Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Automating Scoliosis Measurements in Radiographic Studies with Machine Learning: Comparing Artificial Intelligence and Clinical Reports

Journal of Digital Imaging - Scoliosis is a condition of abnormal lateral spinal curvature affecting an estimated 2 to 3% of the US population, or seven million people. The Cobb angle is the...     

Ketorolac use and anastomotic leak in patients with esophageal cancer

ObjectivesRecent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential.MethodsRecords of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak.ResultsA total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak.ConclusionsKetorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak.     

Evaluation of Structured Assessment and Mediating Factors of Suicide-Focused Group Therapy for Veterans Recently Discharged from Inpatient Psychiatry

The current study investigated the impact of adding the Suicide Status Form (SSF) to a suicide-focused group therapy for veterans recently discharged from an inpatient psychiatry setting. A sample of 141 veterans was enrolled and randomized into a Usual Assessment Group Therapy or SSF-Assessment Group Therapy. Participants completed interviews at baseline, 1, and 3 months. No significant differences were observed between groups regarding group attendance (IRR?=?1.01, Std. Err?=?0.08, 95% CI?=?0.87, 1.18) or client satisfaction (β?=?0.23, Std. Err?=?0.66, p?=?0.73, d?=??.25). No main effects were observed across the study on secondary outcomes of interest for suicidal ideation and overall symptom distress, although participants in both treatment conditions reported significant improvements on these outcomes over the course of the study. Patients in the Usual Assessment Group Therapy demonstrated greater reductions in overall symptom distress across the 3-month follow-up window (β?=?6.08, Std. Err?=?2.04, p?=?0.003; f²?=?0.05). Follow-up path analyses revealed that more frequent session attendance was significantly related to less suicidal ideation at 1-month, higher working alliance between individual members and group facilitators was associated with greater suicidal ideation at 1-month, and higher group cohesion among group members at 1-month was significantly associated with less thwarted belongingness at 1-month. Although the SSF did not improve the impact of an existing suicide-focused group therapy, the study findings support future research on group treatments for suicidal veterans.