Objective Whether severe inflammation in the background liver cirrhosis might correlate with the development of poorly differentiated human hepatocellular carcinoma (HCC) was studied in hepatitis C virus (HCV)-associated liver cirrhosis.
Methods Out of 214 HCC patients who underwent curative hepatic resection, 148 patients were HCV-associated liver cirrhosis (LC) patients. Out of these 148, 31 patients with small solitary HCC nodule (diameter ≤3 cm) were included in this study. Inflammation in the background LC was evaluated by modified histology activity index (HAI). To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (each 0-4) were estimated. In each case, the average HAI was calculated. The grade of malignancy of HCC was determined by World Health Organization (WHO) classification.
Results The average HAI score in the cirrhotic portion in 17 patients with poorly differentiated HCC (5.21±1.15, mean ± standard deviation (SD)) was significantly larger than that in 14 patients without poorly differentiated HCC (4.05±0.83, p<0.005). The occurrence rate of HCC containing poorly differentiated HCC component in the patients whose HAI was more than 5.0 was 80.0% (12 out of 15), and was significantly higher compared with those in patients whose HAI was less than 5.0 (5 out of 16, 31.3%, p<0.025). In univariate and multivariate analyses for contribution to poorly differentiated HCC development, HAI was the only significant contributor (p=0.011, p=0.012 respectively).
Conclusion It is suggested that severe inflammation in the background cirrhosis accelerates the promotion in the HCC development from HCV-associated LC.

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Backgroud Previous randomized studies have reported conflicting results on the efficacy of omega-3 fatty acids in preventing atrial fibrillation (AF) recurrences after cardioversion.
Objective A systematic review and meta-analysis of the role of omega-3 fatty acids in the prevention of atrial fibrillation recurrences after cardioversion was conducted.
Methods PubMed, Cochrane Library, Elsevier, Science Online database were searched up to the end of January 2012 to identify all of the studies in human subjects that reported the effects of omega-3 fatty acids on the prevention of atrial fibrillation recurrences after cardioversion.
Results Overall, omega-3 fatty acids had no significant effect on the prevention of AF recurrences after cardioversion (OR: 0.63,95% CI 0.35-1.13; p=0.12). The heterogeneity among the studies was significant (p=0.01, I²=66%). Subgroup analysis showed that by administering omega-3 fatty acids at least 4 weeks prior to cardioversion and continuing thereafter, the recurrence rate of AF is significantly low (OR: 0.39, 95% CI 0.25-0.61; p<0.0001).
Conclusion In the subgroup administered omega-3 fatty acids at least 4 weeks prior to cardioversion and continued thereafter, the recurrence rate of AF was significantly low. More double-blind, randomized, placebo-controlled, multicenter studies with high quality and longer follow-up periods are needed to affirm our conclusion.

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Objective The Jikei Optimal Antihypertensive Treatment (JOINT) study originally evaluated the effect of a fixed-dose formulation of losartan (LOS) (50 mg) plus 12.5 hydrochrolthiazide (HCTZ) for achieving better blood pressure (BP) control in patients with uncontrolled hypertension. This study is a sub-analysis of the JOINT study, focusing on the effect of LOS/HCTZ on the uric acid (UA) metabolism.
Methods Among 228 participants in the JOINT study, a total of 164 patients whose blood and urinary UA specimens were available were included in the present analyses.
Results Six months after switching from the prior antihypertensive agent(s) to a single tablet formulation of LOS/HCTZ, the overall serum UA concentration (sUA) increased from 6.0 ± 1.6 mg/dL to 6.2 ± 1.6 mg/dL (p=0.029). The urinary UA/creatinine (Cr) ratio increased from 0.45 +/- 0.21 to 0.50 +/- 0.25 (p=0.014), and the fractional excretion of UA (FEUA) also increased, from 7.1 +/- 3.6 to 7.0 +/- 4.3, p=0.04). Multivariate regression analyses of the basal parameters showed the change in sUA (ΔUA) to correlate with the basal sUA (β=-0.483, p<0.001), estimated glomerular filtration rate (eGFR) (β=-0.202, p=0.007) and systolic BP (β=0.147, p=0.038). In addition, the ΔUA also correlated with the changes in the estimated glomerular filtration rate (ΔeGFR) (β=-0.332, p<0.001). When the patients were classified into two groups depending on their basal sUA, those with a basal sUA ≥7 mg/dL exhibited a decrease in their sUA, whereas the rest of those with a sUA <7 mg/dL experienced an increase. Furthermore, patients who had previously been treated with LOS alone had a greater increase in the sUA than those treated with an angiotensin II blocker (ARB) other than LOS alone.
Conclusion Antihypertensive therapy with a single tablet formulation of LOS/HCTZ is considered to be a useful option for controlling both BP and sUA, especially in uncontrolled hypertensive patients with hyperuricemia.

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Objective Tracheobronchial foreign bodies (FBs) are frequently present in adults. This study reports our experience with the managements of FB and FB-related complications using flexible bronchoscopy.
Methods We retrospectively reviewed the adult patients with FBs treated between 2001 and 2011 in China. The demographic and endoscopic data were collected and analyzed.
Results A total of 200 adult patients (136 men and 64 women) with an average age of 51 years were analyzed. The most common FBs included bones (51.0%), nut shells (15.0%), food boluses (7.0%), plastic toys or pen caps (6.5%). After FB aspiration occurred, only 11.0% were diagnosed within three days, while more than half of the patients (58.0%) delayed the diagnosis by more than one month. The incidence of FB-related complications was 79.5%, including granulation formation (76.5%), obstructive pneumonia (22.0%), hemorrhage (14.5%), atelectasis (10.0%) and endobronchial stenotic scarring (8.0%). In 96.5% of the patients, the FBs were successfully removed under flexible bronchoscopy. A total of 53 out of the 153 patients with granulation (34.6%) were managed by argon plasma coagulation (APC) or cryotherapy; two out of the sixteen patients with endobronchial stenotic scars were treated by balloon dilation under flexible bronchoscopy.
Conclusion A high incidence of FB-related complications occurs, likely as a result of the long delay between aspiration and diagnosis, a proportion of which require endoscopic intervention. The removal of FBs under flexible bronchoscopy has a high success rate and therefore should be recommended for adults.

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Objective The CURB-65 score is a simple well validated tool for the assessment of severity in community-acquired pneumonia (CAP). The weight of each criterion in very low-mortality-rate settings is unclear. The purpose of this study was to determine the weight in such setting.
Methods This study retrospectively reviewed 1,230 adult patients admitted for CAP from 2005 to 2009.
Results The 30-day mortality rose sharply from 0%, 1.0%, 8.2% and 16.7%, respectively, for patients with CURB-65 scores of 0, 1, 2 and 3 to 100.0% for patients with the scores of 4 (x² = 219.494, p<0.001). Confusion had the strongest association with mortality (odds ratio, 22.148). The presence of low blood pressure was not associated with mortality. Confusion, urea >7 mmol・L^-1 and age ≥65 yrs showed independent relationships with mortality (Odds ratio, 11.537, 5.988 and 10.462; respectively). Urea >7 mmol・L^--1 was most strongly associated with the sequential organ failure assessment (SOFA) scores [rank correlation coefficient (r_s), 0.352]. Confusion had the closest relationship with hospital length of stay (r_s, 0.114). Age ≥65 yrs had the strongest association with costs (r_s, 0.223).
Conclusion The individual CURB-65 criteria were of unequal weight for predicting the 30-day mortality, SOFA scores, hospital length of stay and costs in a very low-mortality-rate setting, and a low blood pressure was not associated with mortality.

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Objective To investigate the clinical characteristics, diagnostic approaches, short-term efficacy of treatment and prognosis of lymphoma patients presenting with a fever of unknown origin (FUO).
Methods We reviewed the records of 132 patients finally diagnosed with lymphoma in Huashan Hospital, half of whom initially presented with a FUO. The other 66 lymphoma patients without a history of FUO were diagnosed within a month when several patients in the FUO group were also diagnosed.
Results The patients presenting with a FUO were predominantly young men (71.21%, p=0.35) characterized by a temperature ≥39°C (55/66, 83.33%). Compared with the non-FUO group, patients in the FUO group more often had pancytopenia and hypohepatia, 61.54% with hypoalbuminemia (p<0.0001), 15.50% with significantly elevated lactate dehydrogenase (LDH) (p<0.0001), 92.45% with elevated serum β₂ microglobulin (p=0.017), 93.48% with elevated urine β₂ microglobulin (p=0.002) and 30.77% with elevated alkaline phosphatase (p=0.001). Ninety-four percent of the FUO patients had aggressive lymphomas (p=0.012), with a poor performance status (96.97%, p=0.003), stage III/IV disease (96.97%, p<0.0001), night sweats (21.21%, p=0.026), unexplained weight loss (46.97%, p=0.002) and more than one extranodal site involved (65.15%, p=0.002). The patients in the FUO group also showed poor prognoses, and most of them were in the high-intermediate or high risk classification of the disease (96.61%, p<0.0001), with a low complete remission (CR) rate (61.11% vs. 93.75%, p=0.043). Twenty-one (15.91%) of all the patients were diagnosed based on the finding of lesion sites by Positron Emission Tomography/Computed Tomography (PET/CT) scanning, which had not been detected by conventional scans.
Conclusion Lymphoma presenting as FUO has a rapid progression and poor prognosis, and is difficult to diagnose. PET/CT scans can provide complementary information for an etiological diagnosis of a FUO and biopsy examinations are significant to establish an early diagnosis for patients presenting with a FUO.

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Objective The aim of this study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of patients with nursing and healthcare-associated pneumonia (NHCAP); a new category of pneumonia proposed by the Japanese Respiratory Society.
Methods We conducted a retrospective analysis of a prospectively collected database of patients with NHCAP and community-acquired pneumonia (CAP) hospitalized at a single center between January 2008 and December 2010, and compared their clinical characteristics. The criteria for NHCAP were as follows: (1) residence in a nursing home or an extended-care ward, (2) a discharge from a hospital in the preceding 90 days, (3) an elderly or handicapped patient who needs long-term care, (4) a patient who regularly requires vascular access in an outpatient setting.
Results A total of 442 NHCAP patients and 451 CAP patients were evaluated. The NHCAP patients were older and had a higher frequency of underlying diseases. Aspiration was thought to be associated with the NHCAP in 63% of patients. Streptococcus pneumoniae was the leading pathogen in both groups, whereas the frequency of multidrug-resistant pathogens was higher in the NHCAP patients. The most frequently used antimicrobials in NHCAP patients were penicillins with beta-lactamase inhibitors. The in-hospital mortality and recurrence rates were significantly higher in NHCAP patients than in CAP patients (13.1% vs. 5.1%, p<0.001 and 18.8% vs. 5.5%, p<0.001).
Conclusion The clinical picture of NHCAP is consistent with that of HCAP described in the past. It is thought to be of benefit to modify the healthcare-associated pneumonia (HCAP) criteria considering the healthcare and social health insurance system in Japan.

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Yersinia enterocolitica (YE) infection is a rare cause of intestinal intussusception, especially in adults. We herein, report a case of adult intussusception due to YE enterocolitis. A 24-year-old woman was admitted because of severe abdominal pain. She was clinically diagnosed with ileocolic intussusception on the basis of the findings of computed tomography (CT) and a gastrografin enema. Manual surgical reduction was sufficient to alleviate the intussusception. A histological examination of the lymph nodes around the ileocecum excluded lymphoma. Serological testing revealed that the cause of the intussusception was a YE infection. The patient's postoperative course was good and no recurrence was seen during the follow-up.

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Few clinical studies have so far focused on gastrointestinal motility in patients with eosinophilic gastroenteritis. A 29-year-old man was evaluated for epigastralgia of unknown origin. A histopathological examination of biopsy specimens from the duodenum revealed numerous eosinophilic infiltrations. Eosinophilic enteritis was therefore diagnosed. The patient received oral prednisolone and his symptoms improved. Both at the onset and at relapse of the disease, the maximal ¹³CO₂ excretion time (T_max) of ¹³C-acetate breath test was noted to have increased levels of excretion. Recovery of this parameter was observed in parallel with clinical improvements after treatments. This is the first report of a case of eosinophilic enteritis in which the ¹³C-acetate breath test was effective for assessing the disease activity and evaluating the effectiveness of treatment.

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Gastrointestinal stromal tumors (GISTs) can present with focal calcification. However, the presence of extensive calcification that constitutes the major portion of a GIST is extremely rare and can be associated with diagnostic pitfalls. We herein present the first two cases of rare gastric GIST with predominantly calcified components that mimicked pancreatic solid and pseudopapillary neoplasms with extensive calcification. In patients presenting with hyper-dense, heavily calcified masses in the abdominal cavity, the possibility of GIST should be considered in the differential diagnosis. A careful search for cellular areas and the judicious application of immunostaining will thus make it possible to make a correct diagnosis.

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We herein report the case of a 61-year-old woman with dilated phase of hypertrophic cardiomyopathy (D-HCM) who had been diagnosed with HCM 17 years previously. On admission, her left ventricle (LV) had marked dilation, dyssynchrony with diffuse severe hypokinesis, and ventricular tachycardia. She had two mutations in the cardiac myosin binding protein-C gene, which were suspected to be the causes of the D-HCM. We performed LV reconstruction surgery and cardiac resynchronization therapy with a defibrillator for her drug-resistant severe heart failure. After surgery, her New York Heart Association class dramatically improved, and she has not been re-hospitalized since these treatments.

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A 67-year-old woman was referred to our hospital with a sudden syncopal attack. She suffered from cardiogenic shock due to left ventricular (LV) outflow stenosis with simultaneous complete atrioventricular (AV) block. An endomyocardial biopsy of the left ventricle demonstrated myocardial disarray and myocardial fibrous and edematous tissue with infiltration of mononuclear cells. Cardiac magnetic resonance imaging (cMRI) detected a damaged septal area that was likely associated with the conduction disturbance. The diagnosis was hypertrophic cardiomyopathy accompanied by acute myocarditis. Although the LV outflow stenosis was transient, the complete AV block was persistent, thus requiring permanent pacemaker implantation.

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We herein report a case of premature atherosclerosis in a patient with familial partial lipodystrophy (FPL), diabetes mellitus, hypertension and hypertriglyceridemia. Sequencing of the candidate genes LMNA, PPARG and CAV1 associated with FPL revealed no genetic abnormalities, which indicated the activity of a novel gene in this patient. The patient's son showed milder fat loss and similar fat distribution compared to the proband; however, the son showed no signs of any atherosclerotic disease. Although a cluster of atherogenic risk factors is likely to be the primary causes of atherosclerosis in our patient, other factors, including an unknown gene associated with FPL, the severity of fat loss and gender, might affect the development of atherosclerosis.

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We herein describe a 59-year-old woman who had undergone a total gastrectomy for gastric carcinoma and suffered from postprandial hypoglycemia characterized by a loss of consciousness and spasms. She was diagnosed with reactive hypoglycemia and treated with nutrition therapy, but the frequency and severity of the hypoglycemic episodes did not decrease. She was subsequently treated successfully with miglitol, an alpha-glucosidase inhibitor (α-GI) taken twice a day; other α-GIs (acarbose and voglibose) were not effective. In conclusion, the administration of miglitol was effective for preventing reactive hypoglycemia secondary to late dumping syndrome.

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Patients with bacterial endocarditis often have renal complications. This report presents the case of an elderly man with rapidly progressive glomerulonephritis (RPGN) associated with subacute bacterial endocarditis (SBE) due to Enterococcus faecalis infection. The patient was positive for anti-proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) and rheumatoid factor (RF) with hypocomplementemia. Treatment for SBE with antibiotics and the surgical replacement of the affected valves resulted in an improvement of RPGN, the disappearance of PR3-ANCA and RF, and the normalization of hypocomplementemia. This rare case suggests the importance of recognizing the cause of positive PR3-ANCA, because SBE could be an occult cause of RPGN mimicking ANCA-associated vasculitis.

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Acid-base imbalances and electrolyte disorders induced by proton pump inhibitors (PPIs) are extremely rare. However, under certain conditions, PPIs may cause metabolic acidosis or hypokalemia, probably due to an inhibitory action on the proton pump that contributes to H⁺ and K⁺ homeostasis in the kidney. We herein present a case of marked hypokalemia accompanied by distal renal tubular acidosis in which a PPI appeared to contribute to the pathophysiology of metabolic acidosis.

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We herein report three cases of Nephrotic Syndrome (NS) with idiopathic membranous nephropathy (IMN) in which the patients were resistant to steroid (PSL) and cyclosporine (CyA) therapy. All three patients had a high risk of renal failure because of persistently high levels of proteinuria. We performed low-density lipoprotein apheresis (LDL-A) and achieved complete remission in two cases. The third patients developed NS relapse and a deteriorating renal function; however, withdrawal from dialysis therapy was achieved. There are no proven therapies for treating patients with PSL- and CyA-resistant IMN with acute deteriorating renal function or difficulties in maintaining fluid balance. We evaluated the treatment course and physiological mechanisms and reviewed similar cases in the pertinent literature.

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We herein report a case of pulmonary tumor embolism caused by hematogenous metastasis that mimicked pulmonary thromboembolism in a 62-year-old Japanese woman with a history of uterine corpus carcinosarcoma. The case suggests that tumor embolism must be included in the differential diagnoses of respiratory symptoms in patients with a history of malignancy. It also illustrates the usefulness of such findings as beaded, dilated pulmonary arteries by computed tomography (CT) and high ¹⁸F-fluorodeoxyglucose (FDG) uptake by fusion FDG positron emission tomography/CT imaging for differentiating a pulmonary tumor embolism from pulmonary thromboembolism.

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Cardiac tamponade caused by perforation is a rare but potentially lethal complication of central venous catheter (CVC) insertion. We herein report a case of cardiac perforation associated with the use of a soft J-tipped guide wire. Twenty minutes after the insertion of a CVC, the patient developed unexpected cardiac arrest. An autopsy revealed 400 mL of pericardial blood. The right ventricular wall was 1 mm thick with about 10 myocyte layers, which is one-third that of the normal heart. A histological analysis revealed widespread fatty infiltration of the right ventricular wall (right ventricular lipomatosis).

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Paroxysmal nocturnal hemoglobinuria (PNH) makes patients susceptible to intravascular hemolysis and thrombosis, and it can be life-threatening in stressful situations. Eculizumab, a humanized monoclonal antibody that inhibits the complement protein C5, has been evaluated as a novel therapy for PNH. We herein describe the case of a 59-year-old Japanese woman with classic PNH, who had been successfully treated with eculizumab, but who later developed acute cholecystitis/cholangitis from gallstones. Although the severe obstructive jaundice requiring endoscopic therapy following cholecystectomy was complicated, critical intravascular hemolysis and thrombosis were not observed. Therefore, utilizing eculizumab during the peri-operative management of PNH patients should be carefully taken into consideration.

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We herein report the case of a 60-year-old man showing overexpression of creatine kinase (hyperCKemia) related to initial and recurrent attacks of neuromyelitis optica (NMO). He showed reduced vision, ataxia and dysesthesia, but no symptoms originating in the muscles. Magnetic resonance imaging (MRI) revealed lesions in the optic nerve, medulla oblongata, and spinal cord similar to typical NMO patients. However, femoral MRI and whole positron emission tomography (PET) demonstrated no abnormal findings during an episode of hyperCKemia. This case suggests that hyperCKemia is partly involved in the pathogenesis of NMO in both the central nervous system and myofiber surface, which is usually difficult to detect by clinical imaging modalities alone.

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A 36-year-old, previously healthy man presented with Miller Fisher syndrome (MFS) five days after he was diagnosed with an influenza A infection by a rapid antigen test. He had not received any recent vaccinations. He had no loss of consciousness. Bilateral ophthalmoplegia, blepharoptosis, areflexia, and ataxic gait were noted. One week after treatment with intravenous immunoglobulin, his ophthalmoplegia, blepharoptosis, and ataxic gait had gradually improved, and his deep tendon reflexes returned. Anti-GQ1b IgG antibodies were detected in his serum. There has been no previous report of postinfectious MFS following confirmed an influenza A infection in an adult.

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A 60-year-old woman developed type 1 diabetes mellitus and anti-aquaporin-4 antibody positive optic neuritis during type 1 interferon therapies for chronic hepatitis C. The diabetes mellitus was elicited by interferon-α plus ribavirin therapy, while the optic neuritis was induced after interferon-β treatment, followed by interferon-α and ribavirin therapy. It is possible that type 1 interferons lead to the onset of the two autoimmune diseases by inducing disease-specific autoantibodies. Autoimmune disease is an infrequent complication of type 1 interferon treatment; however, once it has occurred, it may result in severe impairments. Patients undergoing type 1 interferon therapy should therefore be carefully monitored for any manifestations of autoimmune diseases.

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Syncope is a common presentation in the neurology clinic and emergency room. However, pulmonary embolism (PE) as a cause of syncope is not common or well recognized. Four aged patients presented to our clinic with episodic syncope, and PE was finally identified as the underlying cause. The significant clinical presentations included transient loss of consciousness and hypoxemia on admission. Syncope with hypoxia should therefore be highlighted as an important clue to the diagnosis of PE in aged patients. A negative D-dimer test will be encountered in patients with a very short history. Repeated D-dimer testing is necessary.

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Patients with ankylosing spondylitis (AS) have an approximately two-fold increased death rate compared to the general population, which is predominately caused by increased cardiovascular risk. The prevalence rate for myocardial infarction is approximately 2-3 fold increased as compared with the general population. The inflammatory process appears to have an important role in causing this excess cardiovascular risk. In this paper, we present a case of severe coronary artery disease which could be demonstrated clearly by computer tomography in a 27-year-old woman who is being followed with AS.

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Acute pharyngitis is commonly encountered, but a definite etiological diagnosis is difficult. Although co-infection with Group A Streptococci (GAS) and Epstein-Barr virus (EBV) is uncommon, general physicians should consider the possibility of EBV co-infection in patients with GAS pharyngitis who fail to show prompt remission of symptoms following appropriate antibiotic treatment. In this article, we present a rare case of a 16-year-old girl who had co-infection with GAS and EBV. She developed acute glomerulonephritis and left ventricular dysfunction in an overlapping manner. We were able to follow her until she healed, and herein describe the pathogenesis of her systemic and pulmonary edema.

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17-year-old man had been involved in a traffic accident. He underwent a bilateral craniotomy with artificial dura mater to remove bilateral acute subdural hematomas. Seven months later, a right cranioplasty was performed using frozen auto-bone, and he developed extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae meningitis and an epidural abscess. Since his general status was poor, we could not remove the foreign body (artificial dura mater). He was successfully treated with meropenem and chronic suppression with oral trimethoprim-sulfamethoxazole. By describing this case and the results of a review of the pertinent literature, we discuss the importance of ESBL-producing Klebsiella pneumoniae meningitis in posttraumatic/postoperative patients.

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The patient was a 68-year-old woman who had experienced recurrent febrile episodes since 66 years of age. Despite various examinations and treatments, the etiology remained unclear. Further examinations following another referral failed to uncover the cause. Therefore, despite her age, it was presumed that she had familial Mediterranean fever. An analysis of the familial Mediterranean fever (MEFV) gene detected heterozygous L110P, E148Q, and R202Q mutations. No further febrile episodes occurred after colchicine treatment was initiated. Familial Mediterranean fever presenting in patients in their sixties is extremely rare.

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A 53-year-old man developed bilateral pleural effusion with respiratory failure. The amylase level in the pleural effusion was elevated. He had neither abdominal symptoms nor abdominal physical findings. Abdominal computed tomography (CT) also showed no abnormalities. Magnetic resonance cholangiopancreatography (MRCP) was non-diagnostic, but endoscopic retrograde cholangiopancreatography (ERCP) and subsequent CT showed a fistula connecting the pancreatic duct with the right pleural cavity. The pleural effusion was refractory to drug therapy, leading to the need for surgical intervention. The pathological findings revealed chronic pancreatitis without pseudocysts. The elevated pancreatic amylase in the pleural effusion offered an important clue to the correct diagnosis.

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