Aims
USP6 rearrangement underpins self‐limiting fibroblastic/myofibroblastic neoplasms, including nodular fasciitis (NF), myositis ossificans (MO), aneurysmal bone cyst (ABC), and related variants. ...The aim of this study was to characterise UPS6 and fusion partners in order to delineate the clinicopathological, genetic and bone‐forming features in such lesions of soft tissue (ST).
Methods and results
Break‐apart fluorescence in‐situ hybridisation (FISH) validated USP6 rearrangement in 31 of 35 NF comprising three of three fasciitis ossificans (FO) cases, seven of eight cellular variant of fibroma of tendon sheath (C‐FTS), four of six MO, three of three ST‐ABC, and two of two fibro‐osseous pseudotumours of digits (FOPD). As determined with FISH and reverse transcription polymerase chain reaction, MYH9–USP6 was the commonest fusion in four C‐FTS and 20 NF, including one intravascular case and two infantile (one retroperitoneal) cases. The presence of MYH9–USP6 confirmed the diagnosis of two NFs> 50 mm with prominent ischaemic necrosis. COL1A1–USP6 was predominant in ossifying lesions, including all FO, MO, ST‐ABC and FOPD with identified partner genes, and was also present in non‐ossifying head and neck NF (HN‐NF) and C‐FTS in two cases each. A cervical NF of a 14‐month‐old girl harboured the novel COL1A2–USP6. Ossifying lesions showed considerable genetic and morphological overlaps. Sharing COL1A1–USP6, FO and FOPD showed similar central or haphazard bone matrix deposition. Besides zonation of outward bone maturation, four COL1A1–USP6‐positive MO had incipient to sieve‐like pseudocysts reminiscent of ST‐ABC.
Conclusion
MYH9–USP6 is present in some C‐FTS and most NF, including rare variants, but is unrelated to bone formation. All bone‐forming USP6‐rearranged lesions adopt COL1A1 as the 5′ partner, indicating close genetic kinships. However, COL1A1/COL1A2 also contributes to the pathogenesis of minor subsets of non‐ossifying USP6‐rearranged HN‐NF and C‐FTS.
Ovarian cancer has a unique tumor microenvironment (TME) that enables cancer-associated fibroblasts (CAFs) to interact with cellular and matrix constituents and influence tumor development and ...migration into the peritoneal cavity. Collagen type XI alpha 1 (COL11A1) is overexpressed in CAFs; therefore this study examines its role during CAF activation in epithelial ovarian cancer (EOC). Coculturing human ovarian fibroblasts (HOFs) with high COL11A1-expressing EOC cells or exposure to the conditioned medium of these cells prompted the expression of COL11A1 and CAF phenotypes. Conversely, coculturing HOFs with low COL11A1-expressing EOC cells or COL11A1-knockdown abrogated COL11A1 overexpression and secretion, in addition to CAF activation. Increased p-SP1 expression attributed to COL11A1-mediated extracellular signal-regulated kinase activation (ERK) induced p65 translocation into the nucleus and augmented its binding to the insulin-like growth factor binding protein 2 (IGFBP2) promoter, ultimately inducing TGF-β3 activation. The CAF-cancer cell crosstalk triggered interleukin-6 release, which in turn promoted EOC cell proliferation and invasiveness. These in vitro results were confirmed by in vivo findings in a mouse model, showing that COL11A1 overexpression in EOC cells promoted tumor formation and CAF activation, which was inhibited by TGF-β3 antibody. Human tumors with high TGF-β3 levels showed elevated expression of COL11A1 and IGFBP2, which was associated with poor survival. Our findings suggest the possibility that anti-TGF-β3 treatment strategy may be effective in targeting CAFs in COL11A1-positive ovarian tumors.
Objective
Artificial intelligence (AI) prediction is increasingly used for decision making in health care, but its application for adverse outcomes in emergency department (ED) patients with acute ...pancreatitis (AP) is not well understood. This study aimed to clarify this aspect.
Methods
Data from 8274 ED patients with AP in three hospitals from 2009 to 2018 were analyzed. Demographic data, comorbidities, laboratory results, and adverse outcomes were included. Six algorithms were evaluated, and the one with the highest area under the curve (AUC) was implemented into the hospital information system (HIS) for real‐time prediction. Predictive accuracy was compared between the AI model and Bedside Index for Severity in Acute Pancreatitis (BISAP).
Results
The mean ± SD age was 56.1 ± 16.7 years, with 67.7% being male. The AI model was successfully implemented in the HIS, with Light Gradient Boosting Machine (LightGBM) showing the highest AUC for sepsis (AUC 0.961) and intensive care unit (ICU) admission (AUC 0.973), and eXtreme Gradient Boosting (XGBoost) showing the highest AUC for mortality (AUC 0.975). Compared to BISAP, the AI model had superior AUC for sepsis (BISAP 0.785), ICU admission (BISAP 0.778), and mortality (BISAP 0.817).
Conclusions
The first real‐time AI prediction model implemented in the HIS for predicting adverse outcomes in ED patients with AP shows favorable initial results. However, further external validation is needed to ensure its reliability and accuracy.
OBJECTIVES
Whether early medication reconciliation and integration can reduce polypharmacy and potentially inappropriate medication (PIM) in the emergency department (ED) remains unclear. ...Polypharmacy and PIM have been recognized as significant causes of adverse drug events in older adults. Therefore, this pilot study was conducted to delineate this issue.
DESIGN
An interventional study.
SETTING
A medical center in Taiwan.
PARTICIPANTS
Older ED patients (aged ≥65 years) awaiting hospitalization between December 1, 2017, and October 31, 2018 were recruited in this study. A multidisciplinary team and a computer‐based and pharmacist‐assisted medication reconciliation and integration system were implemented.
MEASUREMENTS
The reduced proportions of major polypharmacy (≥10 medications) and PIM at hospital discharge were compared with those on admission to the ED between pre‐ and post‐intervention periods.
RESULTS
A total of 911 patients (pre‐intervention = 243 vs post‐intervention = 668) were recruited. The proportions of major polypharmacy and PIM were lower in the post‐intervention than in the pre‐intervention period (−79.4% vs −65.3%; P < .001, and − 67.5% vs −49.1%; P < .001, respectively). The number of medications was reduced from 12.5 ± 2.7 to 6.9 ± 3.0 in the post‐intervention period in patients with major polypharmacy (P < .001).
CONCLUSION
Early initiation of computer‐based and pharmacist‐assisted intervention in the ED for reducing major polypharmacy and PIM is a promising method for improving geriatric care and reducing medical expenditures. J Am Geriatr Soc 67:2298–2304, 2019
Lysophosphatidic acid (LPA) is a bioactive lipid mediator primarily derived from membrane phospholipids. LPA initiates cellular effects upon binding to a family of G protein-coupled receptors, termed ...LPA receptors (LPAR1 to LPAR6). LPA signaling drives cell migration and proliferation, cytokine production, thrombosis, fibrosis, angiogenesis, and lymphangiogenesis. Since the expression and function of LPA receptors are critical for cellular effects, selective antagonists may represent a potential treatment for a broad range of illnesses, such as cardiovascular diseases, idiopathic pulmonary fibrosis, voiding dysfunctions, and various types of cancers. More new LPA receptor antagonists have shown their therapeutic potentials, although most are still in the preclinical trial stage. This review provided integrative information and summarized preclinical findings and recent clinical trials of different LPA receptor antagonists in cancer progression and resistance. Targeting LPA receptors can have potential applications in clinical patients with various diseases, including cancer.
Venetoclax, a selective B cell leukemia/lymphoma-2 (BCL2) inhibitor, has recently shown activity in relapsed or refractory (R/R) acute myeloid leukemia (AML). Effective biomarkers for identifying ...patients most likely to respond to venetoclax-based treatment are of clinical utility. In this study, we aimed to evaluate the efficacy and safety profiles of venetoclax-based therapy in a total 40 R/R AML patients and identify the potentially predictive factors for response. Overall response rate was 50%, including 9 (22.5%) complete response (CR) or CR with incomplete hematologic recovery of either neutrophil or platelet counts (CRi). Median time to best response was 1.4 months and the median overall survival (OS) was 6.6 months. Presence of intermediate-risk cytogenetics predicted better OS compared to unfavorable-risk cytogenetics. Patients harboring
NPM1
,
RUNX1
, or
SRSF2
mutations seemed to have higher CR/CRi rates and median OS was significantly longer in
RUNX1
-mutated patients. On the contrary, patients with
FLT3
-ITD,
TP53
, or
DNMT3A
mutations did not reach any objective response and had worse OS. No laboratory or clinical tumor lysis syndrome was observed and the most common adverse events were prolonged cytopenias which resulted in 67.5% of febrile neutropenia. Patients with concurrent use of azole antifungals had similar incidence of cytopenias compared with those without azole antifungals. In summary, we demonstrate that venetoclax is an effective and well-tolerated salvage option for R/R AML patients. Survival benefits were particularly remarkable in patients with intermediate-risk cytogenetics or
RUNX1
mutations. In contrast,
TP53
,
NRAS
, and
DNMT3A
mutations as well as
FLT3
-ITD conferred negative impact on survival.
Tumor‐associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and are key cells in regulating tumor development, metastasis, immune responses, inflammation, and ...chemoresistance. In response to TME stimulation, circulating monocytes are recruited and differentiated as TAMs. Most TAMs are defined as alternatively activated (M2) phenotype to create immunosuppressive TME and support tumor progression. In contrast, classically activated (M1) TAMs can produce pro‐inflammatory cytokines and enhance immune responses against tumor development. Autophagy is a conserved catabolic process to control cellular homeostasis and biological function. Emerging evidence reveals crucial contribution of autophagy in modulating TAM plasticity and functional polarization in TME. In this review, we introduce the current understanding of autophagy‐regulated TAM function in development of cancer. We focus on how autophagy modulates antigen presentation, LC3‐associated phagocytosis, cytokine secretion, inflammasome regulation, recruitment, differentiation, and polarization of TAMs and suggest strategies for potential therapeutics by targeting autophagy in TAMs. We expect this review can provide a new notion of future cancer immunotherapy.
The COVID‐19 pandemic has had a global impact on the environment and economy and has affected hospital administration and patient behaviour. Since human‐to‐human coronavirus transmission occurs via ...droplets and physical contact, health care professionals are particularly vulnerable to contracting COVID‐19. Many cytopathology laboratories updated their workflow, established new standard biosafety protocols, and built digital pathology or telescope platforms to mitigate these risks and deal with the shortage of health care personnel. The COVID‐19 pandemic also disrupted medical education—all indoor training events, including conferences, multidisciplinary tumour boards, seminars, and microscope inspections were postponed. As a result, many laboratories now use new web‐based applications and platforms to maintain educational programs and multidisciplinary tumour boards. To comply with government directives, health care facilities postponed non‐emergency surgeries, reduced the number of routine medical examinations, restricted visitor numbers, and scaled back cancer screening activities, resulting in a sharp decline in cytopathology diagnoses, cancer screening specimens, and molecular testing for cancer. Subsequent misses or delays in the diagnosis and treatment of cancer were not uncommon. This review aims to provide comprehensive summaries of the consequences of the COVID‐19 pandemic for cytopathology, particularly in terms of cancer diagnosis, workload, human resources, and molecular testing.
This article summarizes the effects of the COVID‐19 pandemic on cytopathology and cancer detection, focusing on workload, human resources, education, and molecular testing.
Background
Artificial intelligence of things (AIoT) may be a solution for predicting adverse outcomes in emergency department (ED) patients with pneumonia; however, this issue remains unclear. ...Therefore, we conducted this study to clarify it.
Methods
We identified 52,626 adult ED patients with pneumonia from three hospitals between 2010 and 2019 for this study. Thirty‐three feature variables from electronic medical records were used to construct an artificial intelligence (AI) model to predict sepsis or septic shock, respiratory failure, and mortality. After comparisons of the predictive accuracies among logistic regression, random forest, support‐vector machine (SVM), light gradient boosting machine (LightGBM), multilayer perceptron (MLP), and eXtreme Gradient Boosting (XGBoost), we selected the best one to build the model. We further combined the AI model with the Internet of things as AIoT, added an interactive mode, and implemented it in the hospital information system to assist clinicians with decision making in real time. We also compared the AIoT‐based model with the confusion‐urea‐respiratory rate‐blood pressure‐65 (CURB‐65) and pneumonia severity index (PSI) for predicting mortality.
Results
The best AI algorithms were random forest for sepsis or septic shock (area under the curve AUC = 0.781), LightGBM for respiratory failure (AUC = 0.847), and mortality (AUC = 0.835). The AIoT‐based model represented better performance than CURB‐65 and PSI indicators for predicting mortality (0.835 vs. 0.681 and 0.835 vs. 0.728).
Conclusions
A real‐time interactive AIoT‐based model might be a better tool for predicting adverse outcomes in ED patients with pneumonia. Further validation in other populations is warranted.
Anastomosing Hemangioma of the Nasal Cavity Huang, Zheng‐Yi; Chen, Chien‐Chin; Thingujam, Bipin
The Laryngoscope,
February 2020, 2020-Feb, 2020-02-00, 20200201, Volume:
130, Issue:
2
Journal Article
Peer reviewed
Anastomosing hemangioma (AH) is an uncommon benign vascular neoplasm first described in the genitourinary tract. Symptomatically and histologically mimicking malignant angiosarcoma, a few rare cases ...have been described in the nonrenal genitourinary tract. Here, we report a 37‐year‐old man with a nasal AH and epistaxis. To the best of our knowledge, this is the first case of AH reported in the nasal cavity. Awareness of this entity in the nasal cavity can be helpful in diagnosis and distinction from angiosarcoma. Laryngoscope, 130:354–357, 2020
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