Self-reported changes in the expanded disability status scale score in patients with multiple sclerosis after autologous stem cell transplants: real-world data from a single center.

In order to reset the immune system to baseline function, autologous hematopoietic stem cell transplantation (HSCT) has been performed in patients with multiple sclerosis (MS). After June 2015, 617 new consecutive patients with MS were autografted in our center with non-frozen peripheral blood stem cells. The autografts were performed on an out-patient basis, after conditioning with cyclophosphamide and rituximab. The aim of the study was the assessment of both safety and efficacy of the method. The study's primary co-end-points were recovery of granulocyte and platelet counts and transplant-related mortality. Secondary end-points were overall survival and clinical response (improvement or stabilization of the self-reported expanded disability status scale score). The protocol was registered in ClinicalTrials.gov identifier NCT02674217.0. We included 401 females and 216 males, with a median age of 46 years. A total of 259 patients had relapsing-remitting MS (RRMS), 228 had secondary progressive (SPMS) and 130 had primary progressive (PPMS) multiple sclerosis. All procedures were initially performed on an out-patient basis and only 32 individuals (5%) required hospitalization. One to three aphereses (median 1) were required to harvest at least 1 × 106 /kg viable CD34+ cells. The total number of viable CD34+ infused cells ranged between 1 and 37·83 × 106 /kg (median 5·68). Patients recovered more than 0·5 × 109 /l absolute granulocytes by day 8 (median, range = 2-14), and platelet values were above 20 × 109 /l by day 4 (median, range = 0-11). Eleven individuals required red blood cells and six needed platelet transfusions. To date, there have been no deaths attributable to the transplant, yielding a 30-month overall survival of 100%. Patients have been followed for 3-42 months (median = 12). The overall response rate (decrease or stabilization of the self-reported EDSS score) at 12 months was 78% for all patients (83% in RRMS, 78% in PPMS and 73% in SPMS), while the disability progression-free survival was 82% for all patients (86% in RRMS, 78·5% in SPMS and 78% in SPMS). Changes in the self-reported EDSS score in parallel with neurological improvement were observed in people with all types of MS after HSCT, employing the 'Mexican method'.

Factors Related to the Acute Cellular Rejection During the First Year After Heart Transplant.

INTRODUCTION: The acute cellular rejection is recognized as a factor related to the long-term viability of the heart graft. We intend to establish which factors are associated with the acute cellular rejection during the first year post heart transplant using a longitudinal model with repeated measures. METHODS: A retrospective cohort study was performed with all the patients who underwent heart transplant between 2005-2018 at the Hospital Universitario San Ignacio in Bogota, Colombia. In order to determine the factors associated with the development of acute cellular rejection, a generalized estimating equation approach was used, with an interchangeable correlation structure. The lowest value of quasi-likelihood information criterion and P < .05 was considered significant. RESULTS: Fifty-five patients (49.3 ± 11.1 years old) were included. The mortality during the first month was 16.3% and the accumulated mortality during the first year was 23.6%. The incidence of the acute cellular rejection was higher during the third month after the transplant (79.9%); most of them were acute cellular rejection grade 1. The factors associated with the development of the rejection were the cyclosporine levels out of the therapeutic range in several periods of evaluation (P < .03) and the age of the receptor (P = .049). CONCLUSIONS: Using advanced modeling methodologies of longitudinal data we identified that the factors associated with acute cellular rejection during the first year after the transplant are related to the therapeutic levels of the calcineurin inhibitor (cyclosporin) during the first 6 months of follow-up and the age of the receptor.

Laser generation of elliptical nanometre and sub-nanometre bump arrays on NiP/Al data storage disks and their effect on stiction performance.

Elliptical nano-bumps on nickel-phosphorus coated aluminium (NiP/Al) hard disks were fabricated by a laser texturing system (maximum power 8 W, maximum frequency 300 kHz). By carefully selecting the level of laser power attenuation and defocus offset distance, bump height can be controlled below 6 nm and down to the sub-nanometre scale. This type of laser-induced texture (elliptical shape) on a disk surface is expected to provide better control of the stiction force along with the smallest separation distance between the head slider and the disk. Quantitative modelling based on the classical Hertzian theory for elliptic contacts has been carried out with the purpose of predicting the stiction behaviour of the presented elliptical shaped sub-10 nm bumps. It has been found that an elliptical shape not only reduces the overall stiction performance of the laser texturing zone (LZT) compared to the conventional circular shape but also extends the occurrence of the 'stiction wall' towards the sub-10 nm regime for ultra-low-glide applications.

Epidermal growth factor receptors lose ligand binding ability as WI-38 cells progress from short-term to long-term quiescence.

WI-38 cells, density arrested for short periods of time, can be stimulated to re-enter the cell cycle by epidermal growth factor (EGF) alone. However, cells density arrested for longer periods have a prolonged prereplicative phase when serum stimulated and cannot be stimulated by EGF alone. Radio-ligand binding studies performed on WI-38 cells showed that actively growing cells bind [125I]EG at relatively low levels that increase to a maximum as the cells become contact inhibited. As the cells enter a state of deeper quiescence, EGF binding falls to one-third to one-fifth the short-term growth arrested levels, remaining constant thereafter. The EGF-receptor complexes internalize more slowly in long-term growth arrested cells, and the rate of ligand association to the receptor is lower than short-term growth arrested cells. The amount of EGF receptor protein in lysates of equal numbers of both short- and long-term quiescent cells remains the same. These results suggest that the failure of long-term growth arrested cells to respond to EGF is not due to dramatic changes in the amount of receptor protein during prolonged quiescence but more likely to an alteration in the ability of these receptors to bind ligand and/or activate the EGF signal transduction pathway.