Therapeutic plasma exchange for fulminant hepatic failure secondary to Wilson's disease

Wilson's disease (WD) is an autosomal‐recessive disorder of impaired copper metabolism resulting in accumulation of copper primarily in the liver but ultimately in many organs and tissues. A small number of patients with WD initially present with fulminant hepatic failure (FHF), hypercupremia, and intravascular hemolysis. The therapeutic goals for these patients include quickly removing the copper and preparing the patient for liver transplantation. Here, we report on a 6‐year‐old male with WD in FHF with anemia, renal insufficiency, and coagulopathy. The patient received a series of therapeutic plasma exchanges (TPE) as adjunctive therapy to remove copper and stabilize his coagulopathy and anemia until a transplant was possible. A total of five single plasma volume (1500 mL) TPE were performed over the course of 11 days with plasma as the replacement fluid. Laboratory results demonstrated temporary improvement after each procedure. Liver transplantation was performed 12 days after beginning TPE and 35 days after admission to the hospital. TPE was a successful adjunctive therapy to bridge this patient with WD to transplantation. J. Clin. Apheresis 27:282–286, 2012. © 2012 Wiley Periodicals, Inc.     

The Financial Impact of a Hospital-Based Care Coordination Program for Children With Special Health Care Needs

Care coordination programs are important in caring for medically complex pediatric patients, particularly for children with special health care needs. This study is a retrospective financial analysis of a hospital-based care coordination program involving one procedural subgroup of children with special health care needs: those receiving pediatric tracheostomy. Hospital records were reviewed for patients who received a tracheostomy at a large Midwestern U.S. hospital from 1999 through 2015. The population was divided into two subgroups: patients who received a tracheostomy before the development of a care coordination program and patients who received a tracheostomy after enrollment in the care coordination program. Patient records were reviewed for length of stay, readmissions related to respiratory and tracheostomy management, and total hospital charges. Enrollment in a care coordination program for the pediatric tracheostomy patient resulted in a decrease in mean length of stay and reduced hospital charges and a slight increase in readmissions. Further analysis using larger sample sizes and multiple centers is necessary to determine whether such outcomes are the direct result of enrollment in a care coordination program.     

PDE5 inhibitors enhance the lethality of standard of care chemotherapy in pediatric CNS tumor cells

We determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with clinically relevant chemotherapies to kill medulloblastoma cells. In medulloblastoma cells PDE5 inhibitors interacted in a greater than additive fashion with vincristine/etoposide/cisplatin to cause cell death. Knockdown of PDE5 expression recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy drugs. Expression of dominant negative caspase 9 did not significantly inhibit chemotherapy lethality but did significantly reduce enhanced killing in combination with the PDE5 inhibitor sildenafil. Overexpression of BCL-XL and c-FLIP-s suppressed individual and combination drug toxicities. Knockdown of CD95 or FADD suppressed drug combination toxicity. Treatment with PDE5 inhibitors and chemotherapy drugs promoted autophagy which was maximal at ~12 h post-treatment, and in a cell type-dependent manner knockdown of Beclin1 or ATG5 either suppressed or enhanced drug combination lethality. PDE5 inhibitors enhanced the induction of chemotherapy-induced DNA damage in a nitric oxide synthase-dependent fashion. In conclusion, our data demonstrate that the combination of PDE5 inhibitors with standard of care chemotherapy agents for medulloblastoma represents a possible novel modality for future treatment of this disease.     

Effect of finish line design on stress distribution in bilayer and monolithic zirconia crowns: a three‐dimensional finite element analysis study

This study evaluated the influence of different finish line designs and abutment materials on the stress distribution of bilayer and monolithic zirconia crowns using three‐dimensional finite element analysis (FEA). Three‐dimensional models of two types of zirconia premolars – a yttria‐stabilized zirconia framework with veneering ceramic and a monolithic zirconia ceramic – were used in the analysis. Cylindrical models with the finish line design of the crown abutments were prepared with three types of margin curvature radius (CR): CR = 0 (CR0; shoulder margin), CR = 0.5 (CR0.5; rounded shoulder margin), and CR = 1.0 (CR1.0; deep chamfer margin). Two abutment materials (dentin and brass) were analyzed. In the FEA model, 1 N was loaded perpendicular to the occlusal surface at the center of the crown, and linear static analysis was performed. For all crowns, stress was localized to the occlusal loading area as well as to the axial walls of the proximal region. The lowest maximum principal stress values were observed when the dentin abutment with CR0.5 was used under a monolithic zirconia crown. These results suggest that the rounded shoulder margin and deep chamfer margin, in combination with a monolithic zirconia crown, potentially have optimal geometry to minimize occlusal stress.     

Occupational Risk Factors for Breast Cancer among Nurses

Abstract

A case-referent study nested in a cohort was used to evaluate occupational variables in the incidence of breast cancer among nurses. There were 59 cases and 118 randomly chosen referents. The participation rate was 97%. Odds ratios (ORs) and 95% confidence intervals (Cls) were calculated and the weights of potential confounding factors estimated by unconditional logistic regression. The odds ratio for breast cancer in a sister was 2.83 (95% CI 1.03–7.81). Specialization in pediatric, psychiatric, general (surgical and medical), geriatric, and primary care nursing, and “other kinds of nursing,” gave an adjusted OR of 1.95 (95% CI 0.84–4.54). When working in different wards was accounted for, the highest adjusted ORs were found among nurses handling cytotoxic drugs, OR 1.65 (95% CI 0.53–5.17), and among pediatric nurses, OR 1.47 (95% CI 0.63–3.41); the lowest ORs were found among nurses in primary health care, OR 0.44 (95% CI 0.20–0.96). Analyses of the data stratified on age showed similar results. Occupational risks were not ascertained. Not only occupation but also career-related lifestyles should be taken into account in studies of health outcomes among working women.     

Acute Invasive Fungal Rhinosinusitis in Children With Hematologic Malignancies: Outcome of Surgical Treatment

The incidence of acute invasive fungal rhinosinusitis (AIFR) is rising due to more aggressive chemotherapy and longer survival of immunosuppressed patients. Early diagnosis and appropriate but nonmutilating surgical treatment are particularly problematic in the pediatric population. This study aimed to evaluate the outcome of surgery for pediatric AIFR. Medical records of children surgically treated for AIFR between 1998 and 2014 were reviewed. Diagnosis was based on both histopathological and microbiological confirmation. Surgery was performed with curative intent and repeated for any resectable extension. The children underwent endoscopy and magnetic resonance imaging every 2 and 6 months, respectively, during the first postoperative year. Thirteen patients (2–18 years old) met the EORTC/MSG criteria for proven invasive fungal sinusitis; fungal invasion was diagnosed by preoperative biopsy and confirmed in the surgical specimen. All patients underwent an average of two endoscopic procedures (range 1–3), and four of them also underwent an open surgery. The local control rate was at least 79%. There was no facial disfiguration during follow-up (average 41 months). Although AIFR is still associated with high mortality, aggressive medical and surgical treatment provides local control in most cases. Fair outcome should encourage a maximal joint effort of pediatric hemato-oncologists and otorhinolaryngologists in the management of AIFR.     

The role of CDKN2A/B deletions in pediatric acute lymphoblastic leukemia

The CDKN2A/B genes in the 9p21 chromosomal region are frequently involved in human cancer, including pediatric acute lymphoblastic leukemia (ALL). These genes encode 3 proteins that belong to the RB1 and TP53 pathways and act as tumor suppressors by regulating the G1/S checkpoint of the cell cycle. The prognostic value of deletions in the CDKN2A/B locus in ALL is controversial in part due to the limitations of the methodologies used. Further studies with advanced technologies are needed for elucidation. Future studies would also highlight whether CDK4/CDK6 selective inhibitors might be useful therapies for children with these genetic aberrations.