3714 research outputs found
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Immunotherapy in malignant pleural mesothelioma: a long story ended in success
No full textMalignant pleural mesothelioma (MPM) is an aggressive and rare disease, mainly due to asbestos exposure, characterized by a poor prognosis. For almost two decades, platinum-based chemotherapy has been the only approved therapeutic regimen for first-line MPM, with an overall survival of 12 months. In the last years, the therapeutic scenario of different tumor types, including MPM, has dramatically changed due to immune checkpoint inhibition. The promising results of this approach have promoted new efforts into clinical research, and many trials investigating novel therapeutic combinations are currently ongoing. The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced MPM
More efficient clinical trials in pancreatic cancer: develop better treatment options, faster
No full textClinical development of new treatment options for patients with pancreatic cancer has been slow and expensive and resulted in few effective therapies. With a dismal five-year survival rate of 11% in the U.S., pancreatic cancer remains the third leading cause of cancer-related deaths and is poised to move to second by 2030. Standard clinical trials typically compare one investigational treatment to one standard of care, encompass one phase of clinical investigation at a time, and treat one patient population. Accrual and data analysis are often very slow, and unfortunately, the vast majority of clinical trials targeting pancreatic cancer patients are unsuccessful. More efficient clinical trial designs can include combining phases I and II or phases II and III, and trials that involve a master protocol approach can also answer multiple clinical questions simultaneously. These modern clinical trial designs can allow a faster, more efficient and cost-effective approach to testing investigational therapies in patients with pancreatic cancer and, most importantly, fewer patients may be required to determine the efficacy of treatment. Herein we summarize some of the recent innovative clinical trials in pancreatic cancer to provide meaningful data toward developing new treatment options to benefit patients with a dismal disease like pancreatic cancer
Antithrombotic therapy in patients undergoing transcatheter aortic valve replacement (TAVR): from current evidence to perspective
No full textThe use of transcatheter aortic valve replacement (TAVR) for care of symptomatic severe aortic stenosis has increased over the last years; after initially treating patients at prohibitive or high surgical risk, nowadays the procedure can be considered for intermediate or low surgical risk. Although thrombotic events (ischemic stroke, myocardial infarction, and leaflet thrombosis) decreased in patients at lower risk, antithrombotic therapy after TAVR is still recommended. However, the optimal antithrombotic regimen is a still matter of debate due to the lack of randomized data and the concomitant increased risk of bleeding events. In the present review, we analyze current data, recommendations of international guidelines and consensus documents, and potential future scenarios with a rational approach of separation of patients with or without a pre-procedural indication for long-term oral anticoagulant therapy
Lysosome-mediated chemoresistance in acute myeloid leukemia
No full textDespite the outstanding advances in understanding the biology underlying the pathophysiology of acute myeloid leukemia (AML) and the promising preclinical data published lastly, AML treatment still relies on a classic chemotherapy regimen largely unchanged for the past five decades. Recently, new drugs have been approved for AML, but the real clinical benefit is still under evaluation. Nevertheless, primary refractory and relapse AML continue to represent the main clinical challenge, as the majority of AML patients will succumb to the disease despite achieving a complete remission during the induction phase. As such, treatments for chemoresistant AML represent an unmet need in this disease. Although great efforts have been made to decipher the biological basis for leukemogenesis, the mechanism by which AML cells become resistant to chemotherapy is largely unknown. The identification of the signaling pathways involved in resistance may lead to new combinatory therapies or new therapeutic approaches suitable for this subset of patients. Several mechanisms of chemoresistance have been identified, including drug transporters, key secondary messengers, and metabolic regulators. However, no therapeutic approach targeting chemoresistance has succeeded in clinical trials, especially due to broad secondary effects in healthy cells. Recent research has highlighted the importance of lysosomes in this phenomenon. Lysosomes’ key role in resistance to chemotherapy includes the potential to sequester drugs, central metabolic signaling role, and gene expression regulation. These results provide further evidence to support the development of new therapeutic approaches that target lysosomes in AML
Development and early evaluation of clinical decision support for long QT syndrome population screening
No full textAim: Long QT syndrome (LQTS) is an inherited condition that predisposes individuals to prolongation of the QT interval and increased risk for Torsade de Pointes. Pathogenic variants in three genes - KCNH2, KCNQ1 and SCN5A - are responsible for most cases of LQTS, and recent advances in genetic testing have improved knowledge of the disease, increased access to follow-up, and reduced adverse cardiovascular outcomes. Methods: Based around our preemptive genetic screening platform which includes the three long QT genes listed above, we developed and implemented a clinical decision support (CDS) module that alerts prescribers whenever a QT-prolonging medication is ordered for patients with a genetic predisposition to LQTS. Results: Of the 13,777 individuals screened, twenty-seven tested positive for a pathogenic or likely pathogenic variant of KCNH2, KCNQ1 or SCN5A. In a subsequent early evaluation of the CDS and clinical processes, the number of QT-prolonging medications in this cohort decreased by 20% and new QT-prolonging medications were avoided in approximately 1/3 of new prescription orders. Conclusions: While long-term evaluation is needed, early data support the benefit of utilizing CDS in expanded roles, such as drug-gene-disease interactions where rare genetic variants intersect with everyday prescribing
Towards extracellular vesicle delivery systems for tissue regeneration: material design at the molecular level
No full textThe discovery and development of extracellular vesicles in tissue engineering have shown great potential for tissue regenerative therapies. However, their vesicle nature requires dosage-dependent administration and efficient interactions with recipient cells. Researchers have resorted to biomaterials for localized and sustained delivery of extracellular vesicles to the targeted cells, but not much emphasis has been paid on the design of the materials, which deeply impacts their molecular interactions with the loaded extracellular vesicles and subsequent delivery. Therefore, we present in this review a comprehensive survey of extracellular vesicle delivery systems from the viewpoint of material design at the molecular level. We start with general requirements of the materials and delve into different properties of delivery systems as a result of different designs, from material selections to processing strategies. Based on these differences, we analyzed the performance of extracellular vesicle delivery and tissue regeneration in representative studies. In light of the current missing links within the relationship of material structures, physicochemical properties and delivery performances, we provide perspectives on the interactions of materials and extracellular vesicles and the possible extension of materials. This review aims to be a strategic enlightenment for the future design of extracellular vesicle delivery systems to facilitate their translation from basic science to clinical applications
Enantioselective 1,1-diarylation of terminal alkenes catalyzed by palladium with a chiral phosphoric acid
No full textThe enantioselective 1,1-diarylation of allyl sulfones and vinyl sulfones is reported for the first time, enabled by a combination of Pd2dba3 and a chiral SPINOL-derived phosphoric acid. Various chiral sulfones containing 1,1-diarylalkane motifs were obtained in moderate to good yields with moderate to high enantioselectivities. Control experiments suggested that the sulfone group plays a key role in providing enantioselectivity and reactivity control and might serve as a directing group
The challenges of deep learning in artificial intelligence and autonomous actions in surgery: a literature review
No full textAim: Artificial intelligence (AI) is rapidly evolving in healthcare worldwide, especially in surgery. This article reviews important terms used in machine learning and the challenges of deep learning in surgery.Methods: A review of the English literature was carried out focused on the terms “challenges of deep learning” and “surgery” using Medline and PubMed between 2018 and 2022.Results: In total, 54 articles discussed the challenges of deep learning in general. We include 25 articles from various surgical specialties discussing challenges corresponding to their respective specialties.Conclusion: The increased utilization of AI in surgery is faced with a wide variety of technical, ethical, clinical, and business-related challenges. The best way to expedite its expansion in surgery in the safest and most cost-efficient manner is by ensuring that as many surgeons as possible have a clear understanding of basic AI concepts and how they can be applied to the preoperative, intraoperative, postoperative, and long-term follow-up phases of the surgical patient care
Rat models of major neurodegenerative disorders
No full textNo single animal model can recapitulate all the features of a particular human disease on its own. Historically, rats have been used to study neurobiology and underlying functional networks. Likewise, rat models have been created to study neurodegenerative mechanisms and therapeutic interventions. In the last decades, a shift towards the use of mice has been observed in many research fields, not least because of the comparatively easier genetic manipulation of mice. However, with the full sequence of the rat genome being available, advances in genetic manipulation of the rat, and advanced test regimens and biomarkers at hand, the rat presents itself once more as a valuable model organism for studying neurodegenerative disorders. This review provides an overview of currently available, well-characterized rat models of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, as well as their advantages for studying neurodegenerative disorders and evaluating therapeutic interventions
Glycaemic control strategies in people with type 2 diabetes mellitus undergoing elective surgery
No full textPeople with diabetes mellitus (DM) undergo more elective surgery than those without DM; however, up to half of the patients are undiagnosed when referred for surgery. This is an opportunity to intervene and instigate a management plan. Preoperative strategies may vary based on coexisting medical diseases such as obesity and the availability of resources with the aim of achieving glycaemic control while also treating coexisting conditions. In the context of obesity, there is substantial overlap in some of the treatment strategies. Guidelines, such as those from the UK Centre for Perioperative Medicine, suggest target glycated haemoglobin levels, preoperative fasting blood glucose levels, and when to defer an elective operation or instigate treatment to proceed if deemed safe. Preoperatively glycaemic control is often achieved pharmacologically, and newer agents, including glucagon-like peptide one receptor agonists (GLP1-RA) and sodium-glucose co-transporter 2 (SGLT2) inhibitors, are emphasised in the preoperative management of diabetes mellitus, particularly if obesity is also present. A very low-energy diet is an underutilised but well-evidenced method of achieving both glycaemic control and weight loss with a particularly dominant effect on liver fat which is helpful for people who are due to undergo abdominal surgery. Bariatric-metabolic procedures are of growing interest as bridging interventions to surgery and are more commonly used for obesity, but they also have a well-recognized impact on the improvement and remission of DM. This review gives an overview of the necessity of preoperative identification of DM and strategies for management. Intra-operative glycaemic control is also discussed, and the role of stress hyperglycaemia perioperatively
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