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Clinical pathways

Sarah Thiele, Maximilian Pfau, Petra P Larsen, Monika Fleckenstein, Frank G Holz, Steffen Schmitz-Valckenberg
Purpose: To evaluate the development of central atrophy in eyes with age-related macular degeneration (AMD). Methods: Six-year longitudinal multimodal retinal imaging data (MODIAMD study) from 98 eyes of 98 subjects with non-late-stage AMD in the study eye at baseline were analyzed for the presence of central atrophy at each annual follow-up visit. Development, manifestation, and further progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) by multimodal imaging data were compared with atrophy detection based on color fundus photography only...
March 20, 2018: Investigative Ophthalmology & Visual Science
Dawei Cai, Zongjian Liu, Guangqi Kong
BACKGROUND Circular RNAs (circRNAs) have emerged as important regulators in carcinogenesis and metastasis. However, the knowledge of circRNAs in bladder cancer remains limited. This study aimed to investigate the role and mechanism of circRNAs in the development and progression of bladder cancer. MATERIAL AND METHODS Three pairs of bladder carcinomas (including high- and low-grade tumors) and adjacent normal tissues were collected from patients. The total RNAs were extracted from these samples and subjected to Clariom D microarray assays to detect the differentially expressed circRNAs and mRNAs...
March 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jelena Krstic, Markus Galhuber, Tim J Schulz, Michael Schupp, Andreas Prokesch
Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the prevalence of liver pathologies is steadily increasing in modern societies, there are currently no approved drugs other than chemotherapeutic intervention in late stage HCC. Hence, there is a pressing need to identify and investigate causative molecular pathways that can yield new therapeutic avenues...
March 20, 2018: International Journal of Molecular Sciences
Céline Hernandez, Peter Huebener, Jean-Philippe Pradere, Daniel J Antoine, Richard A Friedman, Robert F Schwabe
Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD...
March 20, 2018: Journal of Clinical Investigation
Ulkem Kocoglu Barlas, Hasan Serdar Kıhtır, Nilufer Goknar, Melike Ersoy, Nihal Akcay, Esra Sevketoglu
BACKGROUND: Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant mortality and high risk of progression to end-stage kidney disease. It is mostly caused by dysregulation of the alternative complement pathway. Cobalamin C (Cbl C) defect is a genetic disorder of cobalamin metabolism and is a rare cause of HUS. CASE-DIAGNOSIS/TREATMENT: We present a 6-month-old male infant who was admitted to the pediatric intensive care unit (PICU) due to restlessness, severe hypertension, anemia, respiratory distress, and acute kidney injury...
March 20, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Zuzanna Podemska-Jedrzejczak, Agnieszka Malinska, Patrycja Sujka-Kordowska, Michal Nowicki, Mateusz Puslecki, Marek Jemielity, Bartlomiej Perek
The vascular endothelial growth factor (VEGF) family of peptides and caveolins (CAVs) are reported to contribute, in early graft failure in patients, a coronary artery bypass grafting (CABG). To investigate the possible association of ultimate luminal occlusion to VEGFs and CAVs expression, a functional analysis (based on the molecular biology, bioinformatics, histology, and clinical studies) was performed. Twenty-four hundred and sixty-eight CABG patients diagnosed with multivessel stable coronary artery disease (CAD) were enrolled into prospective study and assigned to two subgroups: double- and triple-vessel CAD subjects...
March 20, 2018: Heart and Vessels
Lewis S Gall, Paul Vulliamy, Scarlett Gillespie, Timothy F Jones, Rochelle S J Pierre, Sabine E Breukers, Christine Gaarder, Nicole P Juffermans, Marc Maegele, Jakob Stensballe, Pär I Johansson, Ross A Davenport, Karim Brohi
OBJECTIVE: To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. BACKGROUND: Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent...
March 19, 2018: Annals of Surgery
Liwei Lang, Austin Y Shull, Yong Teng
Coordination between amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho have been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has been implicated in driving specific tumorigenic events including cancer cell proliferation, apoptosis resistance, and metastasis by activating a myriad of downstream signaling cascades. As an attractive target, several strategies implemented to disrupt the FGF19-FGFR4 axis have been developed in recent years, and FGF19-FGFR4 binding inhibitors are being intensely evaluated for their clinical use in treating FGF19-FGFR4 implicated cancers...
March 18, 2018: Current Cancer Drug Targets
Delia De Lisi, Ugo De Giorgi, Cristian Lolli, Giuseppe Schepisi, Vincenza Conteduca, Cecilia Menna, Giuseppe Tonini, Daniele Santini, Alberto Farolfi
To date, results of combination therapy studies have shown no meaningful clinical benefit over monotherapy and an unacceptably high degree of toxicity in the treatment of metastatic renal cell carcinoma (RCC), with the exception of a combination of immune-checkpoint inhibitors and the association of lenvatinib with everolimus. Lenvatinib is a potent multi-targeted tyrosine kinase inhibitor that targets VEGFR pathways. Everolimus inhibits primarily mTORC1 complex, a downstream effecter of the intracellular PI3K/AKT/mTOR pathway...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
Shelly A Cruz, Zhaohong Qin, Alexandre F R Stewart, Hsiao-Huei Chen
Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK) associated with the tumor necrosis factor-alpha (TNF-α)/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations...
February 2018: Neural Regeneration Research
Jessica M Hogestyn, David J Mock, Margot Mayer-Proschel
Human herpesviruses (HVs) have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS). The ability of HVs to enter a state of latency, a defining characteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors...
February 2018: Neural Regeneration Research
Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop, Andreas Wollenberg
Dupilumab is a new treatment option for patients with moderate-to-severe atopic dermatitis. It blocks IL-4/IL13-signaling and thereby inhibits receptor signaling downstream the JAK-STAT-pathway. Three of the main disease mechanisms of atopic dermatitis are affected by blocking this pathway; the decrease of skin barrier function, the class switch to IgE and the TH2-differentiation. Areas Covered: Dupilumab showed promising results in clinical trials of phase I-III. Clinical outcome parameters such as SCORAD, EASI, IGA and BSA improved with dupilumab...
March 20, 2018: Expert Review of Clinical Pharmacology
Michael A Überall
BACKGROUND: Transient exacerbation of pain in cancer patients (breakthrough cancer pain, BTCP) despite adequately controlled background pain should be regarded as an independent disease and receive targeted treatment. The opioid of choice is fentanyl, a rapid onset and highly potent WHO category III analgesic. Fentanyl has a strong first pass effect when administered orally and resorbed enterally, however it is well suited for transmucosal administration, e.g. on the oral or nasal mucosa...
October 2017: MMW Fortschritte der Medizin
Philip R Holland, Peter J Goadsby
Migraine is a highly prevalent, severe, and disabling neurological condition with a significant unmet need for effective acute therapies. Patients (~50%) are dissatisfied with their currently available therapies. Calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide involved in the pathophysiology of migraines. As reviewed in this manuscript, a number of small molecule antagonists of the CGRP receptor have been developed for migraine therapy. Incredibly, the majority of the clinical trials conducted have proven positive, demonstrating the importance of this signalling pathway in migraine...
March 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Carmen Pheiffer, Stephanie Dias, Paul Rheeder, Sumaiya Adam
BACKGROUND AND OBJECTIVE: In recent years circulating microRNAs (miRNAs) have attracted interest as biomarkers of metabolic disease. MiRNA expression varies across population groups; thus, the aim of this study was to investigate whether serum miRNAs that have previously been shown to be associated with gestational diabetes mellitus (GDM) in other populations, are similarly regulated in South African women with GDM. METHODS: In this case-control study, women (n = 81) were selected from a prospective cohort study in which pregnant women were recruited at their first clinic visit and requested to return for fasting blood glucose concentration measurements and serum collection (median 27 weeks; range 13-31 weeks)...
March 19, 2018: Molecular Diagnosis & Therapy
Chunyao Zhou, Yongheng Wang, Xing Liu, Yuchao Liang, Ziwen Fan, Tao Jiang, Yinyan Wang, Lei Wang
BACKGROUND: The newly proposed putamen classification system shows good prognostic value in patients with insular LGGs, yet no study towards the molecular profiles of putamen involved LGGs has been proposed. METHODS: Clinical information and imaging data of patients diagnosed with insular low-grade gliomas were collected retrospectively. Genetic information of the 34 tumors was assessed using RNA-sequencing. Gene set enrichment analysis was further performed to identify the genes showing differential expression between putamen-involved tumors and putamen non-involved tumors...
March 19, 2018: Journal of Neuro-oncology
Wasim Khasawneh, Salar Bani Hani
Medication errors remain among the major problems seen in hospitals. Such errors can relate to the prescription, dispensation, or administration of drugs. Human factors account for most of these mistakes, but other factors such as infusion pump programming defects should always be considered. Worldwide, medication errors have been reported to affect 2-30% of patients, depending on the institution. Intravenous lipid emulsion (ILE) infusion is frequently used as part of total parenteral nutrition in patients of all ages with feeding and gastrointestinal issues...
March 19, 2018: Drug Safety—Case Reports
Gurpreet Kaur, Praveen Sharma, Nilambra Dogra, Sandeep Singh
The cells of malignant cancers result in the evolution of cells with stem-like characteristics, commonly known as cancer stem cells (CSCs). Progress of anticancer therapies is severely hampered because of disease relapse mostly in a more aggressive form due to CSCs. These CSCs are more or less like embryonic or tissue stem cells, known for their capacity of self-renewal, exactly recapitulate of the original tumor. Deregulation of key stem cell pathways like Wnt, Hedgehog (Hh), and Notch is attributed towards the rise of CSCs...
March 20, 2018: Current Treatment Options in Oncology
Nicolas Palaskas, Kara Thompson, Gregory Gladish, Ali M Agha, Saamir Hassan, Cezar Iliescu, Peter Kim, Jean B Durand, Juan C Lopez-Mattei
PURPOSE OF REVIEW: Our purpose is to discuss the importance of multimodality imaging in the assessment of cardiac tumors and management. We have compiled a recent review of the scientific literature and embedded our clinical pathways and recommendations based on data and clinical experience. RECENT FINDINGS: The use of contrast echocardiography in the assessment of cardiac masses has been shown to be helpful in distinguishing tumor from thrombus. Deformation imaging of cardiac tumors has been shown to differentiate better rhabdomyomas from fibromas in pediatric patients...
March 20, 2018: Current Treatment Options in Cardiovascular Medicine
B Yun, T Zhang, M A K Azad, J Wang, C J Nowell, P Kalitsis, T Velkov, D F Hudson, J Li
Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0...
March 20, 2018: Archives of Toxicology
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