Primary malignant mesothelioma of the peritoneum

Mesothelioma of the peritoneum represents an extremely rare malignancy of the abdominal cavity and forms about 10% of all mesotheliomas. The annual incidence of the tumor in the general population is 1-2 cases per million. The causative relationship between chronic exposure to asbestos and mesothelioma has been proved. Since the symptomatology of the tumor is usually not specific, the diagnosis is made in the advanced stages of the disease, which is the limiting factor for therapy. Most patients die within 2 years from the diagnosis. We report a case of a primary malignant mesothelioma of the peritoneum in a 60-year old male, who presented with three-month history of ascites, weakness and appetite loss. The patient gave the information that he had been living for 15 years in a loft which was insulated by material consisting of asbestos. After investigations, primary neoplasm of the peritoneum was suspected, which was confirmed by the biopsy and the morphopathological examination. Due to the advanced spread of the tumor and the poor general condition, the patient underwent palliative therapy. The patient died 3 months after the diagnosis. Epidemiological data for chronic exposure to asbestos have to be considered as the etiological factor of disease in this particular patient.     

HLA targeting efficiency correlates with human T-cell response magnitude and with mortality from influenza A infection

Experimental and computational evidence suggests that HLAs preferentially bind conserved regions of viral proteins, a concept we term “targeting efficiency,” and that this preference may provide improved clearance of infection in several viral systems. To test this hypothesis, T-cell responses to A/H1N1 (2009) were measured from peripheral blood mononuclear cells obtained from a household cohort study performed during the 2009–2010 influenza season. We found that HLA targeting efficiency scores significantly correlated with IFN-γ enzyme-linked immunosorbent spot responses (P = 0.042, multiple regression). A further population-based analysis found that the carriage frequencies of the alleles with the lowest targeting efficiencies, A*24, were associated with pH1N1 mortality (r = 0.37, P = 0.031) and are common in certain indigenous populations in which increased pH1N1 morbidity has been reported. HLA efficiency scores and HLA use are associated with CD8 T-cell magnitude in humans after influenza infection. The computational tools used in this study may be useful predictors of potential morbidity and identify immunologic differences of new variant influenza strains more accurately than evolutionary sequence comparisons. Population-based studies of the relative frequency of these alleles in severe vs. mild influenza cases might advance clinical practices for severe H1N1 infections among genetically susceptible populations.     

Supporting research,protecting data: one institution’s approach to clinical data warehouse governance

Institutions must decide how to manage the use of clinical data to support research while ensuring appropriate protections are in place. Questions about data use and sharing often go beyond what the Health Insurance Portability and Accountability Act of 1996 (HIPAA) considers. In this article, we describe our institution’s governance model and approach. Common questions we consider include (1) Is a request limited to the minimum data necessary to carry the research forward? (2) What plans are there for sharing data externally?, and (3) What impact will the proposed use of data have on patients and the institution? In 2020, 302 of the 319 requests reviewed were approved. The majority of requests were approved in less than 2 weeks, with few or no stipulations. For the remaining requests, the governance committee works with researchers to find solutions to meet their needs while also addressing our collective goal of protecting patients.     

Circulating insulin-like growth factors in patients infected with Helicobacter pylori

OBJECTIVES: The level of insulin-like growth factors (IGFs) and their binding proteins may change in acutely ill humans. The aim of this work was to examine the changes in the IGF system in patients suffering from infection induced by Helicobacter pylori (H. pylori). DESIGN AND METHODS: The serum concentrations of IGF-I, IGF-II and cortisol were measured by radioimmunoassay. IGFBP patterns were characterized by ligand-affinity blotting, and a lectin-binding assay was used to investigate the possible changes in the glycocomponent of IGFBP-3. RESULTS: Both IGF-I and IGF-II concentrations were significantly lower in patients with H. pylori infection (P < 0.001 for IGF-I and P = 0.016 for IGF-II) compared to healthy individuals, whereas the level of cortisol was significantly elevated in analyzed patients (P < 0.001). Autoradiography demonstrated the increased presence of IGFBP-2 and IGFBP-1, together with a decreased level of IGFBP-3. CONCLUSIONS: The circulating IGF/IGFBP system is altered in patients infected with H. pylori. The increased level of cortisol suggests the involvement of the hypothalamic/pituitary/adrenal axis that stimulates the elevation of blood glucose, probably in coordination with decreased IGF activity to minimize anabolic metabolism.     

Extensive HLA class I allele promiscuity among viral CTL epitopes

Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development.     

Clinical and pathological tools for identifying microsatellite instability in colorectal cancer

Aim. To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). Method. Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results. Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. Conclusion. The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing.     

Demographics and treatment of the American family

There have been numerous changes to the US family over the past several decades. Traditional family roles have changed, and the conception of what Americans consider a 'family' has likewise shifted with differing societal views regarding gender, gender roles, race, and ethnicity. This review examines demographics of the American family as well as a number of family therapies that have been historically and are presently used to treat family problems. We expect that with the changes present in US society, family therapies will need to continue to be sensitive and adaptive to these shifts in order to be effective.