Once-daily Compared With Twice-daily Enoxaparin Maintenance Therapy Appears Safe and Efficacious in Pediatric Venous Thromboembolism.

INTRODUCTION: Once-daily enoxaparin (ODE), considered standard of care for venous thromboembolism (VTE) treatment in adults, has been infrequently assessed in children. To contribute available data to a limited field, we reviewed our center's experience with ODE in treating pediatric VTE compared with twice-daily enoxaparin (TDE). MATERIALS AND METHODS: A retrospective analysis of children and adolescents 18 years of age or below diagnosed with VTE and treated at our institution with ODE or TDE maintenance therapy between April 2015 and December 2020 was performed. Patient demographics, clinical and laboratory data pertaining to VTE diagnosis, and management were gathered from electronic medical records and compared between the 2 cohorts. RESULTS: Seventy-one children met the eligibility criteria. All patients were initially treated with TDE for 2 weeks before transitioning to ODE maintenance therapy (n=39; 55%) or continuing with TDE dosing (n=32; 45%).Extremity VTE was more common in ODE ( P =0.051) versus pulmonary/intracardiac sites in TDE ( P =0.002) when compared with other sites. Median enoxaparin dosing was 1.5 and 1.1 mg/kg/dose in ODE and TDE cohorts, respectively. Bleeding episodes were rare without any difference between the cohorts. Two patients (6%) were lost to follow up in TDE cohort. All evaluable patients in both cohorts had either complete/partial response (ODE n=35 [90%]; TDE n=24 [75%] or stable thrombus ODE n=4 [10%]; TDE n=6 [19%]). CONCLUSIONS: Our results indicate that ODE, used after the initial TDE treatment period, is as safe and efficacious as TDE maintenance for the treatment of pediatric VTE. The difference in VTE sites may have contributed to the equal efficacy of both the cohorts. Future prospective studies in pediatric VTE are needed to validate these results.

Non-myeloablative umbilical cord blood transplantation for atypical dyskeratosis congenita.

BACKGROUND: Short telomere syndrome (STS) in children may result in phenotypically heterogenous clinical spectrum ranging from completely asymptomatic to typical dyskeratosis congenita (DC). Patients with this cancer predisposition syndrome may have multiple organ dysfunctions including pulmonary fibrosis, liver cirrhosis, and bone marrow failure. Not all mutations in telomerase or telomere genes have been identified, and STS may pose a diagnostic and management challenge. METHODS: A retrospective chart review and literature search were done for this report. RESULTS: Here, we report a case of atypical DC with a heterozygous germline missense mutation in the postmeiotic segregation increased 2 (PMS2) gene, exon 5, (c.466A>G (p. Thr156Ala)). The PMS2 (a mismatch repair protein) gene is known to be an important mediator of telomere-induced aging. The patient was transfusion dependent and underwent successful umbilical cord blood transplant using a non-myeloablative regimen with alemtuzumab, fludarabine, cyclophosphamide, and total body irradiation. CONCLUSION: In this case of atypical DC with a previously unreported germline missense mutation in PMS2, the patient was successfully treated with an umbilical cord blood transplant with a non-myeloablative regimen.

Pediatric Deep Venous Thrombosis Associated With Staphylococcal Infections: Single Institutional Experience.

Deep venous thrombosis (DVT) has been previously reported in children with methicillin-resistant Staphylococcus aureus (MRSA). This study reviews our institutional experience by evaluating characteristics and outcomes of children with DVT and staphylococcal infections. Retrospective clinical data from 16 pediatric patients with DVT and staphylococcal infections over a 5-year period was obtained via medical record abstraction. Sixteen patients with a median age at diagnosis of 8 years were included. The most common infection encountered was osteomyelitis (56%). The most common isolated organism was MRSA (63%). Central venous catheters were present in 50% of cases. All patients received anticoagulation with low molecular weight heparin except 1 patient with superficial venous thrombosis who was managed conservatively. Fifty percent of patients had complete resolution of DVT by the end of treatment, 25% of the patients had early disappearance of the thrombus at 7 to 10 days. Only 2 patients (12.5%) had persistent thrombus at 6 months. Staphylococcal infections may increase the risk of DVT in children. Therefore, a high index of suspicion for DVT is warranted in children with Staphylococcal infections (particularly MRSA) to promptly diagnose, treat and minimize complications. Prophylactic anticoagulation in presence of staphylococcal infection, particularly MRSA, may be considered in future studies.

COX-2 expression correlates with survival in patients with osteosarcoma lung metastases.

SUMMARY: The purpose of this study was to determine whether a correlation exists between tumor cyclooxygenase (COX)-2 expression and disease-specific survival in patients with osteosarcoma lung metastases. Thirty-six patients diagnosed with osteosarcoma lung metastases between the years 1990 and 2001 were included in this retrospective study. The majority of the patients (72%) presented newly -diagnosed osteosarcoma lung metastases whereas the remaining patients (28%) presented recurrent disease. Clinicopathologic parameters were obtained from patients' clinical records. Tissue samples were obtained at the time of resection of the lung metastases and stained for COX-2 using immunohistochemistry. Samples were graded according to the intensity of COX-2 staining (grade 0: negative, grade 1: very weak, grade 2: weak, grade 3: moderate, and grade 4: strong). COX-2 staining was correlated with disease-specific survival and clinicopathologic parameters using the Jonckheere-Terpstra and the Kruskal-Wallis tests. All patients with grade 3 or 4 COX-2 expression died of osteosarcoma lung metastases. Ten percent of patients with grade 2 COX-2 expression and 29% of patients with grade 1 expression were alive and free of disease at the last follow-up. By contrast, 60% of the patients with grade 0 COX-2 expression were alive and free of disease at the last follow-up. No association between COX-2 expression and clinicopathologic parameters was found. However, COX-2 expression correlated inversely with disease-specific survival in patients with osteosarcoma lung metastases. Our data indicate that COX-2 expression in metastatic osteosarcoma may have prognostic significance.

Advances in hemophilia: experimental aspects and therapy.

This article describes recent clinical and research advances in hemophilia therapy. Different prophylactic regimens for the management of severe hemophilia are described along with the use of adjuvant treatment options to achieve hemostasis. The safety and efficacy of radionuclide synovectomy with phosphorus 32-sulfur colloid to treat existing joint arthropathy also are described. The development of inhibitors to factor VIII or IX remains a challenge for hemophilia care and recent approaches to achieve immune tolerance induction are discussed. Finally, recent advances in hemophilia are mentioned, including the role of iron, inflammation, and angiogenesis in the pathogenesis of hemophilic arthopathy.

Cerebral sinovenous thrombosis associated with iron deficiency anemia secondary to severe menorrhagia: a case report.

Cerebral sinovenous thrombosis is a rare condition presenting with a wide spectrum of nonspecific symptoms that can make early diagnosis difficult. Cerebral sinovenous thrombosis has been associated with various etiologies. Iron deficiency anemia associated with cerebral sinovenous thrombosis in teenagers is rare. We present a teenage patient with complete thrombosis of the vein of Galen, straight sinus, and left internal cerebral vein associated with iron deficiency anemia due to severe menorrhagia. Mechanisms that can explain the association between iron deficiency anemia and thrombosis are discussed.

Multiple Comorbid Conditions among Middle-Aged and Elderly Hemophilia Patients: Prevalence Estimates and Implications for Future Care.

Introduction. Advances in hemophilia care and treatment have led to increases in the life expectancy among hemophiliacs. As a result, persons with hemophilia are reaching an older age and experiencing various age-related health conditions never seen before in this population. Aim. To determine the prevalence of comorbidities among middle-aged and elderly hemophilia A and hemophilia B patients. Methods. Retrospective chart review among all hemophilia patients, who attended the Gulf States Hemophilia and Thrombophilia Center. Results. All patients had at least one comorbid condition other than hemophilia, and the majority had between 3 and 6 comorbidities. The most common conditions identified were chronic hepatitis C, hypertension, HIV, chronic arthropathy, and overweight/obesity. Conclusions. Since persons with comorbidities are more likely to have poorer health outcomes and require greater care in managing their health needs, caring for aging hemophiliacs is likely to pose various social and economic challenges for both patients and providers.

Advances in hemophilia: experimental aspects and therapy.

This article describes recent clinical and research advances in hemophilia therapy. Different prophylactic regimens for the management of severe hemophilia are described along with the use of adjuvant treatment options to achieve hemostasis. The safety and efficacy of radionuclide synovectomy with phosphorus 32-sulfur colloid to treat existing joint arthropathy also are described. The development of inhibitors to factor VIII or IX remains a challenge for hemophilia care and recent approaches to achieve immune tolerance induction are discussed. Finally, recent advances in hemophilia are mentioned, including the role of iron, inflammation, and angiogenesis in the pathogenesis of hemophilic arthropathy.

Expression of granulocyte-colony-stimulating factor and its receptor in human Ewing sarcoma cells and patient tumor specimens: potential consequences of granulocyte-colony-stimulating factor administration.

BACKGROUND: Ewing sarcoma (ES) is a highly vascular malignancy. It has been demonstrated that both angiogenesis and vasculogenesis contribute to the growth of ES tumors. Granulocyte-colony-stimulating factor (G-CSF), a cytokine known to stimulate bone marrow (BM) stem cell production and angiogenesis, is routinely administered to ES patients after chemotherapy. Whether ES cells and patient tumor samples express G-CSF and its receptor (G-CSFR) and whether treatment with this factor enhances tumor growth was examined. METHODS: Human ES cell lines were analyzed for expression of G-CSF and G-CSFR in vitro and in vivo. Sixty-eight paraffin-embedded and 15 frozen tumor specimens from patients with ES were also evaluated for the presence of G-CSF and G-CSFR. The in vivo effect of G-CSF on angiogenesis and BM cell migration was determined. Using a TC/7-1 human ES mouse model, the effect of G-CSF administration on ES tumors was investigated. RESULTS: G-CSF and G-CSFR protein and RNA expression was identified in all ES cell lines and patient samples analyzed. In addition, G-CSF was found to stimulate angiogenesis and BM cell migration in vivo. Tumor growth was found to be significantly increased in mice treated with G-CSF. The average tumor volume for the group treated with G-CSF was 1218 mm(3) compared with 577 mm(3) for the control group (P = .006). CONCLUSIONS: The findings that ES cells and patient tumors expressed both G-CSF and its receptor in vitro and in vivo and that the administration of G-CSF promoted tumor growth in vivo suggest that the potential consequences of G-CSF administration should be investigated further.