Outbreak or coincidental cases of tuberculosis? Genotyping provides the clue

We illustrate how genotyping of mycobacterial strains contributed to the discovery of an undetected outbreak of tuberculosis in a hospital ward, ruling out misleading assumptions of transmission chains. Genotyping should be taken into account in routine tests for the control of tuberculosis.     

Valor predictivo de la infiltración por linfocitos T intraepiteliales (CD3) en el pronóstico del cáncer colorrectal resecado

Introduction

Colorectal cancer (CRC) can induce an anti-tumoral immune response mediated by T-lymphocytes, which express CD3.

Objectives

To analyze the prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall and in the early tumoral stages.

Methods

We revised 251 patients with resected CRC and favorable clinical course. CD3I expression was analyzed by immunohistochemistry. Multivariate analysis was used to analyze the variables independently associated with survival. We analyzed CD3I(+) expression in relation to survival and tumoral progression, both overall and in patients with pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CD3I expression were analyzed.

Results

A total of 25.9% of patients with CRC were CD3I(+). After a mean follow-up of 74 months, CD3I(+) expression showed a favorable prognostic value for survival in the multivariate analysis (p = 0.045). Survival curves and absence of tumoral progression were more favorable in CD3I(+) cases, both overall (p = 0.009 and p = 0.004, respectively), and in stages I-II (p = 0.029 and p = 0.015). The specificity and positive predictive value of CD3I(+) were as follows: Survival: overall: specificity =0.89; positive predictive value =0.91. Stage (I-II): specificity =0.94; positive predictive value =0.98. Absence of tumoral progression: overall: specificity = 0.89; positive predictive value =0.88. Stage (I-II): specificity =0.92; positive predictive value =0.96.

Conclusions

CD3I expression has an favorable independent prognostic value, with statistically significantly higher percentages of survival and absence of tumoral progression. This more favorable outcome is maintained in the less advanced stages (I-II). CD3I expression shows high specificity and positive predictive value.     

Leiomyoma in Meckel's diverticulum

Meckel's diverticulum (MD) is a persistent embryonic remnant occurring in 2% of the general population. This entity is usually clinically silent and is only discovered when complications occur. Diagnosis is rarely made preoperatively. Surgical resection of symptomatic MD is widely accepted but the most appropriate management of asymptomatic MD remains unclear. We present a case of MD that summarizes some of the complications that may occur. The peculiarity of this case was that the complications were caused by a leiomyoma. The presence of tumoral disease in MD accounts for 3.2% of complications. The most common neoplasm is carcinoid tumor. Few publications have reported benign neoplasms in MD, probably due to their low incidence.     

Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation

Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy.     

Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody-positive versus antimitochondrial autoantibody-negative primary biliary cirrhosis

Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function, and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable AMAs, but a minority (<5%) are AMA negative (AMA(-)), even with recombinant diagnostic technology. This issue prompted us to examine the nature of B-cell infiltrates surrounding the portal areas in AMA-positive (AMA(+)) and AMA(-) patients, because they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA(+) PBC than those observed in AMA(-) PBC patients. The portal areas from AMA(-) patients had a significant increase of cluster of differentiation (CD)5(+) cells infiltrating the ductal regions, and the levels of B-cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5(+) and CD20(+) cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5(+) cells, which remain sustained and predominate over CD20(+) cells. CONCLUSION: Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC.     

Nonalcoholic fatty liver disease and HIV infection

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome that includes a range of disorders associated with fatty liver from steatosis to cirrhosis and hepatocellular carcinoma, defined by the presence of liver fat accumulation exceeding 5% of hepatocytes in the absence of other causes of liver disease such as alcohol consumption, viral hepatitis, or any other specific etiology. Half the patients with human immunodeficiency virus (HIV) who undergo additional testing for unexplained liver test abnormalities may suffer from NAFLD, which is the hepatic manifestation of the metabolic syndrome. In HIV-infected patients, NAFLD can result from the HIV itself, highly active antiretroviral therapy (HAART), and/or lipodystrophy. Evaluation of the liver impact of NAFLD remains mainly based on liver biopsy, but numerous noninvasive procedures are under evaluation. In HIV/hepatitis C virus (HCV-) coinfected patients, steatosis seems more frequent and severe by comparison with HCV-monoinfected patients, and is associated with significant liver fibrosis, which may contribute to the more rapid progression of liver disease. First-line treatment of NAFLD is mainly based on the adequate management of the metabolic syndrome, including lifestyle changes. Specific therapeutic approaches are under investigation.