Horn of plenty:Value of the international registry for pediatric chronic myeloid leukemia

Chronic myeloid leukemia(CML)in minors is a rare disease which can be effectively treated by tyrosine kinase inhibitors(TKIs)since the year 2000.A majority of pediatricians will encounter one or two CML patients in the course of their careers and will typically have to rely on written information along with their own intuition to provide care.Knowledge of response to TKIs and of agespecific side effects has an impact on the design of pediatric CML trials in many ways aiming to contribute toward greater predictability of clinical improvements.Information from a registry on a rare disease like CML offers the enormous benefit of enabling treating physicians to interact and share their collective experience.The International Registry on Pediatric CML(IR-PCML)was founded at Poitiers/France almost 10 years ago.Since then,the number of collaboration centers and in parallel of registered patients continuously increased(>550 patients as of December 2019).Ideally,from a given treatment center in a country data are transferred to a national coordinator who interacts with the IR-PCML.In the sense of quality assurance,the registry can offer dissemination of knowledge on state-of-the-art diagnostics(including reference appraisal),optimal treatment approaches,and follow-up procedures within a network that is exerting its strength via participation.With continuous growth during the recent years,very rare subgroups of patients could be identified(e.g.,CML diagnosed at age<3 years,children presenting with specific problems at diagnosis or during course of treatment)which had not been described before.Publications coming from the IR-PCML disseminated this useful information derived from patients who robustly participate and share information about their disease,among themselves and with their caregivers and clinicians.Patient input driving the collection of data on this rare leukemia is the basis for the considerable success of bringing new therapeutics into clinical use.

An international survey of classification and treatment choices for group D retinoblastoma

AIM: To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region.METHODS: An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism.RESULTS: The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children's Hospital of Los Angeles(CHLA) version, 33% used the Children's Oncology Group(COG) version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center(P<0.0001). CONCLUSION: Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.

Construction,expression and binding specificity of bispecific CD3×VEGFR-2 and CD3×NCAM antibodies in the single chain and diabody format

Bispecific antibodies are recombinant proteins with novel immunological properties and therapeutic potential. Recombinant protein quality and activity of several bispecific antibodies comprising different variable domain combinations with respect to the parental monospecific single chain fragments (scFv) were evaluated after expression in bacteria or mammalian cells. The parental scFv proteins humanized anti-NCAM scFv, murine anti-VEGFR-2 scFv, murine and humanized anti-CD3 scFv, respectively, could successfully be expressed in E. coli, whereas the murine anti-NCAM scFv version could not be reliably detected. Bispecific CD3 × VEGFR-2 and CD3 × NCAM anti-bodies were expressed in the bispecific single chain and the single chain diabody format. However, the diabody derived from the murine anti-NCAM scFv could not efficiently be expressed in E. coli or in mammalian cells. Significant binding of the CD3 × NCAM single chain diabody comprising the humanized version of anti-CD3 and humanized version of anti-NCAM was efficient to both antigens. Nevertheless, binding of the bispecific single chain version to the NCAM antigen was inefficient in comparison to CD3 binding. In conclusion, the data could indicate that the result of scFv expression in bacteria may be predictive for the chances of success for functional expression of more complex bispecific derivatives.

Thrombotic Events in Patients with Antiphospholipid Syndrome: A Single Center Study

Background: There is limited literature regarding risk factors for development of thrombosis and long-term thrombotic outcomes in Armenian APS patients. The aim of the study is to identify patients with APS with thrombotic complications and to evaluate the epidemiological statistics of thrombosis and thrombophilia and their complications in Armenia. Methods: We analyzed medical records of Patients with APS from January 2018 to December 2021 treated at the Armenian Thrombosis and Hemostasis Center was enrolled. Results: Both acquired and hereditary thrombophilia increase the risk of thrombosis. Thrombophilia was present in 61.5% of 123 patients. It was found that 38 pregnant women with thrombosis had a family history of VTE, myocardial infarction or stroke in the next of kin under 50 years of age. The prevalence of this history was 31.4% (11 patients) compared to 68.6% (27 patients), who did not have 41.6% of postpartum thrombotic events up to two months postpartum. Conclusion: Thrombosis in pregnancy is a redoubtable complication requiring an excellent cooperation between the obstetrician and hematologist. Clear detection of thrombosis in APS patients in all types allows to accurately predicting the method and duration of anticoagulant treatment and to prevent thrombotic complications.

Complementary and alternative medicine in pediatrics in Turkey

Background:Complementary and alternative medicine(CAM)is applied both to children and adults widely throughout the world.A previous pan-European survey showed a surprisingly high CAM-use in Turkish children.This review aimed to survey information on the use of CAM in pediatrics in Turkey.Data sources:A narrative,non-systematic review was conducted by melding expert opinions with a thorough and balanced review of available evidence.An unrestricted literature search using the key words,"alternative","complementary","integrative","prevalence"and"pediatric"or"children"and"Turkey"was performed by internet search in March,2012 using PubMed and Google Scholar.Results:CAM use was examined in general pediatrics,pediatric oncology,patients with asthma,and patients with diabetes.A frequency of CAM use was 87%in Turkish pediatric patients,with a mean of 60%.The primary sources of information about CAM are family and friends.Communication with patients/parents and health care professionals showed that most parents do not speak about CAM use with their physicians or nurses.Conclusions:CAM is extensively used in Turkish pediatric patients.This might be due to Turkey's status as a developing country in which a traditional medical system still dominates in comparison to developed countries.Thus,larger studies are required to prove an extensive use of CAM in Turkey,as this review article does not have the capacity for in-depth analysis.Knowledge about CAM and its related topics is essential for physicians and nurses in order to meet the patients'wish for a competent consultation concerning all aspects of a possible therapy.

Rhythmical massage improves autonomic nervous system function:a single-blind randomised controlled trial

Background: Rhythmical massage therapy(RMT) is a massage technique used in anthroposophic medicine.Objective: The authors aimed to investigate the physiological action of RMT on the cardiovascular system by analysing heart rate variability(HRV).Design, setting, participants and intervention: This study was a randomised, controlled and single-blinded trial, involving 44 healthy women(mean age:(26.20 ± 4.71) years). The subjects were randomised to one of three arms: RMT with aromatic oil(RA), RMT without aromatic oil(RM) or standardised sham massage(SM). In the study the subjects were exposed to a standardised stress situation followed by one of the study techniques and Holter electrocardiograms(ECGs) were recorded for 24 h.Main outcome measures: HRV parameters were calculated from linear(time and frequency domain) and nonlinear dynamics(symbolic dynamics, Poincare plot analysis) of the 24-h Holter ECG records.Results: Short-and long-term effects of massage on autonomic regulation differed significantly among the three groups. Immediately after an RMT session, stimulation of HRV was found in the groups RA and RM. The use of an aromatic oil produced greater short-term measurable changes in HRV compared with rhythmic massage alone, but after 24 h the effect was no longer distinguishable from the RM group.The lowest stimulation of HRV parameters was measured in the SM group.Conclusion: RMT causes specific and marked stimulation of the autonomic nervous system. Use of a medicinal aromatic oil had only a temporary effect on HRV, indicating that the RM causes the most relevant long-term effect. The effect is relatively specific, as the physiological effects seen in the group of subjects who received only SM were considerably less pronounced.

Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors

Background Vitamin D(25-OHD)has a role in bone health after treatment for cancer.25-OHD deficiency has been associated with risk factors for cardiovascular disease,but no data focusing on this topic in childhood cancer survivors have been published.We investigated the 25-OHD status in children treated for acute lymphoblastic leukemia(ALL),and evaluated its influence on vascular function.Methods 25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy controls.Patients were grouped according to 25-OHD level(<20 ng/m or≥20 ng/ml).Auxological parameters,biochemical and hemostatic markers of endothelial function(AD,HMW-AD,ET-1,vWFAg,TAT,D-dimers,Fbg,and hs-CRP),ultrasound markers of vascular endothelial function(flow-mediated dilatation,FMD,common carotid intima-media thickness,C-IMT,and antero-posterior diameter of infra-renal abdominal aorta,APAO)were evaluated in the patients.Results Cases showed higher prevalence of 25-OHD deficiency than controls(p=0.002).In univariate analysis via mean comparisons,25-OHD deficient(<20 ng/ml)patients showed higher C-IMT values compared to the 25-OHD non-deficient(≥20 ng/ml)group(P=0.023).Significant differences were also found for ET-1(P=0.035)and AD-HMW(P=0.015).In the multiple regression models controlling for some confounders,25-OHD still was associated with C-IMT(P=0.0163),ET-1(P=0.0077),and AD-HMW(P=0.0008).Conclusions Childhood ALL survivors show higher prevalence of 25-OHD deficiency as compared to controls.The 25-OHD levels appear to be linked to indicators of endothelial and vascular dysfunction.Careful monitoring of 25-OHD balance may help to prevent cardiovascular diseases in childhood ALL survivors,characterized by high cardiovascular risk.

Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

Background and Aims: To evaluate the effect of intrapar-enchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). Methods: Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation. Results: On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplanta-tion, consistent with structural improvements in mitochondria and nuclear compartments. Conclusions: Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.