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Background: Older people with end-stage kidney disease (ESKD) are vulnerable to frailty, which impacts on clinical and experiential outcomes. With kidney transplantation in older people increasing, a better understanding of patient experiences is necessary for guiding decision making. The Kidney Transplantation in Older People (KTOP):impact of frailty on outcomes study aims to explore this. We present a secondary analysis of the Edmonton Frail Scale (EFS) and its relationship with patient experience scores., Methods: The KTOP study is a single centre, prospective study, which began in October 2019. All ESKD patients aged ≥60 considered for transplantation at Imperial College Renal and Transplant Centre were eligible. Frailty was assessed using the EFS and 5 questionnaires assessed patient experience and quality of life (QoL) (Short Form-12(v2), Palliative Care Outcome Scale-Symptoms Renal, Depression Patient Health Questionnaire-9, Illness Intrusiveness Ratings Scale, Renal Treatment Satisfaction Questionnaire). The EFS was divided into 4 subdomains (psychosocial, physical function, medical status, and general health) and then compared with the questionnaire scores., Results: 210 patients have been recruited (aged 60-78), 186 of whom completed EFS assessments. 118 (63.4%) participants were not frail, 36 (19.4%) vulnerable, and 32 (17.2%) were frail. Worse frailty scores were associated with poorer patient experience and QoL scores across all questionnaires. Severe deficits in the EFS psychosocial subdomain showed a statistically significant association with higher depression screen scores (coefficient 4.9, 95% CI 3.22 to 6.59), lower physical (coefficient -4.35, 95% CI -7.59 to -1.12) and mental function scores (coefficient -8.33, 95% CI -11.77 to -4.88) from the Short Form-12(v2), and lower renal treatment satisfaction scores (coefficient -5.54, 95% CI -10.70 to -0.37). Deficits in the physical function and medical status EFS subdomians showed some association with patient experience scores., Conclusion: In the KTOP study cohort at recruitment vulnerable and frail candidates reported worse QoL and patient experiences. Severe deficits in the psychosocial subdomains of the EFS showed a strong association with patient experience and QoL, whilst physical function and medical status deficits showed a lesser association. This has highlighted specific EFS domains that may be suitable for targeted interventions to improve experiences and optimise outcomes., Competing Interests: EB – Baxter Healthcare: speaker fees and advisory board; AWAK – advisory board; liberDi – advisory board. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Thind, Levy, Wellsted, Willicombe and Brown.)

Frailty, characterized by a decreased physiological reserve and an increased vulnerability to stressors, is common among kidney transplant (KT) candidates and recipients. In this review, we present and summarize the key arguments for and against the assessment of frailty as part of KT evaluation. The key arguments for including frailty were: (i) sheer prevalence and far-reaching consequences of frailty on KT, and (ii) the ability to conduct a more holistic and objective evaluation of candidates, removing the inaccuracy associated with 'eye-ball' assessments of transplant fitness. The key argument against were: (i) lack of agreement on the definition of frailty and which tools should be used in renal populations, (ii) a lack of clarity on how, by whom and how often frailty assessments should be performed, and (iii) a poor understanding of how acute stressors affect frailty. However, it is the overwhelming opinion that the time has come for frailty assessments to be incorporated into KT listing. Although ongoing areas of uncertainty exist and further evidence development is needed, the well-established impact of frailty on clinical and experiential outcomes, the invaluable information obtained from frailty assessments, and the potential for intervention outweigh these limitations. Proactive and early identification of frailty allows for individualized and improved risk assessment, communication and optimization of candidates., Competing Interests: A.W. is member of the CKJ editorial board. The results presented in this paper have not been published previously in whole or part, except in abstract format., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Kidney transplantation in older people has increased, however older transplant recipients experience mixed outcomes that invariably impacts on their quality of life. The increased vulnerability of older end stage kidney disease patients to frailty and cognitive impairment, may partially explain the differences in outcomes observed. The Kidney Transplantation in Older People (KTOP): impact of frailty on clinical outcomes study is an active clinical study aiming to explore the experience of older people waiting for and undergoing transplantation. In this manuscript we present the study protocol, the study cohort, and the prevalence of frailty and cognitive impairment identified at recruitment., Methods: The KTOP study is a single centre, prospective, mixed methods, observational study. Recruitment began in October 2019. All patients aged 60 or above either active on the deceased donor waitlist or undergoing live donor transplantation were eligible for recruitment. Recruited participants completed a series of questionnaires assessing frailty, cognition, and quality of life, which are repeated at defined time points whilst on the waitlist and post-transplant. Clinical data was concurrently collected. Any participants identified as frail or vulnerable were also eligible for enrolment into the qualitative sub-study., Results: Two hundred eight participants have been recruited (age 60-78). Baseline Montreal Cognitive Assessments were available for 173 participants, with 63 (36.4%) participants identified as having scores below normal (score < 26). Edmonton Frail Scale assessments were available for 184 participants, with 29 participants (15.8%) identified as frail (score ≥ 8), and a further 37 participants (20.1%) identified as being vulnerable (score 6-7)., Conclusion: In the KTOP study cohort we have identified a prevalence of 36.4% of participants with MoCA scores suggestive of cognitive impairment, and a prevalence of frailty of 15.8% at recruitment. A further 20.1% were vulnerable. As formal testing for cognition and frailty is not routinely incorporated into the work up of older people across many units, the presence and significance of these conditions is likely not known. Ultimately the KTOP study will report on how these parameters evolve over time and following a transplant, and describe their impact on quality of life and clinical outcomes., (© 2022. The Author(s).)

Introduction: Pericardial effusions and uremic pericarditis have been described in patients with kidney disease since 1836 [1] when they were considered a pre-terminal sign [2]. Fortunately today this pathology is less frequently encountered [3]; however, this has resulted in highly variable management., Aims: This report aims to describe the case of a 61-year-old female presenting with a large pericardial effusion prior to kidney transplantation, and how local activity was reviewed to guide management., Materials and Methods: We performed a retrospective service evaluation project, where 44 cases of pericardial effusion encountered at a tertiary renal center over 8 years were reviewed. Clinical data, investigation results, and outcomes were collected to identify the common clinical categories encountered and the role pericardial intervention may have had in those cases., Results: A total of 44 cases of pericardial effusion were encountered, grouped into the following clinical categories; procedural (8), classical (3), uremic (15), and other etiology (18). Pericardial intervention occurred in 50% of cases due to current or impending hemodynamic compromise. Aspiration was of limited diagnostic use, providing a clinically relevant culture result in only one of the cases reviewed. No deaths were observed in the classical group, and 1-year survival was 86%, 67% and 43% in the uremic, other, and procedural groups, respectively., Conclusion: Our findings suggest that in patients with advanced kidney disease requiring renal replacement therapy and pericardial effusions, aspiration should largely be reserved for cases with hemodynamic compromise only, as in this series aspiration did not significantly improve diagnosis or guide subsequent treatment.

Background: The rapidly evolving novel coronavirus 2019 (COVID-19) pandemic bought many kidney transplant (KT) programs to a halt. Integral to resuming KT activity is understanding the perspectives of potential transplant candidates during this highly dynamic time., Methods: From June 1 to July 7, 2020, a telephone survey of KT candidates on the deceased donor waiting list at Imperial College Renal and Transplant Centre in West London was conducted. The survey captured ongoing COVID-19 exposure risks and patients' views on waitlist (WL) reactivation and undergoing transplantation., Results: Two hundred seven responses were received. Of the respondents, 180 patients (87%) were happy to be reactivated onto the WL; with 141 patients (68%) willing to give consent to transplantation currently, while 53 patients (26%) felt unsure, and 13 patients (6%) would decline a KT. The vast majority of patients had no concerns. In the responses from those who were uncertain or who would decline a KT, concerns about COVID-19 infection and the need for reassurance from transplant units dominated. Universally patients wanted more information about COVID-19 infection risk with KT and the precautions being taken to reduce this risk., Conclusions: The majority of surveyed patients are in favor of reactivation and receiving a KT despite the ongoing COVID-19 pandemic. Reactivation of candidates cannot be assumed and should take an individualized approach, incorporating clinical risk with patient perspectives. Improved communication with KT candidates is highly requested., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Introduction: Liver cirrhosis and its complication - hepatocellular carcinoma (HCC) - have been associated with increased exhaled limonene. It is currently unclear whether this increase is more strongly associated with the presence of HCC or with the severity of liver dysfunction., Methods: We compared the exhaled breath of 40 controls, 32 cirrhotic patients, and 12 cirrhotic patients with HCC using the Breath Biopsy platform. Breath samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. Limonene levels were compared between the groups and correlated to bilirubin, albumin, prothrombin time international normalized ratio, and alanine aminotransferase., Results: Breath limonene concentration was significantly elevated in subjects with cirrhosis-induced HCC (M: 82.1 ng/L, interquartile range [IQR]: 16.33-199.32 ng/L) and cirrhosis (M: 32.6 ng/L, IQR: 6.55-123.07 ng/L) compared with controls (M: 6.2 ng/L, IQR: 2.62-9.57 ng/L) (P value = 0.0005 and 0.0001, respectively) with no significant difference between 2 diseased groups (P value = 0.37). Levels of exhaled limonene correlated with serum bilirubin (R = 0.25, P value = 0.0016, r = 0.51), albumin (R = 0.58, P value = 5.3e-8, r = -0.76), and international normalized ratio (R = 0.29, P value = 0.0003, r = 0.51), but not with alanine aminotransferase (R = 0.01, P value = 0.36, r = 0.19)., Discussion: Exhaled limonene levels are primarily affected by the presence of cirrhosis through reduced liver functional capacity, as indicated by limonene correlation with blood metrics of impaired hepatic clearance and protein synthesis capacity, without further alterations observed in subjects with HCC. This suggests that exhaled limonene is a potential non-invasive marker of liver metabolic capacity (see Visual abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A388).

Background: Recent improvements in DNA sequencing and genome scaffolding have paved the way to generate high-quality de novo assemblies of pseudomolecules representing complete chromosomes of wheat and its wild relatives. These assemblies form the basis to compare the dynamics of wheat genomes on a megabase scale., Results: Here, we provide a comparative sequence analysis of the 700-megabase chromosome 2D between two bread wheat genotypes-the old landrace Chinese Spring and the elite Swiss spring wheat line 'CH Campala Lr22a'. Both chromosomes were assembled into megabase-sized scaffolds. There is a high degree of sequence conservation between the two chromosomes. Analysis of large structural variations reveals four large indels of more than 100 kb. Based on the molecular signatures at the breakpoints, unequal crossing over and double-strand break repair were identified as the molecular mechanisms that caused these indels. Three of the large indels affect copy number of NLRs, a gene family involved in plant immunity. Analysis of SNP density reveals four haploblocks of 4, 8, 9 and 48 Mb with a 35-fold increased SNP density compared to the rest of the chromosome. Gene content across the two chromosomes was highly conserved. Ninety-nine percent of the genic sequences were present in both genotypes and the fraction of unique genes ranged from 0.4 to 0.7%., Conclusions: This comparative analysis of two high-quality chromosome assemblies enabled a comprehensive assessment of large structural variations and gene content. The insight obtained from this analysis will form the basis of future wheat pan-genome studies.

Cereal crops such as wheat and maize have large repeat-rich genomes that make cloning of individual genes challenging. Moreover, gene order and gene sequences often differ substantially between cultivars of the same crop species. A major bottleneck for gene cloning in cereals is the generation of high-quality sequence information from a cultivar of interest. In order to accelerate gene cloning from any cropping line, we report 'targeted chromosome-based cloning via long-range assembly' (TACCA). TACCA combines lossless genome-complexity reduction via chromosome flow sorting with Chicago long-range linkage to assemble complex genomes. We applied TACCA to produce a high-quality (N50 of 9.76 Mb) de novo chromosome assembly of the wheat line CH Campala Lr22a in only 4 months. Using this assembly we cloned the broad-spectrum Lr22a leaf-rust resistance gene, using molecular marker information and ethyl methanesulfonate (EMS) mutants, and found that Lr22a encodes an intracellular immune receptor homologous to the Arabidopsis thaliana RPM1 protein.

"Map-based cloning" is a frequently used approach to isolate rust resistance genes. A critical step during map-based cloning is the transition from genetic information, i.e., a genetic map, to physical sequence information. Bacterial artificial chromosome clones are often used to establish sequence information spanning a genetic interval. However, a major limitation of BAC clones consists in their small insert size of 100-200 kb. Targeted chromosome-based cloning via long-range assembly (TACCA) is a method that can replace BAC library screening. This approach involves chromosome flow-sorting and the establishment of a long-range de novo assembly. This chapter provides an overview of TACCA as well as a detailed description of sequence analyses, molecular marker development, and candidate gene identification.