Project description:Uveal melanoma is a rare cancer in adults, but its treatment is one of the clinical unmet needs in the melanoma field. Metastatic disease develops in approximately 50% of patients and is associated with poor survival due to the lack of effective treatment options. It provides a paradigm for cancers that show evidence of aberrant G protein-coupled receptor signaling, tumor dormancy, and liver-selective metastatic tropism and are associated with the loss of the BAP1 tumor suppressor. At the Melanoma Research Foundation CURE OM Science Meeting at the Society for Melanoma Research Meeting held in Utah on November 20, 2019, clinicians and researchers presented findings from their studies according to three themes within uveal melanoma: (i) ongoing clinical trials, (ii) molecular determinants, and (iii) novel targets that could be translated into clinical trials. This meeting underscored the high interest in the uveal melanoma research field and the unmet need for effective treatment strategies for late-stage disease. Findings from ongoing clinical trials are promising, and multiple studies show how novel combinatorial strategies increase response rates. Novel targets and tumor vulnerabilities identified bioinformatically or through high-throughput screens also reveal new opportunities to target uveal melanoma. The future directions pursued by the uveal melanoma research field will likely have an impact on other cancer types that harbor similar genetic alterations and/or show similar biological properties.
Project description:Abstract The surprising outbreak of an anticipated virus has exposed that the profit?centered mode of production renders a dysfunctional society, with a high incidence of pandemic?prone diseases. Consequently, the global health crisis and subsequent economic collapse threatening the existence of billions reveal the ultimate market failure from both heterodox and radical theoretical viewpoints. The demise of markets and capitalist systems calls for a straightforward economic intervention and radical transformation of the way societal production is conceptualized. This paradigm shift must deprioritize economic growth driven by the omnipresent commodification of all social relations and must furnish a viable alternative provided by the political economy. The starting point for such fundamental change in the dominant discourse must be rooted in balancing between the needs and wants, and in creating an environment in which properly understood self?interest would bring about a sustainable and equitable increase in societal well?being.
Project description:In the last hundred years surgery has experienced a dramatic increase of scientific knowledge and innovation. The need to consider best available evidence and to apply technical innovations, such as minimally invasive approaches, challenges the surgeon both intellectually and manually. In order to overcome this challenge, computer scientists and surgeons within the interdisciplinary field of "cognitive surgery" explore and innovate new ways of data processing and management. This article gives a general overview of the topic and outlines selected pre-, intra- and postoperative applications. It explores the possibilities of new intelligent devices and software across the entire treatment process of patients ending in the consideration of an "Intelligent Hospital" or "Hospital 4.0", in which the borders between IT infrastructures, medical devices, medical personnel and patients are bridged by technology. Thereby, the "Hospital 4.0" is an intelligent system, which gives the right information, at the right time, at the right place to the individual stakeholder and thereby helps to decrease complications and improve clinical processes as well as patient outcome.
Project description:Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. This review summarizes seminal findings from clinical and translational studies recently presented or published at important meetings or in top-tier journals, respectively. For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Regarding cellular immunotherapy, recent studies confirmed safety and efficacy of CAR T cells in larger cohorts of patients with acute lymphoblastic leukemia or diffuse large B cell lymphoma. Different strategies to translate the striking success of CAR T cells in B cell malignancies to other hematological and solid cancer types are currently under clinical investigation. Regarding the regional distribution of registered clinical immunotherapy trials a shift from PD-1 / PD-L1 trials (mainly performed in the US and Europe) to CAR T cell trials (majority of trials performed in the US and China) can be noted.
Project description:Opinion statementThe treatment of advanced GIST is rapidly evolving with the development of novel molecular compounds such as avapritinib and ripretinib, but also promising results have been achieved with cabozantinib in a phase II trial. The availability of over five lines of treatment for patients with advanced GIST is likely to completely shift the current second-line and third-line treatment options, and will also potentially enable a personalised approach to treatment. Imatinib will most likely remain as the first-line treatment of choice for the vast majority of GIST patients. However, for GIST patients with tumours harbouring a D842V mutation in PDGFRA exon 18, avapritinib has shown efficacy and will become first-line therapy for this molecular subgroup. For second- and third-line treatment, results are awaited of a number of clinical trials. However, second-line and further treatment could potentially be tailored depending on secondary mutations found in imatinib-resistant GISTs. As secondary resistance to TKIs remains the biggest challenge in the treatment of GIST and despite negative results with alternating regimens in phase II, combination treatments should be further evaluated to tackle this issue. Moreover, the favourable safety profiles observed with avapritinib and ripretinib suggest that combination treatments are feasible, for instance, combining two TKIs or a TKI with drugs targeting downstream signalling pathways, such as PI3K inhibitors or MEK inhibitors. Finally, in line with further personalisation of treatment in GIST, a multidisciplinary approach is essential, and local treatment options, such as RFA, resection in case of unifocal progression, and radiotherapy, should be considered.
Project description:While there is no proven treatment available for coronavirus disease 2019 (COVID-19), convalescent plasma (CP) may provide therapeutic relief as the number of cases escalate steeply world-wide. At the time of writing this review, vaccines, monoclonal antibodies or drugs are still lacking for the recent large COVID-19 outbreak, which restores the interest in CP as an empirical life-saving treatment. However, formal proof of efficacy is needed. The purpose of this review is to summarize all historical clinical trials on COVID-19 infected patients treated with CP to provide precise evidence for the efficacy and effectiveness of CP therapy in severe COVID-19 patients. Although there are many clinical trials in progress, high-quality clinical evidence is still lacking to analyze the existing problems. Meanwhile, based on the previous successful outcomes, we recommend healthcare systems to use CP therapy cautiously in critically ill COVID-19 patients.
Project description:The development of biological disease-modifying antirheumatic drugs (bDMARDs) and target synthetic DMARDs (tsDMARDs), also known as small molecule inhibitors, represent a breakthrough in rheumatoid arthritis (RA) treatment. The tsDMARDs are a large family of small molecules targeting mostly the several types of kinases, which are essential in downstream signaling of pro-inflammatory molecules. This review highlights current challenges associated with the treatment of RA using small molecule inhibitors targeting intracellular JAKs/MAPKs/NF-κB/SYK-BTK signaling pathways. Indeed, we have provided the latest update on development of small molecule inhibitors, their clinical efficacy and safety as a strategy for RA treatment. On the other hand, we have highlighted the risk and adverse effects of tsDMARDs administration including, among others, infections and thromboembolism. Therefore, performance of blood tests or viral infection screening should be recommended before the tsDMARDs administration. Interestingly, recent events of SARS-CoV-2 outbreak have demonstrated the potential use of small molecule inhibitors not only in RA treatment, but also in fighting COVID-19 via blocking the viral entry, preventing of hyperimmune activation and reducing cytokine storm. Thus, small molecule inhibitors, targeting wide range of pro-inflammatory singling pathways, may find wider implications not only for the management of RA but also in the controlling of COVID-19.
Project description:Venetoclax is a specific B-cell lymphoma-2 (BCL-2) inhibitor that can restore activation of apoptosis in malignancies, the survival of which depends on dysregulation of this pathway. Preclinical data, using various model systems including cell lines and patient samples, suggested targeting BCL-2 could be a successful therapeutic strategy in patients with acute myeloid leukemia (AML). As predicted by this work, the use of venetoclax in the clinical setting has resulted in promising outcomes for patients with this disease. Although venetoclax showed limited activity as a single agent in the relapsed disease setting, recent studies have shown that when combined with a backbone therapy of a hypomethylating agent or low-dose cytarabine, high response rates with encouraging remission durations for older patients with newly diagnosed AML who were not candidates for intensive induction chemotherapy were observed. Furthermore, venetoclax-based therapies allowed for rapid responses and were able to effectively target the leukemia stem cell population. Here we review the preclinical data that supported the development of venetoclax in AML, as well as the results of the promising clinical trials.
Project description:Until vaccination for the SARS-CoV-2 becomes a reality, it appears that the infection is here to stay. With many countries lifting lockdown restrictions, aesthetic clinics have started reopening with strict standard operating procedures in place. It is pertinent that the physician today understands the infection, disinfection measures, and personal protective equipment to reduce chances of viral transmission and provide safe clinical settings for oneself, the staff and the patients. An online meeting of eight experts in the field of aesthetic dermatology was convened, which particularly focussed on PPE in detail, risk categorization of aesthetic procedures, preprocedure recommendations, and generalized and specialized SOP's for aesthetic procedures. These recommendations were aimed to bridge the gap between published guidelines and clinical practice and are by no means fully conclusive, but signify learnings over the past few months in an active clinical aesthetic practice.
Project description:T cell immunoglobulin domain and mucin domain-3 (TIM-3) is an important immune checkpoint (IC) protein in cancer immunosuppression that is considered a novel target for immunotherapy. Moreover, TIM-3, an immuno-myeloid regulator, is highly expressed on the cells of several solid tumors and myeloid leukemia stem cells (LSCs). TIM-3 blockade was shown to have dual effects for directly inhibiting leukemia cells and restoring T cell activation. We summarize several of the latest reports on the role of TIM-3 in immunotherapy for hematological malignancies from the 2022 ASH Annual Meeting (ASH2022).