Outcomes in ANCA-associated vasculitis patients with end-stage kidney disease on renal replacement therapy-A meta-analysis.

BACKGROUND: End-stage kidney disease (ESKD) is associated with poor prognosis in patients with anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study summarizes the existing evidence regarding outcomes in AAV patients with ESKD on renal replacement therapy. METHODS: Searches of the MEDLINE and Embase databases were performed from inception until December 2021. Any study reporting outcomes after ESKD in patients with AAV on haemodialysis or peritoneal dialysis was included. The mortality rate per 100 person-years (100 py) calculated with a random-effects meta-analysis model was the primary outcome. Rates of infections and relapses were secondary outcomes. RESULTS: 2470 citations were found; 22 studies of 952 adult patients with over 3600 person-years of follow-up were included. The pooled mortality rate was 10.90 per 100 py (95% CI: 7.11 - 14.68, I2 = 90.8%). The pooled 1-year survival was 80.9% (95% CI: 75.6 - 86.1%, I2 = 86.1%) while the pooled 5-year survival was 61.0% (95% CI: 46.0 - 76.0%, I2 = 0.0%). The pooled severe infection rate was 66.57 per 100 py (95% CI: 13.64 - 119.50, I2 = 99.6%). The pooled relapse rate was 6.22 per 100 py (95% CI: 4.64 - 7.80, I2 = 46.6%). Only 1 paediatric study met the inclusion criteria and reported a mortality rate of 11.7 ± 1.9 deaths per 100 py (95% CI: 0.23 - 23.20) amongst 9 patients. CONCLUSIONS: Patients with AAV and ESKD have a lower risk of relapse, but higher infection and mortality rates. More prospective research exploring the role of immunosuppression after ESKD is needed.

Mutational Landscape of Patients Referred for Elevated Hemoglobin Level.

Background: Since the identification of JAK2 V617F and exon 12 mutations as driver mutations in polycythemia vera (PV) in 2005, molecular testing of these mutations for patients with erythrocytosis has become a routine clinical practice. However, the incidence of myeloid mutations other than the common JAK2 V617F mutation in unselected patients referred for elevated hemoglobin is not well studied. This study aimed to characterize the mutational landscape in a real-world population of patients referred for erythrocytosis using a targeted next-generation sequencing (NGS)-based assay. Method: A total of 529 patients (hemoglobin levels >160 g/L in females or >165 g/L in males) were assessed between January 2018 and May 2021 for genetic variants using the Oncomine Myeloid Research Assay (ThermoFisher Scientific, Waltham, MA, USA) targeting 40 key genes with diagnostic and prognostic implications in hematological conditions (17 full genes and 23 genes with clinically relevant "hotspot" regions) and a panel of 29 fusion driver genes (>600 fusion partners). Results: JAK2 mutations were detected in 10.9% (58/529) of patients, with 57 patients positive for JAK2 V617F, while one patient had a JAK2 exon 12 mutation. Additional mutations were detected in 34.5% (20/58) of JAK2-positive patients: TET2 (11; 19%), DNMT3A (2;3.4%), ASXL1 (2; 3.4%), SRSF2 (2; 3.4%), BCOR (1; 1.7%), TP53 (1; 1.7%), and ZRSR2 (1; 1.7%). Diagnosis of PV was suspected in 2 JAK2-negative patients based on the 2016 World Health Organization (WHO) diagnostic criteria. Notably, one patient carried mutations in the SRSF2 and TET2 genes, and the other patient carried mutations in the SRSF2, IDH2, and ASXL1 genes. Three JAK2-negative patients with elevated hemoglobin who tested positive for BCR/ABL1 fusion were diagnosed with chronic myeloid leukemia (CML) and excluded from further analysis. The remaining 466 JAK2-negative patients were diagnosed with secondary erythrocytosis and mutations were found in 6% (28/466) of these cases. Conclusion: Mutations other than JAK2 mutations were frequently identified in patients referred for erythrocytosis, with mutations in the TET2, DNMT3A, and ASXL1 genes being detected in 34.5% of JAK2-positive PV patients. The presence of additional mutations, such as ASXL1 mutations, in this population has implications for prognosis. Both the incidence and mutation type identified in patients with secondary erythrocytosis likely reflects incidental, age-associated clonal hematopoiesis of indeterminate potential (CHIP).

Video assessment of laparoscopic skills by novices and experts: implications for surgical education.

BACKGROUND: Previous investigators have shown that novices are able to assess surgical skills as reliably as expert surgeons. The purpose of this study was to determine how novices and experts arrive at these graded scores when assessing laparoscopic skills and the potential implications this may have for surgical education. METHODS: Four novices and four general laparoscopic surgeons evaluated 59 videos of a suturing task using a 5-point scale. Average novice and expert evaluator scores for each video and the average number of times that scores were changed were compared. Intraclass correlation coefficients were used to determine inter-rater and test-retest reliability. Evaluators were asked to define the number of videos they needed to watch before they could confidently grade and to describe how they were able to distinguish between different levels of expertise. RESULTS: There were no significant differences in mean scores assigned by the two evaluator groups. Novices changed their scores more frequently compared to experts, but this did not reach statistical significance. There was excellent inter-rater reliability between the two groups (ICC = 0.91, CI 0.85-0.95) and good test-retest reliability (ICC > 0.83). On average, novices and experts reported that they needed to watch 13.8 ± 2.4 and 8.5 ± 2.5 videos, respectively, before they could confidently grade. Both groups also identified similar qualitative indicators (e.g., instrument control). CONCLUSION: Evaluators with varying levels of expertise can reliably grade performance of an intracorporeal suturing task. While novices were less confident in their grading, both groups were able to assign comparable scores and identify similar elements of a suturing skill as being important in terms of assessment.