scholarly journals Pharmacogenomics and Pharmacogenetics in Osteosarcoma: Translational Studies and Clinical Impact

2020 ◽  
Vol 21 (13) ◽  
pp. 4659 ◽  
Author(s):  
Claudia Maria Hattinger ◽  
Maria Pia Patrizio ◽  
Silvia Luppi ◽  
Massimo Serra
Keyword(s):  
Care Management ◽  
Scientific Evidence ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Clinical Settings ◽  
Genetic Biomarkers ◽  
Recent Developments ◽  
High Grade Osteosarcoma ◽  
Genetic Events ◽  
Pharmacogenomic Studies

High-grade osteosarcoma (HGOS) is a very aggressive bone tumor which primarily affects adolescents and young adults. Although not advanced as is the case for other cancers, pharmacogenetic and pharmacogenomic studies applied to HGOS have been providing hope for an improved understanding of the biology and the identification of genetic biomarkers, which may impact on clinical care management. Recent developments of pharmacogenetics and pharmacogenomics in HGOS are expected to: i) highlight genetic events that trigger oncogenesis or which may act as drivers of disease; ii) validate research models that best predict clinical behavior; and iii) indicate genetic biomarkers associated with clinical outcome (in terms of treatment response, survival probability and susceptibility to chemotherapy-related toxicities). The generated body of information may be translated to clinical settings, in order to improve both effectiveness and safety of conventional chemotherapy trials as well as to indicate new tailored treatment strategies. Here, we review and summarize the current scientific evidence for each of the aforementioned issues in view of possible clinical applications.

Radiotherapy for Brain Tumors: Current Practice and Future Directions

2020 ◽  
Vol 16 (3) ◽  
pp. 182-195
Author(s):  
Sarah Baker ◽  
Natalie Logie ◽  
Kim Paulson ◽  
Adele Duimering ◽  
Albert Murtha
Keyword(s):  
Brain Tumors ◽  
Treatment Strategies ◽  
Brain Parenchyma ◽  
Benign Tumors ◽  
Tumor Control ◽  
Normal Brain ◽  
Neurocognitive Deficits ◽  
Close Proximity ◽  
Recent Developments ◽  
High Level

Radiotherapy is an important component of the treatment for primary and metastatic brain tumors. Due to the close proximity of critical structures and normal brain parenchyma, Central Nervous System (CNS) radiotherapy is associated with adverse effects such as neurocognitive deficits, which must be weighed against the benefit of improved tumor control. Advanced radiotherapy technology may help to mitigate toxicity risks, although there is a paucity of high-level evidence to support its use. Recent advances have been made in the treatment for gliomas, meningiomas, benign tumors, and metastases, although outcomes remain poor for many high grade tumors. This review highlights recent developments in CNS radiotherapy, discusses common treatment toxicities, critically reviews advanced radiotherapy technologies, and highlights promising treatment strategies to improve clinical outcomes in the future.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals “A debriefer must be neutral” and other debriefing myths: a systemic inquiry-based qualitative study of taken-for-granted beliefs about clinical post-event debriefing

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Julia Carolin Seelandt ◽  
Katie Walker ◽  
Michaela Kolbe
Keyword(s):  
Interpersonal Relationships ◽  
Western Europe ◽  
Ad Hoc ◽  
Scientific Evidence ◽  
Clinical Event ◽  
Clinical Settings ◽  
Healthcare Organizations ◽  
The Usa ◽  
Open Coding ◽  
Healthcare Administrators

Abstract Background The goal of this study was to identify taken-for-granted beliefs and assumptions about use, costs, and facilitation of post-event debriefing. These myths prevent the ubiquitous uptake of post-event debriefing in clinical units, and therefore the identification of process, teamwork, and latent safety threats that lead to medical error. By naming these false barriers and assumptions, the authors believe that clinical event debriefing can be implemented more broadly. Methods We interviewed an international sample of 37 clinicians, educators, scholars, researchers, and healthcare administrators from hospitals, universities, and healthcare organizations in Western Europe and the USA, who had a broad range of debriefing experience. We adopted a systemic-constructivist approach that aimed at exploring in-depth assumptions about debriefing beyond obvious constraints such as time and logistics and focused on interpersonal relationships within organizations. Using circular questions, we intended to uncover new and tacit knowledge about barriers and facilitators of regular clinical debriefings. All interviews were transcribed and analyzed following a comprehensive process of inductive open coding. Results In total, 1508.62 min of interviews (25 h, 9 min, and 2 s) were analyzed, and 1591 answers were categorized. Many implicit debriefing theories reflected current scientific evidence, particularly with respect to debriefing value and topics, the complexity and difficulty of facilitation, the importance of structuring the debriefing and engaging in reflective practice to advance debriefing skills. We also identified four debriefing myths which may prevent post-event debriefing from being implemented in clinical units. Conclusion The debriefing myths include (1) debriefing only when disaster strikes, (2) debriefing is a luxury, (3) senior clinicians should determine debriefing content, and (4) debriefers must be neutral and nonjudgmental. These myths offer valuable insights into why current debriefing practices are ad hoc and not embedded into daily unit practices. They may help ignite a renewed momentum into the implementation of post-event debriefing in clinical settings.

scholarly journals Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2878
Author(s):  
Claudia Maria Hattinger ◽  
Maria Pia Patrizio ◽  
Leonardo Fantoni ◽  
Chiara Casotti ◽  
Chiara Riganti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Cure Rate ◽  
Acquired Drug Resistance ◽  
Unselected Patient ◽  
Dismal Prognosis ◽  
Non Coding Rnas ◽  
High Grade Osteosarcoma

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.

Magical Practice

2021 ◽  
Author(s):  
Timothy de Waal Malefyt
Keyword(s):  
Practical Knowledge ◽  
Scientific Evidence ◽  
Magical Thinking ◽  
Gaming Industry ◽  
Alternative Facts ◽  
Contemporary Life ◽  
Theatrical Performances ◽  
Recent Developments ◽  
Agent Of Change ◽  
Magical Beliefs

The word “magic” refers to a broad range of beliefs and practices that include animism, charm(s), divination, enchantment, fantasy, fetish, glamour, illusion, miracles, the occult, shamanism, sorcery, spells, the supernatural, superstition, taboos, trickery, and witchcraft. Magic―once thought a core feature of “primitive societies,” abandoned by more rational, bureaucratic and progressive beliefs―is, in fact, thriving in contemporary life, and central to practices of capitalism as well as to everyday behaviors. Magic is practiced in fields of finance, government, law, medicine and health, technology, advertising, marketing, sports, the gaming industry, and theatrical performances, among other institutions. When situations allow for the assemblage of a “magician,” “rite,” and “representation” within these complex social networks and when professional skills, ideas, conditions, contexts, media, and meanings align, magic acts as an agent of change. Magic is also practiced in everyday situations in which people need to feel a sense of control in circumstances where it’s lacking, such as performing well under competitive conditions or during times of crisis with indefinite outcomes. Consequently, they rely on magical thinking—in the forms of superstitions, wishful thinking, and taboo avoidance—which is often accompanied by charms, amulets, or acts of faith to guide them through uncertainty. Conjuring terms such as “fate” and “luck” to ward off illness or improve one’s chances at getting a hit in baseball, are, in fact, ways of expressing ambiguities and dealing with conflicts of temporal existence that all humans face in one form or another. Magic structured in institutions and practiced in everyday situations is a prime example of contradiction in contemporary life. Objective knowledge of facts is increasingly understood as contingent rather than permanent, leaving room for uncertainty, mystery, the unknown, and seemingly nonrational alternatives. Scientific evidence becomes as valid as alternative facts. Documenting recent developments, it is suggested that rationality and magic are not mutually exclusive. Rather, rational behaviors and practices are suffused with magic. Magical beliefs and specific rituals complement practical knowledge so as to enhance knowledge as a way to secure success. All of these ways of thinking and social practices have something at stake, in that risk, uncertainty, and ambiguity of outcome are prevalent, and hence call on magical practices to bring about change.

scholarly journals Datasets collected in general practice: an international comparison using the example of obesity

2018 ◽  
Vol 42 (5) ◽  
pp. 563 ◽  
Author(s):  
Elizabeth Sturgiss ◽  
Kees van Boven
Keyword(s):  
Primary Care ◽  
General Practice ◽  
The Netherlands ◽  
Care Management ◽  
Clinical Care ◽  
International Comparisons ◽  
Health Condition ◽  
Practice Management ◽  
Number Of Patients ◽  
Primary Care Management

International datasets from general practice enable the comparison of how conditions are managed within consultations in different primary healthcare settings. The Australian Bettering the Evaluation and Care of Health (BEACH) and TransHIS from the Netherlands collect in-consultation general practice data that have been used extensively to inform local policy and practice. Obesity is a global health issue with different countries applying varying approaches to management. The objective of the present paper is to compare the primary care management of obesity in Australia and the Netherlands using data collected from consultations. Despite the different prevalence in obesity in the two countries, the number of patients per 1000 patient-years seen with obesity is similar. Patients in Australia with obesity are referred to allied health practitioners more often than Dutch patients. Without quality general practice data, primary care researchers will not have data about the management of conditions within consultations. We use obesity to highlight the strengths of these general practice data sources and to compare their differences. What is known about the topic? Australia had one of the longest-running consecutive datasets about general practice activity in the world, but it has recently lost government funding. The Netherlands has a longitudinal general practice dataset of information collected within consultations since 1985. What does this paper add? We discuss the benefits of general practice-collected data in two countries. Using obesity as a case example, we compare management in general practice between Australia and the Netherlands. This type of analysis should start all international collaborations of primary care management of any health condition. Having a national general practice dataset allows international comparisons of the management of conditions with primary care. Without a current, quality general practice dataset, primary care researchers will not be able to partake in these kinds of comparison studies. What are the implications for practitioners? Australian primary care researchers and clinicians will be at a disadvantage in any international collaboration if they are unable to accurately describe current general practice management. The Netherlands has developed an impressive dataset that requires within-consultation data collection. These datasets allow for person-centred, symptom-specific, longitudinal understanding of general practice management. The possibilities for the quasi-experimental questions that can be answered with such a dataset are limitless. It is only with the ability to answer clinically driven questions that are relevant to primary care that the clinical care of patients can be measured, developed and improved.

scholarly journals Osteosarcoma Models: From Cell Lines to Zebrafish

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Alexander B. Mohseny ◽  
Pancras C. W. Hogendoorn ◽  
Anne-Marie Cleton-Jansen
Keyword(s):  
Age Of Onset ◽  
Treatment Strategies ◽  
Early Age ◽  
Zebrafish Embryos ◽  
High Grade ◽  
Aggressive Tumor ◽  
Histological Heterogeneity ◽  
High Grade Osteosarcoma

High-grade osteosarcoma is an aggressive tumor most commonly affecting adolescents. The early age of onset might suggest genetic predisposition; however, the vast majority of the tumors are sporadic. Early onset, most often lack of a predisposing condition or lesion, only infrequent (<2%) prevalence of inheritance, extensive genomic instability, and a wide histological heterogeneity are just few factors to mention that make osteosarcoma difficult to study. Therefore, it is sensible to design and use models representative of the human disease. Here we summarize multiple osteosarcoma models establishedin vitroandin vivo, comment on their utilities, and highlight newest achievements, such as the use of zebrafish embryos. We conclude that to gain a better understanding of osteosarcoma, simplification of this extremely complex tumor is needed. Therefore, we parse the osteosarcoma problem into parts and propose adequate models to study them each separately. A better understanding of osteosarcoma provides opportunities for discovering and assaying novel effective treatment strategies.

scholarly journals PHYTO-MEDICINAL EFFECTS OF SYZYGIUM CUMINI ON DIABETES: A REVIEW

2020 ◽  
pp. 392-402
Author(s):  
Md. Mahmudul Amin
Keyword(s):  
Plant Extracts ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Scientific Evidence ◽  
Research Result ◽  
Treatment Strategies ◽  
Pharmaceutical Preparations ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Current State

Diabetes is a major public health problem which has been increasing day by day throughout the world with an alarming rate. In recent years, several plant extracts have been examined for their anti-diabetic properties to identify alternative treatment strategies that pose less risk for diabetes. It has been shown that different parts of these plants are collected from diverse regions and administered in different pharmaceutical preparations. The aim of the present review is to provide an overview of the phytochemicals present in S. cumini plants and their potent anti-diabetic activity, toxicological and biological effects of these plant extracts, their current state, limitation and future prospects in developing countries that are not included in the European Pharmacopoeia. In addition, a prospective research result of synergistic use of this plant with other plant (Ficus racemosa) done presently in our laboratory has been included. Based on the available evidence, we highlight the ways in which their therapeutic potential can be properly harnessed and provide scientific evidence for the discovery of novel leads for herbal drug development.

scholarly journals Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Joel Jihwan Hwang ◽  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Clinical Applications ◽  
Clinical Settings ◽  
Positive Outcomes ◽  
Joint Function ◽  
Safety And Efficacy ◽  
High Expectations ◽  
Recent Developments

Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.

Value of P-Glycoprotein and Clinicopathologic Factors as the Basis for New Treatment Strategies in High-Grade Osteosarcoma of the Extremities

2003 ◽  
Vol 21 (3) ◽  
pp. 536-542 ◽  
Author(s):  
Massimo Serra ◽  
Katia Scotlandi ◽  
Gemma Reverter-Branchat ◽  
Stefano Ferrari ◽  
Maria C. Manara ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Tumor Volume ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
High Dose ◽  
Postoperative Phase ◽  
High Grade ◽  
Treatment Protocols ◽  
P Glycoprotein ◽  
High Grade Osteosarcoma

Purpose: To evaluate the prognostic value of P-glycoprotein and clinicopathologic parameters in a large series of high-grade osteosarcoma (OS) patients treated at the Rizzoli Institute. Patients and Methods: With the use of immunohistochemistry, P-glycoprotein was assessed in 149 patients with primary, nonmetastatic, high-grade OS who were homogeneously treated with chemotherapy protocols based on doxorubicin, high-dose methotrexate, and cisplatin and the addition of ifosfamide in the postoperative phase. Results: P-glycoprotein positivity was found in 47 of 149 cases (32%) and was significantly associated with a higher incidence of relapse and a worse outcome, as was age younger than 12 years and tumor volume greater then 150 mL at diagnosis. Multivariate analysis further confirmed the prognostic value of these parameters, which all were independent adverse prognostic factors. Event-free survival and proportional hazards regression analyses confirmed that overexpression of P-glycoprotein at clinical onset is the most important adverse prognostic factor for high-grade OS patients treated with these chemotherapy protocols. Conclusion: Increased P-glycoprotein levels, together with tumor volume and age, should be taken into consideration to identify, at time of diagnosis, subgroups of OS patients with a higher risk of recurrence. This subgroup identification will constitute the basis for drawing individualized treatment protocols on the basis of risk evaluation, with the aim of using more aggressive chemotherapy, or combination chemotherapy with other adjuvants, only in those patients for which more aggressive regimens are strictly necessary and warranted.

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