Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, PPeer reviewe

Bacteremic community-acquired pneumonia due to Klebsiella pneumoniae: Clinical and microbiological characteristics in Taiwan, 2001-2008

<p>Abstract</p> <p>Background</p> <p><it>Klebsiella pneumoniae </it>is the major cause of community-acquired pyogenic infections in Taiwan. This retrospective study evaluated the clinical and microbiological characteristics of bacteremic community-acquired pneumonia due to <it>K. pneumoniae </it>in Taiwanese adults.</p> <p>Methods</p> <p>The clinical characteristics of bacteremic community-acquired pneumonia (CAP) in adults due to <it>K. pneumoniae </it>were compared to those of adults with bacteremic CAP due to <it>Streptococcus pneumoniae </it>at a tertiary medical center in Taiwan from 2001-2008. Risk factors for mortality of bacteremic CAP due to <it>K. pneumoniae </it>were analyzed. All clinical isolates of <it>K. pneumoniae </it>were examined for capsular serotypes, hypermucoviscosity phenotype, aerobactin and <it>rmpA </it>gene.</p> <p>Results</p> <p><it>K. pneumoniae </it>was the dominant cause of bacteremic CAP and was associated with a more fulminant course and a worse prognosis than bacteremic CAP due to <it>Streptococcus pneumoniae</it>. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality. Serotype K1 and K2 comprised around half of all isolates. There were no significant differences in the clinical characteristics of patients with bacteremic CAP due to K1/K2 and non-K1/K2 isolates. Hypermucoviscosity phenotype as well as the aerobactin and <it>rmpA </it>genes were highly prevalent in the <it>K. pneumoniae </it>isolates.</p> <p>Conclusions</p> <p><it>K. pneumoniae </it>continued to be the dominant cause of bacteremic CAP in Taiwanese adults during 2001-2008. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality from <it>K. pneumoniae </it>bacteremic CAP. Serotypes K1/K2 comprised around half of all isolates, but did not predispose patients to a poor clinical outcome. Physicians should be aware of the poor prognosis of any patient with bacteremic <it>K. pneumoniae </it>CAP and monitor these patients more closely.</p

Seroprevalence of Immunoglobulin G antibodies against pertussis toxin among asymptomatic medical students in the west of Iran: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Pertussis is a highly communicable, vaccine-preventable respiratory infection. Immune response against this disease can be induced by infection or vaccination. Protection after childhood vaccination is minimal after ten years. Our aim was to assess pertussis immunity state in a population of healthy young medical students.</p> <p>Methods</p> <p>In this seroepidemiological survey, blood samples were obtained from 163 first-year medical students in Hamedan University, Iran. Serum level of IgG against pertussis toxin (IgG-PT) was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. For qualitative assessment, IgG-PT levels more than 24 unit (U)/ml were considered positive. Data was analysed qualitatively and quantitatively considering gender and age groups.</p> <p>Results</p> <p>There were 83 males and 80 females, with a mean age of 19.48 years, Prevalence of IgG-PT was 47.6% with mean level of 71.7 u/ml (95% confidence interval: 68.1–75.3). No statistically significant difference was observed with respect to sero-positivity of IgG-PT between males and females (45 cases (54%) vs. 34 cases (42%); P = 0.06). Mean IgG-PT levels in males and females were 84 U/ml and 58.8 U/ml, respectively (P = 0.91).</p> <p>Conclusion</p> <p>A considerable proportion of our study population with a positive history of childhood vaccination for pertussis was not serologically immune to pertussis. A booster dose of acellular pertussis vaccine may be indicated in Iranian, medical students regarding their serologic conditions and outstanding role in health care systems.</p

Co-Administration of IL-1+IL-6+TNF-α with Mycobacterium tuberculosis Infected Macrophages Vaccine Induces Better Protective T Cell Memory than BCG

BCG has been administered globally for more than 75 years, yet tuberculosis (TB) continues to kill more than 2 million people annually. Further, BCG protects childhood TB but is quite inefficient in adults. This indicates that BCG fails to induce long-term protection. Hence there is a need to explore alternative vaccination strategies that can stimulate enduring T cell memory response. Dendritic cell based vaccination has attained extensive popularity following their success in various malignancies. In our previous study, we have established a novel and unique vaccination strategy against Mycobacterium tuberculosis (M. tb) and Salmonella typhimurium by utilizing infected macrophages (IM). In short-term experiments (30 days), substantial degree of protection was observed. However, remarkable difference was not observed in long-term studies (240 days) due to failure of the vaccine to generate long-lasting memory T cells. Hence, in the present study we employed T cell memory augmenting cytokines IL-1+IL-6+TNF-α and IL-7+IL-15 for the induction of the enhancement of long-term protection by the vaccine. We co-administered the M. tb infected macrophages vaccine with IL-1+IL-6+TNF-α (IM-1.6.α) and IL-7+IL-15 (IM-7.15). The mice were then rested for a reasonably large period (240 days) to study the bona fide T cell memory response before exposing them to aerosolized M. tb. IM-1.6.α but not IM-7.15 significantly improved memory T cell response against M. tb, as evidenced by recall responses of memory T cells, expansion of both central as well as effector memory CD4 and CD8 T cell pools, elicitation of mainly Th1 memory response, reduction in the mycobacterial load and alleviated lung pathology. Importantly, the protection induced by IM-1.6.α was significantly better than BCG. Thus, this study demonstrates that not only antigen-pulsed DCs can be successfully employed as vaccines against cancer and infectious diseases but also macrophages infected with M. tb can be utilized with great efficacy especially in protection against TB

Co-variations and Clustering of Chronic Disease Behavioral Risk Factors in China: China Chronic Disease and Risk Factor Surveillance, 2007

BACKGROUND: Chronic diseases have become the leading causes of mortality in China and related behavioral risk factors (BRFs) changed dramatically in past decades. We aimed to examine the prevalence, co-variations, clustering and the independent correlates of five BRFs at the national level. METHODOLOGY/PRINCIPAL FINDINGS: We used data from the 2007 China Chronic Disease and Risk Factor Surveillance, in which multistage clustering sampling was adopted to collect a nationally representative sample of 49,247 Chinese aged 15 to 69 years. We estimated the prevalence and clustering (mean number of BRFs) of five BRFs: tobacco use, excessive alcohol drinking, insufficient intake of vegetable and fruit, physical inactivity, and overweight or obesity. We conducted binary logistic regression models to examine the co-variations among five BRFs with adjustment of demographic and socioeconomic factors, chronic conditions and other BRFs. Ordinal logistic regression was constructed to investigate the independent associations between each covariate and the clustering of BRFs within individuals. Overall, 57.0% of Chinese population had at least two BRFs and the mean number of BRFs is 1.80 (95% confidence interval: 1.78-1.83). Eight of the ten pairs of bivariate associations between the five BRFs were found statistically significant. Chinese with older age, being a male, living in rural areas, having lower education level and lower yearly household income experienced increased likelihood of having more BRFs. CONCLUSIONS/SIGNIFICANCE: Current BRFs place the majority of Chinese aged 15 to 69 years at risk for the future development of chronic disease, which calls for urgent public health programs to reduce these risk factors. Prominent correlations between BRFs imply that a combined package of interventions targeting multiple BRFs might be appropriate. These interventions should target elder population, men, and rural residents, especially those with lower SES

High Levels of Exosomes Expressing CD63 and Caveolin-1 in Plasma of Melanoma Patients

BACKGROUND: Metastatic melanoma is an untreatable cancer lacking reliable and non-invasive markers of disease progression. Exosomes are small vesicles secreted by normal as well as tumor cells. Human tumor-derived exosomes are involved in malignant progression and we evaluated the presence of exosomes in plasma of melanoma patients as a potential tool for cancer screening and follow-up. METHODOLOGY/PRINCIPAL FINDINGS: We designed an in-house sandwich ELISA (Exotest) to capture and quantify exosomes in plasma based on expression of housekeeping proteins (CD63 and Rab-5b) and a tumor-associated marker (caveolin-1). Western blot and flow cytometry analysis of exosomes were used to confirm the Exotest-based findings. The Exotest allowed sensitive detection and quantification of exosomes purified from human tumor cell culture supernatants and plasma from SCID mice engrafted with human melanoma. Plasma levels of exosomes in melanoma-engrafted SCID mice correlated to tumor size. We evaluated the levels of plasma exosomes expressing CD63 and caveolin-1 in melanoma patients (n = 90) and healthy donors (n = 58). Consistently, plasma exosomes expressing CD63 (504+/-315) or caveolin-1 (619+/-310) were significantly increased in melanoma patients as compared to healthy donors (223+/-125 and 228+/-102, respectively). While the Exotest for CD63+ plasma exosomes had limited sensitivity (43%) the Exotest for detection of caveolin-1+ plasma exosomes showed a higher sensitivity (68%). Moreover, caveolin-1+ plasma exosomes were significantly increased with respect to CD63+ exosomes in the patients group. CONCLUSIONS/SIGNIFICANCE: We describe a new non-invasive assay allowing detection and quantification of human exosomes in plasma of melanoma patients. Our results suggest that the Exotest for detection of plasma exosomes carrying tumor-associated antigens may represent a novel tool for clinical management of cancer patients