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The potential role of multifunctional human amniotic epithelial cells in pancreatic islet transplantation.
No full textPancreatic islet cell transplantation has proven efficacy as a treatment for type 1 diabetes mellitus, chiefly in individuals who are refractory to conventional insulin replacement therapy. At present its clinical use is restricted, firstly by the limited access to suitable donor organs but also due to factors associated with the current clinical transplant procedure which inadvertently impair the long-term functionality of the islet graft. Of note, the physical, biochemical, inflammatory, and immunological stresses to which islets are subjected, either during pretransplant processing or following implantation are detrimental to their sustained viability, necessitating repeated islet infusions to attain adequate glucose control. Progressive decline in functional beta (β)-cell mass leads to graft failure and the eventual re-instatement of exogenous insulin treatment. Strategies which protect and/or preserve optimal islet function in the peri-transplant period would improve clinical outcomes. Human amniotic epithelial cells (HAEC) exhibit both pluripotency and immune-privilege and are ideally suited for use in replacement and regenerative therapies. The HAEC secretome exhibits trophic, anti-inflammatory, and immunomodulatory properties of relevance to islet graft survival. Facilitated by β-cell supportive 3D cell culture systems, HAEC may be integrated with islets bringing them into close spatial arrangement where they may exert paracrine influences that support β-cell function, reduce hypoxia-induced islet injury, and alter islet alloreactivity. The present review details the potential of multifunctional HAEC in the context of islet transplantation, with a focus on the innate capabilities that may counter adverse events associated with the current clinical transplant protocol to achieve long-term islet graft function
Facilitating better postnatal care with women-held documents in The Gambia: a mixed-methods study.
No full textBACKGROUND
Women-held documents are a basic component of continuity of maternity care. The use and completion of women-held documents following discharge could improve treatment and care for postnatal women. Using a mixed-methods study design, we aimed to assess the number, type, quality and completeness of women-held discharge documents, identify factors contributing to document completeness and facilitators or barriers for effective use of the documents.
METHODS
Documents given to women at discharge from three hospitals in the Greater Banjul Area, The Gambia, were reviewed for content and quality. All women completed a questionnaire on the use of the documents. Poisson regression was used to estimate factors predicting document completion. Semi-structured interviews (n = 21) and focus groups (n = 2) were carried out with healthcare professionals (HCPs).
RESULTS
Nearly all (n = 211/212; 99%) women were given a document to take home. The most complete document (maternal record) had on average 17/26 (65%) items completed and 10% of women held an illegible document. None of the women's sociodemographic or clinical characteristics predicted document completeness. The following facilitators for effective use of documents were identified from the women's responses to the questionnaire and interviews with HCPs: 94% of women thought written information is important, 99% plan to have postnatal check-ups and 67% plan to use their documents, HCPs understand the importance of the documents and were familiar with the document's use and content. The following barriers for effective use of documents were identified: HCPs had too many women-held documents to complete at discharge, there is no national protocol and HCPs think women do not understand the documents due to a lack of education and that women often lose or forget their documents.
CONCLUSIONS
Women-held documents are well established in The Gambia; though quality and completeness needs improving. Future research should determine the impact of using only one document at discharge, protocols and training on completeness, among other outcomes, and on ways to ensure all women are using the documents for their postnatal care
Patient experience of scar assessment and the use of scar assessment tools during burns rehabilitation: a qualitative study.
No full textBackground
Scar assessment plays a key role during burns aftercare, to monitor scar remodelling and patients' psychosocial well-being. To aid assessment, subjective scar assessment scales are available that use health-care professionals' and patients' opinions to score scar characteristics. The subjective scales are more widely used in clinical practice over objective scar measures. To date, there is no research that considers patients' views on scar assessment and the role of subjective and objective assessment tools. Therefore, the aim of this qualitative study was to explore patients' perspectives on scar assessment and the utility of scar assessment tools during burns rehabilitation.
Methods
Semi-structured interviews were conducted with 10 adult burn patients who were being reviewed in clinic for scarring. Participants were recruited via their clinical care team and research nurses at the Queen Elizabeth Hospital, Birmingham, UK. Topics covered during interview included patient experience of scar assessment, the use of scar assessment tools and discussion surrounding important factors to be addressed when assessing scars. A thematic analysis using the Framework Method was conducted.
Results
Participants identified key subthemes that contribute towards the overarching theme of patient-centred scar assessment. These are: patient-led care; continuity in care; learning how to self-manage scarring; and psychological assessment. Links were demonstrated between these subthemes and the remaining themes that describe scar assessment strategies, indicating their potential patient-centred contributions. The subjective opinions of clinicians were found to be valued above the use of subjective or objective scar assessment tools. Scar assessment scales were perceived to be a beneficial method for self-reflection in relation to psychosocial functioning. However, minimal feedback and review of completed assessment scales led to uncertainty regarding their purpose. Patients perceived objective tools to be of primary use for health-care professionals, though the measures may aid patients' understanding of scar properties.
Conclusions
Scar assessment tools should be used to support, rather than replace, health-care professionals' subjective judgements of scarring. Adapting the way in which clinicians introduce and use scar assessment tools, according to patient needs, can support a patient-centred approach to scar assessment
Complete response to neoadjuvant chemoradiotherapy in rectal cancer is associated with RAS/AKT mutations and high tumour mutational burden.
No full textBACKGROUND
Pathological complete response (pathCR) in rectal cancer is beneficial, as up to 75% of patients do not experience regrowth of the primary tumour, but it is poorly understood. We hypothesised that the changes seen in the pre-treatment biopsies of pathCR but not seen in residual tumour after chemoradiotherapy were the determinants of responsiveness.
METHODS
Two groups of patients with either complete response (pathCR group, N = 24) or no response (poor response group, N = 24) were retrieved. Pre-treatment biopsies of cancers from these patients underwent high read depth amplicon sequencing for a targeted panel, exome sequencing, methylation profiling and immunohistochemistry for DNA repair pathway proteins.
RESULTS
Twenty four patients who underwent pathCR and twenty-four who underwent poor response underwent molecular characterisation. Patients in the pathCR group had significantly higher tumour mutational burden and neoantigen load, frequent copy number alterations but fewer structural variants and enrichment for driver mutations in the PI3K/AKT/mTOR signalling pathway. There were no significant differences in tumour heterogeneity as measured by MATH score. Methylation analysis demonstrated enrichment for hypomethyation in the PI3K/AKT/mTOR signalling pathway.
DISCUSSION
The phenomenon of pathCR in rectal cancer may be related to immunovisibility caused by a high tumour mutational burden phenotype. Potential therapy resistance mechanisms involve the PI3K/AKT/mTOR signalling pathway, but tumour heterogeneity does not seem to play a role in resistance
Pre-Kidney Transplant Screening for Coronary Artery Disease: Current Practice in the United Kingdom.
No full textHealth related quality of life in young, steroid-naïve boys with Duchenne muscular dystrophy.
No full textKnowledge of health related quality of life (HRQOL) in the immediate phase following DMD diagnosis has not been well-characterized. It is important to understand HRQOL early in disease for both clinical care and studies of treatment. The relationship between parent-proxy and child self-report HRQOL and their associations with medical, psycho-social and behavioral symptoms deserve study. In this study HRQOL was measured using the PedsQL inventory in parent/caregiver and corticosteroid-naïve boys (ages 4 to 7 years) participating in the FOR-DMD study. Agreement between the parent-proxy report and the boys' self-report HRQOL was measured using intraclass correlation coefficients (ICCs). Factors associated with HRQOL, including standardized psychosocial and behavioral measures in this cross-sectional sample, were explored using correlations. The results showed that the level of agreement between 70 dyads of child self-report and parent-proxy ratings of HRQOL was poor for the generic PedsQL total score (ICC=0.48, 95% CI (0.23, 0.66)) and its subscale scores, and was similarly low for the neuromuscular disease module (ICC=0.24, 95% CI (0.00, 0.45)). Parents rated their child's HRQOL as poorer than the children rated themselves in all scales. Psychosocial outcome measures were more highly associated with HRQOL measures than disease severity or patient demographic variables. In the early phases of DMD, child and parent-proxy HRQOL ratings were discordant. In early DMD, psychosocial and behavioral aspects appear to be more relevant to HRQOL than disease severity factors
Does the posterior glenoid osteotomy reduce the rate of recurrence in patients with posterior shoulder instability - A systematic review.
No full textBACKGROUND
Posterior shoulder instability (PSI) is becoming an increasingly recognised condition. A number of different treatment modalities exist to treat PSI including arthroscopic or open surgeries when non-operative treatment has failed. The primary aim of this systematic review was to analyse the rate of recurrent instability after posterior glenoid osteotomy (PGO) for recurrent PSI, while secondary aim was to identify complication rate and the amount of retroversion correction.
PATIENTS AND METHODS
A review of the online databases MEDLINE and Embase was conducted on 1 November 2019 according to PRISMA guidelines. The review was registered prospectively in the PROSPERO database (Registration No. CRD42020161984). Clinical studies reporting either the recurrence rate, complications or amount of retroversion correction after PGO for PSI were included. The studies were appraised using the Methodological Index for Non-Randomized Studies (MINORS) tool.
RESULTS
The search strategy identified 9 studies eligible for inclusion. Of the 9 studies, 4 showed an improvement in retroversion with a mean change in retroversion of 10. All 9 studies reported on recurrence rate with an overall rate of 22%. Complications were discussed in only 7 of the studies with overall rate of 18.3%. The most common complication reported in the studies were degenerative changes of the glenohumeral joint (7.3%) and iatrogenic fractures (5.5%).
CONCLUSION
PGO is a viable option in patients with recurrent PSI that have increased retroversion and have failed non-operative or arthroscopic treatment. It does however carry a significant risk of complications.
LEVEL OF EVIDENCE
IV; Systematic review
Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party.
No full textAllogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR = 6.6; p = 0.001 and OR = 3.3; p = 0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria
When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.
No full textBACKGROUND
Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility.
METHODS
Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement.
RESULTS
The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or 1 μg/kg per minute and a serum lactate level >9 mmol/L.
CONCLUSIONS
Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented
