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New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study ies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.Colorectal cancer (CRC), despite the advances in screening and surveillance, remains the second most common cause of cancer death worldwide. The biological inadequacy of pre-clinical models to fully recapitulate the multifactorial etiology and the complexity of tumor microenvironment and human CRC's genetic heterogeneity has limited cancer treatment development. This has led to the development of Patient-derived models able to phenocopy as much as possible the original inter- and intra-tumor heterogeneity of CRC, reflecting the tumor microenvironment's cellular interactions. Implantation of patient tissue into immunodeficient mice hosts and the culture of tumor organoids have allowed advances in cancer biology and metastasis. This review highlights the advantages and limits of Patient-derived models as innovative and valuable pre-clinical tools to study progression and metastasis of CRC, develop novel therapeutic strategies by creating a drug screening platform, and predict the efficacy of clinical response to therapy.Clinical trial transparency forms the foundation of evidence-based medicine, and trial sponsors, especially publicly funded institutions such as universities, have an ethical and scientific responsibility to make the results of clinical trials publicly available in a timely fashion. We assessed whether the thirty UK universities receiving the most Medical Research Council funding in 2017-2018 complied with World Health Organization best practices for clinical trial reporting on the US Clinical Trial Registry ( ClinicalTrials.gov ). Firstly, we developed and evaluated a novel automated tracking tool ( clinical-trials-tracker.com ) for clinical trials registered on ClinicalTrials.gov . This tracker identifies the number of due trials (whose completion lies more than 395 days in the past) that have not reported results on the registry and can now be used for all sponsors. Secondly, we used the tracker to determine the number of due clinical trials sponsored by the selected UK universities in October 2020. Thirdlov (i) efforts to improve clinical trial reporting in the UK have to date focused on the European clinical trial registry (EU CTR), (ii) the absence of a tracking tool for timely reporting on ClinicalTrials.gov has limited the visibility of institutions' reporting performance on the US registry and (iii) there is currently a lack of repercussions for UK sponsors who fail to report results on ClinicalTrials.gov which should be addressed in the future.
Acute DeBakey typeI and typeII aortic dissections are indications for emergent surgical repair; however, there are currently no standard protocols in the management of isolated supra-aortic dissections. Prompt diagnosis and management of an isolated innominate artery dissection are necessary to prevent distal malperfusion and thromboembolic sequelae.
A 50-year-old Caucasian gentleman presented with chest pain radiating to his jaw and right arm. He had no recent history of trauma. On physical exam, he was neurologically intact and malignantly hypertensive. Computed tomographic angiography of the chest and neck confirmed a spontaneous isolated innominate artery dissection without ascending aorta involvement. Given the lack of evidence for rupture, distal emboli, and/or end-organ malperfusion, the decision was made for initial non-operative management-anti-impulse regimen, antiplatelet therapy, and close follow-up.
Medical management of a spontaneous isolated innominate artery dissection is appropriate for short-term and potentially long-term therapy. This not only spares the patient from a potentially unnecessary surgical operation but also provides the surgeon and the patient the time to plan for a surgical approach if it becomes necessary.
Medical management of a spontaneous isolated innominate artery dissection is appropriate for short-term and potentially long-term therapy. This not only spares the patient from a potentially unnecessary surgical operation but also provides the surgeon and the patient the time to plan for a surgical approach if it becomes necessary.
Metagenomic next-generation sequencing (mNGS) of body fluids is an emerging approach to identify occult pathogens in undiagnosed patients. selleck chemical We hypothesized that metagenomic testing can be simultaneously used to detect malignant neoplasms in addition to infectious pathogens.
From two independent studies (n = 205), we used human data generated from a metagenomic sequencing pipeline to simultaneously screen for malignancies by copy number variation (CNV) detection. In the first case-control study, we analyzed body fluid samples (n = 124) from patients with a clinical diagnosis of either malignancy (positive cases, n = 65) or infection (negative controls, n = 59). In a second verification cohort, we analyzed a series of consecutive cases (n = 81) sent to cytology for malignancy workup that included malignant positives (n = 32), negatives (n = 18), or cases with an unclear gold standard (n = 31).
The overall CNV test sensitivity across all studies was 87% (55 of 63) in patients with malignancies confirmed by conventional cytology and/or flow cytometry testing and 68% (23 of 34) in patients who were ultimately diagnosed with cancer but negative by conventional testing.
Homepage: https://www.selleckchem.com/products/d-lin-mc3-dma.html
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