Meningeal leukaemia in the blastic phase of chronic granulocytic leukaemia

A 51/2-year-old boy is presented with chronic granulocytic leukaemia and blastic transformation whose clinical course is complicated by meningeal leukaemia. In the authors' opinion prophylactic central nervous system therapy should be part of the initial therapy of blastic transformation.Abbreviations CGL chronic granulocytic leukaemia - PAS periodic acid-schiff     

Regulation of cathepsin B activity by modulators of arachidonic acid metabolism in human monocytes

Cathepsin B (CB), a lysosomal cysteine proteinase, is implicated in tumour invasion and metastasis. Although direct exposure of THP-1 cells to arachidonic acid did not stimulate the induction of CB activity, cells treated with arachidonic acid followed by interferon-gamma (IFN-gamma), as well as concurrently treated cultures with arachidonic acid and lipopolysaccharide (LPS) or phorbol ester (PMA) increased CB activity in a dose-dependent manner. LPS and IFN-gamma-induced increases in CB were down-regulated by dexamethasone, an inhibitor of phospholipase A(2) (PLA(2)). Whereas dibutyryl cAMP, which increases PLA(2) activity, caused elevations in CB in THP-1 cells; inhibition of protein kinase A by H-89, which reduces PLA(2) expression, blocked the effect of dibutyryl cAMP. On the other hand, indomethacin, an inhibitor of cyclooxygenase, and ketoconazole, an inhibitor of lipoxygenase, up-regulated CB activity dose-dependently, indicating that the balance among PLA(2), cyclooxygenase and lipoxygenase activities might regulate the levels of CB synthesis. These data suggest that arachidonic acid may be associated with part of the intracellular signal pathway in the induction of CB activity by LPS, PMA and IFN-gamma.     

Pediatric sublingual immunotherapy efficacy: evidence analysis, 2009-2012

ObjectiveTo perform a structured analysis of the latest scientific evidence obtained for the clinical efficacy of sublingual immunotherapy (SLIT) in children.Data SourcesPubMed, Embase, reference lists from reviews, and personal databases were reviewed for original articles on clinical trials with SLIT in patients younger than 18 years published from January 1, 2009, through December 31, 2012, using broad search and medical subject heading terms.Study SelectionsClinical trials, irrespective of their design, of SLIT in the treatment of respiratory and food allergy in patients 18 years or younger were selected. Clinical outcomes (symptom scores, medication use, provocation tests, pulmonary function tests, skin prick tests, and adverse events) and immunologic changes were tabulated. Quality of each trial and total quality of compounded evidence was analyzed with the Grading of Recommendations Assessment, Development and Evaluation system.ResultsOf 56 articles, 29 met the inclusion criteria. New evidence is robust for the precoseasonal tablet and drop grass pollen SLIT efficacy in allergic rhinitis and scarce for seasonal asthma. Some evidence for Alternaria SLIT efficacy is appearing. For house dust mite (HDM) SLIT in asthma, there is high-quality evidence for medication reduction while maintaining symptom control; evidence for HDM SLIT efficacy in allergic rhinitis is of moderate-low quality. There is moderate evidence for efficacy of dual grass pollen–HDM SLIT after 12 months of treatment and 1 year after discontinuation. Specific provocation test results (nasal, skin) improve with grass pollen and HDM SLIT but nonspecific bronchial provocation testing does not. Food oral immunotherapy is more promising than food SLIT. Possible new surrogate markers have been reported. No anaphylaxis was found among 2469 treated children.ConclusionEvidence for efficacy of SLIT in children with respiratory or food allergy is growing.     

Long-term effects of specific immunotherapy, administered during childhood, in asthmatic patients allergic to either house-dust mite or to both house-dust mite and grass pollen

In a retrospective study, asthmatic patients allergic to either house-dust mite (HDM) (Dermatophagoides pteronyssinus) (n = 34) or to both HDM and grass pollen (GP) (n = 14), and who were treated with specific immunotherapy (SIT) during childhood (mean duration of SIT: 61 +/- 9.70 months), were re-evaluated in early adulthood after mean cessation of SIT for 9.3 +/- 2.76 years. The results were compared to those of a control group of asthmatic patients (n = 42) with comparable asthma features, who were treated with appropriate antiasthmatic drugs during childhood, but who never received SIT. Re-evaluation was carried out with a standardized questionnaire, skin prick tests (SPT), and lung-function assessments. At the time of re-evaluation, the mean age in the SIT-treated group was 23.1 +/- 3.50 years; in the control group, it was 22.7 +/- 3.40 years. At re-evaluation, the risk of frequent asthmatic symptoms was three times higher in the control group than in the SIT-treated group (prevalence ratio: 3.43; P = 0.0006). The frequent use of antiasthmatic medication was also more pronounced in the control group, although the difference was not statistically significant (P=0.38). Lung-function parameters and results of SPT with HDM were comparable in both groups. It is concluded that SIT has long-term effects on asthmatic symptoms in young adults.     

COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis

Background/AimsData of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody.MethodsWe collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses.ResultsTwenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76–90%) and 91% (95% CI, 83–95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76–86%) in chronic hepatitis B, 96% (95% CI, 93–97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75–91%) in cirrhosis and 85% (95% CI, 78–90%) in non-cirrhosis, 86% (95% CI, 78–92%) for inactivated vaccine and 89% (95% CI, 71–96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55–75%) after two doses of mRNA vaccines and 88% (95% CI, 58–98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30–89%). Prevalence of adverse events was 27% (95% CI, 18–38%) and 63% (95% CI, 39–82%) among CLD and LT groups, respectively.ConclusionsCLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.     

Differences in circulating dendritic cell subtypes in cord blood and peripheral blood of healthy and allergic children

BACKGROUND: Different types of circulating dendritic cells have been described. Dendritic cells influence differentiation of naive T lymphocytes into T helper type 1 (Th1) and Th2 effector cells. OBJECTIVE: The purpose of this study was to evaluate the number of circulating DC subtypes in peripheral blood of allergic and healthy children and in cord blood of neonates from allergic and non-allergic parents. METHODS: Circulating dendritic cells were flow cytometrically identified in whole blood samples as lineage (CD3, CD14, CD16, CD19, CD20, CD56) negative, CD34 negative and HLA-DR-positive cells. According to the expression of CD123 and CD11c, different DC subtypes were identified. RESULTS: Apart from DC1 (CD11c+ CD123dim+) and DC2 (CD11c- CD123high+), a third DC population was described with less differentiated phenotypic characteristics, namely CD11c- CD123dim+, and therefore defined here as less differentiated DC (ldDC). These ldDC represented the major DC population in cord blood and showed an age-depended decrease. The highest level of ldDC was detected in children with atopic dermatitis, whereas asthmatic children showed the lowest ldDC counts. Furthermore, high-dose inhaled corticosteroid treatment in asthmatic children was related to a decreased ldDC number. The number of circulating DC2 was significantly lower in allergic children, especially in asthmatics, compared to healthy children. In cord blood, no differences in DC subtypes were detectable between neonates at low and high risk for allergic disorders. CONCLUSION: These results indicate that, apart from DC1 and DC2, a third population of dendritic cells, identified as CD11c- CD123dim+ cells and defined as less differentiated DC, must be considered in the evaluation of circulating DC. Furthermore, DC2 counts were decreased in allergic children, especially in asthmatics, which might be the consequence of an increased recruitment to the target organs.     

Primary Squamous Cell Carcinoma of a Gastric Remnant

A 77-yr-old male developed primary gastric squamous cell carcinoma 33 yr after gastric resection for peptic ulcer disease. At the time of diagnosis, he was being endoscopically followed for large irregular stomal polyps. Infiltrating squamous cell carcinoma with focal keratinization and stomal polypoid hypertrophic gastritis was found. Previous reports describe adenocarcinoma and adenosquamous carcinoma in gastric remnants. There are various theories as to how such a tumor may arise in this setting.