Short-term decreased post transplant lymphoproliferative disorder risk after kidney transplantation using two novel regimens.

BACKGROUND: Belatacept is employed alongside calcineurin inhibitor (CNI) therapy to prevent graft rejection in kidney transplant patients who are Epstein-Barr virus (EBV) seropositive. Preliminary data suggested that rates of post-transplant lymphoproliferative disorder (PTLD) were higher in individuals treated with belatacept compared to CNI therapy alone. METHODS: The records of 354 adults who underwent kidney only transplantation from January 2015 through September 2021 at one medical center were evaluated. Patients underwent treatment with either low-doses of mycophenolate, tacrolimus and sirolimus (B0, n = 235) or low-doses of mycophenolate, tacrolimus and belatacept (B1, n = 119). All recipients underwent induction with antithymocyte globulin and a rapid glucocorticosteroid taper. Relevant donor and recipient information were analyzed and endpoints of PTLD were assessed. RESULTS: There were no cases of PTLD in either cohort within the study period. Recipients in the belatacept cohort experienced lower estimated glomerular filtration rates at 12 months (B0: 67.48 vs. B1: 59.10, p = 0.0014). Graft failure at 12 (B0: 1.28% vs. B1: 0.84%, p = 1.0) and 24 months (B0:2.55% vs. B1: 0.84%, p = 0.431) were similar. There was no difference in rejection rates at 12 (B0: 1.27% vs. B1: 2.52%, p = 0.408) or 24 months (B0: 2.12% vs. B1: 2.52%, p = 1.000). Both groups had similar rates of malignancy, mortality and CMV/BK viremia. CONCLUSION: Non-belatacept (MMF, tacrolimus and sirolimus) and belatacept-based (MMF, tacrolimus and belatacept) regimens do not appear to pose any increased risk of early onset PTLD. Both cohorts benefited from low rates of rejection, malignancy, mortality and graft failure. Recipients will continue to be monitored as PTLD can manifest as a long-term complication.

Comparison of brain microstructure after prenatal spina bifida repair by either laparotomy-assisted fetoscopic or open approach.

OBJECTIVE: To compare prenatal and postnatal brain microstructure between infants that underwent fetoscopic myelomeningocele (MMC) repair and those that had open-hysterotomy repair. METHODS: This was a longitudinal retrospective cohort study of 57 fetuses that met the Management of Myelomeningocele Study (MOMS) trial criteria and underwent prenatal MMC repair, by a fetoscopic (n = 27) or open-hysterotomy (n = 30) approach, at 21.4-25.9 weeks' gestation. Fetoscopic repair was performed under CO2 insufflation, according to our protocol. Diffusion-weighted magnetic resonance imaging (MRI) was performed before surgery in 30 cases (14 fetoscopic and 16 open), at 6 weeks postsurgery in 48 cases (24 fetoscopic and 24 open) and within the first year after birth in 23 infants (five fetoscopic and 18 open). Apparent diffusion coefficient (ADC) values from the basal ganglia, frontal, occipital and parietal lobes, mesencephalon and genu as well as splenium of the corpus callosum were calculated. ADC values at each of the three timepoints (presurgery, 6 weeks postsurgery and postnatally) and the percentage change in the ADC values between the timepoints were compared between the fetoscopic-repair and open-repair groups. ADC values at 6 weeks after surgery in the two prenatally repaired groups were compared with those in a control group of eight healthy fetuses that underwent MRI at a similar gestational age (GA). Comparison of ADC values was performed using the Student's t-test for independent samples (or Mann-Whitney U-test if non-normally distributed) and multivariate general linear model analysis, adjusting for GA or age at MRI and mean ventricular width. RESULTS: There were no differences in GA at surgery or GA/postnatal age at MRI between the groups. No significant differences were observed in ADC values in any of the brain areas assessed between the open-repair and fetoscopic-repair groups at 6 weeks after surgery and in the first year after birth. No differences were detected in the ADC values of the studied areas between the control and prenatally repaired groups, except for significantly increased ADC values in the genu of the corpus callosum in the open-hysterotomy and fetoscopic-repair groups. Additionally, there were no differences between the two prenatally repaired groups in the percentage change in ADC values at any of the time intervals analyzed. CONCLUSIONS: Fetoscopic MMC repair has no detectable effect on brain microstructure when compared to babies repaired using an open-hysterotomy technique. CO2 insufflation of the uterine cavity during fetoscopy does not seem to have any isolated deleterious effects on fetal brain microstructure. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Early Hemodynamic Response Assessment of Stereotactic Radiosurgery for a Cerebral Arteriovenous Malformation Using 4D Flow MRI.

Brain AVMs treated with stereotactic radiosurgery typically demonstrate a minimum latency period of 1-3 years between treatment and nidus obliteration. Assessment of treatment response is usually limited to evaluation of AVM nidus structural changes using conventional MR imaging and MRA techniques. This report describes the use of 4D Flow MRI to also measure radiation-induced hemodynamic changes in a Spetzler-Martin grade III AVM, which were detectable as early as 6 months after treatment.

Using a scripted data entry process to transfer legacy immunization data while transitioning between electronic medical record systems.

BACKGROUND: Transitioning between Electronic Medical Records (EMR) can result in patient data being stranded in legacy systems with subsequent failure to provide appropriate patient care. Manual chart abstraction is labor intensive, error-prone, and difficult to institute for immunizations on a systems level in a timely fashion. OBJECTIVES: We sought to transfer immunization data from two of our health system's soon to be replaced EMRs to the future EMR using a single process instead of separate interfaces for each facility. METHODS: We used scripted data entry, a process where a computer automates manual data entry, to insert data into the future EMR. Using the Center for Disease Control's CVX immunization codes we developed a bridge between immunization identifiers within our system's EMRs. We performed a two-step process evaluation of the data transfer using automated data comparison and manual chart review. RESULTS: We completed the data migration from two facilities in 16.8 hours with no data loss or corruption. We successfully populated the future EMR with 99.16% of our legacy immunization data - 500,906 records - just prior to our EMR transition date. A subset of immunizations, first recognized during clinical care, had not originally been extracted from the legacy systems. Once identified, this data - 1,695 records - was migrated using the same process with minimal additional effort. CONCLUSIONS: Scripted data entry for immunizations is more accurate than published estimates for manual data entry and we completed our data transfer in 1.2% of the total time we predicted for manual data entry. Performing this process before EMR conversion helped identify obstacles to data migration. Drawing upon this work, we will reuse this process for other healthcare facilities in our health system as they transition to the future EMR.

Extracranial venous drainage patterns in patients with multiple sclerosis and healthy controls.

BACKGROUND AND PURPOSE: CCSVI hypothesizes an association between impaired extracranial venous drainage and MS. Published sonographic criteria for CCSVI are controversial, and no MR imaging data exist to support the CCSVI hypothesis. Our purpose was to evaluate possible differences in the extracranial venous drainage of MS and healthy controls using both TOF and contrast-enhanced TRICKS MRV. MATERIALS AND METHODS: Healthy subjects (n = 20) and patients with MS (n = 19) underwent axial 2D-TOF neck MRV (to assess flattening) and TRICKS MRV (to assess collaterals) at 3T. Two neuroradiologists blinded to cohort status scored IJV flattening and the severity of non-IJV collaterals by using a 4-point qualitative scale (normal = 0, mild = 1, moderate = 2, severe = 3). κ was used to assess reader agreement. Comparisons between groups were performed by using the Wilcoxon rank sum test. The Spearman rank correlation was used to assess the relationship between IJV flattening and collateral scores and, in patients with MS, EDSS scores. RESULTS: The 2 groups were matched for age and sex (MS, 45 ± 8 years, 79% female; healthy controls, 47 ± 10 years, 65% female). Reader agreement for IJV flattening and collateral severity was good (κ = 0.74) and moderate (κ = 0.58), respectively. While IJV flattening was seen in both patients with MS and healthy controls, scores for the patients with MS were significantly higher (P = .002). Despite a trend, there was no significant difference in collateral scores between groups (P = .063). There was a significant positive correlation between flattening and collateral scores (ρ = 0.32, P = .005) and EDSS and flattening scores (ρ = 0.45, P = .004) but not between EDSS and collateral scores (ρ = 0.01, P = .97). CONCLUSIONS: These results indicate that patients with MS have greater IJV flattening and a trend toward more non-IJV collaterals than healthy subjects. The role that this finding plays in the pathogenesis or progression of MS, if any, requires further study.

Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization.

Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARgamma ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecular and functional characteristics of insulin resistant subjects and distinctions between TZD treatment responder and nonresponder subjects. Insulin resistant subjects exhibited alterations in skeletal muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose tissue (e.g., mitochondrial metabolism and inflammation) that improved relative to TZD-induced insulin sensitization. Pre-TZD treatment expression of MLXIP in muscle and HLA-DRB1 in adipose tissue from insulin resistant subjects was linearly predictive of post-TZD insulin sensitization. We have uniquely characterized coordinated cellular and tissue functional pathways that are characteristic of insulin resistance, TZD-induced insulin sensitization, and potential TZD responsiveness.

Variance-modeled posterior inference of microarray data: detecting gene-expression changes in 3T3-L1 adipocytes.

MOTIVATION: Microarrays are becoming an increasingly common tool for observing changes in gene expression over a large cross section of the genome. This experimental tool is particularly valuable for understanding the genome-wide changes in gene transcription in response to thiazolidinedione (TZD) treatment. The TZD class of drugs is known to improve insulin-sensitivity in diabetic patients, and is clinically used in treatment regimens. In cells, TZDs bind to and activate the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPAR-gamma). Large-scale array analyses will provide some insight into the mechanisms of TZD-mediated insulin sensitization. Unfortunately, a theoretical basis for analyzing array data has not kept pace with the rapid adoption of this tool. The methods that are commonly used, particularly the fold-change approach and the standard t-test, either lack statistical rigor or resort to generalized statistical models that do not accurately estimate variability at low replicate numbers. RESULTS: We introduce a statistical framework that models the dependence of measurement variance on the level of gene expression in the context of a Bayesian hierarchical model. We compare several methods of parameter estimation and subsequently apply these to determine a set of genes in 3T3-L1 adipocytes that are differentially regulated in response to TZD treatment. When the number of experimental replicates is low (n = 2-3), this approach appears to qualitatively preserve an equivalent degree of specificity, while vastly improving sensitivity over other comparable methods. In addition, the statistical framework developed here can be readily applied to understand the implicit assumptions made in traditional fold-change approaches to array analysis.

The dual-task SRT procedure: fine-tuning the timing.

In the standard sequential reaction time study, subjects are presented with a repeating sequence of targets to which they must respond as rapidly as possible. With practice reaction times decrease, suggesting a learned ability to exploit the repeating patterns in the display. In a common variation, a second task is interposed, typically a tone-counting task in which subjects must keep track of the frequency with which particular tones occur. In the canonical experiment, these tones appear at varying times in the interval between the subjects' response to a target and the next target. Data are presented that show that this latter variable (the RSOA, response-secondary stimulus onset asynchrony) actually plays an important but previously hidden role in these experiments. A model based on an extension of the notion of the psychological refractory period is introduced to explain these findings.

A dual-snake model of high penetrability for ultrasound image boundary extraction.

Most deformable models require the initial contour to be placed close to the boundary of the object of interest for boundary extraction of ultrasound (US) images, which is impractical in many clinical applications. To allow a distant initial contour, a new dual-snake model promising high penetrability through the interference of the noises is proposed in this paper. The proposed dual-snake model features a new far-reaching external force, called the discrete gradient flow, a connected component-weighted image force, and an effective stability evaluation of two underlying snakes. The experimental results show that, with a distant initial contour, the mean distance from the derived boundary to the desired boundary is less than 1.4 pixels, and most snake elements are within 2.7 pixels of the desired boundaries for the synthetic images with CNR > or =1. For the clinical US images, the mean distance is less than 1.9 pixels, and most snake elements are within 3 pixels of the desired boundaries.

Another wrinkle on the dual-task SRT experiment: it's probably not dual task.

In the standard serial reaction time (SRT) experiment, subjects are required to respond rapidly to a structured sequence of visual targets. Evidence that subjects have acquired knowledge of the structure is obtained by modifying the structured nature of the sequence and noting whether reaction times increase. In the dual-task SRT experiment, a "secondary" tone-counting task is introduced, and the extent to which learning of the "primary" target sequence is compromised is noted. Here we present data that strongly imply that while the psychologists who designed this "dual-task" experiment may have viewed it this way, this may not be the best way to characterize it. The suggestion is that this "duality" is illusory and that we should probably be treating the tone-counting task as a potential source of additional patterns of covariation in a complex, multicomponent display and not as a "secondary," attention-diverting factor.

Translation, adaptation, and validation of the SF-36 Health Survey for use in Japan.

Development of the Japanese SF-36 was completed in two phases: Phase 1: Japanese version 1.1 was produced according to International Quality of Life Assessment (IQOLA) project guidelines, but some results of psychometric tests were unexpected. First, scores varied little across physical-functioning items. Second, using factor analysis, we could not clearly distinguish the scales designed to measure the "physical" component of quality of life from those designed to measure the "mental" component. Phase 2: Focus-group discussions revealed that limited had often been interpreted as limited by a doctor. Therefore, is difficult to do was used instead (version 1.2). Results of two surveys indicated that version 1.2 yields scores that are reliable by internal consistency and test-retest standards and yields two principal components. In Japan, however, the pattern of correlations between some scales and the principal components differs from that in the United States. Iterative use of qualitative and quantitative methods was very important in developing the Japanese SF-36.

Injection of ultrasmall samples and single molecules into tapered capillaries.

A novel injection scheme is described in which ultrasmall samples in the attoliter (10(-18) L) and low femtoliter (10(-15) L) range, or even single molecules, are controllably introduced into a tapered capillary so that electrophoretic separation can be carried out. To match the dimensions of the capillary inlet with that of the sample, capillary tips are tapered to an inside diameter ranging from hundreds of nanometers to a few micrometers. To inject an ultrasmall sample, optical trapping is used to immobilize and manipulate the sample in order to place it inside or next to the capillary inlet. A small controlled suction results in the loading of the sample into the capillary.

Role of the emergency medical services system in regionwide health monitoring and referral.

The emergency medical services (EMS) system of the future has the opportunity to serve as a regional community health monitoring and referral system. Such a system would shift attention from care of the individual to cost-effective community health efforts using community resource integration, while emphasizing individual responsibility for health. This health care system model requires the establishment of a centralized monitoring agency, the "regional center." The regional center would coordinate the monitoring of regional EMS use and linkage of patients with essential health promotion and behavior change organizations. Many of these supporting organizations are in place but are functioning without the benefit of communitywide health monitoring or effective referral and follow-up links with other resources. Coordination through the EMS system and a regional center would permit these resources to be used in an efficient and accountable fashion. We propose a model in which the EMS system could contribute to coordinated regional health monitoring and maintenance, timely and appropriate health care legislation and regulation, and high-impact health care education and intervention in the setting of self-destructive individual behavior.

Implementation of stereotactic focal radiotherapy for intracranial arteriovenous malformations using a linear accelerator.

A system of stereotactic focal radiotherapy using a linear accelerator has been developed in cooperation with a neurosurgeon. The treatment is delivered using a carefully calibrated 10 MV machine and the Cosman-Roberts-Wells (CRW) system. The precision of the method as well as its quality assurance is described. Eight patients with intracranial arteriovenous malformations (AVM) received irradiation from August 1990 to November 1991. The prescribed dose at the periphery of the AVM was 8 Gy per session, with six patients receiving two sessions and two patients receiving one session. The field size, encompassing the 90% isodose, ranged from 20 mm to 35 mm. In four patients, follow-up angiography was performed one year after the full course of therapy; total obliteration of the AVM was noted in three (75%) with a partial response in the other. In the other four patients, follow-up angiography was not performed; one patient, who had only one session of irradiation, experienced rebleeding six months later and died, and the other three patients had no further episodes of bleeding during their follow-up of 28, 18 and 14 months, respectively. Linear accelerator-based stereotactic focal radiotherapy can attain a precisely defined and reproducible dose distribution. The effects of this treatment may take one to two years to develop. Our preliminary study suggests that it is an effective alternative treatment for surgically inaccessible lesions. Patients with a small cavernous sinus dural AVM appear to have a better and more rapid response.

Emergent intubation and CT scan pathology of blunt trauma patients with Glasgow Coma Scale scores of 3-13.

INTRODUCTION: Widely accepted guidelines for use of pharmacologic agents for prehospital intubation have not been fully developed. Toward the goal of formulating specific guidelines, this study sought to determine how well the Glasgow Coma Scale (GCS) score stratifies the need for emergent intubation (within 30 minutes of emergency department arrival or in the prehospital setting). METHODS: A one-year, retrospective review of the charts of blunt trauma patients with presumed head injury who presented to the emergency department of a Level 1 trauma center with a GCS score of less than or equal to 13 was performed. A total of 120 patients met the inclusion and exclusion criteria. RESULTS: A significant number of patients presenting with a GCS score of less than or equal to 9 required emergent intubation. A significant minority of patients presenting with a GCS score of 10-13 required emergent intubation (20%) or had intracranial pathology on head CT scan (23%), and the majority of patients from this subgroup did not require subsequent intubation. Alcohol or substance intoxication and communication barriers such as deafness and language difficulties limited the clinical examination. CONCLUSIONS: Patients with a presenting GCS score of less than or equal to 9 represent candidates for the use of pharmacologic agents to facilitate aggressive airway control by well-trained and supervised emergency medical technicians (EMTs). Emergent intubation of patients with a GCS score of 10-13 is problematic. Patients with a presenting GCS score of 10-13 must be evaluated individually and closely monitored.(ABSTRACT TRUNCATED AT 250 WORDS)

[Implementation of stereotactic focal radiotherapy using 10 MV x-ray].

Stereotactic focal irradiation is also called stereotactic radiosurgery by some neurosurgeons. This irradiation is used for the treatment of brain AVM (arterio-venous malformation) and small tumor. Application of stereotactic focal irradiation was developed with CRW (Cosman-Roberts-Wells) stereotactic device and two dimensional (2D) computer treatment planning system using 10 MV x-ray from a linear accelerator. This process of irradiation includes: (a) Identification and localization of a target volume in CRW stereotactic frame by CT scan or angiography. (b) To verify the alignment, a linear accelerator was used as a simulator to take portal films in anterior and lateral views. This was done to ascertain the angles between arc therapy, to encompass the target volume, and to exclude the critical organs such as lens at 0 degrees, 45 degrees, 90 degrees and 315 degrees couch angles. (c) A 2D computer treatment planning system was used to generate an isodose curve distribution for each couch angle. Then this was used to calculate the monitor unit per degree for rotation treatment. (d) 10 MV x-ray was used to implement the stereotactic focal radiotherapy.