135 research outputs found

    Fibromyalgia and Shoulder Surgery : a Systematic Review and a Critical Appraisal of the Literature

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    Fibromyalgia is a common musculoskeletal syndrome characterized by chronic widespread pain and other systemic manifestations, which has demonstrated a contribution to higher postoperative analgesic consumption to other surgeries such as hysterectomies and knee and hip replacements. The aim of this review is to search current literature for studies considering the impact of fibromyalgia on clinical outcomes of patients undergoing shoulder surgery. A systematic literature review was conducted in PubMed/Medline, Embase, and ClinicalTrials.gov in February 2019. Studies were selected based on the following participants, interventions, comparisons, outcomes, and study design criteria: adult patients undergoing surgery for shoulder pain (P); diagnosis of fibromyalgia (I); patients without fibromyalgia (C); outcome of surgery in terms of pain or analgesic or non-steroidal anti-inflammatory drugs consumption (O); case series, retrospective studies, observational studies, open-label studies, randomized clinical trials, systematic reviews and meta-analyses were included (S). Authors found 678 articles, of which four were found eligible. One retrospective study showed that patients with fibromyalgia had worse clinical postoperative outcomes; two retrospective studies reported a higher opioid prescription in patients with fibromyalgia and one prospective observational study found that a higher fibromyalgia survey score correlated with lower quality of recovery scores two days after surgery. The scarce and low-quality evidence available does not allow confirming that fibromyalgia has an impact on postoperative outcomes in shoulder surgery. Future studies specifically focusing on shoulder surgery outcomes may help improvement and personalization of the management of patients with fibromyalgia syndrome (PROSPERO 2019, CRD42019121180)

    Analysis of oxidative stress-related markers in Crohn’s disease patients at surgery and correlations with clinical findings

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    Crohn’ disease (CD) patients are at high risk of postoperative recurrence and new tools for the assessment of disease activity are needed to prevent long-term complications. In these patients, the over-production of ROS generated by inflamed bowel tissue and inflammatory cells activates a pathogenic cascade that further exacerbates inflammation and leads to increased oxidative damage to DNA, proteins, and lipids. We measured the products of protein/lipid oxidation and the total antioxidant capacity (ferric reducing ability of plasma, FRAP) in the serum of CD patients with severe disease activity requiring surgery with the aim to characterize their redox status and identify associations between oxidative stress-related markers and their clinical characteristics. At the systemic level, CD was associated with increased levels of protein and lipid oxidation products when compared to healthy volunteers, even though the FRAP values were similar. Advanced oxidation protein product (AOPP) levels showed the highest difference between patients and the controls (11.25, 5.02–15.15, vs. 1.36, 0.75–2.70, median, interquartile range; p < 0.0001) and the analysis of receiver operating characteristic (ROC) curves, indicated for AOPP, the best area under the curve (AUC) value for CD prediction. Advanced glycated end-products (AGEs) were also significantly higher in CD patients (p < 0.01), which is of interest since AOPP and AGEs are both able to activate the membrane receptor for advanced glycation end products (RAGE) involved in inflammatory diseases. Thiobarbituric acid reactive substance (TBARS) levels were significantly higher in CD patients with ileal localization and aggressive disease behavior, in smokers, and in patients suffering from allergies. In conclusion, our data indicate that circulating oxidative stress biomarkers may be attractive candidates as disease predictors as well as for clinical or therapeutic monitoring of CD. Our results also suggest that AOPP/AGEs and RAGE signaling may represent a pathogenic factor and a potential therapeutic target in CD

    Hydrochlorothiazide Use and Risk of Nonmelanoma Skin Cancers: A Biological Plausibility Study

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    Recent studies reported the association between increased risk of nonmelanoma skin cancers (NMSCs) and the use of hydrochlorothiazide (HCTZ), one of the most commonly prescribed diuretic, antihypertensive drug, over the world. Although HCTZ is known to be photosensitizing, the mechanisms involved in its potential prophotocarcinogenic effects remain unclear. Under acute exposure, therapeutically relevant concentrations of HCTZ (70, 140, and 370 ng/mL) amplified UVA-induced double-strand breaks, oxidative DNA, and protein damage in HaCaT human keratinocytes, and this effect was associated to a defective activity of the DNA repair enzyme, OGG1. Oxidative damage to DNA, but not that to proteins, was reversible within few hours. After chronic, combined exposure to HCTZ (70 ng/mL) and UVA (10 J/cm(2)), for 9 weeks, keratinocytes acquired a dysplastic-like phenotype characterized by a multilayered morphology and alterations in cell size, shape, and contacts. At the ultrastructural level, several atypical and enlarged nuclei and evident nucleoli were also observed. These transformed keratinocytes were apoptosis resistant, exhibited enhanced clonogenicity capacity, increased DNA damage and inflammation, defective DNA repair ability, and increased expression of the oncogene ΔNp63α and intranuclear β-catenin accumulation (a hallmark of Wnt pathway activation), compared to those treated with UVA alone. None of these molecular, morphological, or functional effects were observed in cells treated with HCTZ alone. All these features resemble in part those of preneoplastic lesions and NMSCs and provide evidence of a biological plausibility for the association among exposure to UVA, use of HCTZ, and increased risk of NMSCs. These results are of translational relevance since we used environmentally relevant UVA doses and tested HCTZ at concentrations that reflect the plasma levels of doses used in clinical practice. This study also highlights that drug safety data should be followed by experimental evaluations to clarify the mechanistic aspects of adverse events
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