General outcomes and risk factors for minor and major amputations in Brazil.

Objectives Major and minor amputations are associated with significant rates of mortality. However, little is known about the impact of unplanned redo-amputation during the same hospitalization on outcomes. The objectives of this study were to identify the risk factors associated with in-hospital mortality after both major and minor amputations as well as the results of unplanned redo-amputation on outcome. Methods Retrospective study of 342 consecutive patients who were treated with lower extremity amputation in Brazil between January 2013 and October 2014. Results The in-hospital mortality rate was higher in major compared to minor amputation (25.6% vs. 4.1%; p < 0.0001). Whereas chronic kidney disease, chronic obstructive pulmonary disease, and planned staged amputation predicted in-hospital mortality after major amputation, age, and congestive heart failure predicted mortality after minor amputation. The white blood cell count predicted in-hospital mortality following both major and minor amputation. However, postoperative infection predicted in-hospital mortality only following major amputation. Conclusions In-hospital mortality was high after major amputations. Unplanned redo-amputation was not a predictor of in-hospital mortality after major or minor amputation. Planned staged amputation was associated with reduced survival after major but not minor amputation. Postoperative infection predicted mortality after major amputation. Systemic diseases and postoperative white blood cell were associated with in-hospital mortality. This study suggests a possible link between a pro-inflammatory state and increased in-hospital mortality following amputation.

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a complex disorder with a worldwide incidence estimated at 1:700. Among the putative susceptibility loci, the IRF6 gene and a region at 8q24.21 have been corroborated in different populations. To test the role of IRF6 in NSCL/P predisposition in the Brazilian population, we conducted a structured association study with the SNPs rs642961 and rs590223, respectively, located at 5' and 3' of the IRF6 gene and not in strong linkage disequilibrium (LD), in patients from five different Brazilian locations. We also evaluated the effect of these SNPs in IRF6 expression in mesenchymal stem cells (MSC). We observed association between rs642961 and cleft lip only (CLO) (P=0.009; odds ratio (OR) for AA genotype=1.83 [95% Confidence interval (CI), 0.64-5.31]; OR for AG genotype=1.72 [95% CI, 1.03-2.84]). This association seems to be driven by the affected patients from Barbalha, a location which presents the highest heritability estimate (H2=0.85), and the A allele at rs642961 is acting through a dominant model. No association was detected for the SNP rs590223. We did not find any correlation between expression levels and genotypes of the two loci, and it is possible that these SNPs have a functional role in some specific period of embryogenesis.

Genetic contribution for non-syndromic cleft lip with or without cleft palate (NS CL/P) in different regions of Brazil and implications for association studies.

Non-syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (Santarém, Fortaleza, Barbalha, Maceió, and Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santarém (44%) and the lowest in Maceió (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarém (71%), Rio de Janeiro (70%), Fortaleza (64%), and Maceió (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5-1.6%, varying according to the location studied (0.6-0.7% in Maceió to 2.2-2.8% in Barbalha). Our findings show that the degree of genetic contribution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consanguinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analyses and show that care must be taken when pooling samples from different populations for association studies.