MDM2 analysis in the management of benign lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas: A useful prognostication tool?

INTRODUCTION: Well-differentiated liposarcomas (WDLS) are low-grade lipomatous tumors with low malignant potential. Previous review identified controversy on whether upfront wide resection is necessary when they occur on the trunk or the extremities. MDM2 amplification is a genetic mutation typically present in WDLS and absent in benign lipomas (BL). We aimed to study the influence of MDM2 status on the management/recurrences of lipomatous tumors in the trunk or the extremities. METHODS: All patients with lipomatous tumors with MDM2 testing in the Province of Alberta between 2015 and 2020 were identified from the Cancer Cytogenetics Laboratory dataset. High grade sarcomas, retroperitoneal, head/neck, or groin tumors were excluded. Primary outcome measures including MDM2 status, surgical margin, local recurrence, reoperation rate, dedifferentiation, and metastasis were abstracted from chart review. Descriptive statistics were used to analyse treatment patterns and recurrence rates according to MDM2 status. RESULTS: Total of 764 charts were retrieved, and 282 were included for analysis. 33 showed MDM2 amplification (11.7%), and 2 of them had local recurrence (6.1%). Two patients with recurrent tumors underwent limb-salvaging reoperation (6.1%), but no dedifferentiation or metastasis was seen. CONCLUSION: Findings in this study confirmed the benign behaviour of truncal/extremities lipomas with no MDM2 amplification. Given we found a 6.1% recurrence rate in MDM2 amplified tumors, a prolong follow up of this subset of patients is warranted. Overall, regardless of the MDM2 status, we believe an initial marginal excision is a reasonable surgical approach as recurrences are rare, and they can be managed with re-excision when they occur.

Development and initial implementation of electronic clinical decision supports for recognition and management of hospital-acquired acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with poor patient outcomes and high costs of care. The implementation of clinical decision support tools within electronic medical record (EMR) could improve AKI care and outcomes. While clinical decision support tools have the potential to enhance recognition and management of AKI, there is limited description in the literature of how these tools were developed and whether they meet end-user expectations. METHODS: We developed and evaluated the content, acceptability, and usability of electronic clinical decision support tools for AKI care. Multi-component tools were developed within a hospital EMR (Sunrise Clinical Manager™, Allscripts Healthcare Solutions Inc.) currently deployed in Calgary, Alberta, and included: AKI stage alerts, AKI adverse medication warnings, AKI clinical summary dashboard, and an AKI order set. The clinical decision support was developed for use by multiple healthcare providers at the time and point of care on general medical and surgical units. Functional and usability testing for the alerts and clinical summary dashboard was conducted via in-person evaluation sessions, interviews, and surveys of care providers. Formal user acceptance testing with clinical end-users, including physicians and nursing staff, was conducted to evaluate the AKI order set. RESULTS: Considerations for appropriate deployment of both non-disruptive and interruptive functions was important to gain acceptability by clinicians. Functional testing and usability surveys for the alerts and clinical summary dashboard indicated that the tools were operating as desired and 74% (17/23) of surveyed healthcare providers reported that these tools were easy to use and could be learned quickly. Over three-quarters of providers (18/23) reported that they would utilize the tools in their practice. Three-quarters of the participants (13/17) in user acceptance testing agreed that recommendations within the order set were useful. Overall, 88% (15/17) believed that the order set would improve the care and management of AKI patients. CONCLUSIONS: Development and testing of EMR-based decision support tools for AKI with clinicians led to high acceptance by clinical end-users. Subsequent implementation within clinical environments will require end-user education and engagement in system-level initiatives to use the tools to improve care.

Surgical management of truncal and extremities atypical lipomatous tumors/well-differentiated liposarcoma: A systematic review of the literature.

INTRODUCTION: Atypical lipomatous tumors or well-differentiated liposarcomas (ALT/WDLS) are low-grade soft tissue tumors that are commonly located on the trunk and extremities. There is no consensus on the best surgical approach for ALT/WDLS. METHODS: A systematic literature review of PubMed, Medline, Embase, Scopus, and google scholar was performed. All published studies on trunk or extremities ALT/WDLS with reported outcome data were considered and independently screened for inclusion by at least two of the authors. RESULTS: A total of eighteen studies comprising 793 patients with ALT/WDLS were included. 580 patients underwent marginal excision, with local recurrence observed in 69 (11.9%). 213 patients underwent wide excision with local recurrence in 7(3.3%). Recurrent tumors were successfully re-resected with marginal or wide excision. Dedifferentiation was confirmed in 9 patients (1.1%), and a distant pulmonary metastasis in 1 patient (0.1%). DISCUSSION: Marginal excision of truncal or extremities ALT/WDLS results in a slightly higher local recurrence rate. However, recurrences are almost always amenable to re-resection. The findings support the use of marginal excision for truncal or extremities ALT/WDLS.

Identification of Mature Atherosclerotic Plaque Proteome Signatures Using Data-Independent Acquisition Mass Spectrometry.

Atherosclerosis is a chronic inflammatory disease with complex pathobiology and one of the most common causes of cardiovascular events. The process is characterized by complex vascular remodeling processes that require the actions of numerous proteins. The composition of atherosclerotic plaque is increasingly recognized as a major factor governing the occurrence of cardiovascular or neurological symptoms. To gain deeper insights into the composition of atherosclerotic plaques, we created quantitative proteome profiles of advanced plaque tissues of six male patients undergoing carotid endarterectomy for stroke prevention. Using a quantitative, data-independent proteome approach, we identified 4181 proteins with an average protein coverage of 45%. An analysis of the quantitative composition of the tissue revealed key players of vascular remodeling processes. Moreover, compared with proximal arterial tissue, 20 proteins in mature plaques were enriched, whereas 52 proteins were found in lower quantities. Among the proteins with increased abundance were prominent extracellular matrix proteins such as biglycan and lumican, whereas cytoskeletal markers for contractile smooth muscle cells (SMCs) were decreased. Taken together, this study provides the most comprehensive quantitative assessment of mature human plaque tissue to date, which indicates a central role of SMCs in the structure of advanced atherosclerotic plaques.