6 research outputs found
How crises work:A model of error cause and effect in surgical practice
No full textIntroduction: Surgical crises have major consequences for patients, staff and healthcare institutions. Nevertheless, their aetiology and evolution are poorly understood outside the remit of root-cause analyses. Aims: To develop a crisis model in surgery in order to aid the reporting and management of safety critical events. Methods: A narrative review surveyed the safety literature on failure causes, mechanisms and effects in the context of surgical crises. Sources were identified using non-probability sampling, with selection and inclusion being determined by author panel consensus. The data underwent thematic analysis and reporting followed the recommendation of the SALSA framework. Results: Data from 133 sources derived five principal themes. Analysis suggested that surgical care processes become destabilized in a step-wise manner. This crisis chain is initiated by four categories of threat or risk: (i) the systems in which surgeons operate; (ii) surgeons' technical, cognitive and behavioural skills; (iii) surgeons’ physiological and psychological state (operational condition); and (iv) professional culture. Once triggered, the crisis chain is driven by only three types of errors: Type I. Performance errors consist of failures to diagnose, plan or execute tasks; Type II. Awareness errors are failures to recognise, comprehend or extrapolate the impact of performance failures; Type III. Rescue errors represent failures to correct faulty performance. The co-occurrence of all three error types gives rise to harm, which can lead to a crisis in the absence of mitigating actions. Conclusion: Surgical crises may be triggered by four categories of threat and driven by only three types of error. These may represent universal targets for safety interventions that create new opportunities for crisis management.</p
Incidental renal stones in potential live kidney donors:prevalence, assessment and donation, including role of ex vivo ureteroscopy
No full textObjectivesTo evaluate the prevalence of asymptomatic renal stones in our potential donor population.To assess the safety and success of ex vivo ureteroscopy (ExURS) to remove stones from explanted donor kidneys before transplantation.Patients and MethodsWe conducted a retrospective analysis of 377 computed tomography (CT) angiograms of potential kidney donors between October 2004 and May 2007 to assess the prevalence of asymptomatic renal stones in our donor population.Between October 2005 and October 2011, kidneys from suitable donors underwent ExURS. Stones were removed using basket extraction or were fragmented with holmium laser on bench before transplantation.Immediate and long-term complications of the transplanted recipients were recorded.Donors were followed with yearly ultrasonography of the remaining kidney in addition to standard follow-up protocol.ResultsReview of 377 CT angiograms between October 2004 to May 2007 showed a 5% prevalence of asymptomatic renal stones.Out of 55 potential donors (19 identified between October 2004 to May 2007 and a further 36 identified since May 2007), 20 donors with stones proceeded to donation, with stone size ranging from 2 to 12 mm.Of the patients, 17 proceeded to ExURS. Stones were removed in 10 patients; five with basket retrieval, four with laser fragmentation and one with both laser fragmentation and basket retrieval.There were no early or late allograft stone-related complications and no evidence of stones on follow-up imaging at a mean (range) of 10 (1-24) months.There has been no reported stone recurrence in any of the donors to date and no stone on ultrasonography of eight donors with > 1-year follow-up (mean 26 months, range 12-49 months).ConclusionsAsymptomatic renal stones are present in 5% of our donors.ExURS can be safely used to remove stones in these kidneys before transplantation, without the risk of subjecting the donor to an additional stone-removing procedure.Continued long-term follow-up of donors and recipients is still required to ensure the safety of this approach.</p
Nephrectomy in autosomal dominant polycystic kidney disease: A consensus statement of the ERA Genes & Kidney Working Group
No full text\ua9 2025 The Author(s). A substantial number of patients with autosomal dominant polycystic kidney disease (ADPKD) undergo a nephrectomy, especially in workup for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians about which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD. A literature review was performed and extended to a meta-analysis when possible. For this purpose, PubMed and EMBASE were searched up to May 2024. Fifty-four publications, describing a total of 2391 procedures, were included. In addition, an exploratory questionnaire was sent to urologists, nephrologists, and transplant surgeons. These sources were used to develop practice points about indications, complications, mortality, and timing and technique of nephrectomy. In addition, data on renal embolization as a potential alternative to nephrectomy were explored and summarized. To reach consensus, practice points were defined and improved in three Delphi survey rounds by experts of the European Renal Association Working Group Genes & Kidney and the European Association of Urology Section of Transplantation Urology. A total of 23 practice points/statements were developed, all of which reached consensus. Among others, it was deemed that nephrectomy can be performed successfully for various indications and is an intermediate risk procedure with acceptable mortality and minimal impact on kidney graft function when performed before, in the same session or after transplantation. The complication rate seems to increase when the procedure is performed as an emergency. During the workup for transplantation, patient complaints should be assessed routinely by questionnaires to indicate symptom burden. Deciding on the need for nephrectomy and exploring potential alternatives such as kidney embolization should be a process of shared decision-making, preferably after multidisciplinary consultation
Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
No full textWith the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches
Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma
No full textADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action
