Large-scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis.

The prevalence, clinical characteristics, and outcomes of patients with antimitochondrial antibodies (AMAs), but no clinical evidence of primary biliary cholangitis (PBC), are largely unknown. A prospective study of AMA incidence was conducted through a nation-wide network of 63 French immunology laboratories. Clinical data from 720 of 1,318 AMA-positive patients identified in 1 year were collected. Patients were categorized as either newly diagnosed with PBC (n = 275), previously diagnosed with PBC (n = 216), or with nonestablished diagnosis of PBC (n = 229). The latter group was specifically evaluated. Follow-up data were collected for up to 7 years after detection of AMAs. Prevalence of AMA-positive patients without evidence of PBC was 16.1 per 100,000. These patients had the following characteristics: 78% female; median age 58 years; median AMA titer 1:160; extrahepatic autoimmune disorders 46%; normal serum alkaline phosphatases (ALP) 74%; ALP above 1.5 times the upper limit of normal 13%; and cirrhosis 6%. Compared to those newly diagnosed with PBC, the patients were slightly younger, had lower AMA titers, and lower sex-ratio imbalance. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%. Whereas no patients died from PBC, the 5-year survival rate was 75%, as compared to 90% in a control, standardized population matched for age and sex (P < 0.05). CONCLUSION: Nearly half of the newly detected AMAs in clinical practice does not lead to a diagnosis of PBC. PBC is unrecognized in 13% of those cases. Only 1 in 6 patients with AMAs and normal ALP will develop PBC after 5 years. The mortality of AMA-positive patients without PBC is increased irrespective of the risk of PBC development. (Hepatology 2017;65:152-163).

Transmissibility and geographic spread of the 1889 influenza pandemic.

Until now, mortality and spreading mechanisms of influenza pandemics have been studied only for the 1918, 1957, and 1968 pandemics; none have concerned the 19th century. Herein, we examined the 1889 "Russian" pandemic. Clinical attack rates were retrieved for 408 geographic entities in 14 European countries and in the United States. Case fatality ratios were estimated from datasets in the French, British and German armies, and morbidity and mortality records of Swiss cities. Weekly all-cause mortality was analyzed in 96 European and American cities. The pandemic spread rapidly, taking only 4 months to circumnavigate the planet, peaking in the United States 70 days after the original peak in St. Petersburg. The median and interquartile range of clinical attack rates was 60% (45-70%). The case fatality ratios ranged from 0.1% to 0.28%, which is comparable to those of 1957 and 1968, and 10-fold lower than in 1918. The median basic reproduction number (R(0)) was 2.1, which is comparable to the values found for the other pandemics, despite the different viruses and contact networks. R(0) values varied widely from one city to another, and only a small minority of those values was within the range in which modelers' mitigation scenarios predicted effectiveness. The 1889 and 1918 R(0) correlated for the subset of cities for which both values were available. Social and geographic factors probably shape the local R(0) , and they could be identified to design optimal mitigation scenarios tailored to each city.

Exploring the risk of hypospadias in children born from mothers living close to a vineyard.

Hypospadias (H) is a common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of H by altering urethral development. However, whether H risk is increased in places heavily exposed to agricultural pesticides, such as vineyards, remains debated and difficult to ascertain. The objective of the work is to test the possible association of H with residential proximity to vineyards. Residential address at birth of 8,766 H cases born 1980-2011 was taken from 17 specialized surgery centers. The geographical distribution of vineyards was obtained from the European Land Parcel Identification System (LPIS) and the distance of address to the nearest vineyard was computed. A first estimate of the variation of H relative risk with distance to vineyards was obtained using as controls 13,105 cryptorchidism (C) cases operated during the same period in the same centers. A separate estimate was obtained from a case-control study using "virtual controls" (VC) defined as points of the map sampled to match the demographic distribution of births within the recruitment territories of the study centers. Non-exposed patients were defined as those with a residence between 5,000 and 10,000 m from the closest vineyard. The residential distance to vineyard was smaller for H than for C cases (p<10-4). We found 42/8766 H cases (0.48%) and 50/13,105 C cases (0.38%) born to mothers living within 20 m of a vineyard. The odds ratios for H were 2.48 (CI: 1.0 to 5.1) and 2.4 (CI: 1.3 to 4.4), vs C or vs VC, respectively, when pregnant mothers lived 10-20 m from a vineyard. In conclusion, our study supports that children born to mothers living close to a vineyard have a two-fold increased risk of H. For environmental research, the use of VC provides an alternative to classical case control technique.