Background
Experimental studies have suggested that end‐ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in ...donation after circulatory death (DCD) liver grafts. The aim of this prospective case–control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation.
Methods
In consecutive DCD liver transplantations, liver grafts were treated with end‐ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End‐stage Liver Disease (MELD) score. All patients were followed for 1 year.
Results
Ten transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6‐month and 1‐year graft and patient survival rates were 100 per cent in the DHOPE group. Six‐month graft survival and 1‐year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5′‐triphosphate (ATP) content increased 11‐fold, from 6 (3–10) to 66 (42–87) µmol per g protein (P = 0·005). All DHOPE‐preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7–1·4) versus 2·6 (0·9–5·1) mg/dl, P = 0·044). None of the ten DHOPE‐preserved livers required retransplantation for non‐anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140).
Conclusion
This clinical study of end‐ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post‐transplant biliary complications.
Increases donor pool
Highlights • I-131 for DTC may cause salivary/lacrimal gland dysfunction, transient gonadal dysfunction and SPM. • I-131 therapy seems to have no deleterious effects on female reproductive outcomes. ...• Adverse effects of I-131 are associated with the given cumulative I-131 activity.
A self-seeding microwell chip is introduced for the isolation and interrogation of single cells. A cell suspension is transferred to a microwell chip containing 6400 microwells, each microwell with a ...single 5 μm pore in the bottom. The fluid enters the microwell and drags a cell onto the pore. After a cell has landed onto the pore, it will stop the fluid flow through this microwell. The remaining fluid and cells will be diverted to the next available microwell. This results in a fast and efficient distribution of single cells in individual microwells. After identification by fluorescence microscopy, the cells of interest are isolated from the microwell by punching the bottom together with the cell. The overall single cell recovery of seeding followed by isolation of the single cell, is >70% with a specificity of 100% as confirmed by the genetic make-up of the isolated cells.
Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers ...may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.
In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.
A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval CI, 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.
Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).
Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We used integrative molecular profiling to discover and characterize molecular ...subtypes of LMS. Gene expression profiling was performed on 51 LMS samples. Unsupervised clustering showed three reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and showed that the molecular subtypes defined by gene expression showed distinct genomic changes. Tumors from the 'muscle-enriched' cluster showed significantly increased copy number changes (P=0.04). A majority of the muscle-enriched cases showed loss at 16q24, which contains Fanconi anemia, complementation group A, known to have an important role in DNA repair, and loss at 1p36, which contains PRDM16, of which loss promotes muscle differentiation. Immunohistochemistry (IHC) was performed on LMS tissue microarrays (n=377) for five markers with high levels of messenger RNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP, CFL2 and MYLK) and showed significantly correlated expression of the five proteins (all pairwise P<0.005). Expression of the five markers was associated with improved disease-specific survival in a multivariate Cox regression analysis (P<0.04). In this analysis that combined gene expression profiling, aCGH and IHC, we characterized distinct molecular LMS subtypes, provided insight into their pathogenesis, and identified prognostic biomarkers.
Coronavirus disease 2019 (COVID-19) has caused many nursing homes to prohibit resident visits to prevent viral spread. Although visiting restrictions are instituted to prolong the life of nursing ...home residents, they may detrimentally affect their quality of life. The aim of this study was to capture perspectives from the relatives of nursing home residents on nursing home visiting restrictions.
A cross-sectional online survey was conducted.
A convenience sample of Dutch relatives of nursing home residents (n = 1997) completed an online survey on their perspectives regarding nursing home visiting restrictions.
The survey included Likert-item, multiselect, and open-answer questions targeting 4 key areas: (1) communication access to residents, (2) adverse effects of visiting restrictions on residents and relatives, (3) potential protective effect of visiting restrictions, (4) important aspects for relatives during and after visiting restrictions.
Satisfaction of communication access to nursing home residents was highest when respondents had the possibility to communicate with nursing home residents by nurses informing them via telephone, contact behind glass, and contact outside maintaining physical distance. Satisfaction rates increased when respondents had multiple opportunities to stay in contact with residents. Respondents were concerned that residents had increased loneliness (76%), sadness (66%), and decreased quality of life (62%), whereas study respondents reported personal sadness (73%) and fear (26%). There was no consensus among respondents if adverse effects of the visiting restrictions outweighed the protective effect for nursing home residents. Respondents expressed the need for increased information, communication options, and better safety protocols.
Providing multiple opportunities to stay in touch with nursing home residents can increase satisfaction of communication between residents and relatives. Increased context-specific information, communication options, and safety protocols should be addressed in national health policy.
Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non‐pathogenic virus, has been proposed as marker ...of functional immunity: higher loads correspond to over‐immunosuppression, and lower loads to under‐immunosuppression. This review offers an overview of the current evidence of the association between TTV‐load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer‐reviewed articles were assessed investigating the association between TTV‐load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)‐tool was used to assess the risk of bias. Meta‐analysis with random‐effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV‐load was measured longitudinally, within the first 2 years post‐transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV‐load and infections, whereas 13 out of 15 reported an association between low TTV‐load and rejection. Meta‐analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03–1.32; HR: 1.05, 95% CI: 0.97–1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87–0.94; HR: 0.74, 95% CI: 0.71–0.76) per 1 log TTV‐load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta‐analysis indicates that blood TTV‐load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT.
Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). ...Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs can be safely combined to improve standard therapy without antagonizing anti-CD20 efficacy. In this study, we aimed to identify rituximab compatible drug-target combinations for DLBCL. For this, we collected gene expression profiles of 1,804 DLBCL patient samples. Subsequently, we performed a guilt-by-association analysis with MS4A1 (CD20) and prioritized the 500 top-ranked CD20-associated gene probes for drug-target interactions. This analysis showed the well-known genes involved in DLBCL pathobiology, but also revealed several genes that are relatively unknown in DLBCL, such as WEE1 and PARP1. To demonstrate potential clinical relevance of these targets, we confirmed high protein expression of WEE1 and PARP1 in patient samples. Using clinically approved WEE1 and PARP1 inhibiting drugs in combination with rituximab, we demonstrated significantly improved DLBCL cell killing, also in rituximab-insensitive cell lines. In conclusion, as exemplified by WEE1 and PARP1, our CD20-based genome-wide analysis can be used as an approach to identify biological relevant drug-targets that are rituximab compatible and may be implemented in phase 1/2 clinical trials to improve DLBCL treatment.
This article provides a tutorial for analyzing pupillometric data. Pupil dilation has become increasingly popular in psychological and psycholinguistic research as a measure to trace language ...processing. However, there is no general consensus about procedures to analyze the data, with most studies analyzing extracted features from the pupil dilation data instead of analyzing the pupil dilation trajectories directly. Recent studies have started to apply nonlinear regression and other methods to analyze the pupil dilation trajectories directly, utilizing all available information in the continuously measured signal. This article applies a nonlinear regression analysis, generalized additive mixed modeling, and illustrates how to analyze the full-time course of the pupil dilation signal. The regression analysis is particularly suited for analyzing pupil dilation in the fields of psychological and psycholinguistic research because generalized additive mixed models can include complex nonlinear interactions for investigating the effects of properties of stimuli (e.g., formant frequency) or participants (e.g., working memory score) on the pupil dilation signal. To account for the variation due to participants and items, nonlinear random effects can be included. However, one of the challenges for analyzing time series data is dealing with the autocorrelation in the residuals, which is rather extreme for the pupillary signal. On the basis of simulations, we explain potential causes of this extreme autocorrelation, and on the basis of the experimental data, we show how to reduce their adverse effects, allowing a much more coherent interpretation of pupillary data than possible with feature-based techniques.
The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve ...the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe.
QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms’ tumour.
With nine prospective clinical trials and two retrospective studies within the active portfolio in March 2022, QUARTET will collect one of the largest repositories of paediatric radiotherapy and imaging data, support the clinical assessment of radiotherapy, and evaluate the role and benefit of radiotherapy quality assurance for this cohort of patients within the context of clinical trials.
•High-quality, protocol compliant radiotherapy is essential in clinical trials.•QUARTET is a platform for centralised prospective radiotherapy quality assurance.•QUARTET facilitates a strong collaborative network for paediatric radiation oncology.•QUARTET improves equity in access to paediatric radiotherapy expertise across Europe.•QUARTET supports central review of diagnostic imaging for treatment failure analysis.
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