Follow-up of newborns treated with extracorporeal membrane oxygenation: a nationwide evaluation at 5 years of age

Introduction  

Extracorporeal membrane oxygenation (ECMO) is a supportive cardiopulmonary bypass technique for babies with acute reversible cardiorespiratory failure. We assessed morbidity in ECMO survivors at the age of five years, when they start primary school and major decisions for their school careers must be made.     

Folic acid supplementation: The new dawn for postmenopausal women with hot flushes

Hot flushes, experienced by 75% of menopausal women, are associated with estrogen deprivation. Estrogen was shown to ameliorate hot flushes by interacting with monoamine neurotransmitters in the brain; reducing noradrenaline and increasing serotonin. Hormone replacement therapy (HRT), the first treatment option, causes concerns over possible increased risks particularly breast cancer. Folic acid is involved in the biosynthesis of serotonin and nordrenaline, which is responsible for its effects on mood and cognition, and degrees of folate inadequacy, not severe enough to produce megaloblastic anaemia, were found to be associated with depression and cognitive malfunctioning. Also, increased age was observed to relate to reduced serum and cerebrospinal fluid folic acid levels. There is emerging evidence that folic acid supplementation ameliorates hot flushes by the same mechanism as estrogen. To explore this hypothesis, a multi-centre, double-blind, placebo-controlled randomized is being set up to compare the effect of 5 mg folic acid vs placebo in reducing the frequency and severity of hot flushes in postmenopausal women, and on the blood level of serotonin and noradrenaline. If folic acid supplementation is demonstrated to be effective, this will be a turning point in the clinical practice since it represents a cheap, safe and well-tolerated alternative to HRT.     

Low incidence of red cell and HLA antibody formation by bone marrow transplant patients

BACKGROUND : Bone marrow transplant (BMT) patients, although immunosuppressed, are at risk for the development of red cell (RBC) and HLA antibodies, and they often are given filtered blood in an effort to prevent the latter complication. This study attempts to determine the rate of formation and the specificity of both RBC and HLA alloantibodies in this patient population. STUDY DESIGN AND METHODS : BMT patients (148 received autologous marrow; 45 received allogeneic marrow) from an 18-month period, including patients with leukemia (57 patients), lymphoma (54), breast cancer (68), myeloma (8), myelodysplastic syndrome (5), and aplastic anemia (1), were studied to determine the rate of alloantibody formation to RBC and HLA antigens. A total of 2,410 RBC antibody screens were performed. The patients received 3,921 packed RBCs and 5,915 single-donor platelet units; all were irradiated and administered via white cell-reduction filters. RESULTS : Seven (3.6%) of 193 patients had RBC antibodies upon hospital admission. Four (2.1%) of 193 developed RBC antibodies during the course of BMT: 3 patients had one RBC antibody and 1 patient had two RBC antibodies. RBC antibodies included anti-E (n = 2), anti-M (n = 1), anti-Jkb (n = 1), and anti-Lu14 (n = 1). Thus, 98 percent of patients (189/193) did not develop new (182/186) or additional (7/7) RBC antibodies during BMT. BMT patients were also screened weekly for HLA antibody formation (60-cell panel). Upon admission, 170 (85%) patients were negative. Of these, 8 (4.7%) developed persistent HLA antibodies (mean panel-reactive antibody score, 33 +/? 29%) and 9 (5.3%) were variably positive. Thus, in our setting and population, RBC antibody formation was 0.1 percent per unit transfused, and the HLA alloimmunization rate was 5 to 10 percent. CONCLUSION : As RBC antibody screens are done every Monday, Wednesday, and Friday on this BMT service and as RBC antibody formation is low in these patients, screening for unexpected antibodies might be possible on a more infrequent basis. Also, the rate of HLA alloimmunization in this population receiving filtered blood components is low.     

Interaction of single-chain urokinase with its receptor induces the appearance and disappearance of binding epitopes within the resultant complex for other cell surface proteins

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI- 1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell- bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.     

Delayed fixation of displaced type II and III pediatric femoral neck fractures

Background:

Time from injury to fixation of femoral neck fractures has been postulated as a vital determinant for rate of complications; however, no prospective study is available in the English literature. Delay, unfortunately, is inevitable in developing countries. The aim of the present study is to retrospectively review the outcome after delayed fixation of displaced type II and III femoral neck fractures in children.

Materials and Methods:

Using a standard assessment chart, we retrospectively reviewed medical records of all pediatric patients having femoral neck fractures presenting to our institution from June 1999 to May 2006. Inclusion criteria were children between 5 and 15 years of age sustaining displaced Delbet type II and III femoral neck fractures having a complete follow-up of at least 2 years. Patients with known metabolic disease, poliomyelitis or cerebral palsy, were excluded from the study. After application of inclusion and exclusion criteria, 22 patients having 22 fractures (13 type II and 9 type III) were studied. Surgery could be performed after a mean delay of 11.22 days (ranging from 2 to 21 days). Closed reduction was achieved in 14 cases and 8 cases required open reduction through anterolateral approach.

Result:

Osteonecrosis was noted in eight patients (36.37%) who included two of nine patients (22.22%) operated in the first week, three of eight patients (37.51%) operated in the second week, and three of five patients (60%) operated in the third week of injury. Nonunion was seen in four (18.18%) cases, and two of them were associated with failure of implants. One was treated by valgus osteotomy and the other by Meyer''s procedure. Fractures united in both children but the latter developed avascular necrosis. Functional results, as assessed using Ratliff''s criteria, were good in 14 (63.63%), fair in 2 (9%), and poor in 6 (27.27%) patients.

Conclusion:

Delay in fixation, type of fracture, and ability to achieve and maintain reduction are factors primarily responsible for the outcome. We also found that delay after the first week further adversely affects the outcome.     

Minimally Invasive Retroperitoneal Approach for Pancreatic Necrosectomy via a Percutaneous Drainage Tract

Aim-Background

Infected pancreatic necrosis (IPN) develops in approximately one third of patients with necrotizing pancreatitis (NP). In the past, open necrosectomy (ON) was the standard treatment for this condition, but it carried significant morbidity and mortality. Currently, minimally invasive procedures (MIPs) have been established for the management of IPN, decreasing the risk of complications compared with ON.

Methods

A prospective study was made of patients with IPN treated by a MIP for necrosectomy via a percutaneous drainage catheter, followed by video-assisted retroperitoneal debridement (VARD).

Results

Between 2013 and 2016, 3 consecutive patients, with a mean age of 58 years, underwent a MIP for the management of IPN. All 3 patients had left lateral retroperitoneal pockets of necrosis, and the first-line procedure consisted of placement of a pigtail catheter. The drain tract was subsequently used to carry out VARD. None of the patients presented major postoperative complications or required re-intervention.

Conclusion

The management of IPN has shifted away from ON, which was associated with high morbidity, towards less invasive techniques. MIPs should be used initially as the surgical treatment of choice in most cases. When this is not feasible, or when the MIP is not successful, ON should be implemented.

     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.     

A controlled trial of recombinant human erythropoietin after bone marrow transplantation

Recombinant human erythropoietin (rHuEPO) stimulates erythropoietic bone marrow cells and increases erythrocyte production. This prospective study was designed to evaluate the effects of rHuEPO on regeneration of erythropoiesis after allogeneic or autologous bone marrow transplantation (BMT). Seventeen centers participated in this randomized, double-blind, placebo-controlled multicenter trial. The randomization was performed centrally for each center and stratified according to allogeneic or autologous BMT and major ABO-blood group incompatibility. One hundred and six patients received rHuEPO after allogeneic BMT and 109 patients received placebo. After autologous BMT, 57 patients were treated with rHuEPO and 57 with placebo. Patients received either 150 IU/kg/day C127 mouse-cell-derived rHuEPO or placebo as continuous intravenous infusion. Therapy started after bone marrow infusion and lasted until independence from erythrocyte transfusions for 7 consecutive days with stable hemoglobin levels > or = 9 g/100 mL or until day 41. After allogeneic BMT, the reticulocyte counts were significantly higher with rHuEPO from day 21 to day 42 after BMT. The median time (95% confidence intervals) to erythrocyte transfusion independence was 19 days (range, 16.3 to 21.6) with rHuEPO and 27 days (range, 22.3 to > 42) with placebo (P < .003). The mean (+/- SD) numbers of erythrocyte transfusions until day 20 after BMT were 6.6 +/- 4.8 with rHuEPO and 6.0 +/- 3.8 with placebo. However, from day 21 to day 41, the rHuEPO-treated patients received 1.4 +/- 2.5 (median, 0) transfusions and the control group received 2.7 +/- 4.0 (median, 2) transfusions (P = .004). In the follow-up period from day 42 up to day 100, 2.4 +/- 5.6 transfusions were required with rHuEPO and 4.5 +/- 9.6 were required with placebo (P = .075). A multivariate analysis (ANOVA) showed that acute graft-versus-host disease (GVHD), major ABO-blood group incompatibility, age greater than 35 years, and hemorrhage significantly increased the number of transfusions. However, after day 20, rHuEPO significantly reduced the number of erythrocyte transfusions in these patient groups, as well as reducing incompatibility in the major ABO-blood group. For the whole study period, rHuEPO reduced the transfusion requirements in GVHD III and IV from 18.4 +/- 8.6 to 8.5 +/- 6.8 U (P = .05). After autologous BMT, there was no difference in the time to independence from erythrocyte transfusions and in the regeneration of reticulocytes. Marrow purging strongly increased the requirement for transfusions as well as the time to transfusion independence.