Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The floating hip injury: a descriptive study and case-control analysis

Peer reviewed: TruePurpose:: A “floating hip” (FH) injury is a rare injury describing the simultaneous ipsilateral fracture of the femur and pelvis or acetabulum (P/A). We describe our experience with patients presenting with FH injuries and compare them to controls with similar P/A fractures but without femoral involvement. Methods:: Medical records and radiographs of FH patients and controls presenting to our tertiary centre between 2015 and 2020 were reviewed. Follow-up data from outpatient clinical records were also extracted. The control group were extensively matched by age, sex, body mass index, fracture classification and energy of injury. Results:: From 1392 recorded P/A fractures, 42 FH cases were identified (average age 39 years, 78.6% males). The most common femoral fracture was the midshaft (35.7%), followed by the neck of femur (26.2%). 90.5% of FH injuries were due to high-energy mechanisms. 64.3% of P/A fractures, and 100% of femoral fractures were managed surgically. Compared to controls, FH cases were more likely to have additional orthopaedic injuries (73.8% vs. 40.5%, p = 0.002), more total theatre admissions (mean 2.5 vs. 1.19, p < 0.001), longer hospital stays (28.3 vs. 14.9 days, p = 0.02), and a higher rates of post-op complications (53.8% vs. 20%, p = 0.025) Conclusions:: We report differences in the presentation, management, and outcomes of FH injuries versus controls, even after extensive matching for confounders. These differences may inform future treatment strategies for the FH injury

Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma

Early intervention for High-Risk Smoldering Multiple Myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered. Here, we interrogated whole genome and whole exome sequencing for 54 patients across two HR-SMM interventional studies (NCT01572480, NCT02279394). We reveal that the genomic landscape of treated HR-SMM is generally simple as compared to Newly Diagnosed (ND)MM counterparts with less inactivation of tumor suppressor genes, RAS pathway mutations, MYC disruption, and APOBEC contribution. The absence of these events parallels that of indolent precursor conditions, possibly explaining overall excellent outcomes. However, some patients harboring genomic complexity fail to sustain response and experience resistant, progressive disease. Overall, clinical risk scores do not effectively discriminate between genomically indolent and aggressive disease. Genomic profiling can contextualize the advantage of early intervention in SMM and guide personalization of therapy

Genomic Profiling to Interpret the Outcomes of Early Intervention for High-Risk Smoldering Myeloma

Introduction Early intervention for High-Risk Smoldering Multiple Myeloma (HR-SMM) achieves deeper and more prolonged responses compared to Newly Diagnosed (ND) MM. Various clinical risk models estimate the risk of SMM progression to MM but there is significant discordance between them (Hill et al., JAMA Onc. 2021). It is unclear if beneficial outcomes of interventional studies in HR-SMM are due to treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered. Methods To gain greater biologic insight into treatment outcomes, we performed the first whole genome sequencing (WGS) analysis of treated HR-SMM for 27 patients treated with carfilzomib, lenalidomide, and dexamethasone (KRd) and R maintenance (NCT01572480, presented in parallel). We pooled genomic features from 27 patients with HR-SMM treated with Elotuzumab (Elo)R+/-d; (E-PRISM). Genomic features were compared to those of 701 patients with NDMM from CoMMpass (NCT01454297). Results After a median follow-up of 52.8 months, median PFS was not reached with KRd/R. After 8 cycles of KRd, 19 (70.3%) achieved minimal residual disease (MRD) negativity (LOD 10 -5). At data cutoff, June 13, 2023, 14 patients (51.9%) achieved sustained MRD-negativity, 6 patients (22.2%) lost an initial MRD-negative response and 5 patients clinically progressed (18.5%). Overall, there was discordance between risk models: 3 patients (11.1%) were HR by Mayo2008 criteria, 14 (51.9%) by Mayo 20/2/20, 18 (66.7%) by PETHEMA, and 21 (77.8%) by Rajkumar/Landgren/Mateos criteria (Rajkumar et al., Blood. 2015). Eighteen (66.7%) met criteria for 2 or more scores. The estimated 5-year risk of progression ranged 4.8 to 82.1% (Pangea, median 18.6%). We compared the pooled HR-SMM to NDMM from CoMMpass. The frequency of HR translocations was similar (t(4;14), t(14;16), t(14;20); p>0.05). Consistent with the early disease stage of SMM, mutations of NRAS were lower in SMM (p = <0.001) as were events at the MYC locus (8q24; p <0.001) and gains of 1q (p = 0.039). Next, tumor suppressor genes (TSG) were interrogated together with copy number loss at their loci. Consistent with their late onset in tumor evolution, aberrations at key TSG were less common in HR-SMM (p < 0.05): CDKN2C, CYLD, TENT5C, FUBP1, MAX, NCOR1, NF1, NFKBIA, PRDM1, RB1, RPL5,and TRAF3 (p < 0.05). In a genome-corrected comparison, APOBEC (SBS2+SBS13) mutational signatures were diminished in KRd WGS compared to 60 Dara-KRd-treated NDMM (Maura et al., ASH. 2021; 48% vs 87%, p < 0.001) and in E-PRISM vs CoMMpass (15% vs 45%, p = 0.001). We next related genomic features associated with HR-SMM to treatment outcomes. Patients treated with KRd/R had yearly MRD testing and gain1q, MYC dysregulation via loss of MAX, and t(4:14) were all associated with failure to sustain MRD-negativity. Across pooled HR-SMM, inactivation of CYLD, CREBBP, MAX, and HIST1H2BK; t(4;14), APOBEC expression, loss at select GISTIC peaks ( Fig 1A) and chromothripsis all were associated with HR-SMM progression in the face of triplet therapy (p<0.05). Presence of any one or more of these features was associated with progression (p = 0.005; Fig1B). Conversely, no clinical risk score was able to discern those with this molecular high risk. Conclusion In patients treated on 2 parallel clinical trials for HR-SMM, we found a uniform and relative genomic simplicity. Moreover, non-progressors appear genomically similar to patients with non-progressive/stable MGUS and SMM under observation (Oben et al., Nat Comm 2021). However, within clinical HR-SMM, a set of high-risk genomic features portends progression despite intervention. These results suggest that clinical risk scores do not effectively discriminate between genomically indolent and aggressive disease. Though possible that results reflect treatment before the acquisition of key drivers, prior data suggest that many of these high-risk features are not acquired within the 5 years preceding clinical diagnosis of MM (Bolli et al., Nat Comm. 2018; Bustoros et al., J Clin Onc. 2020). Altogether, these results support the use of genomics to contextualize the advantage of early intervention in SMM (i.e., to avoid overtreatment of non-progressors and to better identify cases likely to progress without therapy). Fig1A: Heatmap of High-Risk Features in Patients treated with KRD/R and EPRISM. Fig1B: Kaplan-Meier curve for time to progression by presence of HR features for KRD/R