Outcomes of long storage times for cryopreserved vascular grafts in outflow reconstruction in living donor liver transplantation.

The outflow reconstruction of the right anterior sector in a right liver graft (RLG) with cryopreserved vascular grafts (CVGs) is crucial for preventing graft congestion in living donor liver transplantation (LDLT). The impact of the duration of cryopreservation has not been evaluated so far. From 2006 to 2009, 250 LDLT were performed: 47 of these patients (group 1) received CVGs stored for ≦1 year, and 33 patients (group 2) received CVGs stored for >1 year. Single or multiple segment 8 hepatic veins were reconstructed. The number of anastomoses did not affect vascular graft patency (P = 0.21). The length of the cryopreservation time did not affect the histological findings for CVGs. The preoperative and postoperative liver graft volumes were 783.8 ± 129.7 and 1102 ± 194.7 cc, respectively, for group 1 and 753.7 ± 158.5 and 1097.2 ± 178.7 cc, respectively, for group 2. The regeneration indices for liver grafts in the whole patient group, group 1, and group 2 were 48.9%, 47.4%, and 51.05%, respectively. In conclusion, the storage duration has no impact on the patency of CVGs in outflow reconstruction or on the regeneration of RLGs in LDLT. CVGs stored for >1 year can be safely used for the outflow reconstruction of RLGs in LDLT.

Challenges in the PREHOSPITAL emergency management of geriatric trauma patients - a scoping review.

BACKGROUND: Despite a widely acknowledged increase in older people presenting with traumatic injury in western populations there remains a lack of research into the optimal prehospital management of this vulnerable patient group. Research into this cohort faces many uniqu1e challenges, such as inconsistent definitions, variable physiology, non-linear presentation and multi-morbidity. This scoping review sought to summarise the main challenges in providing prehospital care to older trauma patients to improve the care for this vulnerable group. METHODS AND FINDINGS: A scoping review was performed searching Google Scholar, PubMed and Medline from 2000 until 2020 for literature in English addressing the management of older trauma patients in both the prehospital arena and Emergency Department. A thematic analysis and narrative synthesis was conducted on the included 131 studies. Age-threshold was confirmed by a descriptive analysis from all included studies. The majority of the studies assessed triage and found that recognition and undertriage presented a significant challenge, with adverse effects on mortality. We identified six key challenges in the prehospital field that were summarised in this review. CONCLUSIONS: Trauma in older people is common and challenges prehospital care providers in numerous ways that are difficult to address. Undertriage and the potential for age bias remain prevalent. In this Scoping Review, we identified and discussed six major challenges that are unique to the prehospital environment. More high-quality evidence is needed to investigate this issue further.

Current and possible future role of 3D modelling within oesophagogastric surgery: a scoping review protocol.

INTRODUCTION: Three-dimensional (3D) reconstruction describes the generation of either virtual or physically printed anatomically accurate 3D models from two-dimensional medical images. Their implementation has revolutionised medical practice. Within surgery, key applications include growing roles in operative planning and procedures, surgical education and training, as well as patient engagement and education. In comparison to other surgical specialties, oesophagogastric surgery has been slow in their adoption of this technology. Herein the authors outline a scoping review protocol that aims to analyse the current role of 3D modelling in oesophagogastric surgery and highlight any unexplored avenues for future research. METHODS AND ANALYSIS: The protocol was generated using internationally accepted methodological frameworks. A succinct primary question was devised, and a comprehensive search strategy was developed for key databases (MEDLINE, Embase, Elsevier Scopus and ISI Web of Science). These were searched from their inception to 1 June 2020. Reference lists will be reviewed by hand and grey literature identified using OpenGrey and Grey Literature Report. The protocol was registered to the Open Science Framework (osf.io/ta789).Two independent reviewers will screen titles, abstracts and perform full-text reviews for study selection. There will be no methodological quality assessment to ensure a full thematic analysis is possible. A data charting tool will be created by the investigatory team. Results will be analysed to generate descriptive numerical tabular results and a thematic analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was not required for the collection and analysis of the published data. The scoping review report will be disseminated through a peer-reviewed publication and international conferences. REGISTRATION DETAILS: The scoping review protocol has been registered on the Open Science Framework (https://osf.io/ta789).

Association of Enrollment in an Aerodigestive Clinic With Reduced Hospital Stay for Children With Special Health Care Needs.

Importance: Children with special health care needs (CSHCN) have disproportionate health care utilization. Previous studies have demonstrated that a primary medical home improves health care outcomes for this population. Objective: To elucidate if enrollment in a multidisciplinary aerodigestive clinic improves outcomes and reduces health care costs by decreasing admissions and inpatient days. Design, Setting, and Participants: A retrospective medical record review of 113 patients with aerodigestive disorders enrolled in a pediatric multidisciplinary clinic from June 2009 to December 2013 was performed. Of the 113 particpants, 58 (51.3%) were male, 59 (52.2%) had a tracheostomy, and 90 (80.5%) had a gastrostomy tube during their enrollment period. Patient ages at enrollment ranged from 0 to 20 years, with 59 (52.2%) ranging from 0 to 5 years, 23 (20.4%) ranging from 6 to 10 years, 18 (15.9%) ranging from 11 to 15 years, and 13 (11.5%) being 16 years or older. Admissions data before and after enrollment in a pediatric multidisciplinary clinic were examined. Main Outcomes and Measures: The main outcomes studied were changes in admissions and inpatient days before and after enrollment. Financial data were also examined to determine the reduction in technical direct cost. Results: The admissions data for 113 children were analyzed. No significant difference in number of admissions per year was seen with enrollment with a median difference of -0.30 admissions per year (range, -10.6 to 6.7 admissions per year; 95% CI, -3.5 to 2.9). However, there was a significant decrease seen in inpatient days per year following enrollment, with a median decrease of 4.1 inpatient days per year (range, -80 to 283.3 inpatient days per year; 95% CI, 0.33 to 91.0). When examining aerodigestive admissions alone, the median number of aerodigestive hospital days avoided per patient was 0.57 days per month, or 6.8 days per year, representing a 70% reduction in technical direct cost. Conclusions and Relevance: These findings indicate that for children with special health care needs, enrollment in a multidisciplinary aerodigestive clinic may improve health care outcomes by decreasing technical direct cost by 70% and significantly decreasing patient hospital days by an estimated 1 week per year. Furthermore, coordinated aerodigestive care in a medical home setting may lower health care expenditures from a systems-based perspective.

Glucose-induced activation of glucose uptake in cells from the inner and outer blood-retinal barrier.

PURPOSE: The purpose of this study was to elucidate in vitro the effect of elevated glucose on glucose uptake in the cells comprising the inner and outer blood-retinal barriers: human retinal pigment epithelial (hRPE) and human retinal vascular endothelial (hRVE) cells. METHODS: Primary cultures of hRPE and hRVE cells grown in 5.5 or 22 mM glucose or in 22 mM mannitol were used to measure the rates of glucose uptake with [(3)H]-3-O-methyl glucose as a tracer. GLUT1 expression was measured by Northern and western blot analyses. Cellular fractionation was performed by differential centrifugation. GLUT1 overexpression was accomplished by adenoviral transduction. RESULTS: Increasing media glucose from 5.5 to 22 mM for 30 minutes caused a 1.9-fold increase in the V(max) of glucose uptake in hRPE cells and a 2.5-fold increase in hRVE cells. These increases were nonosmotic and glucose specific, in that the exposure to 22 mM mannitol did not affect the V(max) of glucose uptake. mRNA, total protein expression, and translocation of GLUT1, the glucose transporter predominantly expressed in hRPE and hRVE cells, were not affected by 22 mM glucose for up to 48 hours. High-glucose effects on V(max) were abolished with 10 microg/mL of the microtubule assembly inhibitor nocodazole. hRPE cells transduced to overexpress GLUT1 showed a 1.5-fold increase in the V(max) for glucose uptake versus control-transduced cells. However, the magnitude of glucose-induced increase in glucose uptake was the same in GLUT1- and control-transduced cells. CONCLUSIONS: High glucose induced 1.9- and 2.5-fold increases in the V(max) of glucose uptake in hRPE and hRVE cells, respectively. These increases were not due to an increase in GLUT1 expression. The increases were dependent on microtubule integrity, but not on GLUT1 translocation. The mechanism of the increases is unknown. GLUT1 regulating protein(s) and/or novel glucose transporter(s) may be involved in the regulation of glucose uptake by glucose in the cells that comprise the blood-retinal barrier.

Chronic pain in children and adolescents: 24-42 month outcomes of an inpatient/day hospital interdisciplinary pain rehabilitation program.

PURPOSE: The purpose of this research was to describe 24-42 month outcomes of a combined inpatient/day hospital interdisciplinary pain rehabilitation program for children and adolescents with chronic pain and functional disability. METHODS: One-hundred-seventy-three children and adolescents (mean age=15.1 years, SD=2.5) were treated in the three-week program. Mixed effects regression models (MERM) examined changes over time in pain ratings (0-10), school days missed by children and work days missed by parents in the preceding week, and the number of days hospitalized in the preceding month. RESULTS: Participants reported a significant decline in pain from admission to 24-42 month follow-up. The largest declines in pain occurred from discharge to 1-month follow-up (6.20 vs. 4.81 on a 0-10 numerical rating scale) and from 12 months to 24-42 month follow-up (4.90 vs. 3.56). Two distinct trajectories of treatment response were identified using growth mixture modeling: children with initially high pain ratings exhibited large reductions in pain ratings, while those with lower pain ratings at admission showed minimal reductions. Treatment resulted in significant reductions in school and work days missed and the number of days hospitalized (all p's < 0.001), with reductions evident at 1-month follow-up and maintained through 24-42 month follow-up. CONCLUSIONS: These results suggest that interdisciplinary pain rehabilitation is a promising approach to chronic pain and associated disability in children, with enduring improvements found 24-42 months following program completion. Distinct trajectories of treatment response were identified.

Central nervous system reorganization in a variety of chronic pain states: a review.

Chronic pain can develop from numerous conditions and is one of the most widespread and disabling health problems today. Unfortunately, the pathophysiology of chronic pain in most of these conditions, along with consistently effective treatments, remain elusive. However, recent advances in neuroimaging and neurophysiology are rapidly expanding our understanding of these pain syndromes. It is now clear that substantial functional and structural changes, or plasticity, in the central nervous system (CNS) are associated with many chronic pain syndromes. A group of cortical and subcortical brain regions, often referred to as the "pain matrix," often show abnormalities on functional imaging studies in persons with chronic pain, even with different pain locations and etiologies. Changes in the motor and sensory homunculus also are seen. Some of these CNS changes return to a normal state with resolution of the pain. It is hoped that this knowledge will lead to more effective treatments or even new preventative measures. The purpose of this article is to review recent advances in the understanding of the CNS changes associated with chronic pain in a number of clinical entities encountered in the field of physical medicine and rehabilitation. These clinical entities include nonspecific low back pain, fibromyalgia, complex regional pain syndrome, postamputation phantom pain, and chronic pain after spinal cord injury.

Evaluation of descriptors and classification schemes to predict cytochrome substrates in terms of chemical information.

Using a small database of defined substrates in humans for cytochrome P450 mixed function oxidases, a series of descriptors and classification methods were evaluated with respect to how well they correctly classified substrates. The descriptors ranged from structural keys to topological to electronic. A variety of classification schemes were examined in terms of their ability to point out which descriptors are important for predicting the cytochrome P450 specificity for a substrate. Results illustrate the relative effectiveness of the various kinds of descriptors and classification methods, as well as the value of using as well-defined data set as possible.

Are diabetic neuropathy, retinopathy and nephropathy caused by hyperglycemic exclusion of dehydroascorbate uptake by glucose transporters?

Vitamin C exists in two major forms. The charged form, ascorbic acid (AA), is taken up into cells via sodium-dependent facilitated transport. The uncharged form, dehydroascorbate (DHA), enters cells via glucose transporters (GLUT) and is then converted back to AA within these cells. Cell types such as certain endothelial and epithelial cells as well as neurons that are particularly prone to damage during diabetes tend to be those that appear to be dependent on GLUT transport of DHA rather than sodium-dependent AA uptake. We hypothesize that diabetic neuropathies, nephropathies and retinopathies develop in part by exclusion of DHA uptake by GLUT transporters when blood glucose levels rise above normal. AA plays a central role in the antioxidant defense system. Exclusion of DHA from cells by hyperglycemia would deprive the cells of the central antioxidant, worsening the hyperglycemia-induced oxidative stress level. Moreover, AA participates in many cellular oxidation-reduction reactions including hydroxylation of polypeptide lysine and proline residues and dopamine that are required for collagen production and metabolism and storage of catecholamines in neurons. Increase in the oxidative stress level and metabolic perturbations can be expected in any tissue or cell type that relies exclusively or mainly on GLUT for co-transport of glucose and DHA including neurons, epithelial cells, and vascular tissues. On the other hand, since DHA represents a significant proportion of total serum ascorbate, by increasing total plasma ascorbate concentrations during hyperglycemia, it should be possible to correct the increase in the oxidative stress level and metabolic perturbations, thereby sparing diabetic patients many of their complications.

Reoptimization of MDL keys for use in drug discovery.

For a number of years MDL products have exposed both 166 bit and 960 bit keysets based on 2D descriptors. These keysets were originally constructed and optimized for substructure searching. We report on improvements in the performance of MDL keysets which are reoptimized for use in molecular similarity. Classification performance for a test data set of 957 compounds was increased from 0.65 for the 166 bit keyset and 0.67 for the 960 bit keyset to 0.71 for a surprisal S/N pruned keyset containing 208 bits and 0.71 for a genetic algorithm optimized keyset containing 548 bits. We present an overview of the underlying technology supporting the definition of descriptors and the encoding of these descriptors into keysets. This technology allows definition of descriptors as combinations of atom properties, bond properties, and atomic neighborhoods at various topological separations as well as supporting a number of custom descriptors. These descriptors can then be used to set one or more bits in a keyset. We constructed various keysets and optimized their performance in clustering bioactive substances. Performance was measured using methodology developed by Briem and Lessel. "Directed pruning" was carried out by eliminating bits from the keysets on the basis of random selection, values of the surprisal of the bit, or values of the surprisal S/N ratio of the bit. The random pruning experiment highlighted the insensitivity of keyset performance for keyset lengths of more than 1000 bits. Contrary to initial expectations, pruning on the basis of the surprisal values of the various bits resulted in keysets which underperformed those resulting from random pruning. In contrast, pruning on the basis of the surprisal S/N ratio was found to yield keysets which performed better than those resulting from random pruning. We also explored the use of genetic algorithms in the selection of optimal keysets. Once more the performance was only a weak function of keyset size, and the optimizations failed to identify a single globally optimal keyset. Instead multiple, equally optimal keysets could be produced which had relatively low overlap of the descriptors they encoded.