Citations

AbstractNext-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions. We analyzed the diagnostic samples from patients with AML for the detection of pathogenic myeloid mutations in 8 genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (site 1) or the GeneTrails Comprehensive Heme Panel (site 2) at the 2 institutions and compared them with the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. The overall percent agreement was over 95% each in all 8 genes, with almost perfect agreement (κ > 0.906) in all but WT1, which had substantial agreement (κ = 0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze samples from patients with AML enrolled in the BAMT show high concordance, a reassuring finding given the wide use of NGS for therapeutic decision-making in AML.

Background: Dual-mobility (DM) implants reduce the risk of dislocation in patients who have undergone total hip arthroplasty (THA); however, DM implants are at risk for large-head dislocation and intraprosthetic dissociation (IPD), where the inner femoral head dissociates from the outer polyethylene head. This study aimed to report the incidence of DM dislocation and IPD, evaluate the rate of recognition of IPD before and after reduction, investigate the outcomes of these complications, and provide treatment recommendations for their management. Methods: Between 2010 and 2021, 695 primary and 758 revision THAs were performed with DM constructs at a single institution. There were 44 large-head dislocations (3.0%) and 10 IPDs (0.7%). Four additional IPDs occurred during attempted closed reduction, increasing the IPD incidence to 0.96%. We reviewed prior instability history, dislocation management, success of reduction, recognition of IPD, and subsequent rates of revision and complications. The mean follow-up was 2.5 years. Results: Nine of 10 IPDs were missed at presentation and thus not treated as such. Sixty-three percent of attempted closed reductions in the emergency department failed and led to 4 IPDs and 1 periprosthetic fracture. Reduction success was associated with the following factors: use of general anesthesia with paralysis (p = 0.02), having the reduction performed by an orthopaedist (p = 0.03), and undergoing only 1 reduction attempt (p = 0.015). Two-thirds of dislocations required revision. The rate of redislocation was 33%, and 5 hips required subsequent revision at a mean of 1.8 years after the initial dislocation. Conclusions: We present an evaluation of DM-implant dislocation and dissociation along with management recommendations based on these data. Given the low success and high complication rates of attempted closed reduction and the need for eventual revision, we recommend that all patients with dislocated DM implants be brought to the operating room for closed reduction as well as potential revision if the reduction fails. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AbstractBackgroundFor aggressive maxillary sinus and pterygopalatine fossa (PPF) tumors, an en‐bloc pterygomaxillectomy may be indicated.MethodsFive head specimens were used to study the feasibility of an en‐bloc pterygomaxillectomy. Eighty‐five non‐pathological CT scans were used to compare the superior edge of the inferior turbinate (IT) and the middle turbinate tail (MT) as landmarks for the pterygoid osteotomy.ResultsThrough a combined sublabial–subperiosteal incision and transoral route, a mid‐sagittal osteotomy through the hard palate and an axial osteotomy below the infraorbital foramen were performed. For the endoscopic pterygoid osteotomy, an infra‐vidian transpterygoid approach was performed, subsequently removing the pterygomaxillectomy en‐bloc. As landmarks, the osteotomies at the level of the MT tail and IT resected the pterygoid plates completely, but the IT osteotomy was further away from the vidian canal (7.5 vs. 6 mm).ConclusionsThe endoscopic‐assisted en‐bloc pterygomaxillectomy is feasible. The IT landmark is safe and ensures complete resection of the pterygoid plates.

Abstract Accumulating evidence suggests that metabolic demands of the regenerating liver are met via lipid metabolism and critical regulators of this process. As such, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) critically affect hepatic regeneration in rodent models. The present study aimed to evaluate potential alterations and dynamics of circulating GLP-1 and GLP-2 in patients undergoing liver resections, focusing on post-hepatectomy liver failure (PHLF). GLP-1, GLP-2, Interleukin-6 (IL-6) and parameters of lipid metabolism were determined perioperatively in fasting plasma of 46 patients, who underwent liver resection. GLP-1 and GLP-2 demonstrated a rapid and consistently inverse time course during hepatic regeneration with a significant decrease of GLP-1 and increase of GLP-2 on POD1. Importantly, these postoperative dynamics were significantly more pronounced when PHLF occurred. Of note, the extent of resection or development of complications were not associated with these alterations. IL-6 mirrored the time course of GLP-2. Assessing the main degradation protein dipeptidyl peptidase 4 (DPP4) no significant association with either GLP-1 or -2 could be found. Additionally, in PHLF distinct postoperative declines in plasma lipid parameters were present and correlated with GLP-2 dynamics. Our data suggest dynamic inverse regulation of GLP-1 and GLP-2 during liver regeneration, rather caused by an increase in expression/release than by changes in degradation capacity and might be associated with inflammatory responses. Their close association with circulating markers of lipid metabolism and insufficient hepatic regeneration after liver surgery suggest a critical involvement during these processes in humans.