Pediatric Primary Health Care: The Central Role of Pediatricians in Maintaining Children's Health in Evolving Health Care Models.

Pediatric primary health care (PPHC) is of principal importance to the health and development of all children, helping them reach their true potential. Pediatricians, as the clinicians most intensively trained and experienced in child health, are the natural leaders of PPHC within the context of the medical home. Given the rapidly evolving models of pediatric health care delivery, including the explosion of telehealth in the wake of the COVID-19 pandemic, pediatricians, together with their representative national organizations such as the American Academy of Pediatrics (AAP), are the most capable clinicians to guide policy innovations on both the local and national stage.

Survival after recurrence of Ewing's sarcoma family of tumors.

PURPOSE: The overall survival (OS) of patients with relapsed Ewing's sarcoma family of tumors (ESFT) is poor, and the relative benefit of high-dose therapy (HDT) is controversial. PATIENTS AND METHODS: We retrospectively identified 55 consecutive ESFT patients with adequate medical records for review, who were treated at Children's Hospital and Regional Medical Center and who developed disease recurrence between January 1, 1985 and December 31, 2002. RESULTS: The median relapse-free interval (RFI) from diagnosis to first recurrence was 17 months (range, 5 to 90 months). Most recurrences were metastatic only (39 patients) or local and metastatic (10 patients). Twenty-seven patients (49%) achieved a partial or complete response to second-line treatment, with a median duration of response of 27 months (range, 5 to 119+ months). The 5-year OS rate for all relapsed patients was 23% (95% CI, 11% to 35%). By univariate analysis, improved OS was associated with response to second-line treatment versus no response (46% v 0%, respectively; P < .0001), RFI > or = 24 months versus less than 24 months (48% v 12%, respectively; P = .0001), and no metastases at initial diagnosis versus presence of metastases (31% v 12%, respectively; P = .05). Because all 13 patients who received HDT also had responsive relapse, we performed a multivariate analysis. Reduced risk of death was associated with response to second-line therapy (relative risk, 0.14; 95% CI, 0.05 to 0.40), RFI > or = 24 months (relative risk, 0.29; 95% CI, 0.13 to 0.66), and receiving HDT (relative risk, 0.26; 95% CI, 0.08 to 0.85). CONCLUSION: HDT as consolidation therapy for relapsed ESFT seems to be associated with improved OS, even after adjusting for RFI and response to second-line treatment.

Congenital amegakaryocytic thrombocytopenia in three siblings: molecular analysis of atypical clinical presentation.

OBJECTIVE: An 11-year-old girl, presenting with fatigue and bruising, was found to be profoundly pancytopenic. Bone marrow exam and clinical evaluation were consistent with aplastic anemia. Family members were studied as potential stem cell donors, revealing that both younger siblings displayed significant thrombocytopenia, whereas both parents had normal blood counts. We evaluated this pedigree to understand the unusually late presentation of congenital amegakaryocytic thrombocytopenia (CAMT). MATERIALS AND METHODS: The coding region and the intron/exon junctions of MPL were sequenced from each family member. Vectors representing each of the mutations were constructed and tested for the ability to support growth of Baf3/Mpl(mutant) cells. RESULTS: All three siblings had elevated thrombopoietin levels. Analysis of genomic DNA demonstrated that each parent had mutations/polymorphisms in a single MPL allele and that each child was a compound heterozygote, having inherited both abnormal alleles. The maternal allele encoded a mutation of the donor splice-junction at the exon-3/intron-3 boundary. A mini-gene construct encoding normal vs mutant versions of the intron-3 donor-site demonstrated that physiologic splicing was significantly reduced in the mutant construct. CONCLUSIONS: Mutations that incompletely eliminate Mpl expression/function may result in delayed diagnosis of CAMT and confusion with aplastic anemia.

Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

PURPOSE: This study was undertaken to determine the effect, if any, on pregnancy loss, live births, and birthweight of treatment for cancer diagnosed during childhood or adolescence. PATIENTS AND METHODS: We reviewed pregnancy outcome among sexually active male Childhood Cancer Survivor Study (CCSS) participants who responded to a questionnaire before February 3, 2000. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered, the cumulative dose of drug administered for several drugs of interest, and the doses, volumes, and dates of administration of all radiotherapy. RESULTS: There were 4,106 sexually active males; 1,227 reported they sired 2,323 pregnancies (69% live births, 1% stillbirths, 13% miscarriages, 13% abortions, 5% unknown or in gestation). The male-to-female ratio of the offspring of the partners of the male survivors was significantly different from that of the offspring of the partners of the male siblings of the survivors (1.0:1.03 v 1.24:1.0) (P =.016). The proportion of pregnancies of the partners of male survivors that ended with a liveborn infant was significantly lower than for the partners of the male siblings of the survivors who were the control group for comparison (relative risk = 0.77, P =.007). There were no significant differences in pregnancy outcome by treatment. CONCLUSION: This large study did not identify adverse pregnancy outcomes for the partners of male survivors treated with most chemotherapeutic agents. The reversal of the sex ratio and the association observed for procarbazine warrant further investigation.

Sex ratios in congenital malformations of the central nervous system.

Malformations of the central nervous system (CNS) are evaluated and treated by pediatric neurosurgeons. There is a spectrum of morphological variations within each type of malformation and with associated features that may determine whether the defect is isolated or part of a syndrome. Alterations in the normal sex ratio have been found in many malformations of the CNS but the reasons for them are usually unclear. It can be reasoned that some CNS malformations would have unusual sex ratios by chance alone. However there are recurrent patterns. When there is a dominance of one sex for a particular malformation, this information can help predict the likelihood of the malformation in a patient and influence diagnostic approaches. The present report provides information on selected CNS malformations that have altered sex ratios.

Tumors and malformations of the caudal spinal axis.

The early development of the neural tube has been well studied in animals and humans. After axial determinants have been accomplished the processes of primary and secondary neurulation take place. Successful completion results in a spinal cord that has arisen from primary neurulation and a lower sacro-coccygeal portion from secondary neurulation. The latter region is the site of numerous skin-covered clinical lesions, which include tumors and malformations. A listing of selected features in 764 cases of skin-covered sacrococcygeal lesions is presented. The manner in which these lesions arise and the potential for genetic factors being responsible is discussed.

Prescription medication use during pregnancy and risk of infant leukemia (United States).

OBJECTIVE: We explored whether maternal medication use during pregnancy may be an important etiologic area for investigation in studies of infant leukemia. METHODS: In this case-control study, associations were explored between specific medications as recorded in the medical records of 243 mothers of infants who were diagnosed with leukemia at < 18 months of age and 393 mothers ol infants without leukemia identified through random digit dialing. Cases included 157 acute lymphoblastic (ALL), 77 acute myeloid (AML), and nine other leukemias. A total of 27 different drugs that were prescribed for at least six women were analyzed. RESULTS: Overall, non-statistically significant negative associations (Odds ratios, OR < 0.5) were observed with amoxicillin, nystatin, clomiphene, levothyroxine, cefaclor, and trimethobenzamide HCL. When cases were restricted to either myeloid or lymphoblastic leukemia, cotrimoxazole was prescribed for five ALL case mothers and no matched controls; no association with cotrimoxazole was observed with AML. CONCLUSIONS: Given the number of comparisons, chance cannot be ruled out for any of the associations found here. However, a strength of this study is the lack of recall bias. The disparate data observed between AML and ALL in some instances may indicate areas of interest; they will be explored further in a case-control study of infant leukemia that is currently underway.

Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

OBJECTIVE: This study was undertaken to determine the effect, if any, of prior treatment with radiation therapy or chemotherapy for cancer diagnosed during childhood or adolescence on pregnancy loss, live births, and birth weight. STUDY DESIGN: We reviewed pregnancy outcome among female participants in the Childhood Cancer Survivor Study (CCSS) who returned a questionnaire. Eligibility for the CCSS included 5-year survivors who were <21 years old at diagnosis and who were diagnosed with an eligible cancer between January 1, 1970, and December 31, 1986, at the 25 participating CCSS institutions. The questionnaire included items regarding attempts to become pregnant, the occurrence of pregnancy, and the outcome of pregnancy (ie, live birth, stillbirth, miscarriage, abortion). Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered, the cumulative dose of drug administered for several drugs of interest, and the doses, anatomic regions, and dates of administration of all radiation therapy. RESULTS: One thousand nine hundred fifteen females reported 4029 pregnancies (63% live births, 1% stillbirths, 15% miscarriages, 17% abortions, 3% unknown or in gestation). There were no significant differences in pregnancy outcome by treatment. A higher, but not statistically significant, risk of miscarriage was present among women whose ovaries were in the radiation therapy field (relative risk [RR] 1.86, P =.14), were near the radiation therapy field (RR 1.64, P =.06), or were shielded (RR 0.90, P =.88). The rate of live birth was not lower for the patients treated with any particular chemotherapeutic agent. The offspring of the patients who received pelvic irradiation were more likely to weigh <2500 g at birth (RR 1.84, P =.03). CONCLUSIONS: This large study did not identify adverse pregnancy outcomes for female survivors treated with most chemotherapeutic agents. The offspring of women who received pelvic irradiation are at risk for low birth weight.

Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic sarcomas.

BACKGROUND: To increase the dose intensity (DI) of chemotherapy for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen supported by granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cells (PBSC). METHODS: Twenty-three children and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2) on Day 0, doxorubicin 37.5 mg/m(2) per day on Days 0-1, cyclophosphamide 360 mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4, mesna 2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4. Doxorubicin was omitted in Courses 7 and 8. G-CSF was given after each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery permitted. PBSC were collected twice: first, after Course 2 (infused after Courses 3 and 4) and, second, after Course 4 (infused after Courses 5 and 6). Surgical resection followed Course 6, and radiotherapy followed Course 8. RESULTS: PBSC collections were adequate in 91% of all harvests. The mean DI was 82% (standard deviation, 14%) of the intended DI, which was greater than historic data without PBSC support. Seventeen patients (74%) achieved a complete response (CR), 12 patients with chemotherapy alone and 5 more patients after undergoing surgical resection. Fifteen patients developed progressive disease, with a 2-year event free survival (EFS) rate of 39% (95% confidence interval, 19-59%). Hematopoietic toxicity was severe and cumulative, although it was less than that seen previously without PBSC support. CONCLUSIONS: PBSC-supported multicycle chemotherapy is a feasible method to increase chemotherapy DI for pediatric patients with metastatic sarcomas. Although the CR rate compared favorably with previously reported response rates, the 2-year EFS rate was similar to that achieved with other intensive regimens.