Late effects of treatment for germ cell tumors during childhood and adolescence

PURPOSE: To evaluate the long-term sequelae of treatment for malignant germ cell tumors (GCT) during childhood and adolescence. PATIENTS AND METHODS: Of 128 patients treated for GCT at St. Jude Children's Research Hospital between 1962 and 1988, 73 are long-term survivors (continuously disease-free for > or =5 years after diagnosis), with a median follow-up of 11.3 years). Survivors' ages at diagnosis ranged from birth to 18.3 years (median, 9.2 years); 64% (47 patients) were female. Initial surgical resection was followed by observation for stage I germinomas (n = 2), testicular tumors (n = 13), and selected cases of ovarian or sacrococcygeal tumors (n = 2), and by radiation therapy (RT) for patients with stage II to III germinoma (n = 8). The remaining 48 patients received postoperative chemotherapy (vincristine, dactinomycin, and cyclophosphamide [VAC] +/- doxorubicin, 1962 to 1978; VAC and/or cisplatin, vinblastine, and bleomycin [PVB], 1979 to 1988). RT was added to the chemotherapy for 21 patients. Late complications involving various organ systems and their relationship to treatment were evaluated. RESULTS: More than two-thirds of long-term survivors (n = 50) had at least 1 complication, and half (n = 38) had > 1 organ system affected. The systems most often involved included the musculoskeletal (41% of survivors), endocrine (42%), cardiovascular (16% excluding those who had only abnormal chest radiograph), gastrointestinal (25%), genitourinary tract (23%), pulmonary (19%), and neurologic (16%) systems. High-frequency hearing loss occurred in 58% (11 of 19) of patients treated with cisplatin. Musculoskeletal, gastrointestinal, and urinary tract abnormalities were most frequent in patients whose treatment included RT. CONCLUSIONS: A high frequency of late effects after treatment for pediatric GCT, particularly in patients who received RT, was demonstrated. Treatment sequelae could be anticipated from the intensity and type of therapeutic modalities. Treatment-directed screening evaluations may improve quality of life in long-term survivors of pediatric GCT through timely identification of sequelae that can be prevented or ameliorated.     

The changing role of surgery in the management of rhabdomyosarcoma.

A retrospective analysis was performed of 56 patients presenting to Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland, over a 25 year period with a diagnosis of rhabdomyosarcoma, in an effort to assess the changing role of surgery in the management of this disease. There were 38 males and 18 females; the age range at presentation was from birth to 13 years with a median of three years. Head and neck tumors occurred most frequently (23) followed by pelvic (14), paratesticular (6), extremities (6), gastrointestinal (4) and thoracic (3). Prior to 1971 there were no survivors while a doubling of survival has been observed within the past decade (31% to 63%). The minimum period of follow-up was four years. Surgical intervention ranged from total primary excision (20) to biopsy only (21) with total or subtotal resection performed electively in 15. Surgical evaluations, including examinations under anesthesia, staging laparotomy and second look laparotomy were also invaluable in assessing disease status. The incorporation of multiagent chemotherapy together with more selective use of radiotherapy has enabled a more conservative role to be adopted by the surgical oncologist thereby minimizing longterm sequelae.     

Reactivation and risk of sequelae in Langerhans cell histiocytosis

OBJECTIVE: To evaluate disease reactivation in patients with Langerhans cell histiocytosis (LCH) and its impact on adverse sequelae. MATERIALS AND METHODS: A retrospective evaluation of 300 patients diagnosed with LCH between 1987 and 2002 with complete response to initial treatment was performed. RESULTS: Mean age at diagnosis was 5.3 years. With a mean follow-up of 4.8 years, reactivation of the disease occurred in 29.7% (89/300) of the patients, with two or more reactivations in 34.8% (31/89) of those. Reactivation occurred in 17.4, 36.8, 46.5, and 53.5% of the patients with single-system unifocal disease (Group A: 161 patients), single-system multifocal disease (Group B: 53 patients), multi-system disease without (Group C: 58 patients), and with (Group D: 28 patients) risk-organ involvement, respectively. The differences between the incidence rates of Groups A and B (P < 0.0004), A and C (P < 0.0001), and A and D (P < 0.0001) were highly significant. The most common reactivation sites involved were bone, middle ear, and skin; reactivation was rare in risk organs (9.5%). The median time between initial complete response and the first reactivation episode was 1 year for Group A, 1.3 years for Group B, and 9 months for Groups C and D. Most reactivation episodes (88%) occurred within the first 2 years of follow-up. Adverse sequelae were recognized in 242/300 patients: 71% (49/69) of patients with and 25.4% (44/173) without reactivations developed these adverse sequelae (P < 0.0001), respectively. Sites most commonly showing sequelae were bone, middle ear, and hypothalamus (Diabetes Insipidus). CONCLUSIONS: Incidence of reactivation correlates with the stage of the disease at diagnosis. Incidence of sequelae correlates with the occurrence of reactivations.     

Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: A descriptive report from the Intergroup Rhabdomyosarcoma Studies (IRS)-II and - III. IRS Group of the Children's Cancer Group and the Pediatric Oncology Group.

BACKGROUND: This review of children and adolescents with nonorbital soft-tissue sarcoma of the head and neck was undertaken to describe late sequelae of treatment, as manifested primarily by problems with statural growth, facial and nuchal symmetry, dentition, vision and hearing, and school performance. PROCEDURE: Four hundred sixty-nine patients entered the IRS-II and -III protocols with localized, nonorbital soft-tissue sarcomas of the head and neck from 1978 through 1987. Their overall survival rate was 53% (250/469) at 5 years. Two hundred thirteen patients were surviving relapse-free 5 or more years after diagnosis, for whom there were serial height measurements at 2 or more years after initiation of therapy. Their median age at diagnosis was 5 years; the median length of follow-up was 7 years. All received multiple-agent chemotherapy, and all but 3 received irradiation to the primary tumor volume. Sixty-eight percent of the tumors arose in cranial parameningeal sites, 22% in nonparameningeal sites, and 10% in the neck. We reviewed flow sheets submitted to the IRS Group Statistical Office to ascertain which late sequelae were recorded. RESULTS: One hundred sixty-four patients (77%) had one or more problems recorded. One hundred ninety of the two hundred thirteen patients (89%) were under 15 years of age at study entry, and at follow-up 92 (48%) had failed to maintain their initial height velocity, which had decreased by more than 25 percentile points from the original value. Thirty-six of the one hundred ninety patients (19%) were receiving growth hormone injections. Hypoplasia or asymmetry of tissues in the primary tumor site was reported in 74 patients, and 13 underwent reconstructive surgery. Poor dentition or malformed teeth were noted in 61 patients. Impaired vision developed in 37 patients, owing primarily to cataracts, corneal changes, and optic atrophy. Thirty-six patients had decreased hearing acuity, and 9 were fitted with hearing aids; 5 of these 9 had received cisplatin. Thirty-five patients were noted to have problems learning in school. Four patients developed a second malignancy (two sarcomas, one carcinoma, one leukemia). CONCLUSIONS: Late sequelae affected the majority of these patients treated for soft-tissue sarcoma of the head and neck on IRS-II and -III. The potential impact of certain sequelae could be reduced by specific measures, such as surgical reconstruction and hormonal therapy. Late sequelae must be taken into account in designing future curative treatments.     

Pediatric pneumococcal bone and joint infections. The Pediatric Multicenter Pneumococcal Surveillance Study Group (PMPSSG)

OBJECTIVE: To describe the clinical and microbiological characteristics of infants and children with bone and joint infections caused by penicillin-susceptible and penicillin-nonsusceptible strains of Streptococcus pneumoniae. DESIGN: Multicenter, prospective patient accrual; retrospective chart review of identified patients. SETTING: Eight children's hospitals in the United States. PARTICIPANTS: Forty-two children with bone and/or joint infections prospectively enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study from September 1, 1993 to August 31, 1996. OUTCOME MEASURES: Data were collected on multiple variables, including age, gender, race, days of symptoms before and during hospitalization, antibiotic and surgical therapy, laboratory and imaging studies. RESULTS: Of the 42 children enrolled (21 bone, 21 joint infections), 14 had isolates that were not susceptible to penicillin. Eight of 16 (50%) strains isolated from children who received antibiotics within 4 weeks before hospitalization were not susceptible to penicillin, compared with 4 of 15 (27%) strains isolated from children without previous antibiotic exposure. Clinical response to therapy was similar between children infected by penicillin-susceptible strains compared with those infected by penicillin-nonsusceptible strains, including duration of hospitalization (9.1 days vs 11.2 days), days of intravenous antibiotic therapy (25.3 days vs 24.6 days), days of fever (3.6 days vs 3.1 days), and sequelae (14% vs 7%). The most commonly prescribed single agents for parenteral therapy in definitive treatment were ceftriaxone (36%), penicillin (15%), and clindamycin (15%). Oral therapy followed parenteral therapy in 56% of children. The mean (+/- standard deviation) duration of total antibiotic therapy in children with osteomyelitis was 57.5 +/- 48.6 days (range, 23-196 days) and 29.2 +/- 11.8 days (range, 12-67 days) for arthritis. Late sequelae (long-term destructive changes of the bone or joint) were documented in 5 (12%) children, 4 with osteomyelitis, and 1 with arthritis. Sequelae occurred in 30% of children with long bone osteomyelitis associated with infection in the adjacent joint. The age of children with sequelae was younger than those without sequelae (6.4 months vs 18.6 months). CONCLUSIONS: The demographic characteristics and anatomic sites of infection in our patients were similar to previously published series collected from single institutions before the emergence of significant antibiotic resistance in S pneumoniae. Our analysis suggests that children infected by penicillin-nonsusceptible strains have a similar clinical response to therapy when compared with children infected by penicillin-susceptible strains.     

Dysrhythmias after the modified Fontan procedure

Summary The cardiac rhythm before and after the modified Fontan procedure was reviewed in 24 patients. Transient atrial dysrhythmias were common in the immediate postoperative period. Late postoperative premature atrial contractions were detected by ambulatory monitoring in 20 of 23 patients; eight (34.8%) had supraventricular tachycardia. Late ventricular dysrhythmia was detected in 18 of 23 patients: ten had low-grade ventricular dysrhythmias and eight (34.8%) had multiform premature ventricular contractions. Five of the latter had couplets and one of these five plus another had ventricular tachycardia. Seven patients with supraventricular tachycardia and five patients with ventricular dysrhythmia required antiarrhythmic medication. Asymptomatic bradycardia was detected in five patients (21.7%). One patient had intermittent second-degree atrioventricular block. No specific risk factors predicted dysrhythmias. Thus, cardiac dysrhythmias were common in patients after the modified Fontan procedure, but were well tolerated in most patients. No sudden deaths or syncopal episodes have occurred during a mean follow-up of 5 years. One patient's death was related to severe left ventricular dysfunction. Permanent pacing has not been required in any patient.     

Immediate complications and late sequelae of arterial catheterization in children with congenital heart disease

Summary Early vascular complications and late sequelae are reported in relation to 195 left heart catheterizations, 125 performed by brachial arteriotomy (BA), and 70 by percutaneous femoral artery puncture (FAP) with the Seldinger technique. Vascular complications occurred in 25 patients, 11 requiring surgical intervention, which was successful in restoring normal circulation in all. The rate of complications was higher after FAP in children 6 years old or less, while after BA the rate was significantly higher in patients of 2 years or older. In patients under 2 years, brachial artery suture repair resulted in more complications than ligation, but the cases were not randomized.Late follow-up of 101 catheterizations (35 FAP, and 66 BA, of which 38 were ligated and 28 sutured) included clinical evaluation, Doppler pressure measurements, and a comparison of the length and bone development of the catheterized and non-catheterized limbs. All these have indicated an absence of any serious late sequelae in this group 6 months to 9 years (average 4 years) after catheterization.Part of MD Thesis submitted to the Hebrew University, Hadassah Medical School, Jerusalem.     

Mid-term and long-term outcome in newborn infants with periventricular leukomalacia (53 cases)]

During the period 1983-1987, 53 neonates (30 boys, 23 girls, mean birth weight 1,438 +/- 317 g, mean gestational age 30 +/- 2 weeks) were found to have cystic periventricular leukomalacias (CPVL) detected by brain ultrasonography. The neuro-developmental follow-up was 3-7 years. Seventeen CPVL were isolated and CPVL were associated with minor peri-intraventricular hemorrhage (0-1 to II-II) in 36 cases. CPVL included 16 minor forms (11 normal children; 2 minor, 3 moderate sequelae), 29 moderate forms (15 normal children; 4 minor, 7 moderate, 3 major sequelae) and 8 major forms (7 major sequelae, one moderate mental retardation without motor deficit). According to reverse analysis, a normal evolution (26 cases) followed CPVL which were sometimes widely, but thinly spread over the ventricles (thickness 1/5-1/3 of the cerebral mantle); minor sequelae (6 cases) were associated with a 1/4-1/3 thickness, moderate sequelae (11 cases) with a 1/3-1/2 thickness, major sequelae (10 cases) with a 1/2-2/3 thickness of CPVL. The thickness of the lesions appeared to be more predictive of sequelae than the sagittal extent, in particular that of the posterior CPVL which played a major role in the severity of sequelae, and mainly in the presence of motor deficits.     

Epidemiological and clinical study of Mycoplasma pneumoniae respiratory infections in children hospitalized in a pediatric ward between 1999 and 2005 at the Reims University Hospital

OBJECT: To determine the frequency, clinical features, and morbidity of Mycoplasma pneumoniae infections. METHOD: Retrospective study of 76 consecutive children under 16 years of age hospitalized at the Reims University Hospital from 1999 to 2005 with M. pneumoniae pneumonia. The infection was defined by the presence of M antibodies and/or an increase in G antibodies (quantitative Elisa test). RESULTS: M. pneumoniae was the cause of 16% (76/464) of hospitalized pneumonia cases. A significantly increased frequency was observed in 2004 (34%; 19/56) and 2005 (26%; 22/84) versus 11% from 1999 to 2003, p<5.10(-4). The mean age of the patients was 6 years and 8 months, with a peak at 3 years (14/76; 18% of patients). The most frequent clinical feature was cough (80%; 56/70). The chest X-ray showed typical radiological features such as peribronchial and perivascular interstitial infiltrates in only 23% (16/69). Respiratory and extrarespiratory complications were seen in 17 and 12 children, respectively. Only 1 child suffered from respiratory sequelae. CONCLUSION: M. pneumoniae pneumonia is frequent in children over 2 years of age. The diagnosis is sometimes difficult to initially assert because there are no specific features. Respiratory and extrarespiratory complications remain possible. Respiratory sequelae can still exist even if most cases evolve favorably under treatment by macrolides.     

Predictors of long term neurological outcome in bacterial meningitis

Objective To study the long-term neurological and developmental outcome and the clinical and laboratory predictors of sequelae in children with acute bacterial meningitis (ABM). Methods Detailed clinical and demographic data was retrieved from the medical records of study children. Subsequently they were followed up for a minimum of 12 months after discharge for development, neurological and hearing assessment. All sequelae were identified and divided into minor or major. For analysis data was divided into 2 groups those with sequelae and without sequelae at follow-up. Statistical analysis was done using SPSS version 10.00 and Epi Info version 2000. Results 61 boys and 19 girls, a mean age of 31.4±41.9 months at the time of ABM, were included in the study. Of these 62.5% children were infants. Mean age at follow-up was 58.6 ± 47.2 months. Sequelae were observed in 32 (40%) children (8 (10%) minor and 24 (30%) major). Mean social quotient at follow-up was 92.8 ± 32.6. Developmentally 22 (37.9%) children were normal and 20 (34.5%) had global delay. Seizures (P=0.015), cranial nerve palsy (P=0.0065), abnormal deep tendon reflexes (P=0.002), Glasgow coma scale score (GCS) < 8 (P = 0.044) at admission, a CSF culture positive for bacteria and abnormal findings on ultrasonography or computed tomography of head at admission had significant association with sequelae at follow-up. All children (7/7) who had infarct on CT scan (P=0.001) and 12 (80%) of 15 patients who had hydrocephalus (OR-9.0, 95% Cl-2.03-45.6, P=0.001) diagnosed on CT scan developed severe sequelae. On multiple regressions GCS score <8, presence of cranial nerve palsy and abnormal deep tendon reflexes were independent predictors of sequelae. Conclusion Neurological and audiological sequelae and global developmental delay may be seen in about one third of survivors of bacterial meningitis. GCS score <8, presence of infarct or cranial nerve palsy, or hydrocephalous on CT/ultrasound at admission may help in identification of children most likely to need long term follow up and rehabilitation.     

Ultrasound appearance of the brain in very preterm infants and neurodevelopmental outcome at 18 months of age.

The brains of 158 consecutively admitted very preterm infants were repeatedly examined with real time ultrasound. Abnormalities, most commonly periventricular haemorrhage, were detected in 79 (50%). The 109 infants who survived were followed up until they were 16-23 months old. Major or minor neurological or developmental sequelae were found in 5 of 62 infants (8%) with normal ultrasound scans and in an identical proportion, 2 of 25 infants (8%), with uncomplicated periventricular haemorrhage. By contrast, 15 of 21 infants (71%) whose ventricles became enlarged (with or without periventricular haemorrhage) had abnormalities at follow up. The proportion with sequelae depended on the cause and extent of the enlargement. Three of 8 infants (38%) with mild (usually transient) ventricular distension had sequelae, compared with 3 of 4 (75%) with hydrocephalus and 9 of 9 (100%) with cerebral atrophy (2 of whom also had hydrocephalus). Adverse neurodevelopmental sequelae at follow up appeared more often to be attributable to cerebral ischaemia and infarction than to periventricular haemorrhage.     

Longitudinal clinical and functional pulmonary follow-up after megatherapy, fractionated total body irradiation, and autologous bone marrow transplantation for metastatic neuroblastoma

BACKGROUND: A prospective follow-up was undertaken to document longitudinal changes in lung function in children with neuroblastoma treated with the Lyon-Marseille-Curie-East of France Group protocol, consisting of high-dose chemotherapy schedules in combination with total body irradiation (TBI) and autologous bone marrow transplantation (ABMT), to determine the extent and timing of any changes seen and to describe late clinical and functional pulmonary sequelae. PROCEDURES: Eighteen children (1.5-6.9 years of age at TBI) performed pulmonary function tests (PFTs). These included measurement of functional residual capacity (FRC) to assess lung growth and dynamic lung compliance (CLdyn) and lung transfer factor for CO (TLCO) for evaluation of distal bronchi and/or interstitial abnormalities. RESULTS: The clinical follow-up showed that bronchopulmonary symptoms occurred in 12 children. Three of them were clinically severely incapacitated. Serial PFTs showed an initial decrease of all mean values 6 months after TBI, with improvement in mean values of FRC and TLCO at 1 year. Thereafter, a significant decrease of mean FRC and CLdyn was observed from 2 years to 4 years after TBI with preservation of TLCO, suggesting restrictive ventilatory defects rather than pulmonary fibrosis. Individual analysis showed PFT defects in 100% of children 4 years after TBI. There was a higher incidence of lung pathology after two blocks of high-dose chemotherapy than after one block (100% versus 40%) and more severe sequelae. However these children had residual disease present after induction associated with lower baseline PFT. CONCLUSIONS: PFT defects were found in all children 4 years after TBI-ABMT, but they remained within acceptable limits except in very young children.     

Short, middle and long-term outcome of major peri-intraventricular hemorrhages

Within 4 years 10 months (1981-1985), the Port-Royal Neonatal Intensive Care Unit admitted 2,400 neonates, one third with a birthweight below 1,501 g; 4,631 cranial ultrasound studies were performed in 1,488 of those neonates, mostly less than 1,501 g, detecting 392 consecutive peri-intraventricular hemorrhages (PIVH), of which 130 were major forms (from unilateral grade III to bilateral grade IV PIVH). Overall survival rates were 91% in grade I, 85% in grade II, 42% in grade III, 26% in grade IV; survival rate was significantly lower in bilateral than in unilateral grade II and III PIVH. In major PIVH, deaths occurred early (58% in the first week after birth). Post-hemorrhagic dilatation was constant but mostly regressive; true active hydrocephalus appeared in 1 unilateral grade III PIVH and 8 bilateral grade III PIVH, with ventriculo-peritoneal shunt in the second month of life in 5 infants (2 died), and 4 deaths (surgery not feasible). The neurological and developmental outcome of 42 of 46 survivors (4 losts to follow-up) was evaluated beyond one year of age in 12 unilateral grade III PIVH (10 normal children, 1 minor sequela, 1 moderate sequela), 16 bilateral grade III PIVH (7 normal children, 3 minor sequelae, 1 moderate sequela, 5 major sequelae), 13 unilateral grade IV PIVH (8 normal children, 1 minor sequela, 3 moderate sequelae, 1 major sequela), 1 bilateral grade IV PIVH (major sequela). A persistent major dilatation after 6-9 months of age bore an ominous prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-infectious bronchiolitis obliterans: clinical, radiological and pulmonary function sequelae

Background. There are few data on clinical, chest radiograph (CXR) or pulmonary function sequelae in children with post-infectious bronchiolitis obliterans (BO) (pulmonary crepitations, abnormalities on CXR, CT, nuclear medicine scans, or bronchography, with a history of past pulmonary infection and in the absence of other underlying pathology). Objective. To analyse the methodology of diagnosis, long-term clinical imaging and pulmonary function sequelae of post-infectious BO in children. Materials and methods. Imaging (CXRs, CT and nuclear lung scans) and clinical histories of 19 children were analysed. Results. Clinical follow-up (mean 6.8 years), revealed a high incidence of continuing problems (asthma and bronchiectasis). Fixed airway obstruction was the most common pulmonary function sequela. The sequelae on follow-up (mean 5.8 years) CXR were classified into five patterns which are illustrated: unilateral hyperlucency of an enlarged lung/part of lung; complete collapse of the affected lobe; unilateral hyperlucency of a small or normal-sized lung; bilateral hyperlucent lungs and a mixed pattern of persistent collapse, hyperlucency and peribronchial thickening. Conclusion. Long-term observations in children with post-infectious BO should be undertaken to detect bronchiectasis and obstructive airway disease. Sequelae evident on CXR, other than those previously described, can be found. Bronchography and/or lung biopsy are not usually required for the diagnosis of post-infectious BO. Received: 15 January 1997 Accepted: 23 June 1997     

Long-term complications in survivors of advanced stage neuroblastoma

BACKGROUND: Few studies have assessed late effects in neuroblastoma (NB) survivors, particularly those with advanced stage disease. METHODS: Retrospective analysis of a cohort of advanced stage NB survivors followed in a late effect clinic at a single institution. Screening tests to detect late effects were tailored depending on the individual's treatment exposures. RESULTS: The study included 63 survivors (31 males). The median age at diagnosis was 3.0 years. The median follow-up from diagnosis was 7.06 years. All patients had surgery and received chemotherapy, 89% received radiation therapy (RT), 62% immunotherapy, and 56% autologous stem cell transplant. Late complications were detected in 95% of survivors and included: hearing loss (62%), primary hypothyroidism (24%), ovarian failure (41% of females), musculoskeletal (19%), and pulmonary (19%) abnormalities. The majority of complications were moderate, with only 4% being life-threatening. Survivors who received cisplatin were at greater risk to develop hearing loss compared to those not so treated (OR 9.74; 95% CI: 0.9-101.6). A total dose of cyclophosphamide greater than 7.4 g was associated with ovarian failure (P = 0.02). CONCLUSIONS: Late complications occur frequently in survivors of advanced stage NB. The majority of these problems are of mild-moderate severity. Long-term follow-up (LFTU) and screening of this population is essential.     

儿童肺炎链球菌脑膜炎临床特征及药物敏感性单中心临床研究

目的:了解儿童肺炎链球菌脑膜炎(PM)的临床特点、细菌耐药情况及部分菌株的血清型情况。方法:回顾性分析2012年1月至2017年12月首都医科大学附属北京儿童医院住院PM患儿72例的临床资料、随访结果、分离菌株药物敏感性及血清型分型结果,分析PM死亡的危险因素。结果:72例患儿中男46例,女26例;年龄1个月~9岁;住院天数1~363 d,中位数22.0 d。社区获得性感染71例(98.6%)。有明确基础疾病患儿28例(38.9%),其中前3位为脑脊液鼻漏(6例)、头外伤(4例)和免疫缺陷病(4例)。临床症状以发热为最常见(72例,100.0%),其次为精神萎靡(60例,83.3%)、意识改变(46例,63.9%)、呕吐(45例,62.5%)、抽搐(42例,58.3%)、前囟张力增高(27例,37.5%)及头痛(17例,23.6%)等。神经系统并发症44例(61.1%),以硬膜下积液最多见[29例(40.3%)]。再发细菌性脑膜炎2例,均为反复肺炎链球菌感染。脑膜炎和脑膜脑炎占比分别为43.1%(31/72例)和56.9%(41/72例)。脑膜炎菌株对青霉素的不敏感率为74.3%,对红霉素、克林霉素、四环素的耐药率分别为95.7%、95.7%、89.1%;对左氧氟沙星、万古霉素、利奈唑胺均敏感。24例(33.3%)患儿有菌株分型结果,其中19F型8株(33.4%),14型5株,23F型4株,6A型3株,19A型2株,1型和15B型各1株。13价肺炎链球菌结合疫苗(PCV13)覆盖率达95.8%(23/24株)。随访72例,其中好转51例,死亡21例(病死率为29.2%),遗留后遗症患儿21例(29.2%)。多变量Logistic回归分析显示,呼吸衰竭和外周血白细胞数<4×10^9/L为PM患儿死亡的独立危险因素(均P<0.05)。结论:本中心儿童PM病例多发生于5岁以下,脑脊液鼻漏、头外伤和免疫缺陷病是儿童PM常见的基础疾病,病程中有呼吸衰竭或外周血白细胞数减少者可能提示预后不良。     

The future of children cured of cancer: later morbidity

The 476 children treated for solid malignant tumor from 1947 to 1968 at the Institut Gustave-Roussy, and living NED at 5 years, were reviewed after 5 to 36 years of follow-up (median 17 years). Two children were affected in the sibship in 9 families. Thirty patients died after 7 to 32 years, 15 from late evolution of their primary tumor, 7 from second cancer, and 8 from other causes. Late sequellae (3 lethal), mainly neurologic, orthopedic, endocrine, and others were observed in 271 patients, and not known in 48. A second tumor (19 malignant, 46 benign) occurred from 7 to 26 years after treatment, more than half in the previously irradiated area. These patients have presently 164 known children; two died in infancy, two have malformations. None has had tumor up until now. The long-term cure of cancer remains true in 95% of cases in our span of follow-up, with sequellae compatible with a useful life in most cases.     

Long-term follow-up of Langerhans cell histiocytosis: 39 years' experience at a single centre

AIM: To evaluate the long-term outcome of Langerhans cell histiocytosis (LCH) in children. METHODS: We re-evaluated all children (<15 y old at diagnosis) treated at our unit in 1962-1989. Histopathology specimens were reviewed and verified for 49 patients. Forty patients underwent physical examination and laboratory tests, and 38 were subjected to imaging, at a median time of 16 y (range 5.5-33.5) after diagnosis. RESULTS: Altogether, 5/49 (10%) children died, all with multi-system disease and age <2 y at diagnosis. Age at diagnosis (p=0.001) and survival (p=0.014) for the 22 children with multi-system disease was significantly lower compared with the 27 children with single-system disease. The term "maximal extent of disease" was introduced since reactivation of LCH often tends to involve additional organs not previously affected by the disease. At follow-up, late sequelae had developed in 17/40 (42%) patients, including diabetes insipidus in 6/40 (15%), CNS complications in at least 4/40 (10%) (3/16, 19%, of multi-system patients) and late-stage pulmonary disease in 4/38 (11%). Seven out of 21 (33%) of the patients with multi-system disease were alive and healthy without sequelae at follow-up, as compared to 16/24 (67%) of those with single-system disease (p=0.026). Of 14 individuals 25 y at follow-up, senior high school had been completed in 7/9 (78%) with single-system and 1/5 (20%) with multi-system disease (at maximal disease extent) (p=0.091). CONCLUSION: Multi-system LCH is associated not only with increased mortality but also pronounced propensity for severe late sequelae; 51% of the patients (multi-system=33%, single-system=67%) were alive without sequelae at follow-up. Among multi-system patients, at least 19% suffered CNS sequelae.     

Clinico-laboratory profile and outcome of Japanese encephalitis in Nepali children

BACKGROUND: Japanese encephalitis (JE) is associated with high mortality and neurological sequelae. The unpredictable course and lack of specific treatment pose major challenges in management. The tropical climate and paddy ecosystem in Nepal provide a suitable setting. AIMS: To determine the aetiology of febrile encephalopathy and describe the clinico-laboratory profile and outcome of JE in Nepali children. METHODS: A hospital-based prospective and observational study was conducted over a 1-year period (2000-2001). Children aged from >1 month to 14 years with fever >38 degrees C for <2 weeks and altered sensorium were recruited. JE was confirmed by anti-JE IgM in cerebrospinal fluid and/or serum. RESULTS: Of 117 consecutively enrolled patients, 58 had JE. Ten patients had concomitant infections, four with malaria and six with bacterial meningitis, and were excluded from analysis. Clinical findings were as follows: boys, 69%; age 4-14 years, 71%; presentation during summer and autumn, 83%; fever >3 days, 69%; altered sensorium <2 days, 50%; Glasgow coma score 8-12, 63%; seizures, 58%. Four (8.3%) died. At discharge, neurological sequelae were detected in 24 (50%) and hemiparesis was the most common form. Longer duration of vomiting, altered sensorium and focal neurological deficit on admission were independently associated with sequelae at discharge. Sequelae persisted in nine (18.8%) at 6 weeks follow-up. Long duration of altered sensorium (beta co-efficient 0.35, odds ratio 1.4, p=0.042) and presence of focal neurological deficit on admission (beta co-efficient 1.6, odds ratio 5.2, p=0.049) were independent predictors of sequelae at 6 weeks. CONCLUSION: JE was the commonest cause of febrile encephalopathy. Neurological sequelae were common but resolved in two-thirds of cases.     

The burden of pneumococcal meningitis in Austrian children between 2001 and 2008

The present study was conducted to evaluate the burden of pneumococcal meningitis in Austrian children between 2001 and 2008. Clinical outcome was retrospectively analyzed both on discharge and on follow-up investigations. This study was based on a prospective multicentre surveillance study on hospitalized invasive pneumococcal infections in Austrian children with a total annual “study population” of about 399,000 children aged below 5 years per year. Between 2001 and 2008, 74 cases of pneumococcal meningitis were identified in children aged below 5 years. The mean annual incidence rate for pneumococcal meningitis was 2.3 per 100,000 children in this age group. In 57/74 children (mean age on admission 14.5?±?13.3 months), outcome data on hospital discharge were available: 5 deaths (8.8 %), 20 children (35.1 %) with sequelae and 32 children (56.1 %) without sequelae were observed. Sequelae on discharge included motor impairment in 8 children (14.0 %), hearing impairment in 9 children (15.8 %) and/or other complications in 14 children (24.6 %). In 7/8 children with motor deficits, matching cerebral lesions were identified by neuroimaging: cerebral infarction in five children, cerebral vasculitis and cerebral abscess in one child each. In 40/57 children, long-term outcome (18.9?±?20.2 months after discharge) could be assessed: 1 child (2.5 %) died 9 months after hospital discharge, 11 children (27.5 %) had one or two long-term sequelae and 28 children (70.0 %) had no sequelae. Long-term sequelae included motor impairment in three children (7.5 %), hearing impairment in nine children (22.5 %) and other deficits in two children (5.0 %). Conclusion: Our study confirms that pneumococcal meningitis causes high mortality and severe long-term sequelae. On long-term follow-up, we observed improvements of motor impairment, but not of hearing impairment.