Ashkenazi Jewish Centenarians Do Not Demonstrate Enrichment in Mitochondrial Haplogroup J

BACKGROUND: Association of mitochondrial haplogroup J with longevity has been reported in several population subgroups. While studies from northern Italy and Finland, have described a higher frequency of haplogroup J among centenarians in comparison to non-centenarian, several other studies could not replicate these results and suggested various explanations for the discrepancy. METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated haplogroup frequencies among Ashkenazi Jewish centenarians using two different sets of matched controls. No difference was observed in the haplogroup J frequencies between the centenarians or either matched control group, despite adequate statistical power to detect such a difference. Furthermore, the lack of association was robust to population substructure in the Ashkenazi Jewish population. Given this discrepancy with the previous reported associations in the northern Italian and the Finnish populations, we conducted re-analysis of these previously published data, which supported one of several possible explanations: i) inadequate matching of cases and controls; ii) inadequate adjustment for multiple comparison testing; iii) cryptic population stratification. CONCLUSIONS/SIGNIFICANCE: There does not exist a universal association of mitochondrial haplogroup J with longevity across all population groups. Reported associations in specialized populations may reflect genetic or other interactions specific to those populations or else cryptic confounding influences, such as inadequate matching attributable to population substructure, which are of general relevance to all studies of the possible association of mitochondrial DNA haplogroups with common complex phenotypes

PREVENTION OF INFLAMMATORY BOWEL DISEASE COMPLICATIONS AND RECURRENCE

This article describes the need for objective treatment and management goals of inflammatory bowel disease to monitor disease course and progression. We discuss the “treat to target” or “tight control” approach as an evolving treatment strategy in order to prevent future complications. Biochemical, endoscopic, and histologic outcomes are highlighted in this work. Resumen: Este artículo describe la necesidad de utilizar objetivos para el manejo y tratamiento de los pacientes con enfermedad inflamatoria intestinal, para monitorizar el curso y la progresión de la enfermedad. Se discute el enfoque de tratamiento por objetivos (T2T) o control estricto como una estrategia de tratamiento que permitiría prevenir futuras complicaciones. Se destacan en este trabajo marcadores bioquímicos (biomarcadores), endoscópicos e histológicos. Keywords: Inflammatory bowel disease, Outcome, Biomarkers, Endoscopy, Histology, Palabras clave: Enfermedad inflamatoria intestinal, Objetivos, Biomarcadores, Endoscopía, Histologí

Haplogroup frequencies among AJ from various origins.

<p>Ru = Russians Uk = Ukrainians.</p>*<p>AJs from other maternal geographic origins have been omitted from this table.</p

Haplogroup frequencies among AJ centenarians and controls.

<p>Haplogroup frequencies among AJ centenarians and controls.</p

Primary Hypogammaglobulinaemia with Inflammatory Bowel Disease-Like Features: An ECCO CONFER Multicentre Case Series

BACKGROUND: Hypogammaglobulinaemia is a disorder characterized by low serum immunoglobulin levels and a high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease [IBD]. METHODS: This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. RESULTS: This report includes 27 patients with primary hypogammaglobulinaemia and IBD-like features: 20 males and seven females, median age 45.6 years (interquartile range [IQR] 35.2-59). Crohn's disease-like features were noted in 23 patients, and four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinaemia preceded a diagnosis of IBD-like features in 20 patients [median of 7 years prior, IQR 2.6-20.6 years], and followed the appearance of IBD-like features in seven cases [median of 1 year after, IQR 0.45-5.6 years]. Hypogammaglobulinaemia aetiologies were common variable immunodeficiency [66.6%], agammaglobulinaemia [7.4%], selective IgA-deficiency [11.1%], Good's syndrome [7.4%], IgG subclass deficiency with IgA deficiency [3.7%] and hyper-IgM [3.7%]. In addition to antibiotics and intravenous immunoglobulin [IVIG] for hypogammaglobulinaemia, 12 patients received IBD-related treatment including 5-aminosalicylate agents [two patients], corticosteroids [one patient], thiopurines [three patients], anti-tumour necrosis factor [four patients] and vedolizumab [two patients]. By the end of the follow-up (44.5 months [IQR 18-81]), 21/27 [77%] patients were in clinical remission. CONCLUSION: This case series describes IBD-like features in patients with hypogammaglobulinaemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinaemia, with successful recovery in the majority of cases after appropriate treatment

Primary hypogammaglobulinemia with IBD-like features: An ECCO CONFER Multicenter Case Series.

Hypogammaglobulinemia is a disorder characterized by low serum immunoglobulin levels and had high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease (IBD). This was a multicenter case series performed as a part of the European Crohn's and Colitis Organisation (ECCO) Collaborative Network of Exceptionally Rare case reports (CONFER) project. This report includes 27 patients with primary hypogammaglobulinemia and IBD-like features [20 males and 7 females, median age 45.6 years (Interquartile range (IQR) 35.2-59]. Crohn's disease-like features were noted in 23 patients, four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinemia preceded IBD-like features diagnosis in 20 patients (median of 7 years prior, IQR 2.6-20.6 years), and followed IBD-like features appearance in 7 cases (median of one year after, IQR 0.45-5.6 years).Hypogammaglobulinemia etiologies were common variable immunodeficiency (66.6%), agammaglobulinemia (7.4%), selective IgA-deficiency (11.1%), Goods syndrome (7.4%), IgG subclass deficiency with IgA deficiency (3.7%) and hyper-IgM (3.7%). In addition to antibiotics and intravenous immunoglobulin (IVIG) for hypogammaglobulinemia, 12 patients received IBD-related treatment including 5-ASA (2 patients), corticosteroids (1 patient), thiopurines (3 patients), anti-TNFs (4 patients) and vedolizumab (2 patients). By the end of the follow-up [44.5 months (IQR 18-81)], 21/27 (77%) patients were in clinical remission. This case series describes IBD-like features in patients with hypogammaglobulinemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinemia, with successful recovery in the majority of cases after appropriate treatment