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- Di Saverio, Salomone, et al.
(författare)
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Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines
- 2020
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Ingår i: World Journal of Emergency Surgery. - : BMC. - 1749-7922. ; 15:1
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Forskningsöversikt (refereegranskat)abstract
- Background and aims Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy. Methods This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients. Conclusions The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.
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| 2. |
- Karpale, Mikko, et al.
(författare)
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Activation of nuclear receptor PXR induces atherogenic lipids and PCSK9 through SREBP2-mediated mechanism
- 2021
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Ingår i: British Journal of Pharmacology. - : Macmillan Publishers Ltd.. - 0007-1188 .- 1476-5381. ; 178:12, s. 2461-2481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Many drugs and environmental contaminants induce hypercholesterolemia and promote the risk of atherosclerotic cardiovascular disease. The mechanisms involved are poorly defined precluding efficient prediction and prevention. We tested the hypothesis that pregnane X receptor (PXR), a xenobiotic-sensing nuclear receptor, regulates the level of circulating atherogenic lipids in humans and utilized mouse experiments to identify the mechanisms involved.EXPERIMENTAL APPROACH: We performed serum NMR metabolomics in healthy volunteers administered rifampicin, a prototypical human PXR ligand, or placebo in a crossover setting. Furthermore, we used high-fat diet fed wildtype and PXR knockout mice to investigate the mechanisms and pathways mediating the PXR-induced alterations in cholesterol homeostasis.KEY RESULTS: Activation of PXR induced cholesterogenesis both in pre-clinical and clinical settings. In human volunteers, rifampicin increased IDL, LDL and total cholesterol and lathosterol-cholesterol ratio, a marker of cholesterol synthesis, suggesting increased cholesterol synthesis. Mechanistic studies in mice indicated that PXR activation launches widespread induction of the cholesterol synthesis genes including the rate-limiting Hmgcr and upregulates the intermediates in the Kandutsch-Russell cholesterol synthesis pathway in the liver. Additionally, PXR activation induced plasma PCSK9, a negative regulator of hepatic LDL uptake, in both mice and humans. We propose that these effects were mediated through increased proteolytic activation of SREBP2 in response to PXR activation.CONCLUSION AND IMPLICATIONS: PXR activation induces cholesterol synthesis and elevates LDL and total cholesterol in humans. The PXR-SREBP2 pathway is a novel regulator of the cholesterol and PCSK9 synthesis, and a molecular mechanism for drug- and chemical-induced hypercholesterolemia.
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| 4. |
- Roberts, Derek J., et al.
(författare)
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The open abdomen in trauma, acute care, and vascular and endovascular surgery : comprehensive, expert, narrative review
- 2023
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Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 7:5
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Forskningsöversikt (refereegranskat)abstract
- BackgroundThe open abdomen is an innovation that greatly improved surgical understanding of damage control, temporary abdominal closure, staged abdominal reconstruction, viscera and enteric fistula care, and abdominal wall reconstruction. This article provides an evidence-informed, expert, comprehensive narrative review of the open abdomen in trauma, acute care, and vascular and endovascular surgery.MethodsA group of 12 international trauma, acute care, and vascular and endovascular surgery experts were invited to review current literature and important concepts surrounding the open abdomen.ResultsThe open abdomen may be classified using validated systems developed by a working group in 2009 and modified by the World Society of the Abdominal Compartment Syndrome-The Abdominal Compartment Society in 2013. It may be indicated in major trauma, intra-abdominal sepsis, vascular surgical emergencies, and severe acute pancreatitis; to facilitate second look laparotomy or avoid or treat abdominal compartment syndrome; and when the abdominal wall cannot be safely closed. Temporary abdominal closure and staged abdominal reconstruction methods include a mesh/sheet, transabdominal wall dynamic fascial traction, negative pressure wound therapy, and hybrid negative pressure wound therapy and dynamic fascial traction. This last method likely has the highest primary fascial closure rates. Direct peritoneal resuscitation is currently an experimental strategy developed to improve primary fascial closure rates and reduce complications in those with an open abdomen. Primary fascial closure rates may be improved by early return to the operating room; limiting use of crystalloid fluids during the surgical interval; and preventing and/or treating intra-abdominal hypertension, enteric fistulae, and intra-abdominal collections after surgery. The majority of failures of primary fascial closure and enteroatmospheric fistula formation may be prevented using effective temporary abdominal closure techniques, providing appropriate resuscitation fluids and nutritional support, and closing the abdomen as early as possible.ConclusionSubsequent stages of the innovation of the open abdomen will likely involve the design and conduct of prospective studies to evaluate appropriate indications for its use and effectiveness and safety of the above components of open abdomen management.
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| 5. |
- Salonurmi, Tuire, et al.
(författare)
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4β-Hydroxycholesterol Signals From the Liver to Regulate Peripheral Cholesterol Transporters.
- 2020
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Activation of pregnane X receptor (PXR) elevates circulating 4β-hydroxycholesterol (4βHC), an agonist of liver X receptor (LXR). PXR may also regulate 25-hydroxycholesterol and 27-hydroxycholesterol. Our aim was to elucidate the roles of PXR and oxysterols in the regulation of cholesterol transporters. We measured oxysterols in serum of volunteers dosed with PXR agonist rifampicin 600 mg/day versus placebo for a week and analyzed the expression of cholesterol transporters in mononuclear cells. The effect of 4βHC on the transport of cholesterol and the expression of cholesterol transporters was studied in human primary monocyte-derived macrophages and foam cells in vitro. The expression of cholesterol transporters was measured also in rat tissues after dosing with a PXR agonist. The levels of 4βHC were elevated, while 25-hydroxycholesterol and 27-hydroxycholesterol remained unchanged in volunteers dosed with rifampicin. The expression of ATP binding cassette transporter A1 (ABCA1) was induced in human mononuclear cells in vivo. The influx of cholesterol was repressed by 4βHC, as was the expression of influx transporter lectin-like oxidized LDL receptor-1 in vitro. The cholesterol efflux and the expression of efflux transporters ABCA1 and ABCG1 were induced. The expression of inducible degrader of the LDL receptor was induced. In rats, PXR agonist increased circulating 4βHC and expression of LXR targets in peripheral tissues, especially ABCA1 and ABCG1 in heart. In conclusion, PXR activation-elevated 4βHC is a signaling molecule that represses cholesterol influx and induces efflux. The PXR-4βHC-LXR pathway could link the hepatic xenobiotic exposure and the regulation of cholesterol transport in peripheral tissues.
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| 6. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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