Association of Toll-like receptors 4 (TLR-4) gene expression and polymorphisms in patients with severe asthma.

Innate immunity plays a central role in the pathogenesis of severe asthma, and it is closely linked to elevated IgE and Toll-like receptor 4 (TLR-4) levels. However, there is a scarcity of information about the association of the TLR-4 receptor polymorphism in the pathogenesis of severe asthma. This study highlights the level of gene expression of different alleles in asthmatic patients compared to healthy control individuals. This was a randomized control trial, which included 150 patients with asthma (with high serum levels of IgE) with a matching 150 healthy control individuals. Participants had a series of blood tests to measure various immune parameters: interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), intercellular adhesion molecule-1 (ICAM1) and detect allele type and gene expression of the TLR-4 gene. Patients with asthma had significantly higher levels of IL-8 when compared to the healthy control participants. In addition, in the rs91 genotyping, there were significant differences in the levels of IL-8 and TNF between CC and TT genotyping. While in rs90 TLR-4, TNF levels were significantly higher in AA vs. AG and GG genotypes among the asthmatic patients when compared to the control group. The results showed that in TLR-4, rs4986791 were significantly associated with asthma risk. Polymorphisms in TLRs play essential roles in asthma.

Risk of malignancy in pulmonary nodules: A validation study of four prediction models.

OBJECTIVES: Clinical prediction models assess the likelihood of malignancy in pulmonary nodules detected by computed tomography (CT). This study aimed to validate four such models in a UK population of patients with pulmonary nodules. Three models used clinical and CT characteristics to predict risk (Mayo Clinic, Veterans Association, Brock University) with a fourth model (Herder et al. [4]) additionally incorporating (18)Fluorine-Fluorodeoxyglucose (FDG) avidity on positron emission tomography-computed tomography (PET-CT). MATERIALS AND METHODS: The likelihood of malignancy was calculated for patients with pulmonary nodules (4-30mm diameter) and data used to calculate the area under the receiver operating characteristic curve (AUC) for each model. The models were used in a restricted cohort of patients based on each model's exclusion criteria and in the total cohort of all patients. RESULTS: Two hundred and forty-four patients were studied, of whom 139 underwent FDG PET-CT. Ninety-nine (40.6%) patients were subsequently confirmed to have malignant nodules (33.2% primary lung cancer, 7.4% metastatic disease). The Mayo and Brock models performed similarly (AUC 0.895 and 0.902 respectively) and both were significantly better than the Veterans Association model (AUC 0.735, p<0.001 and p=0.002 respectively). In patients undergoing FDG PET-CT, the Herder model had significantly higher accuracy than the other three models (AUC 0.924). When the models were tested on all patients in the cohort (i.e. including those outside the original model inclusion criteria) AUC values were reduced, yet remained high especially for the Herder model (AUC 0.916). For sub-centimetre nodules, AUC values for the Mayo and Brock models were 0.788 and 0.852 respectively. CONCLUSIONS: The Mayo and Brock models showed good accuracy for determining likelihood of malignancy in nodules detected on CT scan. In patients undergoing FDG PET-CT for nodule evaluation, the highest accuracy was seen for the model described by Herder et al. incorporating FDG avidity.

Outcome of acute myeloid leukemia and high-risk myelodysplastic syndrome according to health insurance status.

BACKGROUND: Age, cytogenetic status, and molecular features are the most important prognostic factors in acute myeloid leukemia (AML). This study aimed to analyze the outcomes of patients with AML or high-risk myelodysplastic syndrome (MDS) according to insurance status. PATIENTS AND METHODS: A retrospective chart review was performed, covering all patients with AML and high-risk MDS evaluated and treated at Akron General Medical Center between 2002 and 2012. A Cox regression model was analyzed to account for survival over time, adjusted for insurance type, while controlling for patient age at diagnosis and patient risk of mortality. RESULTS: A total of 130 adult patients (age ≥ 18 years) were identified. Insurance information was available for 97 patients enrolled in the study; 3 were excluded because of self-pay status. Cox regression analysis with insurance type as the predictor found that overall survival declines over time and that the rate of decline may be influenced by insurance type (χ(2)(2) = 6.4; P = .044). The likelihood of survival in patients with Medicaid or Medicare without supplemental insurance was .552 (95% CI, .338-.903; P = .018) times the likelihood in patients who had Medicare with supplemental insurance. To explain the difference, variables of age, gender, and risk of mortality were added to the model. Age and risk of mortality were found to be significant predictors of survival. The addition of insurance type to the model did not significantly contribute (χ(2)(3) = 3.83; P = .147). CONCLUSION: No significant difference in overall survival was observed when patients with AML or high-risk MDS were analyzed according to their health insurance status. The overall survival was low in this study compared with the national average. Early referral to a specialized center or possible clinical trial enrollment may be a good alternative to improve outcome.

Global health language and culture competency.

This article presents findings from a survey conducted to examine the availability of foreign language and culture training to Civil Affairs health personnel and the relevance of that training to the tasks they perform. Civil Affairs forces recognize the value of cross-cultural communication competence because their missions involve a significant level of interaction with foreign governments? officials, military, and civilians. Members of the 95th Civil Affairs Brigade (Airborne) who had a health-related military occupational specialty code were invited to participate in the survey. More than 45% of those surveyed were foreign language qualified. Many also received predeployment language and culture training specific to the area of deployment. Significantly more respondents reported receiving cultural training and training on how to work effectively with interpreters than having received foreign language training. Respondents perceived interpreters as important assets and were generally satisfied with their performance. Findings from the survey highlight a need to identify standard requirements for predeployment language training that focuses on medical and health terminology and to determine the best delivery platform(s). Civil Affairs health personnel would benefit from additional cultural training that focuses on health and healthcare in the country or region of deployment. Investing in the development of distance learning capabilities as a platform for delivering health-specific language and culture training may help ease the time and resources constraints that limit the ability of Civil Affairs health personnel to access the training they need.

Standard therapy for patients with myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by cytopenias, dysplastic changes in the hematopoietic precursors, and an increased risk of evolving into acute leukemia. Treatment for patients with MDS ranges from supportive care with blood products and/or growth factors up to allogeneic stem cell transplantation. Over the past decade, several novel therapeutic agents have been approved for clinical use. In this article, the current approach for the management of patients with MDS according to their risk category is described and mainly focuses on approved novel agents.

Significance of thrombocytopenia in myelodysplastic syndromes: associations and prognostic implications.

PURPOSE: To analyze the incidence and significance of thrombocytopenia in patients with myelodysplastic syndrome (MDS). PATIENTS AND METHODS: A total of 2517 patients with MDS referred to our institution since 1993 were analyzed, with a specific focus on the incidence and associations of thrombocytopenia. RESULTS: The median age of the study group was 66 years. The median survival was 13 months. Platelet counts <100 × 10(9)/L were noted in 65%, and platelets counts <30 × 10(9)/L in 26%. Each platelets count drop below the range of 200 × 10(9)/L has shown a larger magnitude change in terms of worsening effect on survival. Therefore, smaller ranges of platelet counts of <200 × 10(9)/L were studied. Platelet cutoffs of 30, 50, and 200 × 10(9)/L thus were identified to have significant associations with differences in survival. Significant thrombocytopenia was associated with poor performance, other cytopenias, adverse karyotype, and advanced MDS phases. Thrombocytopenia was associated with worse prognosis; it also was predicted for worse outcome within each of the International Prognostic Scoring System risk groups. CONCLUSION: Prognosis in MDS is directly associated with the severity of thrombocytopenia.

Acute pulmonary failure during remission induction chemotherapy in adults with acute myeloid leukemia or high-risk myelodysplastic syndrome.

BACKGROUND: Acute pulmonary failure during remission induction therapy is a serious complication in patients with acute myeloid leukemia (AML). To the authors' knowledge, the course and prognosis of such patients is not well known. METHODS: A total of 1541 patients referred for remission induction chemotherapy of AML or high-risk myelodysplastic syndrome were retrospectively reviewed. RESULTS: A total of 120 (8%) patients developed acute pulmonary failure within 2 weeks of the initiation of chemotherapy; 87 of these patients (73%) died during remission induction, whereas 17 (14%) achieved a complete response. The median survival among the 120 patients with early acute pulmonary failure was 3 weeks. Predictive factors for the development of early acute pulmonary failure by multivariate analysis were: male sex (P = .00038), acute promyelocytic leukemia (P = .00003), poor performance status (P = .001), lung infiltrates at diagnosis (P = .000001), and increased creatinine (P = .000005). Patients who had 0 to 1, 2, 3, or 4 to 5 adverse factors were found to have estimated predictive incidences of acute pulmonary failure of 3%, 13%, 23%, and 34%, respectively. CONCLUSIONS: Preventive approaches at the start of induction therapy in patients at high risk of pulmonary failure may improve the outcome of these patients.