Citations

Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially resolve and quantify proteins and RNA transcripts from tissue sections. The platform is compatible with both formalin-fixed paraffin-embedded and frozen tissues. RNA profiling was developed at the whole transcriptome level for human and mouse samples and protein profiling of 100-plex for human samples. Tissue can be optically segmented for analysis of regions of interest or cell populations to study biology-directed tissue characterization. The GeoMx Breast Cancer Consortium (GBCC) is composed of breast cancer researchers who are developing innovative approaches for spatial profiling to accelerate biomarker discovery. Here, the GBCC presents best practices for GeoMx profiling to promote the collection of high-quality data, optimization of data analysis and integration of datasets to advance collaboration and meta-analyses. Although the capabilities of the platform are presented in the context of breast cancer research, they can be generalized to a variety of other tumor types that are characterized by high heterogeneity.

Background Evidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery. Methods A systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications. Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations. Results Analysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92). Conclusions Based on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes. Recommendation: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

Transmission electron microscopy (TEM) is widely used as an imaging modality to provide high-resolution details of subcellular components within cells and tissues. Mitochondria and endoplasmic reticulum (ER) are organelles of particular interest to those investigating metabolic disorders. A straightforward method for quantifying and characterizing particular aspects of these organelles would be a useful tool. In this protocol, we outline how to accurately assess the morphology of these important subcellular structures using open source software ImageJ, originally developed by the National Institutes of Health (NIH). Specifically, we detail how to obtain mitochondrial length, width, area, and circularity, in addition to assessing cristae morphology and measuring mito/endoplasmic reticulum (ER) interactions. These procedures provide useful tools for quantifying and characterizing key features of sub-cellular morphology, leading to accurate and reproducible measurements and visualizations of mitochondria and ER.

AbstractThe development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.

AbstractWhile most Radiation Oncology clinics have adopted electronic charting in one form or another, no consensus document exists that provides guidelines for safe and effective use of the Radiation Oncology electronic medical records (RO‐EMR). Task Group 262 was formed to provide these guidelines as well as to provide recommendations to vendors for improving electronic charting functionality in future. Guidelines are provided in the following areas: Implementation and training for the RO‐EMR, acceptance testing and quality assurance (QA) of the RO‐EMR, use of the RO‐EMR as an information repository, use of the RO‐EMR as a workflow manager, electronic charting for brachytherapy and nonstandard treatments, and information technology (IT) considerations associated with the RO‐EMR. The report was based on a literature search by the task group, an extensive survey of task group members on their respective RO‐EMR practices, an AAPM membership survey on electronic charting, as well as group consensus.

AimsPRRX1–NCOA1‐rearranged fibroblastic tumour is a recently described, rare mesenchymal tumour. Only four cases have been previously reported. The aim of this article is to report six additional cases of this unusual mesenchymal neoplasm, with an emphasis on its differential diagnosis.Methods and resultsThe six cases were from three females and three males (age, 20–49 years; median, 42 years). Three tumours were located on the abdominal wall; two from the shoulder/axillary areas, and one on the lateral hip. All presented as slow‐growing subcutaneous nodules, ranging from 26 to 55 mm (median, 40 mm). The tumours consisted of circumscribed, variably cellular nodules composed of relatively bland plump spindled to epithelioid cells arranged singly, in cords, and occasionally in nests, embedded in hyalinised and collagenous stroma. Small hypocellular myxoid zones with ropey collagen fibres were present, as were irregularly dilated, gaping, crescent‐shaped or staghorn‐like thin‐walled vessels, best appreciated at the periphery. Immunohistochemistry for CD34, S100, MUC4 and STAT6 was consistently negative. RNA‐sequencing revealed PRRX1–NCOA1 fusions in all cases. Of the four cases with limited follow‐up (1.5–4 months), none recurred following local surgical excision.ConclusionsThe morphological features of PRRX1–NCOA1‐rearranged fibroblastic tumour overlap with those of RB1‐deficient soft‐tissue tumours, solitary fibrous tumour, and low‐grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma. This differential diagnosis can be resolved with a combination of careful morphological study and the application of a panel of immunostains, although molecular genetic study is most definitive. The natural history of PRRX1–NCOA1‐rearranged fibroblastic tumour appears to be quite favourable, although longer‐term study of a larger number of cases is warranted.

Abstract Background Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals. Methods In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population. Results The 386 respondents were predominantly female (58%) with a median age range of 40–49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field. Conclusions The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.

Myringotomy with ventilation tube placement is a common surgical procedure performed in children and adults to remove fluid buildup behind the tympanic membrane. However, retention of tubes beyond achievement of therapeutic response increases risk for complications and additional intervention. This small feasibility study was conducted to demonstrate proof of concept of a novel bioabsorbable ventilation tube that provides the necessary duration of ventilation with absorption shortly thereafter. Tubes were placed in 15 ears of 14 patients meeting indications for short or intermediate duration of middle ear ventilation. Two independent examiners documented tube patency and tube absorption status at 3, 6, and 12 weeks or until absorption was complete. Results indicate that average ventilation time was 12 weeks (range, 3 weeks to 18 months). There was no observation of blockage. These findings support the feasibility of a novel bioabsorbable ventilation tube.

Introduction: Morbidity and mortality attributable to hypertension are higher in African American (AAEH) compared to Caucasian essential hypertensive (EH) patients, possibly related to a differential effect on vascular injury and repair. While circulating endothelial progenitor cells (EPC) preserve endothelial integrity IEC detach from sites of injury and represent markers of vascular damage. We hypothesized that plasma levels of IEC and inflammatory markers would be higher in AAEH compared to EH patients. METHODS: Inferior vena cava levels of CD34+/KDR+ (EPC) and VAP-1+ (IEC) cells were measured by FACS in EH and AAEH under fixed sodium intake (150 mEq/d) and blockade of the renin-angiotensin-system, and compared to systemic levels in normotensive control subjects (n=19 each). Systemic levels of inflammatory cytokines and EPC homing factors were measured by Luminex. Results: Blood pressure, serum creatinine, lipids, antihypertensive medications, and EPC levels did not differ between EH and AAEH patients. Circulating IEC were higher in AAEH, and inversely correlated with EPC levels (Figure). Systemic levels of inflammatory cytokines and EPC homing factors were higher in AAEH compared to EH patients (Table), and correlated directly with IEC. Conclusion: Despite preserved kidney function and controlled BP, circulating inflammatory markers were elevated in AAEH and correlated with increased IEC and decreased EPC levels. Increased release of cytokines and IEC in AAEH may impair EPC reparative capacity and predispose to hypertensive vascular injury. This process may aggravate vascular damage and accelerate hypertension-related morbidity/mortality rates in AAEH.