Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Cirrhosis Confirmed by Liver Histology after 14 Years

A 44-year-old patient progressed from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) cirrhosis. She was diagnosed with NAFL via a liver biopsy. At 56 years old, she was diagnosed with NASH stage 3 via a second liver biopsy. One year later, she was diagnosed with NASH cirrhosis via a third liver biopsy. This is the first study to report the gradual deterioration of liver histology shown via three liver biopsies and fibrosis markers in a patient who progressed from NAFL to NASH cirrhosis. Following menopause, it is necessary to be aware of the rapid development of liver fibrosis.     

A case of cryopyrin-associated periodic fever syndrome during canakinumab administration complicated by inflammatory bowel disease

Clinical Rheumatology - Cryopyrin-associated periodic fever syndrome (CAPS) is a highly debilitating disorder, which is characterized by unregulated interleukin-1β production driven by...     

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders, formerly known as autoimmune pancreatitis (AIP), autoimmune sialadenitis, and autoimmune sclerosing cholangitis, are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease (IgG4-RD). AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody (Ab), accumulation of IgG4-expressing plasmacytes in the affected organs, and involvement of multiple organs. It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity. However, a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype. In addition, disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone. Therefore, it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD. Recently, we found that activation of plasmacytoid dendritic cells producing both interferon-α (IFN-α) and interleukin-33 (IL-33) mediate murine AIP and human IgG4-RD. More importantly, we provided evidence that serum concentrations of IFN-α and IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders. In this Frontier article, we have summarized and discussed biomarkers of AIP and IgG4-RD, including Igs, autoAbs, and cytokines to provide useful information not only for clinicians but also for researchers.     

Rat Small Intestinal Goblet Cell Kinetics in the Process of Restitution of Surface Epithelium Subjected to Ischemia–Reperfusion Injury

Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution. Goblet cells reside throughout the length of the intestine and are responsible for the production of mucus. However, a kinetic analysis of goblet cell dynamics of small intestine in restitution has hitherto not been reported. The aim of the present study was to investigate the role of goblet cells in the process of restitution of rat small intestine subjected to ischemia and ischemia–reperfusion injury, and therefore intestinal epithelium from rats subjected to both ischemia and ischemia–reperfusion was studied. Detachment of enterocytes was observed after 5-min of reperfusion. After 20–30 minutes of reperfusion, the denuded villous tips were covered with goblet cells. Within 75 min of reperfusion the epithelium restitution was complete. On the other hand, restitution was not observed in ischemia group. These data suggest that goblet cells may play an important role in restitution after ischemia–reperfusion injury.     

Platypnea - orthodeoxia syndrome with atrial septal defect.

A 75-year old man was referred to hospital for symptomatic hypoxemia. He did not complain of dyspnea while supine, but while sitting or standing, he experienced dyspnea with severe hypoxemia. He did not have any pulmonary diseases that could cause dyspnea. Transesophageal echocardiography revealed an atrial septal aneurysm with a small atrial septal defect (ASD) and a mild left-to-right shunt through the ASD when the patient was supine. However, when he became upright, a severe right-to-left shunt occurred and the arterial oxygen saturation decreased from 96% to 80% with dyspnea. Cardiac catheterization revealed normal pulmonary artery pressure. He was therefore diagnosed as having platypnea - orthodeoxia syndrome. Magnetic resonance imaging of the chest showed a deformity of the atrium associated with elongation of the ascending aorta. The ASD was closed surgically and the dyspnea and hypoxemia that occurred while he was upright completely resolved.     

Impact of reflux esophagitis on the esophageal function before and after laparoscopic fundoplication

Background

High-resolution manometry (HRM), which is breakthrough testing equipment to evaluate esophageal motor function, was developed in Europe and United State and has garnered attention. Moreover, multichannel intraluminal impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux including not only acid but also non-acid reflux. We examined the impact of the presence of reflux esophagitis (RE) on esophageal motor function before and after laparoscopic fundoplication.

Materials and methods

The subjects included 100 patients (male: 63 patients, mean age: 54.1?±?15.8) among 145 patients who underwent laparoscopic fundoplication for GERD associated diseases during a 4-year period from October 2012 to September 2016, excluding 6 patients who underwent further surgery, 32 patients on whom HRM was not performed, 3 patients who had technical errors during testing, and 4 patients for whom the status of RE was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for the analysis, Mano View version 3.0 from the same company was used, after which data was calculated based on the Chicago Classification advocated by Pandolfino et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill Scientific. Inc. was used and automatic analysis was conducted by a computer. Postoperative assessments were conducted 3 months following surgery for all. Data was described in the median value and inter-quartile range, with a statistically significant difference defined as p?<?0.05 by Chi square, Mann–Whitney, and Wilcoxon tests.

Results

RE+?group (Los Angeles classification A:B:C:D?=?7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE? group (62 vs. 50 years, p?=?0.012) and a higher Body Mass Index value (24.0 vs. 22.5, p?=?0.045); however, no differences were observed in terms of gender and duration of symptoms. In the preoperative findings on MII-pH, the RE+?group demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p?=?0.005), while in the HRM findings, the RE? group demonstrated a significantly longer abdominal esophagus (0 vs. 0.4 cm, p?=?0.049) and maintained esophageal body motor function (DCI: 1054 vs. 1407 mmHg s cm, p?=?0.021, Intact peristalsis ratio: 90 vs. 100%, p?=?0.037). As to the comparison of the treatment effect before and after laparoscopic fundoplication (Toupet fundoplication for all), significant improvements were observed in both groups in various parameters regarding reflux including acid reflux time, total number of liquid reflux episodes and total number of reflux episodes. Moreover, for both groups, the total length of the lower esophageal sphincter (LES) (RE+?group: 2.7 vs. 3.2 cm, p?=?0.001, RE? group: 3.0 vs. 3.4 cm, p?=?0.003) and the total length of the abdominal esophagus (RE+?group: 0 vs. 1.6 cm, p?<?0.001, RE? group: 0 vs. 1.8 cm, p?=?0.001) were significantly extended following surgery; however, no change was observed in DCI before and after surgery.

Conclusions

Regardless of the presence of RE, cardiac function and LES function were improved following laparoscopic Toupet fundoplication, but no changes were observed in esophageal body motor function.

     

Tentative diagnostic criteria and disease severity classification for Castleman disease: A report of the research group on Castleman disease in Japan

Objectives: To determine the tentative diagnostic criteria and disease severity classification for Castleman disease (CD) and describe the clinical and pathologic features among human herpesvirus 8 (HHV-8) negative idiopathic multicentric CD (iMCD) in the Japanese population.

Methods: We established the working groups for the research of CD in Japan and had meetings to discuss and define the tentative diagnostic criteria and disease severity classification for CD. We subsequently analyzed 142 patients classified into iMCD by using the nationwide Japanese patient registry.

Results: We proposed the preliminary diagnostic criteria and disease severity classification for CD based on our discussion. In addition, we made a proposal for the disease activity score. We identified clinical and pathological features of patients with iMCD diagnosed by these diagnostic criteria. In the disease severity classification, 37, 33 and 30% patients were categorized into mild, moderate and severe diseases, respectively.

Conclusion: This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity.     

Elevated serum levels of interleukin-10 in children with acute rubella infection.

Interleukin-10 (IL-10) is known to be an anti-inflammatory cytokine which inhibits cell growth and cytokine production of both Th1 and Th2 cells. Using a human IL-10 ELISA kit we investigated whether serum IL-10 levels increased during the acute and convalescent stages in 45 children with rubella infections. Serum levels of IL-10 were markedly elevated in rubella patients during the acute stage, compared with those at the convalescent stage and those in healthy age-matched children (mean +/- SEM): 18.5 +/- 3.4 vs. 6.0 +/- 0.6 vs. 7.9 +/- 1.3 pg/ml. IL-10 levels determined 5 d after the onset of the disease had returned to the normal range. In patients with rubella, there were significant negative correlations between serum IL-10 levels and both rubella virus-specific IgM and IgG antibodies. These findings suggest that IL-10 may play a role in the pathogenesis of acute rubella infections.     

Vaccination with clumping factor A and fibronectin binding protein A to prevent Staphylococcus aureus infection of an aortic patch in mice

Staphylococcus aureus is a leading cause of ventricular assist device-related infections. This study evaluated the protective effect against S. aureus infection of active and passive immunization that targeted 3 proteins involved in bacterial attachment to a murine intra-aortic polyurethane patch. Active immunization of mice with a combination of the A domains of clumping factor A (ClfA), fibronectin-binding protein A (FnBPA) and fibronectin-binding protein B or passive immunization with monoclonal antibodies against ClfA and FnBPA resulted in a higher level of protection than that obtained by vaccination with either protein or antibody alone. The combination of antibodies or protein antigens appears to provide enhanced protection against prosthetic-device infection.