Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy

Posttraumatic seizures develop in up to 20% of children following severe traumatic brain injury (TBI). Children ages 6–17 years with one or more risk factors for the development of posttraumatic epilepsy, including presence of intracranial hemorrhage, depressed skull fracture, penetrating injury, or occurrence of posttraumatic seizure were recruited into this phase II study. Treatment subjects received levetiracetam 55 mg/kg/day, b.i.d., for 30 days, starting within 8 h postinjury. The recruitment goal was 20 treated patients. Twenty patients who presented within 8–24 h post‐TBI and otherwise met eligibility criteria were recruited for observation. Follow‐up was for 2 years. Forty‐five patients screened within 8 h of head injury met eligibility criteria and 20 were recruited into the treatment arm. The most common risk factor present for pediatric inclusion following TBI was an immediate seizure. Medication compliance was 95%. No patients died; 19 of 20 treatment patients were retained and one observation patient was lost to follow‐up. The most common severe adverse events in treatment subjects were headache, fatigue, drowsiness, and irritability. There was no higher incidence of infection, mood changes, or behavior problems among treatment subjects compared to observation subjects. Only 1 (2.5%) of 40 subjects developed posttraumatic epilepsy (defined as seizures >7 days after trauma). This study demonstrates the feasibility of a pediatric posttraumatic epilepsy prevention study in an at‐risk traumatic brain injury population. Levetiracetam was safe and well tolerated in this population. This study sets the stage for implementation of a prospective study to prevent posttraumatic epilepsy in an at‐risk population.     

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

Background

Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients.

Methods

We examined seven patients with treatment-refractory C4d + AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and anti-metabolite. Estimated glomerular filtration rate (eGFR) calculated by the Schwartz equation, biopsy findings assessed by 2013 Banff criteria, and human leukocyte antigen (HLA) donor-specific antibodies (DSA) performed using the Luminex single antigen bead assay were monitored pre- and post- bortezomib therapy.

Results

Seven patients (86 % male, 86 % with ≥6/8 HLA mismatch, and 14 % with pre-formed DSA) age 5 to 19 (median 15) years developed refractory C4d + AMR between 1 and 145 (median 65) months post-transplantation. All patients tolerated bortezomib. One patient had allograft loss. Of the six patients with surviving grafts (86 %), mean pre-bortezomib eGFR was 42 ml/min/1.73 m² and the mean 1 year post-bortezomib eGFR was 53 ml/min/1.73 m². Five of seven (71 %) had improvement of histological findings of AMR, C4d staining, and/or acute cellular rejection. Reduction in HLA DSAs was more effective for class I than class II.

Conclusions

Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric kidney transplant patients with refractory C4d + AMR.

     

Structural and Socio-cultural Barriers to Prenatal Care in a US Marshallese Community

Objectives Pacific Islanders are disproportionately burdened by poorer perinatal health outcomes with higher rates of pre-term births, low birth weight babies, infant mortality, and inadequate or no prenatal care. The aim of this study is to examine Marshallese mothers’ beliefs, perceptions, and experiences of prenatal care and to identify potential barriers. Methods Three focus groups were conducted with Marshallese mothers, who were 18 years or older, and living in Arkansas. Focus groups focused on mothers’ beliefs, perceptions, and experiences of prenatal care. A thematic qualitative analysis was conducted to identify salient themes within the data. Results The results demonstrated that negotiating health insurance, transportation, and language barriers were all major structural barriers that constrain prenatal care. The social–cultural barriers that emerged included a lack of understanding of the importance of seeking early and consistent prenatal care, as well as how to navigate the healthcare process. The more complicated challenges that emerged were the feelings of shame and embarrassment due to the perception of their age or being unmarried during pregnancy not being acceptable in American culture. Furthermore, the participants described perceived discrimination from prenatal care providers. Lastly, the participants described fear as a barrier to seeking out prenatal care. Conclusions for Practice This study identified both structural and socio-cultural barriers that can be incorporated into suggestions for policy makers to aid in alleviating maternal health disparities among Pacific Islander women. Further research is needed to address the Marshallese mothers’ perceived discrimination from maternal health care providers.     

Management of recurrent rectal prolapse

PURPOSE: Many operations have been described for the management of rectal prolapse. Despite an overall recurrence rate of greater than 15 percent, few reviews address how to deal with this problem. This report summarizes our experience with recurrent rectal prolapse and includes suggestions for reoperative management of failed repairs from both abdominal and perineal approaches. PATIENTS AND METHODS: Fourteen patients (3 male) ranging in age from 22 to 92 (mean, 68) years underwent operative correction of recurrent rectal prolapse. Average time from initial operation to recurrence was 14 (range, 6–60) months. Initial operations (before recurrence) were as follows: perineal proctectomy and levatorplasty (10), anal encirclement (2), Delorme's procedure (1), and anterior resection (1). Operative procedures performed for recurrence were as follows: perineal proctectomy and levatorplasty (7), sacral rectopexy (abdominal approach; 3), anterior resection with rectopexy (2), Delorme's procedure (1), and anal encirclement (1). Average length of follow-up was 50 (range, 9–115) months. RESULTS: No further episodes of complete rectal prolapse were observed during this period. Preoperatively, three patients were noted to be incontinent to the extent that necessitated the use of perineal pads. The reoperative procedures failed to restore fecal continence in any of these three individuals. One patient died in the postoperative period after anal encirclement from an unrelated cause. CONCLUSION: Surgical management of recurrent rectal prolapse can be expected to alleviate the prolapse, but not necessarily fecal incontinence. Perineal proctectomies can be safely repeated. Resectional procedures may result in an ischemic segment between two anastomoses, unless the surgeon can resect a previous anastomosis in the repeat procedure. Nonresectional procedures such as the Delorme's procedure should be strongly considered in the management of recurrent rectal prolapse if a resectional procedure was performed initially and failed.     

Human spleen cell generation of factors stimulating human pluripotent stem cell, erythroid, and myeloid progenitor cell growth

Mitogen-stimulated murine spleen cells produce humoral substances capable of supporting murine hematopoiesis and pluripotent stem cell proliferation in vitro. Thus, we evaluated conditioned media generated by human spleen cells (SCM) in the presence or absence of mitogens for factors stimulatory for human pluripotent (CFU-GEMM), erythroid (BFU- E), and myeloid (CFU-GM) precursors. Two and one half percent to 10% SCM stimulated proliferation of all three types of precursor cells from nonadherent buoyant human marrow target cells. Mitogen-stimulated SCM augmented CFU-GM (175% to 225%), whereas CFU-GEMM and BFU-E growth was essentially unchanged. Cell separation procedures used to determine which cells provided these microenvironmental stimuli indicated that nonadherent mononuclear spleen cells provided the bulk of the CSF-GM, whereas adherent cells (95% nonspecific esterase + monocyte- macrophages) and nonadherent cells provided similar proportions of CSF- mix and erythroid burst-promoting activity (BPA). The nonadherent cells generating high levels of CSF-mix, BPA, and CSF-GM were predominantly Leu-1-negative, ie, non-T, cells. In the presence or absence of mitogens, SCM was a more potent source (1.3- to 3.8-fold) than peripheral leukocyte CM of the growth factors for the three progenitor cell types. Specific in situ cytochemical stains for analyzing morphology of myeloid colonies demonstrated that SCM stimulated the proliferation of the same types and proportions of colonies as human placental CM, suggesting that these CMs may contain similar CSF-GMs. These data show the contribution of spleen cell subsets to the generation of hematopoietic growth factors and the responsiveness of these cells to various mitogenic stimuli.     

Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism

We hypothesized that blood levels of γ-aminobutyric acid (GABA) and γ-hydroxybutyric acid (GHB), biomarkers of succinic semialdehyde dehydrogenase deficiency (SSADHD), would correlate with age. GABA and GHB were quantified in plasma and red blood cells (RBCs) from 18 patients (age range 5–41 years; median 8). Both metabolites negatively correlated with age (P?<?0.05). Plasma and RBC GHB declined with age, reaching a nadir and approximate steady state by 10 years. Declining plasma GABA achieved this approximate steady state at 30–40 years of age. These biomarker relationships may reflect further GABA- and GHB-ergic neurotransmission imbalances that correlate with the onset of adolescent/adulthood neuropsychiatric morbidity and epilepsy in SSADHD.