Articles: function.
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Chronic pain associated with osteoarthritis (OA) remains an intractable problem with few effective treatment options. New approaches are needed to model the disease biology and to drive discovery of therapeutics. We present an in vitro model of OA pain, where dorsal root ganglion (DRG) sensory neurons were sensitized by a defined mixture of disease-relevant inflammatory mediators, here called Sensitizing PAin Reagent Composition or SPARC. ⋯ We screened ∼3000 approved drugs and mechanistically focused compounds, yielding data from over 1.2 million individual neurons with detailed assessment of functional OA-SPARC phenotype rescue and orthogonal "off-target" effects. Analysis of confirmed hits revealed diverse potential analgesic mechanisms including ion channel modulators and other mechanisms including MEK inhibitors and tyrosine kinase modulators. Our results suggest that the Raf-MEK-ERK axis in DRG neurons may integrate the inputs from multiple upstream inflammatory mediators found in osteoarthritis patient joints, and MAPK pathway activation in DRG neurons may contribute to chronic pain in patients with osteoarthritis.
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Observational Study
Incidence and risk factors for non-cardiac syncope in a cohort of patients addressing an accredited Arterial Hypertension Center: the Innocent Study.
Hypotensive susceptibility in hypertensive patients could facilitate orthostatic hypotension, syncope and fall. The aim of this study was to identify incidence, clinical form, complications and risk factors for non-cardiac syncope in a cohort of hypertensive patients. ⋯ To identify hypertensive patients at higher risk for syncope and falls, physicians should focus on comorbidities and current drug regimens, systematically perform an active standing test to identify orthostatic hypotension, employ ABPM to compare BP values with the pre-established target and highlight systolic BP drops and abnormalities suggesting concomitant autonomic dysfunction. The modulation of antihypertensive therapy is an effective tool to counteract the risk of non-cardiac syncope, with possible trauma or other negative influences.
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Case Reports
Local Anesthetic Systemic Toxicity in Cardiac Surgery Patient with Erector Spinae Plane Catheter: A Case Report.
Regional anesthesia nerve blocks are increasingly used for patients undergoing cardiac surgery as part of multimodal pain management. Though rare, local anesthetic systemic toxicity (LAST) is a severe complication that requires vigilant monitoring. ⋯ This episode was determined to be a result of impaired lidocaine metabolism from liver shock caused by worsening pulmonary hypertension. Even under continuous monitoring, patients with cardiac or liver dysfunction are at increased risk of complications from local anesthetics.