scholarly journals Melanoma Targeted Therapies beyond BRAF-Mutant Melanoma: Potential Druggable Mutations and Novel Treatment Approaches

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5847
Author(s):  
Karam Khaddour ◽  
Lucas Maahs ◽  
Ana Maria Avila-Rodriguez ◽  
Yazan Maamar ◽  
Sami Samaan ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Braf Mutations ◽  
Level Of Evidence ◽  
Ongoing Research ◽  
Treatment Approaches ◽  
Molecular Alterations ◽  
Improved Outcomes ◽  
Cancer Cell Survival ◽  
High Level ◽  
Key Pathways

Melanomas exhibit the highest rate of somatic mutations among all different types of cancers (with the exception of BCC and SCC). The accumulation of a multimode of mutations in the driver oncogenes are responsible for the proliferative, invasive, and aggressive nature of melanomas. High-resolution and high-throughput technology has led to the identification of distinct mutational signatures and their downstream alterations in several key pathways that contribute to melanomagenesis. This has enabled the development of individualized treatments by targeting specific molecular alterations that are vital for cancer cell survival, which has resulted in improved outcomes in several cancers, including melanomas. To date, BRAF and MEK inhibitors remain the only approved targeted therapy with a high level of evidence in BRAFV600E/K mutant melanomas. The lack of approved precision drugs in melanomas, relative to other cancers, despite harboring one of the highest rates of somatic mutations, advocates for further research to unveil effective therapeutics. In this review, we will discuss potential druggable mutations and the ongoing research of novel individualized treatment approaches targeting non-BRAF mutations in melanomas.

A Comparison of General Anesthesia and Regional Anesthesia as a Risk Factor for Deep Vein Thrombosis Following Hip Surgery: A Critical Review

1990 ◽  
Vol 64 (04) ◽  
pp. 497-500 ◽  
Author(s):  
Martin H Prins ◽  
Jack Hirsh
Keyword(s):  
Deep Vein Thrombosis ◽  
General Anesthesia ◽  
Regional Anesthesia ◽  
Lower Incidence ◽  
Hip Surgery ◽  
Level Of Evidence ◽  
Vein Thrombosis ◽  
Postoperative Thrombosis ◽  
High Level ◽  
Deep Vein

SummaryWe evaluated the evidence in support of the suggestion that the risk of deep vein thrombosis after hip surgery is lower with regional than with general anesthesia. A literature search was performed to retrieve all articles which reported on the incidence of postoperative thrombosis in both fractured and elective hip surgery. Articles were included if the method of anesthesia used was reported and if they used mandatory venography. Based upon the quality of study design the level of evidence provided by a study was graded.In patients who did not receive prophylaxis there were high level studies in elective and fractured hip surgery. All studies showed a statistically significantly lower incidence of postoperative deep vein thrombosis with regional anesthesia (relative risk reductions of 46-55%). There were no direct comparative studies in patients who received prophylaxis. However, between study comparisons did not show even a trend towards to lower incidence of postoperative thrombosis with regional anesthesia.

A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Second Generation ◽  
Current Data ◽  
Braf Mutations ◽  
Durable Response ◽  
Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

Predictive and prognostic biomarkers with therapeutic targets in colorectal cancer: A 2021 update on current development, evidence, and recommendation

2021 ◽  
pp. 107815522110055
Author(s):  
Clement Chung
Keyword(s):  
Checkpoint Inhibitors ◽  
Therapeutic Targets ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Tumor Location ◽  
Prognostic Biomarkers ◽  
Her2 Gene ◽  
Braf Mutations ◽  
Therapeutic Implications ◽  
Molecular Alterations

Although therapeutically actionable molecular alterations are widely distributed across many cancer types, only a handful of them show evidence of clinical utility and are recommended for routine clinical practice in the management of cancers of colon and rectum (CRC). This 2021 update aims to provide a succinct summary on the use of prognostic and/or predictive biomarkers (expanded RAS, BRAF, microsatellite-high [MSI-H] or deficient mismatch repair [dMMR], neurotrophic tyrosine receptor kinase [ NTRK] fusion genes, and human epidermal growth factor receptor type II [ HER2] gene amplification) associated with CRC. Therapeutic implications of each relevant predictive or prognostic biomarker for patients with CRC are described, along with discussion on new developments on (1) biomarker-driven therapies such as testing of BRAF, MLH1 promoter methylation and MMR germline genes in differentiating sporadic CRC or hereditary conditions such as Lynch syndrome; (2) first-line use of immune checkpoint inhibitors in metastatic CRC; (3) risk stratification and therapy selection based on primary tumor location (left-sided vs. right-sided colon cancer); (3) atypical BRAF mutations; (4) use of EGFR directed therapy in the perioperative oligometastatic disease setting; (5) re-challenge of EGFR directed therapy and (6) personalizing therapy of fluoropyrimidine and irinotecan based on new evidence in pharmacogenomic testing. Data are collected and analyzed from available systematic reviews and meta-analyses of treatments with known therapeutic targets in CRC, which may be associated with predictive and/or prognostic biomarkers. Discussions are presented in an application-based format, with goal to empower pharmacists or other clinicians to gain awareness and understanding in biomarker-driven cancer therapy issues.

scholarly journals Organizational Strategies for End-User Development—A Systematic Literature Mapping

Informatics ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 15
Author(s):  
Augusto S. C. Modesto ◽  
Rejane M. da C. Figueiredo ◽  
Cristiane S. Ramos ◽  
Letícia de S. Santos ◽  
Elaine Venson ◽  
...  
Keyword(s):  
Organizational Strategies ◽  
End User ◽  
Viable Option ◽  
Research Gaps ◽  
Systematic Mapping ◽  
Level Of Evidence ◽  
Body Of Knowledge ◽  
Methods And Techniques ◽  
Literature Mapping ◽  
High Level

In the last few years, several organizations have been looking for strategies to meet the needs of users of Information Technology (IT). The decentralization of IT and the empowerment of nonprofessional users have been a viable option among these strategies. This study aimed to identify the End-User Development (EUD) strategies adopted by organizations. A systematic mapping was performed in order to provide for a structured body of knowledge and find potential research gaps. The results show that EUD methods and techniques are the most common strategies addressed in the literature. Also, most of the EUD strategies identified a focus either on EUD managerial issues, such as risk management, or on more technical elements, such as the implementation of components for EUD applications. The benefits and barriers to the adoption of EUD by organizations are also presented in this study. In general, defining EUD processes is a common gap in EUD surveys. We reinforce the need to carry out more research on the adoption of EUD in organizations, with a high level of evidence to validate the results.

Comparing Midterm Outcomes of High-Level Athletes Versus Nonathletes Undergoing Primary Hip Arthroscopy: A Propensity-Matched Comparison With Minimum 5-Year Follow-up

2021 ◽  
pp. 036354652110417
Author(s):  
Andrew E. Jimenez ◽  
Peter F. Monahan ◽  
David R. Maldonado ◽  
Benjamin R. Saks ◽  
Hari K. Ankem ◽  
...  
Keyword(s):  
Hip Arthroscopy ◽  
Statistical Significance ◽  
Arthroscopic Surgery ◽  
Harris Hip Score ◽  
Control Group ◽  
Level Of Evidence ◽  
Femoroacetabular Impingement Syndrome ◽  
Patient Reported ◽  
High Level

Background: High-level athletes (HLAs) have been shown to have better short-term outcomes than nonathletes (NAs) after hip arthroscopy. Purpose: (1) To report midterm outcomes of HLAs after primary hip arthroscopy and (2) to compare their results with a propensity-matched cohort of NA patients. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed between February 2008 and November 2015 for HLAs (professional, college, or high school) who underwent primary hip arthroscopy in the setting of femoroacetabular impingement syndrome (FAIS). HLAs were included if they had preoperative, minimum 2-year, and minimum 5-year follow-up data for the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), and Hip Outcome Score Sports-Specific Subscale (HOS-SSS). Radiographic and intraoperative findings, surgical procedures, patient-reported outcomes (PROs), patient acceptable symptomatic state (PASS), minimal clinically important difference (MCID), and return to sport were reported. The HLA study group was propensity-matched to a control group of NA patients for comparison. Results: A total 65 HLA patients (67 hips) were included in the final analysis with mean follow-up time of 74.6 ± 16.7 months. HLAs showed significant improvement in all PROs recorded, achieved high rates of MCID and PASS for mHHS (74.6% and 79.4%, respectively) and HOS-SSS (67.7% and 66.1%, respectively), and returned to sport at high rates (80.4%). When compared with the propensity-matched NA control group, HLAs reported higher baseline but comparable postoperative scores for the mHHS and NAHS. HLA patients achieved MCID and PASS for mHHS at similar rates as NA patients, but the HLA patients achieved PASS for HOS-SSS at higher rates that trended toward statistical significance (66.1% vs 48.4%; P = .07). NA patients underwent revision arthroscopic surgery at similar rates as HLA patients (14.9% vs 9.0%, respectively; P = .424). Conclusion: Primary hip arthroscopy results in favorable midterm outcomes in HLAs. When compared with a propensity-matched NA control group, HLAs demonstrated a tendency toward higher rates of achieving PASS for HOS-SSS but similar arthroscopic revision rates at minimum 5-year follow-up.

scholarly journals The Use of a Synthetic Cartilage Implant for Hallux Rigidus

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0045
Author(s):  
Niall Smyth ◽  
Jonathan Kaplan ◽  
Amiethab Aiyer
Keyword(s):  
Polyvinyl Alcohol ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Hallux Rigidus ◽  
Reference List ◽  
Great Toe ◽  
Level Of Evidence ◽  
High Level ◽  
Ability Measure

Category: Other Introduction/Purpose: Hallux rigidus is one of the most common pathologies afflicting the foot. Various joint salvage techniques have been described with a multitude of different implants. Recently, a synthetic cartilage implant composed of polyvinyl alcohol (PVA) received FDA premarket approval for treatment of arthritis of the great toe and has been used in over 4,000 cases. The purpose of this study was to systematically review the clinical evidence supporting the use of a PVA implant in hallux rigidus. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Using the terms “cartiva OR polyvinyl alcohol OR synthetic cartilage OR hemiarthroplasty AND hallux rigidus OR great toe arthritis OR first toe arthritis “ we searched the PubMed/Medline database in December 2017. In addition, the reference list of publications were scanned for further relevant studies. Results: 4 studies met the inclusion criteria, all of which were derived from a single randomized controlled trial. At short-term follow-up (2 years), patients undergoing placement of a PVA implant had significant improvement in Foot and Ankle Ability Measure (FAAM) sports and activity of daily living, as well as VAS pain scores. The outcomes of the surgery were found to be noninferior compared to arthrodesis. At intermediate follow-up (5 years), the improvement in clinical outcomes persisted and implant survivorship was 96%. Conclusion: There are limited studies available detailing the outcomes of a PVA implant for hallux rigidus, however the results that are available demonstrate a high level of evidence. There are no long-term publications assessing the outcomes of a PVA implant for hallux rigidus.

scholarly journals THE PREVENTION METHOD OF SPORTS MEDICINE IMAGING MODELING

2021 ◽  
Vol 27 (8) ◽  
pp. 833-836
Author(s):  
Fei Wu ◽  
Xuejun Ma ◽  
Wenjiang Zhao ◽  
Shuhua Qu
Keyword(s):  
Sports Medicine ◽  
Main Type ◽  
Sports Injury ◽  
Acute Injury ◽  
Chronic Injury ◽  
Level Of Evidence ◽  
Prevention Method ◽  
High Level ◽  
And Control ◽  
Type Of Injury

ABSTRACT Introduction: Sports injury is an important reason to interfere with sports training and physical exercise since it will not only bring unnecessary pain to the injured body, but also bring out negative emotions in athletes. Objective: To study the sports injury characteristics of high level competitive aerobics athletes in China. Methods: Literature data, questionnaire survey, expert interviews, field observation, mathematical statistics and physiotherapy tracking were used. Results: Wrists, ankles, waist and knees were the most frequently injured parts in high level competitive aerobics athletes in China. The main type of injury was acute injury, but chronic injury (48.18%) could not be ignored. Ninety percent of active high-level competitive aerobics athletes train with injuries, and 10 percent of them completely stop training because of injuries. Conclusions: Athletes should pay attention to their physical reserve and strengthen physical training. They must also be attentive to self-supervision, their own subjective feelings, and control the amount of exercise done. Level of evidence II; Therapeutic studies - investigation of treatment results.

scholarly journals Research and Management of Rare Diseases in the COVID-19 Pandemic Era: Challenges and Countermeasures

2021 ◽  
Vol 9 ◽  
Author(s):  
Sanjana Fatema Chowdhury ◽  
Syed Muktadir Al Sium ◽  
Saeed Anwar
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Management Strategies ◽  
Routine Care ◽  
Ongoing Research ◽  
The People ◽  
Number Of Patients ◽  
High Level ◽  
Disease Community

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.

Genomic Alterations in Head and Neck Squamous Cell Carcinoma: Level of Evidence According to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)

2021 ◽  
pp. 215-226
Author(s):  
Grégoire Marret ◽  
Ivan Bièche ◽  
Célia Dupain ◽  
Edith Borcoman ◽  
Pauline du Rusquec ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Targets ◽  
Level Of Evidence ◽  
Egfr Amplification ◽  
Molecular Alterations ◽  
Activating Mutations

Development of high-throughput technologies helped to decipher tumor genomic landscapes revealing actionable molecular alterations. We aimed to rank the level of evidence of recurrent actionable molecular alterations in head and neck squamous cell carcinoma (HNSCC) on the basis of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) to help the clinicians prioritize treatment. We identified actionable alterations in 33 genes. HRAS-activating mutations were ranked in tier IB because of the efficacy of tipifarnib (farnesyltransferase inhibitor) in HRAS-mutated patients with HNSCC (nonrandomized clinical trial). Microsatellite instability (MSI), high tumor mutational burden (TMB), and NTRK fusions were ranked in tier IC because of PD-1 and TRK tyrosine kinase inhibitors tissue-agnostic approvals. CDKN2A-inactivating alterations and EGFR amplification were ranked in tier IIA because of the efficacy of palbociclib (CDK4/6 inhibitor) and afatinib (tyrosine kinase inhibitor) in these respective molecular subgroups in retrospective analyses of clinical trials. Molecular alterations in several genes, including PIK3CA gene, were ranked in tier IIIA because of clinical benefit in other tumor types, whereas molecular alterations in IGF1R and TP53 genes were ranked in tier IVA and tier V, respectively. The most compelling actionable molecular alterations in HNSCC according to ESCAT include HRAS-activating mutations, MSI, high TMB, NTRK fusions, CDKN2A-inactivating alterations, and EGFR amplification.

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