symptoms of GERD (FSSG), and serum concentrations of triglycerides and γ-GTP were compared between the two groups. In the NAFLD group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations were measured and insulin resistance was calculated using the quantitative insulin sensitivity check index (QUICKI).
Results The total FSSG score moderately correlated with the BMI in the NAFLD group (r=0.342, p=0.015), but correlated negatively in the control group (r=-0.014, p=0.831). The FSSG score in the NAFLD group also negatively correlated with the AST/ALT ratio (r=-0.319) and insulin resistance calculated using the QUICKI score (r=-0.288). The BMI in the NAFLD group moderately correlated with the acid-reflux related score on the FSSG (r=0.389), and both the AST/ALT ratio (r=-0.344) and QUICKI score (r=-0.330) negatively correlated with the dyspepsia score on the FSSG.
Conclusion Obesity evaluated by the BMI was a significant risk factor for the exacerbation of GERD symptoms in subjects with NAFLD.

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Objective Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by chronic, relapsing abdominal pain or discomfort and is associated with disturbed defecation. The pathogenesis of IBS is multifactorial. The aim of this study was to investigate the prevalence of IBS using the Rome III criteria and to assess the effects of mental and lifestyle factors on IBS in a community-dwelling population in Japan.
Methods The diagnosis of irritable bowel syndrome was based on the Japanese version of the Rome III Questionnaire. The questionnaire was administered to 993 volunteers who participated in the Iwaki Health Promotion Project 2013. Diet was assessed with a validated brief-type self-administered diet history questionnaire. Dietary patterns based on 52 predefined food groups [energy-adjusted food (g/d)] were extracted using a principal component analysis. The Center for Epidemiologic Studies Depression Scale with a cut-off point of 16 was used to assess the prevalence of depression.
Results A total of 61 subjects (6.1%) were classified as having IBS. Three dietary patterns were identified: "Healthy", "Western" and "Alcohol and accompanying" dietary patterns. After adjusting for potential confounders, the "Alcohol and accompanying" dietary pattern and depression were related to the risk of IBS.
Conclusion We found that an "Alcohol and accompanying" dietary pattern and depression were related to the risk of IBS in a Japanese community population. However, we could not rule out the possibility of some selection bias. Further studies with longitudinal observations are therefore warranted.

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Objective Insulin resistance (IR) modifies the anti-viral effects of interferon (IFN) therapy in patients with chronic hepatitis C (CHC). This prospective study evaluated whether lifestyle interventions improve the anti-viral response to treatment with pegylated (PEG)-IFN plus ribavirin (RBV) in patients with CHC.
Methods The study cohort consisted of 60 patients chronically infected with a high viral load of hepatitis C virus genotype 1b and a homeostasis model assessment of IR (HOMA-IR) value above 2. The patients were divided into two groups, an intervention group (n=26) and a control group (n=34). The patients in the intervention group were prescribed diet and exercise treatment for 3-6 months to reduce their body weight by ≥5% before starting treatment with PEG-IFN plus RBV.
Results Diet and exercise significantly reduced the HOMA-IR values in the intervention group, from 3.4 to 2.5 (p=0.0009), especially among the 15 patients who achieved a body weight reduction of ≥5%. The viral disappearance rate at 12 weeks was significantly higher in the intervention group among the patients with a ≥5% weight reduction than in the control group (53.3% vs. 23.5%, p=0.01). However, the sustained viral response (SVR) rates were similar.
Conclusion Improvements in IR achieved through weight reduction via lifestyle interventions may enhance the early viral response to PEG-IFN plus RBV in patients with CHC. However, this intervention program has no effect on the SVR rate.

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Objective This study aimed to investigate the association between BMI at 65 years of age and the development of hypertension during the subsequent five years.
Methods A total of 1,003 participants (65 years of age) who had no history of myocardial infarction and/or hypertension at baseline health check-ups (1996-2005) and participated in a secondary health check-up when the subjects reached 70 years of age were analyzed.
Results Using fully adjusted models, men with a BMI of <18.5 [odds ratio (OR), 4.08; 95% confidence interval (CI), 1.32-1.83], BMI of 23.0-24.9 (OR, 2.00; 95% CI, 1.18-3.40) and BMI of ≥25.0 (OR, 1.98; 95% CI, 1.10-3.56) were found to be at higher risk of developing hypertension than did those with a BMI of 18.5-22.9.
Conclusion Leanness or being overweight/obese at age 65 increases the risk of subsequent hypertension.

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Objective Immunoglobulin A nephropathy (IgAN) exhibits a peak onset that coincides with the reproductive age. Therefore, many young women with IgAN may become pregnant. However, the outcome of pregnancy in women with renal diseases remains controversial, and the characteristics and outcome of pregnancy in IgAN patients must be further evaluated.
Methods A prospective follow-up study of 64 pregnant women with IgAN was performed by analyzing the laboratory data and prognosis. To clarify the influence of renal insufficiency, we compared these patients according to the chronic kidney disease (CKD) stage with special attention to CKD stage 3 [N=16 in total, N=9 for estimated glomerular filtration rate (eGFR) ≥45 mL/min, N=7 for <45 mL/min].
Results We found that pregnancy and delivery did not produce any significant changes in the renal function for patients with CKD stage 3 (≥45 mL/min) at five years after delivery, although proteinuria was elevated at 30 weeks of pregnancy and at three months after delivery. However, only for patients with CKD stage 3 (<45 mL/min) was there a significant deterioration in the eGFR at five years after delivery. Additionally, the data of pregnant women with CKD stage 3 were compared with those of 22 nonpregnant women with similar clinical and demographic characteristics.
Conclusion Pregnant patients with IgAN (CKD stage 3, eGFR ≥45 mL/min) did not exhibit any significant reduction in the renal function at five years after delivery as compared with the baseline, which was similar to the findings in nonpregnant patients. Thus, while pregnancy with CKD stage 3 (eGFR ≥45 mL/min) was not a risk factor, patients with CKD stage 3 (eGFR <45 mL/min) showed a worsened renal function five years after delivery.

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Objective Atherosclerosis, which causes cardiovascular disease, is a major cause of death in hemodialysis (HD) patients. Eicosapentaenoic acid (EPA), an anti-hyperlipidemic agent, is known to have antioxidative or anti-inflammatory effects, resulting in improvements in atherosclerosis. In the present study, we examined whether EPA improves the all-cause mortality in patients receiving regular HD therapy.
Methods We enrolled 176 patients treated with maintenance HD therapy and performed a longitudinal observational cohort study for three years. We divided the patients into two groups based on whether or not the received EPA treatment [EPA(+) and EPA(-), respectively]. The primary end-point was all-cause death. We also matched the two groups using propensity score matching and examined the effect of EPA.
Results Before matching, the all-cause mortality rates were 24.0% in the EPA(+) and 11.8% in the EPA(-) groups, which were significantly different (p=0.044). After propensity score matching, the EPA(+) group still showed a significantly better prognosis than the EPA(-) group (p=0.038). A multivariate analysis showed that EPA treatment significantly reduced the risk of all-cause mortality both before and after propensity score matching.
Conclusion EPA treatment is independently associated with lower mortality in HD patients.

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Objective The significance of early mild clinical improvement after intravenous tissue plasminogen activator (IVtPA) treatment is unclear. Therefore, we examined whether the timing of clinical improvement after IVtPA predicted the clinical outcome at 3 months.
Methods Consecutive patients with acute cerebral infarction in the anterior circulation who received IVtPA treatment within 3 hours of the onset of symptoms were enrolled in the study. Patients were classified according to the timing of clinical improvement [early responder (ER), National Institutes of Health Stroke Scale (NIHSS) score improved ≥4 points or who had a score of 0 within 2 hours after IVtPA; late responder (LR), a similar improvement between 2 and 24 hours; and non-responder (NR)] and according to the arterial occlusion site (P group, internal carotid artery and proximal middle cerebral artery M1 region; and D group, distal M1 and M2).
Results Ninety-three patients [median age, 74 (67-79) years; 54 men (58%); median NIHSS score, 11 (7-16)] were enrolled in the study. The P group consisted of 48 (52%) patients and the D group consisted of 45 (48%) patients. Thirty-eight patients (41%) were classified as ERs, 20 (22%) as LRs, and 35 (38%) as NRs. On a multivariate regression analysis, the P group [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.08-10.45; p=0.036] and NR (OR, 4.04; 95% CI, 1.29-14.27; p=0.016) were independent predictors of a poor outcome. ER (47%, p=0.01) and LR (45%, p=0.01) patients showed fewer poor outcomes than NR (77%) patients, but the rate did not differ significantly between the ER and LR patients.
Conclusion Early mild clinical recovery did not predict a good outcome. The occlusion site was a stronger predictor of clinical improvement after IVtPA administration.

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Two cases of intravascular lymphoma (IVL) were diagnosed by endoscopic biopsy. Both patients were admitted to our hospital with a fever of an unknown origin. An elevated serum level of soluble interleukin-2 receptor antibody suggested IVL. An upper gastrointestinal endoscopy was performed. A biopsy of both the reddened and normal gastroduodenal mucosa (Case 1) and a biopsy of a gastric antral ulcer, multiple polyploid lesions resembling submucosal tumors in the duodenum, and the patient's normal mucosa (Case 2) revealed vascular infiltration by CD20-positive atypical lymphocytes, confirming the diagnosis of IVL. The performance of a gastrointestinal biopsy for suspected IVL is important, even if there are no visible endoscopic abnormalities.

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We herein describe the case of a 67-year-old woman with a duodenal ulcer thought to be caused by elevated pancreatic ductal pressure. The patient complained of continuous upper abdominal pain. Her medical history included idiopathic chronic pancreatitis. Endoscopy revealed a huge duodenal ulcer located on the inferior duodenal angle, which had not been seen on endoscopic retrograde pancreatography two months previously. A combination study using endoscopy and contrast imaging confirmed the relationship between the duodenal ulcer and the pancreatic branch duct. To our knowledge, this is the first case of duodenal ulcer thought to be caused by elevated pancreatic ductal pressure.

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A 63-year-old patient presented for curative treatment of drug-resistant paroxysmal atrial fibrillation (AF). After pulmonary vein antrum isolation was achieved, AF could be still induced and persisted, while rapid activation at the left atrial appendage was conducted to the left atrium in a decremental conduction manner. A step-wise incremental discrete radiofrequency energy application at the ostium of left atrial appendage completely eliminated the AF. Neither AF nor atrial tachyarrhythmias reappeared, even under isoproterenol infusion and vigorous rapid atrial stimulations. The patient has experienced no symptoms or exhibited ECG evidence of AF during a 6-month follow-up.

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Cardiac papillary fibroelastoma (CPF) is a rare benign primary cardiac neoplasm. In particular, CPF originating from the mitral valve chordae is extremely rare. A 74-year-old man was hospitalized for the evaluation of a cardiac mass in the left ventricle. Echocardiography revealed a mobile, spherical, pedunculated 2.1×2.1 cm mass at the mitral valve chordae with no mitral regurgitation. The patient underwent excision of the mass without repairing the mitral valve. A histological examination confirmed the mass to be a papillary fibroelastoma.

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We report a 72-year-old Japanese woman with severe hypoglycemia. The laboratory data, which revealed the suppression of serum insulin, suggested the existence of non-islet cell tumor hypoglycemia (NICTH). Abdominal computed tomography demonstrated the presence of a huge uterine tumor. The patient was treated with a continuous infusion of glucose, but died of sepsis on day 46. An autopsy revealed the pathological diagnosis to be a carcinosarcoma of the uterus. Interestingly, an immunohistochemical study discovered the expression of insulin-like growth factor (IGF)-II in both the carcinoma and sarcoma cells. In addition, an immunoblot analysis of blood samples revealed the presence of circulating big IGF-II. Therefore, this is a novel case of NICTH that was caused by a uterine carcinosarcoma.

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We describe the case of an 85-year-old man diagnosed with chronic myelomonocytic leukemia whose disease was treated with hydroxyurea for 3 months. He developed respiratory symptoms that were extensively investigated. Despite the intensive treatment, he died of respiratory failure eleven days later. An autopsy revealed diffuse interstitial inflammation of both lungs consistent with drug-induced inflammation. A drug lymphocyte stimulation test was positive for hydroxyurea. Taken together these findings demonstrated that severe interstitial pneumonitis was induced by this drug. Physicians using hydroxyurea must be aware of its potentially life-threatening pulmonary toxicity.

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A 59-year-old man, ex-smoker, was diagnosed with pulmonary aspergillosis according to chest radiography findings of a fungus ball and Aspergillus fumigatus detection in the bronchial lavage fluid. Two years after anti-fungal therapy, he was diagnosed with autoimmune pulmonary alveolar proteinosis (APAP) according to a crazy paving pattern in computed tomography scans of the chest, milky bronchoalveolar lavage effluent, and positive anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody in the serum. The patient ultimately died of respiratory failure caused by APAP four months after GM-CSF therapy commenced. Aspergillus infection may thus be associated with the onset and progression of APAP and tolerance to GM-CSF therapy.

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A 17-year-old teen was hospitalized with bilateral pneumothorax. After the bilateral lungs were expanded using catheter tubes, he fully recovered and he was discharged from our hospital. He had a history of colon perforation. Ehlers-Danlos syndrome (EDS) was suspected due to the combination of colon perforation and pneumothorax, and EDS type IV was confirmed after a genetic study identified a c.1511g>a mutation in the COL3A1 gene. This is the first report of bilateral pneumothorax caused by EDS type IV. Clinicians should consider EDS type IV in the differential diagnosis for bilateral pneumothorax in conjunction with distinct previous histories and radiological findings.

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A 44-year-old woman who was diagnosed with anaplastic lymphoma kinase-positive lung adenocarcinoma developed brain metastases, multiple spinal metastases and meningeal dissemination. Crizotinib was administered after the failure of first-line chemotherapy. Esophagitis and liver damage were induced by the twice-daily administration of crizotinib at 250 mg and 200 mg, respectively. The alternate-day administration of crizotinib (250 mg, twice daily) was able to control disease progression without any adverse effects for several months. We evaluated the relationship between the serum concentration of crizotinib and the development of esophagitis and liver damage. The alternate-day administration of crizotinib is one of the strategies for managing the severe toxicity of crizotinib.

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Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative to emergency laparoscopic cholecystectomy in high-risk patients with acute cholecystitis. Severe complications of this procedure are rare, except for drainage tube-related complications. A case of thoracic empyema, which is a rare complication of PTGBD, is reported; penetration of the pleural cavity seemed to be the cause of the thoracic empyema.

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Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season.

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Immunosuppressive therapy (IST) with a combination of antithymocyte globulin (ATG) and cyclosporine (CsA) is an effective therapeutic modality for patients with aplastic anemia (AA) who are not eligible for allogeneic stem cell transplantation (Allo-SCT) from a human leukocyte antigen-identical sibling donor. However, there have been reports of some patients developing lymphoproliferative disorder (LPD) after IST for AA. We herein report a case of a 26-year-old man with severe AA (SAA) complicated by LPD after a single course of IST, who was successfully treated with Allo-SCT from an unrelated donor. Two months after starting IST for SAA, he developed LPD in the stomach. CsA was reduced, however, his neutrophil counts decreased, and CsA could not be discontinued. The patient was treated with rituximab monotherapy, and LPD resulted in complete remission. However, he failed IST for SAA and underwent Allo-SCT with reduced-intensity conditioning to recover his hematopoiesis. The patient has achieved complete hematopoietic recovery without the recurrence of LPD for five years after transplantation. This is the first report of successful Allo-SCT for SAA after the treatment of LPD caused by the use of rabbit ATG. This case provides useful information for the management of SAA with the development of LPD after IST.

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Anticonvulsant hypersensitivity syndrome is a fatal, idiosyncratic drug reaction that is caused by aromatic antiepileptic drugs. This cutaneous drug reaction is also called pseudolymphoma because of its clinical and histological similarities with malignant lymphoma. The primary clinical findings are fever, skin rashes, enlarged lymph nodes, single or multiple internal organ involvement and hematological abnormalities. Typically, anticonvulsant hypersensitivity syndrome occurs 1-8 weeks after drug administration. We herein present the case of a patient who had been on anticonvulsant therapy for five years and died from late-onset anticonvulsant hypersensitivity syndrome.

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Rituximab treatment may cause or exacerbate Kaposi's sarcoma (KS) in patients with human immunodeficiency virus (HIV)-associated multicentric Castleman's disease. Despite the widespread use of rituximab, rituximab-induced KS has not yet been reported in HIV-negative patients with diffuse large B cell lymphoma (DLBCL). We herein report a case of KS that developed after undergoing rituximab-containing chemotherapy in an HIV-negative patient with DLBCL. An 84-year-old man who received rituximab-containing chemotherapy for the treatment of DLBCL developed severe infection, and subsequently KS. Our observations indicate that serious infections under rituximab treatment may trigger KS. KS should therefore be considered when skin tumors appear in lymphoma patients receiving rituximab-containing chemotherapy.

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Mitochondrial myopathy with episodic hyper-creatine kinase (CK)-emia (MIMECK) is a new disease entity characterized by episodic or persistent muscle weakness and elevated CK levels. We herein report two cases of MIMECK with the findings of histopathological studies. Histopathological examinations revealed strongly succinate dehydrogenase-reactive vessels. Electron microscopy showed abnormal mitochondria in the vessels and proliferating and vacuolated mitochondria under the sarcolemma. Both patients exhibited recurrent severe myalgia, weakness and increased CK levels. L-arginine treatment significantly ameliorated their muscle symptoms. These findings indicate that mitochondrial angiopathy plays an important role in the pathophysiology of MIMECK. L-arginine may be a potential therapeutic agent for this disorder.

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We herein report the long-term outcome (30 years) of a human immunodeticiency virus- and human herpesvirus 8-negative Japanese man who was diagnosed to have multicentric Castleman disease (MCD) of the plasmacytic type after investigation of generalized lymphadenopathy at 34 of age in 1983. He received chemotherapy based on lymphoma regimens (combinations of prednisolone, vincristine, vindesine, cyclophosphamide, etoposide, melphalan, and ranimustine, etc.) for over 20 years. Although the systemic lymphadenopathy resolved, AA amyloidosis-related nephropathy occurred, with a serum creatinine (Cre) level of 0.9 mg/dL and urinary protein excretion (UP) of 7.5 g daily. Rituximab was started, but Cre increased to 2.6 mg/dL in 2010 and UP was unchanged. Therefore, treatment with tocilizmab was started. As a result, his hypergammaglobulinemia was well controlled, C-reactive protein became normal, UP decreased to 3.5 g daily, and Cre remained at 2.5 mg/dL in 2013. When AA amyloid nephropathy occurred after long-term chemotherapy, lituximab could not control it, but tocilizmab stopped the progression of nephropathy. This case suggests that MCD and AA amyloidosis may both have a close relationship to the overproduction of interleukin-6.

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A 56-year-old previously healthy man was hospitalized due to a 10-day history of neck pain and an elevated C-reactive protein level. Gram-negative spiral bacilli were isolated from his blood, and Helicobacter cinaedi was confirmed using 16S rRNA sequencing. The infectious focus was not identified by initial cervical magnetic resonance imaging (MRI); however, repeated MRI demonstrated prominent high signal intensity in the entire region of the C6-C7 vertebrae and C6/C7 disc space. Furthermore, fluorodeoxyglucose-positron emission tomography/computed tomography showed no significant uptake, other than in the C6-C7 region. The patient was successfully treated with ceftriaxone for six weeks without sequelae.

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A 50-year-old Japanese man presented with fever and upper respiratory tract symptoms that required urgent inpatient admission. A physical examination revealed conjunctival hemorrhages and peripheral embolic phenomena. Blood cultures grew Pasteurella multocida, and an echocardiography revealed a mitral valve vegetation suggestive of infective endocarditis (IE), which was confirmed using the Modified Duke Criteria. After several antibiotic regimens proved ineffective, valve replacement was performed, with a good eventual outcome. P. multocida IE is rare and may sometimes have no preceding risk factors. P. multocida infections of the upper respiratory tract are unusual but may be an inciting event for IE. It is essential to check blood cultures and to repeat the performance of physical examinations to appreciate the developing features of IE.

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We report a case of nephrostomy-associated urinary tract infection caused by Elizabethkingia meningoseptica that occurred in a patient with retroperitoneal fibrosis. Though conventional identification methods failed to detect the causative organism, it was identified on the basis of the complete sequencing of 16S rRNA. Four weeks of levofloxacin and minocycline administration successfully eradicated the infection. E. meningoseptica rarely causes urinary tract infections, and we believe that this is the first such case in which the isolate was genetically confirmed. The accurate identification of the organism is necessary for the provision of appropriate treatment and to obtain a better understanding of its epidemiology and pathogenicity.

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Identifying the causative agent of pyogenic osteomyelitis is often challenging, especially when antibiotics are administered before a biopsy. We herein present a case of osteomyelitis in the cervical vertebrae presenting with progressive paralytic symptoms, in which we successfully identified Escherichia coli from a biopsy specimen using broad-range 16S rRNA gene polymerase chain reaction (PCR) even though sensitive antibiotics had been used for more than 50 days before the biopsy. Broad-range 16S rRNA gene PCR is a useful diagnostic method, especially when prebiopsy antibiotics are unavoidably used for a clinically unstable state.

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Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis, which is known to affect various organs; however, there have been no reports of its intrapelvic involvement. We herein describe the case of 69-year-old man who died of a rapidly-growing intrapelvic tumor, which was finally diagnosed as ECD at autopsy. Immunohistochemically, the tumor cells were positive for CD68 and BRAF V600E, and negative for CD1a. Since BRAF V600E has recently been reported to be specific to ECD, it can be a useful biomarker for diagnosis, especially in atypical cases.

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