Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

A review of recent innovative strategies for controlling mycotoxins in foods

Financiaciado para publicación en acceso aberto: Universidade de Vigo/CISUGMycotoxin contamination of foods from mycotoxigenic fungi such as Aspergillus, Alternaria, Fusarium and Penicillium spp. is a significant threat to food safety and quality. Aflatoxins, ochratoxins, fumonisins, deoxynivalenol, zearalenone, trichothecenes and patulin have been demonstrated to show immune toxicity, carcinogenicity, nephrotoxicity, hepatotoxicity, neurotoxicity and teratogenicity activities in humans and animals. Implementation of the prerequisite programs like the HACCP-based procedures can reduce mycotoxin contamination, while conventional chemical, biological and physical methods can be employed for detoxification after contamination. But the increasing fungal resistance and challenges associated with the conventional systems necessitate the development of innovative strategies for rapid elimination with short processing time and negligible impact on quality. This review evaluated recent innovative strategies of cold atmospheric plasma (CAP), polyphenols and flavonoids, magnetic materials and nanoparticles and natural essential oils (NEOs) for controlling mycotoxin in foods. Although the available studies indicated the promising potential of these strategies, complete decontamination was not achieved. The mechanisms for the reduced bioactivity of mycotoxins included the disruption of fungal cell membrane and structural degradation of complex biochemical molecules by the oxidative effects of reactive species, inhibition of enzymes responsible for breakdown of carbohydrates and adsorption and binding of functional groups of mycotoxins in food substrate. Integrated management systems of combining multiple strategies can be explored for achieving higher efficiency and better adaptability to different food matrices. Additional studies on the toxicity of the food matrices, degraded products and industrial up-scaling are necessary for ensuring widespread adoption and cost-effective commercialisation for sustainable food processin

Cancer stem cell as therapeutic target for melanoma treatment

Human malignant melanoma is a highly aggressive skin tumor that is characterized by its extraordinary heterogeneity, propensity for dissemination to distant organs and resistance to cytotoxic agents. Although chemo- and immune-based therapies have been evaluated in clinical trials, most of these therapeutics do not show significant benefit for patients with advanced disease. Treatment failure in melanoma patients is attributed mainly to the development of tumor heterogeneity resulting from the formation of genetically divergent subpopulations. These subpopulations are composed of cancer stem-like cells (CSCs) as a small fraction and non-cancer stem cells that form the majority of the tumor mass. In recent years, CSCs gained more attention and suggested as valuable experimental model system for tumor study. In melanoma, intratumoral heterogeneity, progression and drug resistance result from the unique characteristics of melanoma stem cells (MSCs). These MSCs are characterized by their distinct protein signature and tumor growth-driving pathways, whose activation is mediated by driver mutation-dependent signal. The molecular features of MSCs are either in a causal or consequential relationship to melanoma progression, drug resistance and relapse. Here, we review the current scientific evidence that supports CSC hypothesis and the validity of MSCs-dependent pathways and their key molecules as potential therapeutic target for melanoma treatment

Zygo-Albuside A: New Saponin from <i>Zygophyllum album</i> L. with Significant Antioxidant, Anti-Inflammatory and Antiapoptotic Effects against Methotrexate-Induced Testicular Damage

Chemical investigation of the crude extract of the aerial part of Zygophyllum album L. (Z. album) led to the isolation of a new saponin, Zygo-albuside A (7), together with seven known compounds, one of them (caffeic acid, compound 4) is reported in the genus for the first time. NMR (1D and 2D) and mass spectrometric analysis, including high-resolution mass spectrometry (HRMS), were utilized to set up the chemical structures of these compounds. The present biological study aimed to investigate the protective antioxidant, anti-inflammatory, and antiapoptotic activities of the crude extract from the aerial part of Z. album and two of its isolated compounds, rutin and the new saponin zygo-albuside A, against methotrexate (MTX)-induced testicular injury, considering the role of miRNA-29a. In all groups except for the normal control group, which received a mixture of distilled water and DMSO (2:1) as vehicle orally every day for ten days, testicular damage was induced on the fifth day by intraperitoneal administration of MTX at a single dose of 20 mg/kg. Histopathological examination showed that pre-treatment with the crude extract of Z. album, zygo-albuside A, or rutin reversed the testicular damage induced by MTX. In addition, biochemical analysis in the protected groups showed a decrease in malondialdehyde (MDA), interleukin-6 (IL-6) and IL-1β, Bcl-2-associated-protein (Bax), and an increase in B-cell lymphoma 2 (Bcl-2) protein, catalase (CAT), superoxide dismutase (SOD) in the testis, along with an increase in serum testosterone levels compared with the unprotected (positive control) group. The mRNA expression levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), p53, and miRNA-29a were downregulated in the testicular tissues of the protected groups compared with the unprotected group. In conclusion, the study provides sufficient evidence that Z. album extract, and its isolated compounds, zygo-albuside A and rutin, could alleviate testicular damage caused by the chemotherapeutic agent MTX

Marrubium alysson L. Ameliorated Methotrexate-Induced Testicular Damage in Mice through Regulation of Apoptosis and miRNA-29a Expression: LC-MS/MS Metabolic Profiling

Despite the efficient anti-cancer capabilities of methotrexate (MTX), it may induce myelosuppression, liver dysfunction and testicular toxicity. The purpose of this investigation was to determine whether Marrubium alysson L. (M. alysson L.) methanolic extract and its polyphenol fraction could protect mouse testicles from MTX-induced damage. We also investigated the protective effects of three selected pure flavonoid components of M. alysson L. extract. Mice were divided into seven groups (n = 8): (1) normal control, (2) MTX, (3) Methanolic extract + MTX, (4) Polyphenolic fraction + MTX, (5) Kaempferol + MTX, (6) Quercetin + MTX, and (7) Rutin + MTX. Pre-treatment of mice with the methanolic extract, the polyphenolic fraction of M. alysson L. and the selected pure compounds ameliorated the testicular histopathological damage and induced a significant increase in the serum testosterone level and testicular antioxidant enzymes along with a remarkable decline in the malondialdehyde (MDA) level versus MTX alone. Significant down-regulation of nuclear factor kappa B (NF-&kappa;B), tumor necrosis factor-alpha (TNF-&alpha;), p53 and miRNA-29a testicular expression was also observed in all the protected groups. Notably, the polyphenolic fraction of M. alysson L. displayed a more pronounced decline in the testicular levels of interleukin-1&beta; (IL-1&beta;), interleukin-6 (IL-6) and MDA, with higher testosterone levels relative to the methanolic extract. Further improvements in the Johnsen score, histopathological results and all biochemical assays were achieved by pre-treatment with the three selected pure compounds kaempferol, quercetin and rutin. In conclusion, M. alysson L. could protect against MTX-induced testicular injury by its antioxidant, anti-inflammatory, antiapoptotic activities and through the regulation of the miRNA-29a testicular expression. The present study also included chemical profiling of M. alysson L. extract, which was accomplished by LC-ESI-TOF-MS/MS analysis. Forty compounds were provisionally assigned, comprising twenty compounds discovered in the positive mode and seventeen detected in the negative mode

Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways

Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl3) alone, AlCl3 with cocoa alone, AlCl3 with vinpocetine (VIN), AlCl3 with epigallocatechin-3-gallate (EGCG), AlCl3 with coenzyme Q10 (CoQ10), AlCl3 with wheatgrass (WG), AlCl3 with vitamin (Vit) B complex, and AlCl3 with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl3 administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl3 intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl3-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways