Islet autoimmunity in infants with a Type I diabetic relative is common but is frequently restricted to one autoantibody

Aims/hypothesis. To determine the sequence of development of islet autoantibodies and their relation to HLA genes in infants at risk for Type I diabetes followed from birth.¶Methods. We followed 357 (189 male, 168 female) infants, with a first degree relative with Type I diabetes for a mean of 3 years from birth. Human leukocyte antigen typing and assays for insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADAb) and tyrosine phosphatase IA2 (IA2Ab) antibodies were done on cord blood, and venous blood was sampled every 6 months for IAA, GADAb and IA2Ab.¶Results. We did not find any antibodies in 263 (73 %) infants; 50 (14 %) were positive for a single antibody once, 19 (5 %) for a single antibody more than once and 25 (7 %) for two or more antibodies. Of the latter, 10 (2.8 % overall) were persistently positive; they had higher frequencies of HLA DR4 (p < 0.01) and HLA DR3, 4 (p < 0.05). Of the group persistently positive for two or more antibodies four infants developed diabetes. Insulin autoantibodies were the first ones to develop in 64 % of infants with two or more antibodies.¶Conclusion/interpretation. Infants with high risk HLA-DR alleles and multiple antibodies at high risk for diabetes were identified. A much larger group of infants had transient low level increases usually of a single antibody. Whereas transient low level positivity could be attributed to difficulties with assay technique and cut off levels for normality, the results overall support the phenomenon of transient ’self limited' islet autoimmunity in at risk infants. [Diabetologia (2000) 43: 203–209]     

Prognostic value of preoperative FDG-PET in stage IA lung adenocarcinoma

Background

Maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been found to have prognostic value. We previously reported the correlation between SUVmax and pathological invasive area, and determined an SUVmax cut-off value of 2.15 for predicting the recurrence potential of an invasive area of diameter 5 mm. Here, we evaluate the validity of FDG-PET for prediction of recurrence in pathological stage IA lung adenocarcinoma.

Methods

From February 2006 to May 2008, 100 patients with pathological stage IA lung adenocarcinoma underwent complete resection at our hospital. Tumors were classified as air-type or solid-type based on thin-section computed tomography (TS-CT) findings and the influence of TS-CT classification, SUVmax, and clinicopathologic features were evaluated in terms of the incidence of recurrence.

Results

Unlike air-type adenocarcinomas, recurrent disease was detected in 8 of 62 solid-type adenocarcinomas. SUVmax and diameter of invasive area were significantly correlated with recurrence and a shorter time to recurrence. All 8 recurrent cases had pathological invasive area >5 mm. All except one case of recurrence were solid-type adenocarcinomas with SUVmax ≥ 2.15. Three-year disease-free survival rates were 100% in air-type adenocarcinomas, 97.1% in solid-type adenocarcinomas with SUVmax < 2.15, and 74.1% in solid-type adenocarcinoma with SUVmax ≥ 2.15.

Conclusion

Combined evaluation of TS-CT classification and SUVmax had significant value in predicting recurrence in stage IA lung adenocarcinoma, reflecting the aggressiveness of primary lung adenocarcinoma. Prediction of tumor aggressiveness could contribute to decision-making regarding the choice of surgical procedure and treatment after surgery.     

IA与DA方案诱导治疗初治急性髓系白血病M2a的疗效和预后分析

本研究比较去甲氧柔红霉素（IDA）联合阿糖胞苷（Ara-C） （IA）方案与柔红霉素（DNR）联合阿糖胞苷（Ara-C） （DA）方案治疗初治急性髓系白血病M2a（AML-M2a,急性粒细胞白血病部分分化型）患者的疗效和预后,以寻求更佳的治疗方案.收集2009年5月至2013年5月在本院住院治疗的AML-M2a患者65例,并进行了回顾性分析.结果表明,①IA组诱导完全缓解率和有效率虽略高于DA组,但差异无统计学意义（P＞0.05）.②IA组白细胞最低值[（0.58±0.40）×109/L]明显低于DA组[（0.99±0.67）×109/L],差异有统计学意义（P＜0.05）;IA组中性粒细胞最低值[（0.19±0.09）×109/L]显著低于DA组[（0.21±0.16）×109/L],差异有统计学意义（P＜0.05）;IA组粒缺持续时间（12.59±5.31）d较DA组（9.17±7.04）d明显延长,差异有统计学意义（P＜0.05）.③IA组中位生存期（36.67个月）高于DA组中位生存期（21.45个月）,差异有统计学意义（P＜0.05）.④初诊时乳酸脱氢酶（LDH）值和初次诱导化疗方案是影响患者预后的独立危险因素.结论：IA方案与DA方案比较,可延长中位生存期,且远期疗效较好,可作为初治AML-M2a的首选化疗方案.     

Erythrocyte membrane omega-3 fatty acid levels and omega-3 fatty acid intake are not associated with conversion to type 1 diabetes in children with islet autoimmunity: the Diabetes Autoimmunity Study in the Young (DAISY)

Miller MR, Yin X, Seifert J, Clare‐Salzler M, Eisenbarth GS, Rewers M, Norris JM. Erythrocyte membrane omega‐3 fatty acid levels and omega‐3 fatty acid intake are not associated with conversion to type 1 diabetes in children with islet autoimmunity: The Diabetes Autoimmunity Study in the Young (DAISY). Aim: We investigated whether omega‐3 fatty acid intake and erythrocyte membrane omega‐3 fatty acid levels are associated with conversion to type 1 diabetes in children with islet autoimmunity (IA). Methods: The Diabetes Autoimmunity Study in the Young is following children at increased genetic risk for type 1 diabetes for the development of persistent IA, as defined as being positive for glutamic acid decarboxylase 65, i, or insulin autoantibodies on two consecutive visits, and then for the development of type 1 diabetes, as diagnosed by a physician. One hundred and sixty‐seven children with persistent IA were followed for a mean of 4.8 yr, and 45 of these developed type 1 diabetes at a mean age of 8.7 yr. Erythrocyte membrane fatty acids (as a percent of total lipid) and dietary fatty acid intake (estimated via food frequency questionnaire) were analyzed as time‐varying covariates in proportional hazards survival analysis, with follow‐up time starting at detection of the first autoantibody. Results: Neither dietary intake of omega‐3 fatty acids nor omega‐6 fatty acids were associated with conversion to type 1 diabetes, adjusting for human leukocyte antigen (HLA)‐DR, family history of type 1 diabetes, age at first IA positivity, maternal age, maternal education, and maternal ethnicity. Adjusting for HLA‐DR, family history of type 1 diabetes and age at first IA positivity, omega‐3 and omega‐6 fatty acid levels of erythrocyte membranes were not associated with conversion to type 1 diabetes. Conclusions: In this observational study, omega‐3 fatty acid intake and status are not associated with conversion to type 1 diabetes in children with IA.     

Radical systematic mediastinal lymphadenectomy versus mediastinal lymph node sampling in patients with clinical stage IA and pathological stage T1 non-small cell lung cancer

Purpose  To explore the appropriate method of mediastinal lymph node dissection for selected clinical stage IA (cIA) non-small cell lung cancer (NSCLC). Methods  From 1998 through 2002, the curative-intent surgery was performed to 105 patients with cIA NSCLC who had been postoperatively identified as pathologic-stage T1. According to the method of intraoperative medistinal lymph node dissection, they were divided into radical systematic mediastinal lymphadenectomy (LA) group (n = 42) and mediastinal lymph-node sampling (LS) group (n = 63). The effects of LS and LA on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Also, associations between clinicopathological parameters and survival were analyzed. Results  The mean numbers of dissected lymph nodes per patient in the LA group was significantly greater than that in the LS group (15.59 ± 3.08 vs. 6.46 ± 2.21, P < 0.001), and the postoperative overall morbidity rate was higher in the LA group than that in the LS group (26.2 vs. 11.1%, P = 0.045). There were no significant difference in migration of N staging, OS and DFS between two groups. However, for patients with lesions between 2 and 3 cm, the 5-year OS in LA group was significantly higher than that in LS group (81.6 vs. 55.8%, P = 0.041), and the 5-year DFS was also higher (77.9 vs. 52.5%, P = 0.038). For patients with lesions of 2 cm or less, 5-year OS and DFS were similar in both groups. Multivariate analysis showed that lymph node metastasis was the unique unfavorable prognostic factor (P < 0.001). Conclusions  After being intraoperatively identified as stage T1, patients with lesions between 2 and 3 cm in cIA NSCLC should be performed with LA to get a potentially better survival, and patients with lesions of 2 cm or less should be performed with LS to decrease invasion.     

Geometry and growth of the reconstructed aorta in patients with hypoplastic left heart syndrome and variants

Objective

The interdigitating technique in aortic arch reconstruction in hypoplastic left heart syndrome and variants (HLHS) reduces the recoarctation rate. Little is known on aortic arch growth characteristics and resulting clinical impact.

Meeting Summary: Global Vaccine and Immunization Research Forum, 2021

The 2021 Global Vaccine and Immunization Research Forum highlighted the considerable advances and recent progress in research and development for vaccines and immunization, critically reviewed lessons learned from COVID-19 vaccine programs, and looked ahead to opportunities for this decade.For COVID-19, decades of investments in basic and translational research, new technology platforms, and vaccines targeting prototype pathogens enabled a rapid, global response. Unprecedented global coordination and partnership have played an essential role in creating and delivering COVID-19 vaccines. More improvement is needed in product attributes such as deliverability, and in equitable access to vaccines.Developments in other priority areas included: the halting of two human immunodeficiency virus vaccine trials due to lack of efficacy in preventing infection; promising efficacy results in Phase 2 trials of two tuberculosis vaccines; pilot implementation of the most advanced malaria vaccine candidate in three countries; trials of human papillomavirus vaccines given in single-dose regimens; and emergency use listing of a novel, oral poliomyelitis type 2 vaccine. More systematic, proactive approaches are being developed for fostering vaccine uptake and demand, aligning on priorities for investment by the public and private sectors, and accelerating policy making.Participants emphasized that addressing endemic disease is intertwined with emergency preparedness and pandemic response, so that advances in one area create opportunities in the other. In this decade, advances made in response to the COVID-19 pandemic should accelerate availability of vaccines for other diseases, contribute to preparedness for future pandemics, and help to achieve impact and equity under Immunization Agenda 2030.