Heart transplantation in neonates and children. Intermediate-term results

OBJECTIVE: To assess intermediate-term outcome in children who have undergone orthotopic heart transplantation. METHODS: We carried out a longitudinal and prospective study between October '92 and June '99 comprising 20 patients with ages ranging from 12 days to 7 years (mean of 2.8 years). We employed a double immunosuppression protocol with cyclosporine and azathioprine and induction therapy with polyclonal antithymocyte serum. Survival and complications resulting from the immunosuppression protocol were analyzed. RESULTS:The double immunosuppression protocol and the induction therapy with polyclonal antithymocyte serum resulted in an actuarial survival curve of 90% and 78.2% at 1 and 6 years, respectively, with a mean follow-up period of 3.6 years. One patient died due to acute rejection 40 days after transplantation; another patient died 2 years after transplantation due to lymphoproliferative disorder; a third patient died because of primary failure of the graft; and a fourth patient died due to bronchopneumonia. The major complications were as follows: acute rejection, infection, nephrotoxicity, and systemic hypertension. The means of rejection and infection episodes per patient were 2.9 and 3.4, respectively. After one year of transplantation, a slight reduction in the creatinine clearance and systemic hypertension were observed in 7 (38.9%) patients. CONCLUSION: Heart transplantation made life possible for those patients with complex congenital heart diseases and cardiomyopathies in refractory congestive heart failure constituting a therapeutical option for this group of patients in the terminal phase.

Unsupported valvuloplasty in children with congenital mitral valve anomalies. Late clinical results

OBJECTIVE: To analyze late clinical evolution after surgical treatment of children, with reparative and reconstructive techniques without annular support. METHODS: We evaluated 21 patients operated upon between 1975 and 1998. Age 4.67±3.44 years; 47.6% girls; mitral insufficiency 57.1% (12 cases), stenosis 28.6% (6 cases), and double lesion 14.3% (3 cases). The perfusion 43.10±9.50min, and ischemia time were 29.40±10.50min. The average clinical follow-up in mitral insufficiency was 41.52±53.61 months. In the stenosis group (4 patients) was 46.39±32.02 months, and in the double lesion group (3 patients), 39.41±37.5 months. The echocardiographic follow-up was in mitral insufficiency 37.17±39.51 months, stenosis 42.61±30.59 months, and in the double lesion 39.41±37.51 months. RESULTS: Operative mortality was 9.5% (2 cases). No late deaths occurred. In the group with mitral insufficiency, 10 (83.3%) patients were asymptomatic (p=0.04). The majorit y with mild reflux (p=0.002). In the follow-up of the stenosis group, all were in functional class I (NYHA); and the mean transvalve gradient varied between 8 and 12mmHg, average of 10.7mmHg. In the double lesion group, 1 patient was reoperated at 43 months. No endocarditis or thromboembolism were reported. CONCLUSION: Mitral stenosis repair has worse late results, related to the valve abnormalities and associated lesions. The correction of mitral insufficiency without annular support showed good long-term results.

Assessment of splanchnic perfusion with gastric tonometry in the immediate postoperative period of cardiac surgery in children

OBJECTIVE - A prospective, nonrandomized clinical study to assess splanchnic perfusion based on intramucosal pH in the postoperative period of cardiac surgery and to check the evolution of patients during hospitalization. METHODS - We studied 10 children, during the immediate postoperative period after elective cardiac surgery. Sequential intramucosal pH measurements were taken, without dobutamine (T0) and with 5mcg/kg/min (T1) and 10 (T2) mcg/kg/min. In the pediatric intensive care unit, intramucosal pH measurements were made on admission and 4, 8, 12, and 24 hours thereafter. RESULTS - The patients had an increase in intramucosal pH values with dobutamine 10mcg/kg/min [7.19± 0.09 (T0), 7.16±0.13(T1), and 7.32±0.16(T2)], (p=0.103). During the hospitalization period, the intramucosal pH values were the following: 7.20±0.13 (upon admission), 7.27±0.16 (after 4 hours), 7.26±0.07 (after 8 hours), 7.32±0.12 (after 12 hours), and 7.38±0.08 (after 24 hours), (p=0.045). No deaths occurred, and none of the patients developed multiple organ and systems dysfunction. CONCLUSION - An increase in and normalization of intramucosal pH was observed after dobutamine use. Measurement of intramucosal pH is a type of monitoring that is easy to perform and free of complications in children during the postoperative period of cardiac surgery.

Epidemiological study of congenital heart defects in children and adolescents: analysis of 4,538 cases

OBJECTIVE: To analyze the frequency and prevalence of congenital heart defects in a tertiary care center for children with heart diseases. METHODS: We carried out an epidemiological assessment of the first medical visit of 4,538 children in a pediatric hospital from January 1995 to December 1997. All patients with congenital heart defects had their diagnoses confirmed at least on echocardiography. The frequency and prevalence of the anomalies were computed according to the classification of sequential analysis. Age, weight, and sex were compared between the groups of healthy individuals and those with congenital heart defects after distribution according to the age group. RESULTS: Of all the children assessed, 2,017 (44.4%) were diagnosed with congenital heart disease, 201 (4.4%) with acquired heart disease, 52 (1.2%) with arrhythmias, and 2,268 (50%) were healthy children. Congenital heart diseases predominated in neonates and infants, corresponding to 71.5% of the cases. Weight and age were significantly lower in children with congenital heart defects. Ventricular septal defect was the most frequent acyanotic anomaly, and tetralogy of Fallot was the most frequent cyanotic anomaly. CONCLUSION: Children with congenital heart defects are mainly referred during the neonatal period and infancy with impairment in gaining weight. Ventricular septal defect is the most frequent heart defect.

Study of the cardiac alterations in HIV-infected children consequent to the antiretroviral therapy: prospective study of 47 cases

OBJECTIVE: Detect of cardiac alterations in children with AIDS and compare their evolution with the administration of only one anti-retroviral and the recent cases who received drugs in combination. METHODS: We prospectively studied 47 children in 3 groups: group 1, 20 cases treated only with zidovudine; group 2, 10 patients treated initially with zidovudine and later with a combination of drugs and in group 3, 17 patients, who receiced two or three since the beginning. In all patients it was done chest X-ray, EKG and echocardiography every 6 months and after death complete pathological study. RESULTS: Among the 45 patients cases 26 (57%) were index cases. Malnutrition, diarrhea tachycardia, signs of congestive heart failure, pericardial effusion, abnormal ventricular repolarization and arrhythmias were more frequent in group 1. Echocardiographic abnormalities were present in 10 (50%) children of group 1. They were less frequent in the others two groups. In regard to the outcome in group 1, two patients had worsening of sings of cardiomyopaty and 4 died. Cardiac dysfunction in all cases of group 2 and 3 improved with the medication. CONCLUSION:- The children who received combination and their cardiac alterations had more favorable outcome than those who received only one drug.

Diastolic Function in Paced Children with Cardiac Defects: Septum vs Apex

AbstractIn children with structural congenital heart disease (CHD), the effects of chronic ventricular pacing on diastolic function are not well known. On the other hand, the beneficial effect of septal pacing over apical pacing is still controversial.The aim of this study was to evaluate the influence of different right ventricular (RV) pacing site on left ventricular (LV) diastolic function in children with cardiac defects.Twenty-nine pediatric patients with complete atrioventricular block (CAVB) and CHD undergoing permanent pacing were prospectively studied. Pacing sites were RV apex (n = 16) and RV septum (n = 13). Echocardiographic assessment was performed before pacemaker implantation and after it, during a mean follow‑up of 4.9 years.Compared to RV septum, transmitral E-wave was significantly affected in RV apical pacing (95.38 ± 9.19 vs 83 ± 18.75, p = 0.038). Likewise, parameters at the lateral annular tissue Doppler imaging (TDI) were significantly affected in children paced at the RV apex. The E´ wave correlated inversely with TDI lateral myocardial performance index (Tei index) (R2= 0.9849, p ≤ 0.001). RV apex pacing (Odds ratio, 0.648; confidence interval, 0.067-0.652; p = 0.003) and TDI lateral Tei index (Odds ratio, 31.21; confidence interval, 54.6-177.4; p = 0.025) predicted significantly decreased LV diastolic function.Of the two sites studied, RV septum prevents pacing-induced reduction of LV diastolic function.

Assessment of Intima-Media Thickness in Healthy Children Aged 1 to 15 Years

Abstract Background: Carotid intima-media thickness (CIMT) has been shown to be increased in children and adolescents with traditional cardiovascular risk factors such as obesity, hypertension, and chronic kidney disease, compared with those of healthy children. Objective: To assess the influence of sex, age and body mass index (BMI) on the CIMT in healthy children and adolescents aged 1 to 15 years. Methods: A total of 280 healthy children and adolescents (males, n=175; mean age, 7.49±3.57 years; mean BMI, 17.94±4.1 kg/m2) were screened for CIMT assessment. They were divided into 3 groups according to age: GI, 1 to 5 years [n=93 (33.2%); males, 57; mean BMI, 16±3 kg/m2]; GII, 6 to 10 years [n=127 (45.4%); males, 78; mean BMI, 17.9±3.7 kg/m2], and GIII, 11 to 15 years [n=60 (21.4%); males, 40; mean BMI, 20.9±4.5 kg/m2]. Results: There was no significant difference in CIMT values between male and female children and adolescents (0.43±0.06 mm vs. 0.42±0.05 mm, respectively; p=0.243). CIMT correlated with BMI neither in the total population nor in the 3 age groups according to Pearson correlation coefficient. Subjects aged 11 to 15 years had the highest CIMT values (GI vs. GII, p=0.615; GI vs. GIII, p=0.02; GII vs. GIII, p=0.004). Conclusions: CIMT is constant in healthy children younger than 10 years, regardless of sex or BMI. CIMT increases after the age of 10 years.

Cutaneous allergic reactions to Triatoma infestans after xenodiagnosis

We determined the frequency of cutaneous allergic reactions to bites of Triatoma infestans during xenodiagnosis in a rural community where Panstrongylus megistrus is the only domestic vector of Trypanosoma cruzi. Localized urticaria or more intense cutaneous allergic reactions at 48 and 72 hours were observed in 86.7% and 82.1% respectively of the individuals in our study. Urticaria was more severe in children and older adults and in women than in men. The high frequency of reactions suggests either cutaneous reactivity to T. infestans without prior sensitization or cross reactivity between P. megistus and T. infestans. A single application of topical corticosteroid or antihistamine medication did not reduce the cutaneous reactions.

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

The effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan on perioperative brain injury in children undergoing cardiac surgery with cardiopulmonary bypass: results of a pilot study.

Experimental evidence indicates a role of the N-methyl-D-aspartate receptor in the pathogenesis of brain injury occurring during cardiac surgery with cardiopulmonary bypass (CPB). Dextromethorphan is a noncompetitive antagonist of this receptor with a favorable safety profile. Thirteen children age 3-36 months undergoing cardiac surgery with expected CPB of 60 minutes or more were randomly assigned to treatment with dextromethorphan (36-38 mg/kg/day) or placebo administered by naso-gastric tube. Dextromethorphan was absorbed well and reached putative therapeutic levels in blood and cerebrospinal fluid. Adverse effects were not observed. Mild hemiparesis developed after operation in one child of each group, and severe encephalopathy in one of the placebo group. Sharp waves were recorded in postoperative continuous electroencephalography in all placebo (n = 7) but only in 2/6 dextromethorphan treated children (p = 0.02). Pre- and postoperative cranial magnetic resonance imaging (MRI) revealed less pronounced ventricular enlargement in the dextromethorphan group (not significant). An increase of periventricular white matter lesions was visible in two placebo-treated children only. No elevations of cerebrospinal fluid enzymes were observed in either group. Although children with dextromethorphan showed less abnormalities in electroencephalography and MRI, dissimilarities of the treatment groups by chance diminished conclusions to possible protective effects of dextromethorphan at this time.

Determinants of hepatitis A vaccine immunity in a cohort of human immunodeficiency virus-infected children living in Switzerland.

Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively. Recommendations for initial, catch-up, and additional HAV immunizations were based upon baseline antibody concentrations and vaccine history. HAV IgG was assessed by enzyme-linked immunosorbent assay (ELISA) with a protective cutoff value defined as ≥10 mIU/ml. Eighty-seven patients were included (median age, 11 years; range, 3.4 to 21.2 years). Forty-two patients were seropositive (48.3%) for HAV. Among 45 (51.7%) seronegative patients, 36 had not received any HAV vaccine dose and were considered naïve. Vaccine responses were assessed after the first dose in 29/35 naïve patients and after the second dose in 33/39 children (25 initially naïve patients, 4 seronegative patients, and 4 seropositive patients that had already received 1 dose of vaccine). Seroconversion was 86% after 1 dose and 97% after 2 doses, with a geometric mean concentration of 962 mIU/ml after the second dose. A baseline CD4(+) T cell count below 750 cells/μl significantly reduced the post-2nd-dose response (P = 0.005). Despite a high rate of seroconversion, patients with CD4(+) T cell counts of <750/μl had lower anti-HAV antibody concentrations. This may translate into a shorter protection time. Hence, monitoring humoral immunity may be necessary to provide supplementary doses as needed.

Long-term effect of a school-based physical activity program (KISS) on fitness and adiposity in children: a cluster-randomized controlled trial.

BACKGROUND: School-based intervention studies promoting a healthy lifestyle have shown favorable immediate health effects. However, there is a striking paucity on long-term follow-ups. The aim of this study was therefore to assess the 3 yr-follow-up of a cluster-randomized controlled school-based physical activity program over nine month with beneficial immediate effects on body fat, aerobic fitness and physical activity. METHODS AND FINDINGS: Initially, 28 classes from 15 elementary schools in Switzerland were grouped into an intervention (16 classes from 9 schools, n = 297 children) and a control arm (12 classes from 6 schools, n = 205 children) after stratification for grade (1st and 5th graders). Three years after the end of the multi-component physical activity program of nine months including daily physical education (i.e. two additional lessons per week on top of three regular lessons), short physical activity breaks during academic lessons, and daily physical activity homework, 289 (58%) participated in the follow-up. Primary outcome measures included body fat (sum of four skinfolds), aerobic fitness (shuttle run test), physical activity (accelerometry), and quality of life (questionnaires). After adjustment for grade, gender, baseline value and clustering within classes, children in the intervention arm compared with controls had a significantly higher average level of aerobic fitness at follow-up (0.373 z-score units [95%-CI: 0.157 to 0.59, p = 0.001] corresponding to a shift from the 50th to the 65th percentile between baseline and follow-up), while the immediate beneficial effects on the other primary outcomes were not sustained. CONCLUSIONS: Apart from aerobic fitness, beneficial effects seen after one year were not maintained when the intervention was stopped. A continuous intervention seems necessary to maintain overall beneficial health effects as reached at the end of the intervention. TRIAL REGISTRATION: ControlledTrials.com ISRCTN15360785.

A 10-year experience in paediatric spontaneous cerebral hemorrhage: which children with headache need more than a clinical examination?

INTRODUCTION: When a child is seen in a clinic with a headache, stroke is certainly not the first on the list of differential diagnoses. In western countries, stroke is typically associated with adults and the elderly. Although rare, haemorrhagic strokes are not exceptional in the paediatric population, as their incidence is around 1/100 000/year. Prompt diagnosis is essential, since delayed treatment may lead to disastrous prognosis in these children. MATERIALS AND METHODS: This is a retrospective review of paediatric cases with spontaneous cerebral haemorrhage that presented in two university hospitals in the last ten years. The experience of these primary and tertiary referral centres comprises 22 consecutive cases that are analysed according to aetiology, presenting symptoms, treatment and outcome. RESULTS: 77% of the children diagnosed with haemorrhagic stroke presented with headaches. 41% of them had a sudden onset, while 9% developed headaches over a period of hours to weeks. While 9% presented only with headaches, the majority had either subtle (diplopia, balance problems) or obvious (focal deficits, unilateral weakness and decreased level of consciousness) concomitant neurological signs. 55% had an arteriovenous malformation (AVM), 18% had an aneurysm and 14% had a cavernous malformation. In 14% the aetiology could not be determined. The majority of haemorrhages (82%) were supratentorial, while 18% bled into the posterior fossa. All children underwent an emergency cerebral CT scan followed by specific investigations. The treatment was dependent on the aetiology as well as the mass effect of the haematoma. In 23% an emergent evacuation of the haematoma was performed. Two children (9%) died, and 75% had a favourable clinical outcome. CONCLUSION: Headaches in children are a common problem, and a small minority may reveal an intracranial haemorrhage with poor prognosis if not treated promptly. Although characterisation of headaches is more difficult in a paediatric population, sudden, unusual or intense headaches should lead to imaging work-up. Any neurological finding, even one as subtle as hemianopsia or dysmetria, should alarm the physician and should be followed by emergency imaging investigation. If the cerebral CT reveals a haemorrhage, the child should be referred immediately to a neurosurgical referral centre without further investigation. The outcome is grim for children presenting in coma with fixed, dilated pupils. The long-term result overall for children after spontaneous intracranial haemorrhage is not dismal and depends critically on specialised management.

Viability of Ascaris lumbricoides eggs eliminated after anti-helminthic therapy

The viability of Ascaris lumbricoides eggs passed in the feces was evaluated after treatment of patients with one of the anti-helminthic drugs (thiabendazole, levamisole, cambendazole, pyrantel pamoate, mebendazole or praziquantel). For each drug, a group of 5 children was selected and their feces collected 24 h before treatment and 24, 48 and 72 h after drug administration, except for mebendazole, with the feces being collected throughout the period of treatment. After sedimentation, the total amount of eggs from each collection was transferred to tissue culture flasks containing 10 ml H2So4 O, 1N, with the addtion of 3 drops of a miconazol solution, and incubated at 28 graus centígrados, individually, for 80 days. The flasks wee maintained open and the culture were oxigenated daily by manual agitation. On the 80th day of culture, 20-days-old albino mice were inoculated with 3,200 embryonated eggs, per os. Larvae were recovered from their lungs and hearts, on the 8th day after infection, according to Baerman's method (Morais, 1948). Thiabendazole showed 100.0% ovicidal capacity as early as 48 after treatment. Inhibition of embrionary development was observed when thiabendazole was used. This drug also had an effect on the eggs infectivity when inoculated into normal mice. No significant effect on embrionary development was observed for the other drugs tested.

Peri-prosthetic stress fractures after reversed shoulder arthroplasty

Introduction: Reversed shoulder prostheses have a semi-congruent design. Furthermore, the center of rotation is inferiorly displaced and a significant tension in the deltoid is often necessary to ensure the joint stability. Consequently, stress transmitted to peri-prosthetic bone may be increased, and could lead to stress fractures. We review a series of patients after reversed shoulder arthroplasty (RSA) and look specifically at the occurrence of postoperative peri-prosthetic stress fractures. Methods: Between 2001 and 2006, 46 consecutive RSA were performed. There were 26 women and 20 men with a mean age of 74 years (53-86). All had preoperative MRI or CT-scan, which did not reveal any fracture. All had a delto-pectoral approach with standard rehabilitation. Review was performed at a mean follow up of 30 months (6-60), and consisted of clinical and radiological (plain X-rays) examinations. Every time a fracture was suspected or in case of recurrent unexpected pain, CT-scan evaluations were performed. The occurrence of peri-prosthetic fractures was looked for. Results: Three patients (7%) sustained a scapular fracture (1 spinal and 2 acromial) without any trauma, between 3 and 6 months after the RSA. Furthermore, one of these patients developed 3 months later a spontaneous clavicular fracture, leading to an overall stress fracture rate of 9%. The four fractures were treated conservatively. Three malunions and one acromial non-union occurred. The range of motion in abduction and flexion decreased significantly after the fracture and stayed limited in all cases. All the three patients reported a recurrence of pain. Conclusion: Peri-prosthetic stress fractures, especially in the acromion and in the spine of the scapula are not unusual after RSA. The etiology is not well known. The increase of stress in peri-prosthetic bone may be due to the semi-congruent design and to an overtension of the deltoid. The management of this complication stays difficult. The conservative treatment leads to mal- or non-union, with persistent pain and limited range of motion.