Molecular pathology in bone and soft tissue tumors: a multifunctional key for diagnosis and prediction

In this thesis, the different key roles of molecular pathology in bone and soft tissue tumors are reflected in clinicopathological, immunohistochemical and molecular studies to aid diagnosis and prediction in a range of different bone and soft tissue tumors. LUMC / Geneeskund

Smart technology for healthcare: Exploring the antecedents of adoption intention of healthcare wearable technology

© The Author(s), 2019. Technological advancement and personalized health information has led to an increase in people using and responding to wearable technology in the last decade. These changes are often perceived to be beneficial, providing greater information and insights about health for users, organizations and healthcare and government. However, to date, understanding the antecedents of its adoption is limited. Seeking to address this gap, this cross-sectional study examined what factors influence users’ adoption intention of healthcare wearable technology. We used self-administrated online survey to explore adoption intentions of healthcare wearable devices in 171 adults residing in Hong Kong. We analyzed the data by Partial least squares – structural equation modelling (PLS-SEM). The results reveal that perceived convenience and perceived irreplaceability are key predictors of perceived useful ness, which in turn strengthens users’ adoption intention. Additionally, the results also reveal that health belief is one of the key predictors of adoption intention. This paper contributes to the extant literature by providing understanding of how to strengthen users’ intention to adopt healthcare wearable technology. This includes the strengthening of perceived convenience and perceived irreplaceability to enhance the perceived usefulness, incorporating the extensive communication in the area of healthcare messages, which is useful in strengthening consumers’ adoption intention in healthcare wearable technology

Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy

Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of empty as well as drug-loaded AHCMS to male Balb/c mice, only a moderate increase in i.p. neutrophils was measured. 3 days after injection neutrophil levels were comparable with the controls. No significant increases in the numbers of other cell types were observed, indicating an acute inflammatory response which can be considered to be mild. Antitumour efficacy was tested in an L1210 tumour-bearing mouse model and in a CC531 tumour-bearing rat model. The use of ADR-AHCMS leads to longer survival times of mice and improved tumour growth delay in rats, as compared with untreated controls and free drug treated animals. In both animal models higher adriamycin doses were initially tolerated if the drug was formulated in microspheres, although long-term adriamycin toxicity effects were evident in all treated groups. Doses and dosage schedules may be optimized to further reduce the toxic effects of the drug

Validation of a base deficit-based trauma prediction model and comparison with TRISS and ASCOT

Background: Base deficit provides a more objective indicator of physiological stress following injury as compared with vital signs constituting the revised trauma score (RTS). We have previously developed a base deficit-based trauma survival prediction model [base deficit and injury severity score model (BISS)], in which RTS was replaced by base deficit as a measurement of physiological imbalance. Purpose: To externally validate BISS in a large cohort of trauma patients and to compare its performance with established trauma survival prediction models including trauma and injury severity score (TRI

Conformational dependence of the intrinsic acidity of the aspartic acid residue sidechain in N-acetyl-L-aspartic acid-N '-methylamide

The sidechain conformational potential energy hypersurfaces (PEHS) for the gamma(L), beta(L), alpha(L), and alpha(D) backbone conformations of N-acetyl-L-aspartate-M-methylamide were generated. Of the 81 possible conformers initially expected for the aspartate residue, only seven were found after geometric optimizations at the B3LYP/6-31G(d) level of theory. No stable conformers could be located in the delta(L), epsilon(L), gamma(D), delta(D), and epsilon(D) backbone conformations. The 'adiabatic' deprotonation energies for the endo and exo forms of N-acetyl-L-aspartic acid-N'-methylamide were calculated by comparing their optimized relative energies against those found for the seven stable conformers of N-acetyl-L-aspartate-N'-methylamide. Sideehain conformational PEHSs were also generated for the estimation of 'vertical' deprotonation energies for both endo and exo forms of N-acetyl-L-aspartic acid-N'-methylamide. All backbone-sidechain (N-H...-O-C) and backbone-backbone (N-(HO)-O-...=C) hydrogen bond interactions were analyzed. A total of two backbone-backbone and four backbone-sidechain interactions were found for N-acetyl-L-aspartate-N'-methylamide. The deprotonated sidechain of N-acetyl-L-aspartate-N'-methylamide may allow the aspartyl residue to form strong hydrogen bond interactions (since it is negatively charged) which may be significant in such processes as protein-ligand recognition and ligand binding. As a primary example, the molecular geometry of the aspartyl residue may be important in peptide folding, such as that. in the RGD tripeptide. (C) 2002 Elsevier science B.V. All rights reserved

Ancient Gondwana break-up explains the distribution of the mycoheterotrophic family Corsiaceae (Liliales)

Plant science

Mismatch repair deficiency is rare in bone and soft tissue tumors

Introduction There has been an increased demand for mismatch repair (MMR) status testing in sarcoma patients after the success of immune checkpoint inhibition (ICI) in MMR deficient tumors. However, data on MMR deficiency in bone and soft tissue tumors is sparse, rendering it unclear if routine screening should be applied. Hence, we aimed to study the frequency of MMR deficiency in bone and soft tissue tumors after we were prompted by two (potential) Lynch syndrome patients developing sarcomas.Methods Immunohistochemical expression of MLH1, PMS2, MSH2 and MSH6 was assessed on tissue micro arrays (TMAs), and included 353 bone and 539 soft tissue tumors. Molecular data was either retrieved from reports or microsatellite instability (MSI) analysis was performed. In MLH1 negative cases, additional MLH1 promoter hypermethylation analysis followed. Furthermore, a systematic literature review on MMR deficiency in bone and soft tissue tumors was conducted.Results Eight MMR deficient tumors were identified (1%), which included four leiomyosarcoma, two rhabdomyosarcoma, one malignant peripheral nerve sheath tumor and one radiation-associated sarcoma. Three patients were suspected for Lynch syndrome. Literature review revealed 30 MMR deficient sarcomas, of which 33% were undifferentiated/unclassifiable sarcomas. 57% of the patients were genetically predisposed.Conclusion MMR deficiency is rare in bone and soft tissue tumors. Screening focusing on tumors with myogenic differentiation, undifferentiated/unclassifiable sarcomas and in patients with a genetic predisposition / co-occurrence of other malignancies can be helpful in identifying patients potentially eligible for ICI.Molecular tumour pathology - and tumour geneticsMTG

NTRK fusions are extremely rare in bone tumours

Aims Because of the efficacy of tropomyosin receptor kinase (Trk) inhibitor therapy in tumours with rearrangements of the neurotrophic tyrosine kinase receptor genes (NRTK genes), there has been a surge in demand for NTRK fusion screening. To date, most studies involving mesenchymal tumours have focused on soft tissue tumours, and data on bone tumours are sparse. Hence, we aimed to explore the frequency of NTRK fusions in a large series of primary bone tumours. Methods and results Immunohistochemical expression of pan-Trk was successfully assessed in 354 primary bone tumours by the use of tissue microarrays. In a selection of positive cases, additional molecular analysis for NTRK fusions was performed with anchored multiplex polymerase chain reaction-based targeted next-generation sequencing. Positivity was found in 19 cases (5%), which comprised Ewing sarcoma (n = 6, 33%), osteosarcoma (n = 11, 13%), and giant-cell tumour of bone (n = 2, 3%). In all except one case, cytoplasmic staining was observed. Weak staining was most often observed (n = 13), although five cases showed moderate staining and one case showed focal strong staining. Molecular analysis was successful in six cases, all of which were negative for NTRK fusions. Conclusion The likelihood of finding an NTRK fusion in bone tumours in clinical practice is extremely low. This may imply that, if more comprehensive large-scale molecular studies confirm this, routine predictive NTRK testing in bone tumour patients with advanced disease may be reconsidered.Molecular tumour pathology - and tumour geneticsMTG

Use of plasma DNA to predict mortality and need for intensive care in patients with abdominal pain

Background We investigated the value of plasma deoxyribonucleic acid concentrations in patients presenting with acute abdominal pain to predict need for intensive care or mortality. Methods Plasma deoxyribonucleic acid taken from patients with acute abdominal pain was analyzed for the β-globin gene using the quantitative polymerase chain reaction. The primary outcome measure was the combined 28-day mortality or admission to the intensive care unit. Results Of 287 consecutive patients with acute abdominal pain recruited, 12 patients were admitted to the intensive care unit and/or died. Median plasma DNA concentrations were higher in patients with cancer and major organ inflammation. Mean plasma DNA concentrations were three-fold higher in patients with systemic inflammatory response syndrome, five-fold higher in patients who died within 28 days, and eight-fold higher in patients admitted to the intensive care unit. The area under the receiver operator curve for plasma DNA concentrations and intensive care unit admission/mortality was 0.804. At a cut-off of 1100 GE/ml, the sensitivity was 67% (95%CI 35–90) and specificity was 89% (95%CI 84–92). At a cut-off of 175 GE/ml, the sensitivity was 100% (95%CI 73–100) and specificity was 30% (95%CI 25–36). Plasma DNA concentration predicted need for intensive care unit admission or death (adjusted odds ratio 1.4; P < 0.0001). Conclusions Plasma DNA may have a role in patients with acute abdominal pain as a marker for inflammation and cancer, and a predictor of intensive care unit admission/mortality