Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease.

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn's disease (CD), cause chronic inflammation of the gut, affecting millions of people worldwide. IBDs have been frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is generally characterized by an increase in abundance of Proteobacteria such as Escherichia coli, and a decrease in abundance of Firmicutes such as Faecalibacterium prausnitzii (an indicator of a healthy colonic microbiota). The mechanisms behind the development of IBDs and dysbiosis are incompletely understood. Using samples from colonic biopsies, we studied the mucosa-associated intestinal microbiota in Chilean and Spanish patients with IBD. In agreement with previous studies, microbiome comparison between IBD patients and non-IBD controls indicated that dysbiosis in these patients is characterized by an increase of pro-inflammatory bacteria (mostly Proteobacteria) and a decrease of commensal beneficial bacteria (mostly Firmicutes). Notably, bacteria typically residing on the mucosa of healthy individuals were mostly obligate anaerobes, whereas in the inflamed mucosa an increase of facultative anaerobe and aerobic bacteria was observed. We also identify potential co-occurring and mutually exclusive interactions between bacteria associated with the healthy and inflamed mucosa, which appear to be determined by the oxygen availability and the type of respiration. Finally, we identified a panel of bacterial biomarkers that allow the discrimination between eubiosis from dysbiosis with a high diagnostic performance (96% accurately), which could be used for the development of non-invasive diagnostic methods. Thus, this study is a step forward towards understanding the landscapes and alterations of mucosa-associated intestinal microbiota in patients with IBDs.

Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population.

The double-strand break (DSB) DNA repair pathway has been implicated in breast cancer (BC). RAD51 and its paralogs XRCC3 and RAD51D play an important role in the repair of DSB through homologous recombination (HR). Some polymorphisms including XRCC3-Thr241Met, RAD51-135G>C, and RAD51D-E233G have been found to confer increased BC susceptibility. In order to detect novel mutations that may contribute to BC susceptibility, 150 patients belonging to 150 Chilean BRCA1/2-negative families were screened for mutations in XRCC3. No mutations were detected in the XRCC3 gene. In addition, using a case-control design we studied the XRCC3-Thr241Met, and RAD51D-E233G polymorphisms in 267 BC cases and 500 controls to evaluate their possible association with BC susceptibility. The XRCC3 Met/Met genotype was associated with an increased BC risk (P = 0.003, OR = 2.44 [95%CI 1.34-4.43]). We did not find an association between E233G polymorphism and BC risk. We also analyzed the effect of combined genotypes among RAD51-135G>C, Thr241Met, and E233G polymorphisms on BC risk. No interaction was observed between Thr241Met and 135G>C. The combined genotype Thr/Met-E/G was associated with an increased BC risk among women who (a) have a family history of BC, (b) are BRCA1/2-negative, and (c) were <50 years at onset (n = 195) (P = 0.037, OR = 10.5 [95%CI 1.16-94.5]). Our results suggested that the variability of the DNA HR repair genes XRCC3 and RAD51D may play a role in BC risk, but this role may be underlined by a mutual interaction between these genes. These findings should be confirmed in other populations.

Morbidity and mortality of a failed attempt at mitral valve repair converted to replacement at the same operation.

BACKGROUND AND AIM OF THE STUDY: Although mitral valve repair (MVRpr) is the preferred operation for mitral disease worldwide, some surgeons are reluctant to attempt this, believing that excess morbidity and mortality will result if the attempt fails and conversion to mitral valve replacement (MVR) is necessary during surgery. METHODS: Typical preoperative, operative and postoperative parameters were reviewed retrospectively on 2,017 consecutive adults undergoing mitral valve operations (MVO), with and without additional cardiac surgery, between 1986 and 1999. Morbidity and mortality were compared for all MVRpr, MVR and attempted repairs, which failed and were converted to replacement at the same operation (FRpr). RESULTS: Although cross-clamp and extracorporeal pump times were longer for FRpr than for MVRpr and MVR, neither blood product use, morbidity, nor length of ICU or hospital stay was increased. Perioperative myocardial infarction was higher in FRpr, but less than 5%. Although operative mortality was lower for successful MVRpr compared with MVR, there was no difference between FRpr and either MVRpr or MVR, whether as an isolated or combined procedure. The addition of other cardiac procedures to a specific MVO appeared to be the important variable in mortality in all the groups, rather than the length of cross-clamp or extracorporeal pump times. CONCLUSION: An attempted MVRpr which fails and is converted to replacement at the same operation does not appear to be associated with excess morbidity or mortality, despite longer cross-clamp and pump times. Accordingly, MVRpr can be safely undertaken when indicated, even with additional cardiac procedures.

Trends in mitral valve surgery in a large multi-surgeon, multi-hospital practice, 1979-1999.

BACKGROUND AND AIM OF THE STUDY: Trends in mitral valve operations (MVO) may help to predict the future of mitral valve surgery in the context of changing case mix, population demographics, emerging technology and shifting paradigms. METHODS: All adults undergoing single mitral valve operations (MVO) between 1979 and 1999 were reviewed retrospectively according to age, gender and other typical clinical variables, surgical complexity, specific operation and immediate outcome. RESULTS: A total of 2,055 single MVO was performed. Although coronary artery bypass volumes declined by 15.3% from 1996 to 1999, MVO volumes have continued to increase 58.0% since 1996. For the entire period, there was an insignificant increase in mean age, but an increase in percent male gender and in the prevalence of degenerative and ischemic etiology and mitral regurgitation (MR) pathophysiology. During the 1990s, trends in surgical complexity included a stable 40% prevalence of combined MVO and a stable 9:1 distribution of first operations to reoperations. Technology adoption included a decreased prevalence of mechanical valve usage at the expense of an increased prevalence of mitral valve repair (MVRpr). The prevalence of MVRpr among individual surgeons appeared to be related to a threshold case load of 20 mitral valve operations per year. Predictors of hospital mortality rates for MVO included age > or = 65 years, reoperations and combined MVO. Age > or = 65 years was a predictor of hospital mortality for each category of overall, isolated and combined MVO, mitral valve replacement (MVR) and MVRpr except for combined MVR. Hospital mortality rates for overall MVO, first-op MVO and combined MVO decreased during the 1990s. Hospital mortality comparisons between MVR and MVRpr favored MVRpr, either significantly or by insignificant trend, in every category of overall, isolated and combined groups and when evaluated by age > or = or < 65 year, in overall, isolated and combined groups. CONCLUSION: MVO volumes are steadily increasing apparently as a result of the increase in octogenarians and the beginning of the 'baby boomer' wave. Degenerative and ischemic etiologies with MR pathophysiology are on the rise, while rheumatic and endocarditis etiologies are static. The prevalence of MVR with mechanical prostheses has decreased in favor of MVRpr. The prevalence of MVRpr among individual surgeons appears to be related to an annual threshold volume of overall MVO. Hospital mortality risk is related to age and surgical complexity, but is modest and has continued to trend down during the past decade. Hospital mortality appears to favor MVRpr over MVR in all categorical comparisons, either significantly or by insignificant trend. These opposite trend lines for MVR and MVRpr likely represent a paradigm shift away from mechanical solutions in favor of tissue solutions for mitral valve disease, especially for MVRpr.

Trends in aortic valve surgery in a large multi-surgeon, multi-hospital practice, 1979-1999.

BACKGROUND AND AIM OF THE STUDY: Trends in aortic valve operations (AVO) may help to predict the future of aortic valve surgery in the context of changing case mix, population demographics, emerging technology and shifting paradigms. METHODS: All adults undergoing single AVO between 1979 and 1999 were reviewed retrospectively according to age, gender and other typical clinical variables, surgical complexity, specific operation and immediate outcome. RESULTS: There were 3,917 single AVO. Although coronary artery bypass (CAB) volumes declined by 15.3% between 1996 and 1999, AVO volumes have continued to increase by 11.7% since 1996. Over the entire period, there was no significant change in mean age or percent female gender, but increases in the prevalence of octogenarians and aortic stenosis were noted. During the 1990s, degenerative valve disease predominated and the prevalence of sicker patients according to heart failure class and surgical priority decreased. Trends in surgical complexity included an increase in AVO combined with CAB, but a stable 9:1 distribution of first operations to reoperations. Technology adoption included a decreased prevalence of mechanical valve use at the expense of increased use of tissue valves, especially stented xenografts and homografts. Transient technology adoption included stentless xenografts. Small numbers of pulmonary autografts, aortic valve repairs and valve-sparing aortic replacements were carried out. Predictors of hospital mortality rates for AVO included age 65 years, reoperation and combined AVO. Hospital mortality rates for AVO decreased for most age groups between the 1980s and 1990s, but not during the 1990s. CONCLUSION: AVO volumes are steadily increasing, apparently as a result of the increase in octogenarians and the start of the 'baby boom' wave. Hospital mortality risk is related to age and surgical complexity, but is modest and has stabilized during the past decade. The prevalence of mechanical valve implants has decreased in favor of tissue valve replacement categories. The fastest growth rates have been with stented xenografts, and especially homografts. This may represent a paradigm shift away from mechanical solutions in favor of tissue solutions for aortic valve disease.