Citations

Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.

Background In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). Methods Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. Results Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re‐resection (61.9%). The 5‐year OS rate varied significantly based on the pattern of failure ( P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [ P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [ P < .001]). The 5‐year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. Conclusions Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease‐free survivors were identified after surgery for second LR in patients selected for this intervention.

Objectives: The aim of this study is to directly compare clinical outcomes following the treatment of medium-sized osteochondral lesions of the talus (OLTs) using a microfracture technique augmented with Extracellular Matrix and Bone Marrow Aspirate Concentrate (MFX) versus OAT to determine which treatment is superior for medium-sized lesions. Methods: Patients treated for an OLT between 2015 and 2018 by a single surgeon, fellowship-trained in sports medicine and foot and ankle, were screened for this study. Retrospective chart review determined treatment, lesion size, lesion location, concurrent injuries, and demographic information. Patients at a minimum of 12 months follow-up, treated with MFX or OAT, and lesions sized 80-165mm2 were eligible for inclusion. All surgical repairs were augmented with an adjuvant mixture of micronized cartilage extracellular matrix and bone marrow aspirate concentrate (ECM-BMAC). Patient-reported functional outcomes were collected through our institution’s prospective Registry database. Patients treated prior to March 2016 were administered preoperative Foot and Ankle Outcome Score questionnaires. Those treated after this date were administered preoperative Physical Function, Pain Interference, Global Physical Health, Global Mental Health, Depression, and Pain Intensity Patient-Reported Outcome Information System (PROMIS) domains. Both FAOS and PROMIS were administered postoperatively. Postoperative MRIs were assessed using a modified magnetic resonance observation of cartilage repair tissue (MOCART) score. Student’s paired and two-group t-tests were used to evaluate for statistically significant pre-to-postoperative change and differences between procedure groups (p less than 0.05). Results: Twenty-seven patients treated with MFX (age range, 14-58) and twenty-three patients treated using OAT (age range, 22-64) were identified. All OAT patients received a single-plug transplantation. The final average lesion size ± standard deviation (SD) for patients treated with MFX was 115.44mm2± 22.51 (range, 156-80mm2) and 121.78mm2± 23.98 (range, 165-80mm2) for those treated using OAT (p=0.34). On average, functional outcome scores improved pre-to-postoperatively across all scales within both groups. Statistically significant improvements were detected in PROMIS Physical Function (Δ=8.32, p=0.01), Pain Interference (Δ=-7.15, p=0.02), Global Physical Health (Δ=5.87, p=0.03), and Pain Intensity (Δ=-7.06, p=0.05) domains for the MFX cohort. For the OAT patient group, significant pre-to-postoperative change was seen in the FAOS subcategories of Pain (Δ=28.70, p=0.03), Sports Activities (Δ=43.12, p<0.01), and Quality of Life (Δ=43.75, p=0.01); overall FAOS score (Δ=29.93, p=0.01); and PROMIS Physical Function (Δ=13.66, p=0.01), Pain Interference (Δ=-14.58, p<0.01), Global Physical Health (Δ=12.2, p=0.01), Depression (Δ=-4.13, p=0.02), and Pain Intensity (Δ=-16.56, p=0.02) domains. On average, with the exception of the postoperative Sports Activities subscale, postoperative FAOS and pre-to-postoperative change in FAOS were higher and greater in the OAT patient group. Similarly, on average, the OAT group had better PROMIS t-scores indicating higher function or less pain and greater pre-to-postoperative change in each PROMIS domain. The OAT cohort’s average postoperative Pain Interference t-score (± SD) of 43.09 (± 5.81) and Depression t-score of 40.06 (± 6.84) were significantly lower than their respective counterparts in the MFX cohort: 50.08 (± 9.47) for Pain Interference and 48.09 (± 7.86) in Depression. (Table 1) Finally, the mean overall MOCART score was 55.67 (± 24.11) within the MFX cohort, average follow-up 15.29 months, and 71 (± 15.60) within the OAT cohort average follow-up 15.8 months. This difference was also statistically significant (p=0.04). Conclusion: The OAT group had a higher MOCART score indicating the use of a single osteochondral autograft plug may result in better structural repair than microfracture abrasion chondroplasty augmented with a mixture of adjuvant ECM-BMAC. In addition, higher average FAOS scores, better average PROMIS t-scores, and greater pre-to-postoperative change in the OAT patient group indicate functional results may be better in this group as well. Specifically, significantly lower Pain Interference and Depression domains and significantly higher Global Mental Health scores indicate patients treated using OAT experience less pain and better psychological benefits postoperatively compared to patients treated using MFX. These results suggest filling the lesion with transplanted autograft bone and native, hyaline cartilage may perform better than and the biomechanically inferior fibrocartilage produced following microfracture even when augmented with adjuvant therapy. OAT may result in better overall clinical outcomes, specifically in a population of patients with medium sized lesions (range, 80 mm2 -165 mm2).

AbstractThe COVID-19 pandemic response in the United States has exposed significant gaps in information systems and processes that prevent timely clinical and public health decision-making. Specifically, the use of informatics to mitigate the spread of SARS-CoV-2, support COVID-19 care delivery, and accelerate knowledge discovery bring to the forefront issues of privacy, surveillance, limits of state powers, and interoperability between public health and clinical information systems. Using a consensus-building process, we critically analyze informatics-related ethical issues in light of the pandemic across 3 themes: (1) public health reporting and data sharing, (2) contact tracing and tracking, and (3) clinical scoring tools for critical care. We provide context and rationale for ethical considerations and recommendations that are actionable during the pandemic and conclude with recommendations calling for longer-term, broader change (beyond the pandemic) for public health organization and policy reform.

Abstract Germline mutations in TP53 cause a rare high penetrance cancer syndrome, Li–Fraumeni syndrome (LFS). Here, we identified a rare TP53 tetramerization domain missense mutation, c.1000G&gt;C;p.G334R, in a family with multiple late-onset LFS-spectrum cancers. Twenty additional c.1000G&gt;C probands and one c.1000G&gt;A proband were identified, and available tumors showed biallelic somatic inactivation of TP53. The majority of families were of Ashkenazi Jewish descent, and the TP53 c.1000G&gt;C allele was found on a commonly inherited chromosome 17p13.1 haplotype. Transient transfection of the p.G334R allele conferred a mild defect in colony suppression assays. Lymphoblastoid cell lines from the index family in comparison with TP53 normal lines showed that although classical p53 target gene activation was maintained, a subset of p53 target genes (including PCLO, PLTP, PLXNB3, and LCN15) showed defective transactivation when treated with Nutlin-3a. Structural analysis demonstrated thermal instability of the G334R-mutant tetramer, and the G334R-mutant protein showed increased preponderance of mutant conformation. Clinical case review in comparison with classic LFS cohorts demonstrated similar rates of pediatric adrenocortical tumors and other LFS component cancers, but the latter at significantly later ages of onset. Our data show that TP53 c.1000G&gt;C;p.G334R is found predominantly in Ashkenazi Jewish individuals, causes a mild defect in p53 function, and leads to low penetrance LFS. Significance: TP53 c.1000C&gt;G;p.G334R is a pathogenic, Ashkenazi Jewish–predominant mutation associated with a familial multiple cancer syndrome in which carriers should undergo screening and preventive measures to reduce cancer risk.

Background Anesthesia-focused short courses might be an effective and sustainable way to further the ongoing training and evidence-based practice skills of anesthesia professionals in low- and middle-income countries (LMICs). Instructional design, the process by which formalized learning theory is incorporated into education planning and delivery, is a tool that can strengthen learning in these short courses. As part of an ongoing multilateral project between the University of Minnesota (UMN) and Kabul University of Medical Sciences (KUMS), this project sought to identify the feasibility and potential educational impact of a newly designed postoperative analgesia short-course employing instructional design principles. The Afghan faculty learners’ subjective viewpoint of the short course experience was also investigated and is described in this article. Methods Afghan learners and United States based faculty met in Bangalore, India in August 2018 for this short course. During the 6-day course, learners participated in didactics and workshops discussing regional anesthesia techniques, multimodal analgesia, safety, pain assessment and management, and the influence of ethno-cultural context on pain control. Interactive games, model-based nerve block simulations, and flipped classroom approaches were educational strategies used in the course. The Afghan faculty also participated in instructional design workshops designed to strengthen their teaching skills for use with both students and faculty colleagues. Pretests, posttests, and opinion surveys were completed by the Afghan faculty learners. Results All learners completed the course with full participation. A median of 5 out of 10 technical questions were answered correctly by the learners on the pretest; this score improved to a median of 6.5 on the posttest. The number of learners who ranked their understanding of the role of regional anesthesia in their perioperative care practice as “very well” increased from 2 to 5 faculty. Likewise, the number of learners who described their understanding of postoperative pain and their ability to perform regional anesthesia as “not well at all” decreased from 2 to 0 in both categories. Further, the majority of the participants agreed that at the end of the course their ability to understand and apply instructional design concepts had improved. Conclusions The short course in postoperative pain management appeared to improve short-term knowledge among Afghan faculty participants. Afghan faculty had a favorable opinion of the course and increased confidence in their ability to use instructional design best practices. The results of this project suggest that short courses based in instructional design can be useful and effective for short-term knowledge gain in an LMIC setting such as Afghanistan.

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.