Eosinophilic esophagitis as a side-effect of allergen immunotherapy: protocol for a systematic review and meta-analysis.

Summary: Background. Sensitization to food and airborne allergens is common in the majority of patients with eosinophilic esophagitis (EoE). Although there is not a direct cause-effect relationship of IgE-mediated allergy with the pathogenesis of EoE, there is a growing evidence that oral desensitization to food and sublingual immunotherapy (SLIT) may induce the development of EoE as an adverse effect. As part of the 'EoE and Allergen Immunotherapy (AIT)' Task Force funded by the European Academy of Allergy and Clinical Immunology (EAACI), a systematic approach will be followed to review the evidence from the published scientific literature on the development of EoE in children and adults under any type of AIT. Methods. This systematic review will be carried out following the PRISMA statement guidelines. Studies will be assessed for inclusion in the review according to the Population-Interventions-Comparators-Outcomes (PICO) criteria. Results. Expected outcomes will provide evidence on the AIT-EoE development connection. Conclusions. The findings from this review will be used as a reference to provide useful guidelines for physicians treating patients with EoE and/or are practicing AIT.

Edmonton obesity staging system among pediatric patients: a validation and obesogenic risk factor analysis.

PURPOSE: The Edmonton Obesity Staging System for Pediatrics (EOSS-P) is a useful tool, delineating different obesity severity tiers associated with distinct treatment barriers. The aim of the study was to apply the EOSS-P on a Greek pediatric cohort and assess risk factors associated with each stage, compared to normal weight controls. METHODS: A total of 361 children (2-14 years old), outpatients of an Athenian hospital, participated in this case-control study by forming two groups: the obese (n = 203) and the normoweight controls (n = 158). Anthropometry, blood pressure, blood and biochemical markers, comorbidities and obesogenic lifestyle parameters were recorded and the EOSS-P was applied. Validation of EOSS-P stages was conducted by juxtaposing them with IOTF-defined weight status. Obesogenic risk factors' analysis was conducted by constructing gender-and-age-adjusted (GA) and multivariate logistic models. RESULTS: The majority of obese children were stratified at stage 1 (46.0%), 17.0% were on stage 0, and 37.0% on stage 2. The validation analysis revealed that EOSS-P stages greater than 0 were associated with diastolic blood pressure and levels of glucose, cholesterol, LDL and ALT. Reduced obesity odds were observed among children playing outdoors and increased odds for every screen time hour, both in the GA and in the multivariate analyses (all P < 0.05). Although participation in sports > 2 times/week was associated with reduced obesity odds in the GA analysis (OR = 0.57, 95% CI = 0.33-0.98, P linear = 0.047), it lost its significance in the multivariate analysis (P linear = 0.145). Analogous results were recorded in the analyses of the abovementioned physical activity risk factors for the EOSS-P stages. Linear relationships were observed for fast-food consumption and IOTF-defined obesity and higher than 0 EOSS-P stages. Parental obesity status was associated with all EOSS-P stages and IOTF-defined obesity status. CONCLUSIONS: Few outpatients were healthy obese (stage 0), while the majority exhibited several comorbidities. Since each obesity tier entails different impacts to disease management, the study herein highlights modifiable factors facilitating descend to lower stages, and provides insight for designing tailored approaches tackling the high national pediatric obesity rates.

Process evaluation design and tools used in a kindergarten-based, family-involved intervention to prevent obesity in early childhood. The ToyBox-study.

Process evaluation (PE) is used for the in-depth evaluation of the implementation process of health promotion programmes. The aim of the current paper was to present the PE design and tools used in the ToyBox-intervention. The PE design was based on a three-step approach, including the identification of ToyBox-specific PE elements (step 1), the development of PE tools and harmonization of procedures (step 2), and the implementation of PE using standardized protocol and tools across the intervention countries (step 3). Specifically, to evaluate the implementation of the intervention, teachers' monthly logbooks were recorded (dose delivered, fidelity, dose received); post-intervention questionnaires were completed by parents/caregivers and teachers (dose received); participation and attrition rates were recorded (recruitment, reach); and audit questionnaires and retrospective information on weather conditions were collected (physical and social environment within which the intervention was implemented). Regarding the teachers' training sessions, the researchers who performed the trainings completed evaluation forms and documented teachers' attendance after each training (dose delivered, fidelity, dose received) and teachers completed evaluation forms after each training (dose received). The PE performed in the ToyBox-intervention may contribute in the evaluation of its effectiveness, guide the revision of the intervention material and provide insights for future health promotion programmes and public health policy.

Treatment of anemia in low-risk myelodysplastic syndromes with amifostine. In vitro testing of response.

Amifostine (AMF) promotes in vitro growth and survival of hematopoietic progenitors. In this study we evaluated the efficacy of AMF in the treatment of anemia in patients with low-risk myelodysplastic syndromes (MDS) and the possible predicting value for response to AMF therapy of two types of in vitro clonogenic assays. Two different doses of AMF, 300 mg/m2 (group A, 11 patients) or 400 mg/m2 (group B, 16 patients), were studied. AMF was given three times weekly for 3 weeks, i.v., followed by 2 weeks off therapy. Patients were evaluated after two cycles of treatment. Partially or nonresponding patients of group A received 400 mg/m2 AMF and were reevaluated. An increase of hemoglobin (Hb) values of more than 2 g/dl and a 100% decrease in transfusion requirements for at least 6 weeks were defined as a complete response (CR) while an increase of Hb values of 1-2 g/dl or a 50% decrease in transfusion requirements was considered as a partial response (PR). In group A, two out of 11 (18.1%) patients achieved a CR with the initial dose and one of the nine that received 400 mg/m2 AMF achieved a PR. In group B, three out of 16 (18.7%) patients achieved a PR; the overall response rate in both groups was 22.2%. In group A, bone marrow progenitor assay was performed pre- and post-amifostine treatment. Erythroid burst-forming units (BFU-E) were increased in six out of 11 (54.5%) patients, and this increase preceded the rise in Hb levels in three of them. In group B, a clonogenic assay was performed in 11 out of 16 patients before AMF treatment. In vitro results after pretreatment with 500 microM amifostine confirmed the response of two MDS patients that achieved a PR. No response in vitro was observed in all eight nonresponding patients and in one PR patient. The lack of response in the clonogenic assays predicted for nonresponse to treatment with a predictive power of 91.8%. We conclude that 300 mg/m2 is an adequate initial treatment for low-risk MDS patients and both clonogenic assays have a strong predicting value for response to treatment.

Prognostic evaluation of the microvascular network in myelodysplastic syndromes.

Considering the recently stated suggestion of neovascularization being implicated in myelodysplastic syndromes (MDS) pathogenesis, we evaluated multiple morphometric microvascular characteristics in MDS, in relation to clinicopathologic factors and prognosis. Trephines from 50 newly diagnosed MDS patients were immunostained for factor VIII and compared to those from 20 controls, 10 chronic myelomonocytic leukemia (CMML) and 12 acute myeloid leukemia (AML) patients. Quantitation of microvessel density (MVD), area, total vascular area (TVA), major and minor axis length, perimeter, compactness, shape factor, Feret diameter, and the number of branching vessels was performed by image analysis. Overall, the MDS group had significantly higher MVD, TVA, minor axis and shape factor values and significantly lower compactness than the control group. AML was characterized by increased vascularity compared to MDS and CMML, as well as by the presence of flattened microvessels (lower values of shape factor). Hypercellular MDS showed higher MVD. RA/RARS displayed larger caliber vessels than RAEB, which explains the favorable prognostic effect of increased size-related parameters on progression and/or survival. Moreover, decreased compactness and MVD were independent predictors of longer progression-free survival. It is concluded that angiogenesis is involved in the conversion of normal marrow to MDS and ultimately to AML and that disease progression within MDS is accompanied by qualitative alterations of the microvascular network. Furthermore, size-related parameters affect survival, while shape-related parameters and MVD are more influential with regard to progression-free survival.

Detection of CD55 and/or CD59 deficient red cell populations in patients with aplastic anaemia, myelodysplastic syndromes and myeloproliferative disorders.

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal stem cell disorder characterized by intravascular haemolysis, venous thrombosis, marrow hypoplasia, frequent episodes of infection, and rarely leukaemic conversion. At the cellular level, PNH is characterized by the decrease or absence of glycosylphosphatidylinositol (GPI)-anchored molecules, such as CD55 and CD59, from the cell surface. PNH-like clones have been described in various haematological disorders. The link between PNH and aplastic anaemia (AA) has been established but the relationship of PNH with myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD) remains unclear. In this study, the presence of CD55 and/or CD59 defective (PNH-like) red cell populations was evaluated in 21 patients with AA, 133 with MDS, 197 with MPD, 7 with PNH and in 121 healthy blood donors using the Sephacryl Gel Test microtyping system. Red cell populations deficient in both molecules CD55 and CD59 were detected in 33.3% of AA patients, in 16.5% of MDS patients (50% with hypoplastic bone marrow), in 14.2% of MPD patients (more often in essential thrombocythemia, 21.2%) and in all PNH patients. CD55 deficient red cell populations were found in 14.2% of patients with AA, 12.7% of patients with MDS and 21.3% of patients with MPD. CD59 deficient populations were found in 9.5% of AA patients, 2.2% of MDS patients and 2% of MPD patients. These results indicate an association between PNH, AA and MDS or even between PNH and MPD. Further investigation is necessary to work out the mechanisms of this association, and to define classification criteria for borderline cases, where diagnosis is difficult.

Detection of CD55- and/or CD59-deficient red cell populations in patients with lymphoproliferative syndromes.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria is an acquired clonal stem cell disorder characterized by the decrease or absence of glycosylphosphatidylinositol-anchored molecules from the surface of the affected cells, such as CD55 and CD59, resulting in chronic intravascular hemolysis, cytopenia and increased tendency to thrombosis. PNH-phenotype has been described in various hematological disorders, mainly in aplastic anemia and myelodysplastic syndromes, while it has been reported that complete deficiency of CD55 and CD59 has also been found in patients with lymphoproliferative syndromes, like non-Hodgkin's lymphomas. MATERIALS AND METHODS: The presence of CD55- and/or CD59-defective red cell populations was evaluated in 217 patients with lymphoproliferative syndromes. The study population included 87 patients with NHL, 55 with HD, 49 with CLL, 22 with ALL and four with hairy cell leukemia. One hundred and twenty-one healthy blood donors and seven patients with PNH were also studied as control groups. The sephacryl gel microtyping system was performed for the detection of CD55- and CD59-deficient red cell populations. Ham and sucrose lysis tests were also performed in all samples with CD55 or CD59 negative populations. RESULTS: Red cell populations deficient in both CD55 and CD59 molecules were detected in 9.2% of patients with lymphoproliferative syndromes (more often in ALL and nodular sclerosis type of HD) and in all PNH patients. CD55-deficient red cell populations were found in 8.7% of LPS patients (especially in low grade B-cell NHL), while CD59-deficient populations were found in only two patients with low grade B-cell NHL. CONCLUSION: These data indicate a possible association between paroxysmal nocturnal hemoglobinuria phenotype and lymphoproliferative syndromes, while further investigation is necessary to work out the mechanisms and the significance of the existence of this phenotype in these patients.

Fetal Erythropoiesis after Allogeneic Bone Marrow Transplantation Estimated by the Peripheral Blood Erythrocytes Containing Hemoglobin F (F-cells).

During bone marrow engraftment following BMT there is a re-establishment of fetal erythropoiesis, expressed by the increase of F-cells. This seems to depend on several factors such as underlying disease, conditioning before therapy and other mechanisms concerning both the donor and the recipient bone marrow. The aim of this work was to study the factors influencing F-cell production during bone marrow engraftment following transplantation. We studied 28 patients who underwent allogeneic bone marrow transplantation, for various hematological malignancies (CML, AML, ALL, CMML and SAA). F-cells were estimated on peripheral blood smears by indirect immunofluorescence. Overall, there was an F-cell increase after BMT in comparison with values before BMT; this increase was significant on days 15-50 (p <.01). F-cell on days 18, 25, 32 and 40 following transplantation were significantly higher (p <.01) in patients who have had increased F-cell numbers post-chemotherapy before BMT, compared with the patients who did not show any increase of the F-cell number post chemotherapy. During the first month following transplantation (day 7 to day 40) patients who were transplanted from high F-cell donors failed to show any significant differences in their F-cell numbers in comparison to those transplanted from low F-cell donors. However, the F-cell increase became significantly higher in the former group between days 50 and 120. This observation implies that the stressed erythropoiesis of the initial phase does not allow revealing the varying F-cell production of the capacities donor bone marrow, while later, when the graft has settled, the high F-cell donors reveal this property of the host.

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial.

BACKGROUND: The aim of the current prospective, randomized control study was to investigate the effect of dietary omega-3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well-nourished and malnourished patients with generalized malignancy. METHODS: Sixty patients with generalized solid tumors were randomized to receive dietary supplementation with either fish oil (18 g of omega-3 polyunsaturated fatty acids, PUFA) or placebo daily until death. Each group included 15 well-nourished and 15 malnourished patients. The authors measured total T cells, T-helper cells, T-suppressor cells, natural killer cells, and the synthesis of interleukin-1, interleukin-6, and tumor necrosis factor by peripheral blood mononuclear cells before and on Day 40 of fish oil supplementation. Karnofsky performance status, nutritional state, and survival were also estimated. RESULTS: The ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished patients. Omega-3 PUFA had a considerable immunomodulating effect by increasing this ratio in the subgroup of malnourished patients. There were no significant differences in cytokine production among the various groups, except for a decrease in tumor necrosis factor production in malnourished cancer patients, which was restored by omega-3 fatty acids. The mean survival was significantly higher for the subgroup of well-nourished patients in both groups, whereas omega-3 fatty acids prolonged the survival of all the patients. CONCLUSIONS: Malnutrition appears to be an important predictor of survival for patients with end stage malignant disease. Omega-3 polyunsaturated fatty acids had a significant immunomodulating effect and seemed to prolong the survival of malnourished patients with generalized malignancy.

The effect of dietary omega-3 polyunsaturated fatty acids on T-lymphocyte subsets of patients with solid tumors.

The effect of omega-3 polyunsaturated fatty acids (PUFA) on the immune system seems to be beneficial. There has been a number of studies concerning the effect of dietary omega-3 PUFA on different immune parameters. The aim of our present study was to investigate the effect of dietary omega-3 PUFA on T-cell subsets and natural killer (NK) cells of patients with solid tumors. We studied 20 patients with solid tumors who received 18 g fish oil/day for 40 consecutive days. We detected a significant increase in T-helper/T-suppressor cell ratio 40 days into omega-3 supplementation, due mainly to a decrease in the number of suppressor T cells. We concluded that dietary omega-3 fatty acids may have a beneficial effect on the already compromised immune system of patients suffering from solid tumors.

Three cases of varicella thrombophlebitis as a complication of varicella zoster virus infection.

Three cases of deep venous thrombosis following varicella infection are described which were successfully treated with bed rest and anticoagulants. Two of these patients had severe pulmonary manifestations of varicella and the third was complicated by pulmonary embolism. Deep vein thrombosis is an uncommon systemic manifestation of varicella, possibly associated with vascular endothelium wall damage caused by varicella zoster virus infection.