Late effects of childhood cancer recorded at a single outpatient clinic over the course of one year: implications for the follow-up care.

The paper provides a descriptive analysis of medical data and selected patient-reported outcomes from a group of 133 survivors of childhood cancer recruited at St. Anne's University Hospital in Brno, Czech Republic, over the course of one year. The participants were 18-53 years old (mean age 27.9 years) and had been diagnosed with childhood cancer in the period 1979-2016. Treatment data and data on relevant health outcomes were extracted from the medical records and categorized. Patient-reported outcomes were measured using the clinic's questionnaires completed by survivors prior to the medical examination. The most frequent adverse health outcomes in the study were dyslipidemia (50%) and overweight, obesity, and even morbid obesity (45%, 15%, and 1.5%, respectively). Endocrinopathies were observed in more than one-third (35.3%) of the survivors, followed by nephropathy (33.8%). Cardiovascular abnormalities were found in 9.7% of the survivors and fertility impairment in 9%. 38% of the survivors reported chronic fatigue and one-half (51%) reported pain. 20% of the cohort face mobility impairment. A remarkably high percentage of the survivors (70%) communicated some level of mental health issues. Moderate to severe anxiety and/or depression was reported by 25% of the survivors. 40% of the survivors experienced strong fears of disease recurrence, another 40% reported mild or moderate fears. Fear of late effects was communicated by 83% of the survivors, with 38% experiencing high levels of concerns. Only 8% of the survivors had no adverse health outcome. The rate of somatic and mental health outcomes identified in our sample is high. Some of the most frequent outcomes are mutually interconnected and modifiable, which highlights the need for patient education on a healthy lifestyle. There is also a clear need for improved psychological support for childhood cancer survivors to mitigate unnecessary anxieties resulting from unsubstantiated health concerns. Dissemination of personalized and positive messages should be part of routine follow-up care.

Changes in Nutritional State and Cardiovascular Parameters in Alimentary Obese Children after a Month-Long Stay in Children's Treatment Center.

Childhood and adolescent obesity has become an important public health issue, as it leads to higher risk of cardio−metabolic, orthopedic, and psychological comorbidities. The aim of this study was to evaluate the changes in nutritional state and cardiovascular system parameters in obese children. Sixty respondents aged 9−17 years with alimentary obesity participated in this research. Anthropometric parameters (body weight (BWT), body mass index (BMI), percentage of body fat (%), waist and hip circumference (WC and HC), waist−hip ratio (WHR)) and cardiovascular parameters (systolic and diastolic blood pressure (SP and DP), cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), pulse wave velocity and its variability (PWV and PWVV), and parameters of pulse wave analysis) were measured. Every respondent went through two sets of measurements, the first (I.) after their admission to the children's hospital and the second (II.) at the end of their one-month-long therapeutic stay. Statistically significant differences between measurements I. and II. were observed in the following parameters: BWT (p < 0.01), BMI (p < 0.01), WC (p < 0.01), HC (p < 0.01), DP (p < 0.01), PWV (p < 0.05), and ABI (p < 0.01). The results of this study show that obesity has a mostly negative impact on the cardiovascular health of affected children, with likely negative results in their adulthood.

Prevalence of HHV-6 integrated chromosomally among children treated for acute lymphoblastic or myeloid leukemia in the Czech Republic.

Chromosomal integration of human herpesvirus 6 (HHV-6) is a novel situation found in a small percentage of individuals. While active HHV-6 infection is treatable using antivirals, the abnormally high level of HHV-6 DNA found in chromosomal integration of HHV-6 (CI-HHV-6) is not affected by such drugs. Stored DNA samples taken originally for detection of fusion genes and minimal residual disease from 339 pediatric patients treated for leukemia in the Czech Republic between the years 1995-2007 were tested retrospectively. Using real-time quantitative PCR technology, the quantity of HHV-6 DNA detected was normalized to 100,000 human genome equivalents as assessed by quantitation of the albumin gene. HHV-6 DNA was detected in 107 samples from 91 patients (26.8%). In the majority of samples (99) only a minute level of normalized viral copies (NVCs) (median 1.84 NVCs) was detected. A high viral load of approximately 100,000 NVCs was detected in 5 patients (1.5%; median 140,150 NVCs), in all of whom were confirmed subsequently CI-HHV-6 by a detection of HHV-6 DNA in hair follicles or in the nails. In all but one patient with HHV-6 variant B, variant A of the virus was detected. None of the patients with CI-HHV-6 had complications attributable to HHV-6 infection. The prevalence of CI-HHV-6 in childhood leukemia does not differ from that published for other patients or healthy populations. Where high levels of HHV-6 DNA are present, CI-HHV-6 should be confirmed as soon as possible so that potentially toxic but ineffective antiviral treatment can be stopped.

Interleukin-6 gene variants and the risk of sepsis development in children.

A proinflammatory cytokine interleukin-6 (IL-6) plays an important role in the development, pathogenesis and outcome of SIRS, sepsis and septic shock. We have evaluated the role of the IL-6 gene polymorphisms in pediatric patients. A total of 421 consecutive pediatric patients admitted to the pediatric intensive care unit with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ distress syndrome (MODS) were studied together with 644 healthy controls. DNA was isolated and two IL-6 gene polymorphisms (G-174>C and G-572>C) were analyzed. The frequencies of both analyzed variants differ significantly between the group of patients and healthy controls (p = 0.02 for G-174>C and p = 0.049 for G-572>C). In addition, genetic analysis of the G-174>C IL-6 gene variant revealed significant differences between the subgroup of febrile patients and subgroup of septic shock (p = 0.0319) and between the subgroup of SIRS and septic shock (p = 0.038). In both cases the negative genotype was CC. No statistically significant differences for the IL-6 gene polymorphism G-572>C were found between the groups of patients with different diagnosis. IL-6 gene polymorphisms G-174>C and G-572>C could be the predictors of risk of development and/or the predictors of the severity of sepsis in children.

Bactericidal permeability increasing protein gene variants in children with sepsis.

OBJECTIVE: To evaluate the role of genetic polymorphisms of the bactericidal permeability increasing protein (BPI) in pediatric patients with sepsis. DESIGN: Prospective, single-center, case-control study at the pediatric intensive care unit (PICU) of a university hospital. PATIENTS: 345 consecutive pediatric patients admitted to the PICU with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ distress syndrome (MODS). INTERVENTIONS: DNA was isolated and two BPI gene polymorphisms BPI (G545 > C) Taq and BPI (A645[ > G) 216 were studied in patients and compared with healthy controls. MEASUREMENTS AND RESULTS: Genetic analysis of the BPI Taq gene revealed significant differences between healthy controls and the subgroup of febrile patients (p = 0.0243), the subgroup of SIRS and sepsis (p = 0.0101), and the subgroup of severe sepsis, septic shock, and MODS (p = 0.0027), respectively. No statistically significant differences for the BPI 216 gene polymorphism were found between patient and healthy control groups. A statistically significant predisposition to Gram-negative sepsis in patients carrying the BPI Taq GG variant together with the BPI 216 AG or GG variant was revealed (p = 0.0081), and these haplotypes were also associated with death due to sepsis-related complications. CONCLUSION: BPI Taq gene polymorphism is the accurate predictor of the severity of sepsis in children admitted to the PICU.

Dynamic stress echocardiography in asymptomatic patients who received chemotherapy in childhood because of a malignant disease.

BACKGROUND: Introducing anthracycline antibiotics into the treatment of children's malignancies contributed enormously to the excellent outcome in children and adolescents. Nevertheless, the cardiotoxicity of such was discovered as early as in the 1970's. Only recently stress tests have been used to detect late cardiotoxic effects of anti-neoplastic drugs. AIM: To determine the function of the left ventricle (LV) in asymptomatic patients who were treated with chemotherapy containing anthracyclines in childhood or adolescence. METHODS: We examined 137 patients (81 men, 56 women), aged 16.6+/-4.8 years, in whom a malignant disease was diagnosed at the age of 9.1+/-4.8 years and who were treated with a cumulative dose of anthracyclines of 242+/-110 mg/m(2). The control group comprised 30 subjects (14 men, 16 women, mean age 19.5+/-5.2 years). The echocardiographic examination was carried out at rest and also immediately after a dynamic stress test. RESULTS: A decrease in the fractional shortening (FS) <30% was found in 11 (8%) patients. The values of ejection fraction (EF), mean velocity circumferential fibre shortening, end-systolic wall stress, excursion and systolic thickening of the LV posterior wall were significantly impaired in comparison with the group who had the FS > or =30% as well as with the control group. The maximal decrease in EF was reduced to 40% and FS - to 20%. The values of the index of the global function of LV were, in comparison with the control group, impaired in both subgroups of the patients. We did not find any differences in the exercise tolerance between the groups. The EF values both at rest and at stress were significantly lower in the group with FS <30% when compared with other groups. The values of percentage EF stress increment were increased in all the groups. A decrease in EF after exercise was not observed. CONCLUSIONS: Anthracycline chemotherapy leads to a late impairment of LV function. Asymptomatic patients with a decrease of EF to 40% or FS to 20% show preserved exercise tolerance as well as contractile reserve of the LV. These findings represent a better prognosis for the patient. Echocardiography at rest should be carried out repeatedly after the termination of the treatment and in the case of a pathological finding it is necessary to perform stress tests to evaluate the contractile reserve.

Late anthracycline cardiotoxicity protection by dexrazoxane (ICRF-187) in pediatric patients: echocardiographic follow-up.

BACKGROUND: The authors conducted a retrospective study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for hematological malignancy. PATIENTS AND METHODS: The authors examined 108 patients (63 male, 45 female) 5-29 years old, (median 15 years). All patients were in long-term remission of their malignancy. The cardioprotection was given to 68 patients (39 male, 29 female), and standard treatment was used in 40 patients (24 male, 16 female). Dexrazoxane (cardioxane, Chiron Company, The Netherlands) was given in 20:1 ratio to anthracycline. The follow-up time was 2-20 years (mean 7 years). The control group consisted of 41 volunteers (22 males, 19 females) 4-31 years old (median 18 years). The cardiotoxicity has been defined as the presence of heart failure or the decline of shortening fraction below 30% or ejection fraction (EF) below 55%. The end-systolic wall stress (ESS), myocardial performance index (MPI; Tei index), and parameters of left ventricular diastolic filling were also assessed. RESULTS: The anthracycline cardiomyopathy with the presence of heart failure was diagnosed in only one patient treated with a standard regimen. The pathological decline of fractional shortening was present in three (5%) and six (15%) patients with and without cardioprotection given, respectively. Similarly, none of the patients with cardioprotection revealed a pathological value of EF, while four (10%) patients without cardioprotection showed an EF decrease. Finally, ESS and isovolumic relaxation time were pathologically increased in the group without cardioprotection in comparison to the controls and to the group with cardioprotection. However, the MPI was significantly increased in both groups of patients. CONCLUSIONS: Dexrazoxane reduces the risk of late clinical and subclinical cardiotoxicity and does not affect the response rates to chemotherapy and overall survival during the median follow-up period of 7 years (follow-up period 2-20 years).

Can we detect the development of baroreflex sensitivity in humans between 11 and 20 years of age?

The aim of the study was to determine changes of baroreflex sensitivity in humans between 11 and 20 years of age. Continuous 5 min blood pressure recordings using a Finapres were taken in 415 healthy subjects while in a sitting, resting position (breathing at a frequency of 0.33 Hz). Beat-by-beat values of interbeat intervals (IBI) or heart rate, and systolic and diastolic blood pressures were measured. Baroreflex sensitivity in ms/mmHg (BRS) and in mHz/mmHg (BRSf) was determined at an average frequency of 0.1 Hz by spectral analysis. BRS did not correlate with age, but BRSf significantly decreased with age (p < 0.001). BRS correlated with mean IBI (p < 0.001) in all subjects and also in the particular subgroups, but BRSf was IBI-independent. Results of multiregression equations were BRS = 1.37 - 0.56 x age (years) + 0.02 x IBI (ms) (p < 0.001 for BRS vs. age and for BRS vs. IBI); BRSf = 34.74 - 0.97 x age (years) - 0.001 x IBI (ms) (p < 0.001 only for BRS vs. age), where age was measured in years and IBI was measured in ms. The limits of BRS were estimated for the total group: 5th percentile, 3.9; 50th percentile, 9.1; and 95th percentile, 18.7 ms/mmHg; and limits for BRSf were 5th percentile, 8.5; 50th percentile, 16.4; and 95th percentile, 33.6 mHz/mmHg. We conclude that IBI-dependent BRS was unchanged in the particular age groups, but the standardization of BRS on IBI decreased with age. BRSf was IBI-independent and better reflected the development of the BRS.

Long-term serial echocardiographic examination of late anthracycline cardiotoxicity and its prevention by dexrazoxane in paediatric patients.

UNLABELLED: The authors conducted an 8-year prospective non-randomised study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for haematological malignancy. The authors examined prospectively 75 patients (40 male/35 female) aged 2-17 years (median 6.5 years) at the time of diagnosis. The cardioprotection was given to 53 patients (26 male/17 female) and the standard protocol was used in 22 patients (14 male/8 female). The prospective echocardiographic evaluation was done before and after the chemotherapy and every year during the follow-up period. Dynamic stress echocardiography (DSE) was assessed in the final year. The clinical cardiotoxicity was not diagnosed. Higher cumulative doses of anthracycline were given in the dexrazoxane group (234+/-58 mg/m(2), median 240 mg/m(2) versus 203+/-86 mg/m(2), median 210 mg/m(2), P <0.04) and a significantly higher percentage of patients received cumulative doses >240 mg/m(2) of anthracycline ( P <0.05). During the follow-up period, the fractional shortening (FS) declined in the no-dexrazoxane group only in the 8th year and was significantly lower compared to the dexrazoxane group ( P <0.05). The pathological decrease in FS was present in 24% of patients; 41% in the no-dexrazoxane and 17% in the dexrazoxane groups, respectively ( P <0.05). DSE demonstrated lower rest EF and cardiac index (CI) in the no-dexrazoxane group ( P <0.05); however, neither the response of EF and CI to the stress echocardiography nor the exercise tolerance significantly differed between sub-groups. A higher number of patients in the dexrazoxane group had very good exercise tolerance (ET) >3 Watts/kg ( P <0.05) and a lower number responded with a decreased ET <2 Watts/kg ( P <0.05) compared to the no-dexrazoxane group. CONCLUSION: Dexrazoxane seems to reduce the risk of late subclinical cardiotoxicity. Dexrazoxane-treated patients revealed better exercise tolerance; however the haemodynamic response to the stress was no different in both sub-groups.

Recombinant human interferon alpha-2a therapy in children with chronic immune thrombocytopenic purpura.

BACKGROUND: In a prospective study, 11 children with chronic immune thrombocytopenic purpura between ages 3 and 18 years were treated with recombinant human interferon alpha 2a (rhIFN alpha-2a). PATIENTS AND METHODS: A dose of 3 x 10(6) U/m2 three times weekly for 4 to 5 weeks (one cycle) was administered. Patients were treated with one to four cycles of rhIFN alpha-2a, and the outcomes were measured initially and 18 to 30 months after the last cycle. RESULTS: Good therapeutic responses (defined as platelet count >100 x 10(9)/L) lasting for 18 to 30 months from the last interferon cycle were achieved in 6 of the 11 (55%) patients, including one with a probable spontaneous remission. Fair responses (platelet count 31-60 x 10(9)/L) for 18 months were achieved in 3 of the 11 (27%) patients. Only two patients, each treated only with one interferon cycle, exhibited no response. Side effects of treatment included fever and a flu-like syndrome, which were usually present during the first 14 days of therapy only. CONCLUSIONS: Interferon-alpha appears to be an effective therapeutic approach to children with chronic immune thrombocytopenic purpura, with the potential of sustained long-term remission. A randomized, placebo-controlled study is needed to confirm its role in this population.

The late consequences of anthracycline treatment on left ventricular function after treatment for childhood cancer.

UNLABELLED: The purpose of this study was to determine the incidence of changes in left ventricular function in patients in long-term remission after treatment with anthracyclines for a childhood malignancy. The authors examined 155 patients in disease remission who underwent treatment protocols utilising anthracyclines in childhood. The group comprised 90 males and 65 females aged 15+/-4.9 years (range 5-29 years, median 15 years). The age at the time of diagnosis and start of treatment was 8.6+/-4.9 years (range 1-18 years, median 8 years). The time of follow-up was 7.3+/-4 years (range 1-21 years, median 6.3 years). The patients were given a cumulative dose of doxorubicin or daunorubicin of 250+/-131 mg/m2 (range 50-1200 mg/m2, median 240 mg/m2). The values of ejection fraction below 55% and fractional shortening below 30% assessed by means of echocardiography were considered as pathological. The control group consisted of 41 volunteers. Pathological values of fractional shortening were found in 12 patients (8%). Only one patient (0.64%) showed the development of heart failure due to cardiomyopathy. The group of the patients after chemotherapy revealed significantly worse values of left ventricular endsystolic wall stress, mean velocity of circumferential fibre shortening, Tei index, and isovolumic relaxation period in comparison with the control group. We found a correlation between the given cumulative dose of anthracyclines and indicators of systolic function of the left ventricle, but not a relation to the time indicators (age at diagnosis, time of follow-up). CONCLUSION: in the mean period of 6 years after chemotherapy, subclinical cardiotoxicity was found in 11 patients (7%) and cardiomyopathy with heart failure in one patient. Further indicators of subclinical damage are elevation of afterload (end-systolic stress), impaired relaxation and increased value of the Doppler index of global left ventricular function. Further monitoring and evaluation of the relevant subclinical abnormalities over a longer period of time are needed.