Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011

Background

IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells. Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established. Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists.

Methods

Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan. As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively. Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD.

Results

Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135?mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10?cells/high powered field of biopsy sample. Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz??s disease (MD) and kidney disease (KD). In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP.

Conclusion

Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists.     

Risk of ileal pouch neoplasms in patients with familial adenomatous polyposis

Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.     

The Impact of Marital Transitions on Vegetable Intake in Middle-aged and Older Japanese Adults: A 5-year Longitudinal Study

BackgroundMarital transitions are associated with adverse health events, such as mortality and cardiovascular disease. Since marital transitions (eg, becoming widowed) are unavoidable life events, it is necessary to identify modifiable intermediate outcomes. Thus, we examined the association between marital transitions and vegetable intake among middle-aged and older Japanese adults.MethodsThis longitudinal study included Japanese adults aged 40–79 years who received an annual health checkup between 2007 and 2011 (baseline) and 5 years later (follow-up). Marital transitions were classified as whether and what type of transition occurred during the 5-year period and comprised five groups: consistently married, married to widowed, married to divorced, not married to married, and remained not married. Changes in total vegetable, green and yellow vegetable, and light-colored vegetable intake from baseline to follow-up were calculated using the Food Frequency Questionnaire.ResultsData from 4,813 participants were analyzed (mean age, 59.4 years; 44.1% women). Regarding marital transitions, 3,960 participants were classified as “consistently married,” 135 as “married to widowed,” 40 as “married to divorced,” 60 as “not married to married,” and 529 as “remained not married.” Multivariable linear regression analysis revealed that compared to consistently married, married to widowed was inversely associated with the change in total vegetable intake (β = −16.64, SE = 7.68, P = 0.030) and light-colored vegetable intake (β = −11.46, SE = 4.33, P = 0.008).ConclusionOur findings suggest that being widowed could result in a reduced intake of vegetables. Hence, dietary counseling according to marital situation is necessary.Key words: longitudinal study, marital transition, middle-aged and older adults, vegetable intake     

Streptococcus thermophilus extends lifespan through activation of DAF-16-mediated antioxidant pathway in Caenorhabditis elegans

Streptococcus thermophilus bacteria, which are widely used as fermented starter for dairy production, exert various beneficial health effects. Nevertheless, even though pro-longevity effects of various probiotics have been reported, no report has described Streptococcus thermophilus effects on longevity. This study was conducted to evaluate Streptococcus thermophilus effects on lifespan extension and to elucidate the Streptococcus thermophilus-mediated longevity mechanism using Caenorhabditis elegans worms as a model animal. They were fed standard food (Escherichia coli OP50) or Streptococcus thermophilus from the young adult stage. Feeding with Streptococcus thermophilus, compared to Escherichia coli OP50, to Caenorhabditis elegans extend the lifespan, reduced lipofuscin accumulation, and maintain vigorous locomotion. Feeding with Streptococcus thermophilus did not alter the worm growth curve or the offspring number, indicating that the Streptococcus thermophilus-mediated lifespan extension is not attributable to caloric restriction. The qRT-PCR data showed that Streptococcus thermophilus increased the expression of daf-16 and some of its downstream antioxidant genes. Furthermore, the pro-longevity effects of Streptococcus thermophilus were decreased in loss-of-function mutant of daf-16. Results show that Streptococcus thermophilus extends the lifespan of Caenorhabditis elegans through DAF-16-mediated antioxidant pathway activation.     

3D Printing of Customizable Phantoms to Replace Cadaveric Models in Upper Extremity Surgical Residency Training

Medical phantoms are commonly used for training and skill demonstration of surgical procedures without exposing a patient to unnecessary risk. The discrimination of these tissues is critical to the ability of young orthopedic surgical trainees to identify patient injuries and properly manipulate surrounding tissues into healing-compliant positions. Most commercial phantoms lack anatomical specificity and use materials that inadequately attempt to mimic human tissue characteristics. This paper covers the manufacturing methods used to create novel, higher fidelity surgical training phantoms. We utilize medical scans and 3D printing techniques to create upper extremity phantoms that replicate both osseous and synovial geometries. These phantoms are undergoing validation through OSATS training of surgical residents under the guidance of attendings and chief residents. Twenty upper extremity phantoms with distal radius fracture were placed into traction and reduced by first- and second-year surgical residency students as part of their upper extremity triage training. Trainees reported uniform support for the training, enjoying the active learning exercise and expressing willingness for participation in future trials. Trainees successfully completed the reduction procedure utilizing tactile stimuli and prior lecture knowledge, showing the viability of synthetic phantoms to be used in lieu of traditional cadaveric models.     

Quantitative analysis of the intra-beam respiratory motion with baseline drift for respiratory-gating lung stereotactic body radiation therapy

This study aimed to quantitatively clarify the baseline drift for each respiratory cycle in two respiratory-gating methods using the intra-beam respiratory motion data of lung cancer patients. The residual motion and dose distribution were calculated based on intra-beam respiratory motion data with the baseline drift. To quantify the baseline drift during irradiation, it was defined as the inclination between the detected expiration point and the expiration point in the next cycle in the anterior–posterior (AP), cranial–caudal (CC) and left–right (LR) directions obtained using an in-house programme. The baseline drift value reached up to 0.74 mm/s in the CC direction as per the respiratory motion data of 10 patients. The homogeneity index (HI) of the phase-gating method tended to increase because the target was irradiated even when the amplitude position of the target differed from period to period. In contrast, the amplitude-gating method enabled irradiation considering the amplitude position of the target because the gating window was set considering the amplitude position of the respiratory motion. The respiratory-gating methods and respiratory phase in respiratory-gating lung stereotactic body radiation therapy (SBRT) must be determined based on the respiratory motion of the patients.     

Antibodies to β2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

Objective. To investigate whether anticardiolipin antibodies (aCL) in patients with systemic lupus erythematosus (SLE) bind to β₂-glycoprotein I (β₂GPI), and to search for a relationship between the presence of IgG and/or IgM anti-β₂GPI antibody and clinical manifestations in SLE patients. Methods. IgG and IgM anti-β₂GPI in 308 Japanese SLE patients were measured using phospholipid-independent enzyme immunoassays. Relationships to clinical histories and to various laboratory data were examined. Results. The values of anti-β₂GPI and aCL, as measured by conventional enzyme immunoassay, showed a strong correlation, but the anti-β₂GPI assay was more useful in distinguishing β₂GPI-dependent aCL from β₂GPI-independent aCL. The presence of IgG anti-β₂GPI was associated with an increased frequency of a history of thrombosis. Comparisons of various laboratory data suggested that the titer of anti-β₂GPI may fluctuate with disease activity. Conclusion. The results suggest that pathogenic aCL is directed against structurally altered β₂GPI and that enzyme immunoassay for anti-β₂GPI may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE.     

Expression of the intestinal T-lymphocyte-associated-molecule recognized by the HML-1 antibody on mononuclear cells from HTLV-I-infected subjects

We investigated the expression of a monoclonal antibody (HML-1) defined antigen that appears on human intestinal T-lymphocytes in HTLV-I-related disease. We studied 25 ATL, and 24 healthy HTLV-I carriers. Patients with acute ATL showed a variety of the expression of the HML-1 antigen (range 0.4–74.8%). HML-1 expression on mononuclear cells (MNCs) in blood from patients with chronic ATL ranged from 1.7–43.6% (mean 13.5%). This level of expression was less than that of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of expression ranged from 1.6–13.3% (mean 8.0%). In contrast to patients wtih acute ATL, MNCs from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and B-cell type chronic lymphocytic leukemia (B-CLL) did not express the HML-1 antigen, except for the 2 patients with ALL. Healthy HTLV-I carriers and healthy controls also were negative for HML-1 reactivity. In acute ATL, patients with gastrointestinal tract infiltration tended to have high expression of the HML-1 epitope. After stimulation with phytohemagglutinin (PHA), healthy HTLV-I carriers showed significantly increased expression of the HML-1 epitope (P < 0.05). Recently, the β7 integrin family has been found to play a specific role in mucosal localization or adhesion, and HML-1 protein was found to match the deduced β7 N-terminal sequence. We propose that the cellular gene responsible for HML-1 epitope expression may, like IL-2, IL-2R, etc., be transactivated by infection with HTLV-I, and that HML-1 antigen gene expression by HTLV-I infection may lead to infiltration of ATL cells with highly expressed HML-1 epitope into the gut mucosa.