Infective endocarditis in congenital heart disease: a frequent community-acquired complication.

BACKGROUND: Infective endocarditis (IE) is a severe complication in patients with congenital heart disease (CHD). Epidemiology, etiology, and outcome in this group are different to those of patients with acquired heart disease. METHODS: We reviewed all cases of proven and probable IE (Duke's criteria) diagnosed in our center during the last two decades. RESULTS: We observed 45 cases of IE in patients with CHD (age range 8 months to 35 years); these represented 5.5 % of all the episodes of IE in our institution during the study period. The most frequent CHD were ventricular septal defect (31 %), tetralogy of Fallot (19 %), and atrioventricular septal defect (11 %). Twenty cases of IE (44 %) were recorded in patients with non-corrected native-valve CHD. Of the 24 patients with prosthetic-valve IE, post-operative acquisition during the first 6 months was confirmed in 11 patients (range 4-110 days). IE was community-acquired in 62 % of cases. Streptococcus spp. were the most frequent etiologic agents (33 %), followed by Staphylococcus spp. (32 %). Surgery was required to treat IE in 47 % of patients (52 % in prosthetic-valve IE and 41 % in native-valve IE, p = ns). In comparison to native-valve IE, prosthetic-valve IE was significantly more nosocomial-acquired (61 vs. 14 %, p = 0.002), presented a higher heart failure rate at diagnosis (39 vs. 9 %, p = 0.035), and developed more breakthrough bacteremia episodes (19 vs. 0 %, p = 0.048). Global mortality was 24 % (75 % in patients with prosthetic-valve IE who required surgery and 0 % in patients with native-valve IE who required surgery, p = 0.001). Multivariate analysis excluding breakthrough bacteremia (100 % mortality in this condition) confirmed that nosocomial IE [odds ratio (OR), 23.7; 95 % confidence interval (CI), 2.3-239.9] and the presence of heart failure at diagnosis of IE (OR, 25.9; 95 % CI, 2.5-269.6) were independent factors associated with mortality. CONCLUSION: Half of all cases of IE in patients with CHD occurred in patients with non-corrected native-valve CHD and two-thirds were community-acquired. Streptococcus spp. were the most frequent etiological agents. Patients with prosthetic-valve IE present a worse outcome, especially those requiring surgery. Breakthrough bacteremia, nosocomial IE, and heart failure are independent factors of mortality in patients with CHD presenting IE.

Relationship between serotypes, age, and clinical presentation of invasive pneumococcal disease in Madrid, Spain, after introduction of the 7-valent pneumococcal conjugate vaccine into the vaccination calendar.

To assess invasive pneumococcal disease (IPD) clinical presentations and relationships with age and serotype in hospitalized children (<15 years) after PCV7 implementation in Madrid, Spain, a prospective 2-year (May 2007 to April 2009) laboratory-confirmed (culture and/or PCR) IPD surveillance study was performed (22 hospitals). All isolates (for serotyping) and culture-negative pleural/cerebrospinal fluids were sent to the reference laboratory for pneumolysin (ply) and autolysin (lyt) gene PCR analysis. A total of 330 IPDs were identified: 263 (79.7%) confirmed by culture and 67 (20.3%) confirmed by PCR. IPD distribution by age (months) was as follows: 23.6% (<12), 15.8% (12 to 23), 15.5% (24 to 35), 22.4% (36 to 59), and 22.7% (>59). Distribution by clinical presentation was as follows: 34.5% bacteremic pneumonia, 30.3% pediatric parapneumonic empyema (PPE), 13.6% meningitis, 13.3% primary bacteremia, and 8.2% others. Meningitis and primary bacteremia were the most frequent IPDs in children <12 months old, and bacteremic pneumonia and PPE were most frequent in those >36 months old. Frequencies of IPD-associated serotypes were as follows: 1, 26.1%; 19A, 18.8%; 5, 15.5%; 7F, 8.5%; 3, 3.9%; nontypeable/other 30 serotypes, 27.3%. Serotype 1 was linked to respiratory-associated IPD (38.6% in bacteremic pneumonia and 38.0% in PPE) and children of >36 months (51.4% for 36 to 59 months and 40.0% for >59 months), while serotype 19A was linked to nonrespiratory IPDs (31.1% in meningitis, 27.3% in primary bacteremia, and 51.9% in others) and children of <24 months (35.9% for children of <12 months and 36.5% for those 12 to 23 months old), with high nonsusceptibility rates for penicillin, cefotaxime, and erythromycin. After PCV7 implementation, non-PCV7 serotypes caused 95.5% of IPDs. The new 13-valent conjugate vaccine would provide 79.1% coverage of serotypes responsible for IPDs in this series.

Separación laringotraqueal como tratamiento de la aspiración broncopulmonar grave / Laryngotracheal separation as treatment for severe bronchopulmonary aspiration

Presentamos el caso de una paciente con bronco-aspiración crónica grave debida a un tumor en el tronco encefálico y las secuelas de su tratamiento. La parálisis bilateral de pares craneales bajos y el reflujo gastroesofágico intenso provocaron infecciones respiratorias por aspiración e ingreso continuado durante año y medio, a pesar del tratamiento médico y la traqueotomía e inserción de una cánula con balón. La separación laringotraqueal redujo drásticamente las infecciones y mejoró la calidad de vida (AU)

We present the case of a patient with brain stem tumour and severe chronic aspiration. The bilateral dysfunction of lower cranial nerves and the severe gastroesophageal reflux contributed to the aspirations. Despite medical treatment and cuffed tracheotomy tube, she required almost constant hospitalization for a year and a half due to respiratory infections. Laryngotracheal separation dramatically reduced the infections and improved her quality of life (AU)

[Laryngotracheal separation as treatment for severe bronchopulmonary aspiration]. / Separación laringotraqueal como tratamiento de la aspiración broncopulmonar grave.

We present the case of a patient with brain stem tumour and severe chronic aspiration. The bilateral dysfunction of lower cranial nerves and the severe gastroesophageal reflux contributed to the aspirations. Despite medical treatment and cuffed tracheotomy tube, she required almost constant hospitalization for a year and a half due to respiratory infections. Laryngotracheal separation dramatically reduced the infections and improved her quality of life.

Megatherapy in children with high-risk Ewing's sarcoma in first complete remission.

To improve the prognosis of patients with metastatic or high-risk localized sarcoma in first CR, we explored the role of consolidation therapy with megatherapy and hematopoietic rescue. From 1986 to 1995, of 72 patients with Ewing's sarcoma from three pediatric departments, 30 were diagnosed as high-risk patients. Of these 30 patients, six did not achieve complete remission and four refused megatherapy and received multimodal treatment (chemotherapy + surgery and/or radiotherapy). The remaining 20 patients received megatherapy. There were 15 males and five females with a median age of 10.8 years (range 2-18 years). Five patients had metastatic disease at initial diagnosis, nine patients had primary tumor in the pelvis and 13 had a tumor volume greater than 100 ml. Overall disease-free survival was 62.7+/-11%; 40+/-21.9% for those with metastatic disease, 76.2+/-12.2% for those with tumor volume greater than 100 ml and 64.8+/-16.5% for those with tumor in pelvic bones. In conclusion, megatherapy has improved the outcome of this group of patients relative to that expected following conventional therapy.

Autologous bone marrow transplantation with monoclonal antibody purged marrow for children with acute lymphoblastic leukemia in second remission. Spanish Working Party for BMT in Children.

The purpose of this study was to evaluate the outcome of children with acute lymphoid leukemia (ALL) in second remission who have undergone high-dose chemotherapy and radiotherapy and autologous bone marrow transplantation (ABMT) with monoclonal antibody purged marrow, and to determine the main prognostic factors. From 1987 to 1992, 55 children with ALL in second remission underwent ABMT. The conditioning regimen consisted of total body irradiation (TBI) plus cyclophosphamide in 21 patients and TBI plus cyclophosphamide plus cytarabine or VP-16 in 28 patients; the remaining six patients were treated with chemotherapy alone (cyclophosphamide and busulfan, and/or VP-16). The marrow was purged using monoclonal antibodies and complement or magnetic microspheres in all cases. All patients engrafted. Three patients (5%) died early post transplant from infections. Twenty-six patients (47%) relapsed (median 150 days); 26 patients (47%) are alive and in complete remission (CR) at a median of 36 months. The Kaplan-Meier estimation showed a probability of event-free survival (EFS) of 46 +/- 0.007%. In the univariate analysis, first CR length and conditioning with TBI plus two or more cytotoxic drugs were found to be the most significant predictors of EFS. ABMT with purged marrow is a treatment modality which offers a chance of cure in children with ALL after relapse, including children who relapse early.

Subcutaneous versus intravenous low-dose IL-2 therapy after autologous transplantation: results of a prospective, non-randomized study.

Use of IL-2 therapy after autologous transplantation is currently being explored to reduce relapse rate. Low doses of the cytokine induce significant immunomodulation avoiding the severe side-effects associated with high-dose IL-2 therapy. However, low-dose IL-2 is usually given by continuous infusion through central venous lines with the consequent risks of thrombosis and infections. Twenty-six consecutive patients who received autologous transplants received low-dose IL-2 after stable engraftment had been achieved. The first 13 patients (group A) were scheduled to receive 400,000/IU/m2/day for 3 months by continuous intravenous infusion. Ten of these patients suffered infectious episodes, mainly bacteriemias that often necessitated delaying IL-2 therapy (median delivered dose: 32% of planned). The next 13 patients were then assigned to receive IL-2 (800,000-1,000,000 IU/m2/day for 3 months) subcutaneously (group B). For group B patients, median dose intensity was 84% (P = 0.01 when compared with group A patients). Only one severe infectious episode was observed in these patients. Clinical toxicity in group B patients consisted mainly of s.c. nodules. Immunomodulation, measured as an increase in the absolute number of CD56+ cells and CD56+(bright) cells, was higher in patients who received the cytokine by the subcutaneous route (median peak increase of CD56+ cells: 160 and 220% for group A and B patients respectively; median peak increase of CD56+(bright) cells: 210% and 310% for group A and B respectively, P < 0.05 between groups A and B). No statistically significant increment of T lymphocytes was observed in any group. No hematologic toxicity was observed apart from eosinophilia, which was very marked in group B (P < 0.01). Our results show that low-dose s.c. IL-2 therapy is associated with low clinical and hematologic toxicity after autologous transplantation. The immunomodulation achieved is no less than that achieved with the i.v. approach.

Bone marrow transplantation in chronic granulomatous disease.

UNLABELLED: We present a 5-year-old boy with a severe form of X-linked chronic granulomatous disease and hypersensitivity to sulphamides preventing prophylaxis with trimethoprim-sulphomethoxazole. Bone marrow transplantation was performed after preconditioning with busulphan and cyclophosphamide. The immediate post-transplant period was without complications. Complete chimerism was demonstrated and post-transplant oxidative metabolism was normal. The patient is asymptomatic 30 months after the graft. CONCLUSION: Bone marrow transplantation in cases of chronic granulomatous disease is controversial, although it could be useful in selected very severe cases in which prophylactic therapy is problematic.

[Preoperative and postoperative chemotherapy of osteogenic sarcoma of the limbs in children]. / Tratamiento del sarcoma osteogénico de extremidades en la infancia con quimioterapia pre y postoperatoria.

BACKGROUND: A preoperative and postoperative chemotherapy regimen was applied to nonmetastatic osteosarcoma of the extremities in patients under 16 years of age to prevent the progress to metastatic disease and reduce the volume of the primary tumor in order to assess a conservative surgery. PATIENTS AND METHODS: A modified T-10 chemotherapy regimen was used before surgery, including high dose methotrexate, vincristine, bleomycin, cyclophosphamide and dactinomycin. After surgery patients with a grade of tumor necrosis > 90% received the same regimen up to 45 weeks of treatment. For the cases with necrosis < 90%, this regimen was substituted by adriamycin and cisplatinum. Survival was studied in relation with age, sex, tumor site, levels of alkaline phosphatase and LDH, surgical treatment and tumor necrosis in the surgical specimen after preoperative chemotherapy. Uni and multivariate analysis were performed. RESULTS: Twenty seven patients with ages ranging from 5 to 15 years (median 11 years) were treated. The most common site of primary tumor was femur, followed by humerus and tibia. In 9 cases (33%) tumor necrosis was > 90%. Consecutive surgery was performed in 20 patients and 7 suffered amputation or disarticulation of the extremity. Twenty patients remain alive and disease-free at a median follow-up of 84 months. The probability of disease-free survival at 50 months is 71%. The only factor which influenced significantly the survival was the grade of tumor necrosis. Survival was 100% for the 9 patients with necrosis > 90% and 53% for the 18 cases with necrosis > 90% (p = 0.022). CONCLUSIONS: Preoperative and postoperative chemotherapy achieve disease-free survival in more than two thirds of patients with nonmetastatic osteosarcoma of the extremities and allow a non mutilating surgical treatment in the majority of them.

[Immunologic reconstitution of peripheral blood lymphocytes in patients treated by bone marrow transplantation]. / Reconstitución inmunológica de los linfocitos de sangre periférica en pacientes tratados con trasplante de médula ósea.

BACKGROUND: Lymphocyte subset reconstitution was studied in 65 patients undergoing allogeneic and autologus bone marrow transplantation (BMT). PATIENTS AND METHODS: The expression of molecules on the membrane of lymphocyte subsets was assessed by two-colour flow cytometry and a direct immunofluorescence assay. The functional capacity of the patient's T lymphocytes following transplantation was identified by stimulation whit peripheral blood lymphocytes; B cells from BMT recipients were tested for their ability to respond, in vitro, to pokeweed (PWD) mitogen. RESULTS: 1) The proportion of CD8+ T lymphocytes was higher than the CD4+ T lymphocytes until 1 1/2 year after-BMT, with high percentage of immature T cells (CD3+, CD8+, HLA-DR+, CD25-) in the first nine months post-transplant. Moreover, a large proportion of T lymphocytes lacked CD5 expression in the first year following BMT. 2) T-cell proliferative response to PHA was low with subsequent recovery until normality. 3) Low numbers of B cells in the first two months with a significant increase since then until 1 1/2 year after-BMT; the phenotype of these B cells was mainly CD19+, CD5+. 4) High in vitro spontaneous immunoglobulin production by peripheral blood B lymphocytes and an impaired response to PWM was observed. 5) Increased percentage of cells with natural killer (CD56) cell phenotype was seen during the 2nd and 3rd months after the graft infusion. After 1 1/2 year postgrafting, this percentage returned to normal level. CONCLUSIONS: Taken together, these data indicate the existence of numerous abnormalities in several subsets of peripheral blood lymphocytes after BMT and suggest a slow kinetics of immune recovery after human marrow transplantation being complete between 18 and 24 months following BMT.

Male gonadal function after chemotherapy in survivors of childhood malignancy.

Investigations of adult patients have shown that chemotherapy causes gonadal damage, but much less information is available about the impact of chemotherapy on gonadal function in children with malignant disease. At one time, being prepubertal during therapy was thought to confer some protection against chemotherapy induced gonadal damage. However, recent studies have indicated otherwise. We designed this study to assess gonadal function in 15 postpubertal males who had received polychemotherapy for a malignant disease during childhood and we compared them with 13 control adults males. The mean age of the patients at the time of the study was 18.2 +/- 3.6 years (range 13.8-29.0), and when given chemotherapy treatment was 10.2 +/- 3.0 years (range 6-16). At that time 12 were prepubertal and at the time of the study all were Tanner V. The mean interval from the completion of treatment until the study was 6.42 years (range 2.0-16.5). All patients had received polychemotherapy. We evaluated testicular size, sperm counts, LH and FSH after GnRH test, and testosterone levels. Puberty had progressed normally in all patients. We found no significant differences in testosterone and basal LH levels between patients and controls. However, we detected an appreciable difference in peak LH levels (P < 0.05) and in basal and peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH, indicating dysfunction of the Leydig cells. The results of semen analyses were: 8 patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen analysis. All patients with semen abnormalities presented a basal and peak FSH higher than the mean +2 SD of the control group. In summary, we found no evidence of gonadal protection in prepubertal patients. We found a high incidence of germinal cell damage, whereas Leydig cell abnormalities were found less often. An endocrine study of patients that have received chemotherapy is warranted.

G-CSF after autologous bone marrow transplantation for malignant diseases in children. Spanish Working Party for Bone Marrow Transplantation in Children.

The use of recombinant human granulocyte-stimulating factor (G-CSF) has been shown to effectively accelerate granulocytic recovery after autologous bone marrow transplantation (BMT) in adults. The experience, however, is limited in children. We evaluated the hematopoietic reconstitution in 41 consecutive children undergoing autologous BMT for hematologic malignancies (21 acute lymphoblastic leukemia, five non-Hodgkin's lymphoma) and solid tumours (seven neuroblastoma, two brain tumor, three Ewing's sarcoma, two Wilms' tumor, one rhabdomyosarcoma). Their ages ranged from 2 to 16 years (mean 7.2 years). rhG-CSF was given at a dose of 10 micrograms/kg/day i.v. in a 2h infusion from day +1 until +28 or until the absolute neutrophil count (ANC) was > 1 x 10(9)/L. These patients were compared with a similar historical control group of 38 children who did not receive rhG-CSF after autologous BMT. The number of cells infused was similar in both groups. At the dose and schedule used in the present study, rhG-CSF was well tolerated and no side-effects were observed. The number of cell infused was similar in both groups. At the dose and schedule used in the present study, rhG-CSF was well tolerated and no side-effects were observed. Our data show that rhG-CSF accelerates engraftment and reduces the number of febrile days and antibiotic use. Furthermore, patients who were treated had less infections.

Antibodies to hepatitis C virus in human immunoglobulins: clinical meaning and diagnostic difficulties in children undergoing bone marrow transplant.

Anti-HCV antibodies were detected in 11 children undergoing BMT. All of them had received intravenous immunoglobulins (Ig) at a dose of 500 mg/kg every 2 weeks for the first 100 days post-BMT. Antibody titers appeared after the first dose and became undetectable between 1 and 6 months after the last dose of Ig. Detection of anti-HCV antibodies in these multitransfused patients raised doubts about their clinical significance. The clearance of antibody titers in the ensuing months, negativity of HCV RNA in the serum of the patients and the presence of anti-HCV in some batches of the commercial preparations administered supported the diagnosis of a passive transfer of antibodies and that true HCV infection could be ruled out. Routine screening of donors with the most sensitive tests and exclusion of anti-HCV positive sera from plasma pools should be mandatory. The presence of anti-HCV in these products has important clinical implications, leading to more expensive and time-consuming diagnostic procedures.

Cardiovascular toxicities related to the infusion of cryopreserved grafts: results of a controlled study.

To evaluate cardiovascular toxicities associated with the infusion of cryopreserved grafts, we prospectively monitored the infusions of 29 autologous bone marrow transplant (BMT) recipients. Fifteen allogeneic BMT recipients served as a control group. Cardiac rhythm was recorded continuously with the Holter technique from at least 2 h before the start of graft infusion until 24 h after completion. Blood pressure was closely monitored during the same period. Graft infusions were performed through a standard transfusion filter with breaks between aliquots. When the infusion had commenced, diuretics were given frequently (40 and 40% of allogeneic BMT and autologous BMT recipients, respectively) to avoid fluid overload. Non-cardiovascular clinical toxicities were observed more frequently in autologous BMT patients (41% vs 6%, p = 0.02) and no significant differences were seen between autograft and allograft recipients in any of the measured cardiovascular parameters. The heart rate decreased slightly in both groups but no patient in either group had a heart rate of < 60 b.p.m. or heart block. No significant changes in blood pressure were detected in either group. Ventricular ectopic beats/atrial ectopic beats ratio increased in the autologous BMT group after graft infusion (0.7 vs 0, p = 0.1). Time to engraftment did not differ significantly from other published series. Our results suggest that increasing infusion time of cryopreserved material and using a standard filter may reduce toxicities associated with the infusion of cryopreserved grafts. Early administration of diuretics may contribute to better control of blood pressure.

[Platelet function after allogeneic bone marrow transplantation in Wiskott-Aldrich syndrome]. / Estudio de la función plaquetaria después del trasplante alogénico de medula ósea en el síndrome de Wiskott-Aldrich.

PURPOSE: To assess the platelet characteristics and functionalism in the Wiskott-Aldrich syndrome (WAS) after allogeneic BMT using cyclophosphamide and busulphan for conditioning. MATERIAL AND METHODS: Two WAS patients underwent allogeneic BMT. Platelet aggregation was studied prior to and after BMT, along with the intraplatelet amount of ADP and ATP. RESULTS: Platelet count, size and aggregation wholly recovered after BMT. The post-transplant content of platelet nucleotides was normal. CONCLUSIONS: Platelet function can be totally restored with cyclophosphamide/busulphan conditioned BMT in WAS. Platelet defects in this disease are due to defective thrombopoiesis.