Viral surveillance using PCR during treatment of AML and ALL

1 Background

While viral surveillance of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus using PCR is routine in patients undergoing hematopoetic stem cell transplant and solid organ transplant, the utility in the nontransplant pediatric leukemia population is unknown. Our institution screens patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) for viral DNAemia by PCR as part of clinical care.

2 Procedure

This retrospective chart review included patients treated for newly diagnosed or relapsed AML or ALL between April 2010 and September 2014. We retrieved data for viral PCR screening, detection and quantification, duration of positivity, and prophylaxis or treatment.

3 Results

One hundred eleven patients were included in analyses. Forty (36.0%) had at least one blood PCR positive for EBV, CMV, or adenovirus. Patients with ALL had significantly higher rates of persistent viral detection and treatment than those with AML (P < 0.02, P < 0.01, respectively). International patients had significantly higher rates of viral detection (P < 0.01), persistence (P < 0.01), any treatment (P < 0.03), and antiviral treatment (P < 0.01); 16.9% of patients who received intravenous immunoglobulin (IVIG) prophylactically had viral detection compared to 63% of patients who did not receive prophylactic IVIG (P = 0.0008).

4 Conclusions

Patients with ALL were more susceptible than those with AML to viral reactivation that was persistent or resulted in treatment. Patients with relapsed ALL, refractory ALL, or infantile ALL are most likely to benefit from asymptomatic screening for CMV and adenovirus. International patients are at higher risk for reactivation and may merit screening. EBV reactivation was not significant and does not warrant screening.     

Gender differences in sexual behaviors, sexual partnerships, and HIV among drug users in New York City

We compared sexual behaviors/partnerships and determined sexual risk correlates associated with HIV by gender among street-recruited drug users using chi-square tests and logistic regression. Men reported higher risk sexual behaviors, yet fewer high-risk sexual partners than women. After adjustment, HIV seropositive men were more likely than seronegatives to be older, MSM, use condoms, and have an HIV-infected partner. HIV seropositive women were more likely to be older, have an HIV-infected partner, and not use non-injected heroin. IDU was not associated with HIV. Prospective studies are needed to determine how gender-specific sexual behaviors/partnerships among drug users affect HIV acquisition.     

Leigh syndrome in an infant resulting from mitochondrial DNA depletion

Leigh syndrome is an encephalomyelopathy that results from a heterogeneous group of mitochondrial disorders characterized by symmetric brainstem spongioform lesions. An infant born with hypotonia and lactic acidosis was found to have symmetric brainstem lesions on T(2)-weighted magnetic resonance imaging consistent with Leigh syndrome. Muscle biopsy failed to reveal ragged-red fibers or cells devoid of cytochrome C oxidase or succinate dehyrogenase. Southern blot analysis of mitochondrial DNA isolated from the patient's quadriceps muscle indicated severe mitochondrial DNA depletion, which was suggested as the cause for the Leigh syndrome seen in this patient. Consideration of mitochondrial DNA depletion as an etiology when evaluating the patient with Leigh syndrome is encouraged.     

Persistence and 4-year boosting of the bactericidal response elicited by two- and three-dose schedules of MenB-FHbp: A phase 3 extension study in adolescents

Background

The period of heightened risk of invasive meningococcal disease in adolescence extends for >10?years. This study aimed to evaluate persistence of the immune response to the serogroup B meningococcal (MenB) vaccine MenB-FHbp (Trumenba^®, Bivalent rLP2086) under two- and three-dose primary vaccination schedules, both of which are approved in the United States and the European Union, and to assess safety and immunogenicity of a booster dose.

Altered FDG uptake patterns in pediatric lymphoblastic lymphoma patients receiving induction chemotherapy that includes very high dose corticosteroids

Background  

Altered FDG uptake patterns were noted in certain lymphoblastic lymphoma patients during therapy.     

Vibrio cholerae Phosphoenolpyruvate Phosphotransferase System Control of Carbohydrate Transport,Biofilm Formation,and Colonization of the Germfree Mouse Intestine

The bacterial phosphoenolpyruvate phosphotransferase system (PTS) is a highly conserved phosphotransfer cascade whose components modulate many cellular functions in response to carbohydrate availability. Here, we further elucidate PTS control of Vibrio cholerae carbohydrate transport and activation of biofilm formation on abiotic surfaces. We then define the role of the PTS in V. cholerae colonization of the adult germfree mouse intestine. We report that V. cholerae colonizes both the small and large intestines of the mouse in a distribution that does not change over the course of a month-long experiment. Because V. cholerae possesses many PTS-independent carbohydrate transporters, the PTS is not essential for bacterial growth in vitro. However, we find that the PTS is essential for colonization of the germfree adult mouse intestine and that this requirement is independent of PTS regulation of biofilm formation. Therefore, competition for PTS substrates may be a dominant force in the success of V. cholerae as an intestinal pathogen. Because the PTS plays a role in colonization of environmental surfaces and the mammalian intestine, we propose that it may be essential to successful transit of V. cholerae through its life cycle of pathogenesis and environmental persistence.In water, in soil, and in the eukaryotic host, bacteria survive by monitoring their environment and continuously adjusting their nutrient uptake and catabolism machinery to mirror environmental availability. While the ability to maximize environmental nutrients may not be critical in nutrient-rich environments such as those found in the laboratory, in natural environments where nutrients are scarce and competition for these nutrients may be fierce, rapid and precise adaptation is the key to survival.The bacterial phosphoenolpyruvate phosphotransferase system (PTS) is a multicomponent phosphotransfer cascade that coordinates transport and phosphorylation of selected carbohydrates through PTS-associated transporters. Because transport of PTS substrates rapidly depletes the PTS of phosphorylated intermediates, the phosphorylation states of PTS components serve as cytoplasmic reporters of environmental nutrient availability (5).Phosphotransfer through the PTS is initiated when the cytoplasmic phosphoenolpyruvate-protein phosphotransferase, or enzyme I (EI), accepts a phosphate from phosphoenolpyruvate. EI is required for the transport of all PTS substrates. EI transfers its phosphate group to histidine protein (HPr), another cytoplasmic protein involved in the transport of most PTS substrates. HPr transfers its phosphate to any of a number of enzymes II, which are membrane-associated complexes that carry out the transport and phosphorylation of specific PTS substrates and comprise multiple subunits (EIIA, EIIB, EIIC, and sometimes EIID). A fructose-specific multidomain protein, FPr, which consists of an N-terminal EIIA-like domain, a central domain of unknown function, and a C-terminal HPr-like domain, is also present in many Gram-negative bacteria (15). In the transport of fructose by the Escherichia coli PTS, FPr is favored over HPr in the phosphotransfer cascade. Furthermore, a parallel PTS system is encoded by many bacterial genomes (29, 30). This system is termed the PTS^Ntr because of its chromosomal proximity to the genes encoding the nitrogen-specific sigma factor, σ⁵⁴. The PTS^Ntr includes an EI homolog (EI^Ntr), an HPr homolog (NPr), and an EIIA homolog (EIIA^Ntr). Although there is some evidence of cross talk between the carbon-specific PTS and the PTS^Ntr (26), the latter system is thought to function primarily in regulation rather than transport.Vibrio cholerae is a Gram-negative, halophilic bacterium that inhabits saline and freshwater aquatic environments (6). In these environments, V. cholerae is hypothesized to attach to abiotic surfaces by elaboration of an exopolysaccharide termed VPS in a process known as VPS-dependent biofilm formation (40). Many of the vps genes, which are required for VPS synthesis, are carried in two large operons consisting of vpsA to vpsK and vpsL to vpsQ (39).Some strains of V. cholerae are also able to cause the human diarrheal disease cholera after ingestion in contaminated food or water. Disease requires the presence of the toxin-coregulated pilus, the primary intestinal colonization factor of V. cholerae (9, 35), as well as cholera toxin, which acts on the epithelial cells of the small intestine to produce an intense, osmotic diarrhea. Therefore, the ability to colonize the small intestine is an important component in V. cholerae virulence.We hypothesized that to persist in all these environments, V. cholerae must sense and respond to preferred carbon sources and, therefore, that the regulatory and transport functions of the PTS might figure prominently in its success. Only two studies thus far have examined the transport and regulatory functions of V. cholerae PTS components. One of these documented a regulatory function for the phosphorylated form of EI in the repression of VPS-dependent biofilm formation on abiotic surfaces (12), while the other identified the chitobiose transport apparatus (1). In this work, we performed a mutagenesis-based study of the roles of V. cholerae PTS components in sugar transport and VPS-dependent biofilm formation. To evaluate the role of the PTS signal transduction cascade in the colonization of the adult mammalian intestine, we implemented and characterized an adult germfree mouse model of disease. We have shown that V. cholerae is present in the distal small intestine as well as the large intestine and have found that the requirement for the PTS in intestinal colonization is independent of VPS synthesis. These results suggest a role for the V. cholerae PTS in the colonization of environmental surfaces and the adult mammalian intestine. The PTS is found in almost all bacterial species and has been shown previously to play important roles in the surface attachment and virulence of many of these species (14, 16, 18, 27, 31, 33, 34). Because the PTS is also highly conserved, we suggest that it may be an excellent target for inhibition of colonization of both environmental surfaces and host epithelia by diverse bacteria.     

Dietary calcium and iron: effects on blood pressure and hematocrit in young spontaneously hypertensive rats

Supplemental dietary calcium in spontaneously hypertensive rats (SHRs) aged 21-28 d produces a decrease in blood pressure and hematocrit. The simultaneous fall in hematocrit and blood pressure suggests that the changes in blood pressure may be, in part, a consequence of the decrease in hematocrit and reduction in viscosity. To examine this possibility, SHRs aged 21 d were placed on one of four diets varying in iron content. At age 28, the animals showed iron-induced variations in hematocrit (P less than 0.001) but no difference in blood pressure. Subsequent manipulation of the ratio of calcium and iron in the diets of additional groups of animals resulted in variations in hematocrit that were independent of the calcium-induced alterations in blood pressure. We conclude that the effects of calcium on blood pressure are relatively independent of its effects on hematocrit.