| 61. |
- d'Alessandro, Elisa, et al.
(författare)
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Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
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Tidskriftsartikel (refereegranskat)abstract
- Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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| 62. |
- Desta, Z, et al.
(författare)
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PharmVar GeneFocus: CYP2B6
- 2021
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Ingår i: Clinical pharmacology and therapeutics. - : Wiley. - 1532-6535 .- 0009-9236. ; 110:1, s. 82-97
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Tidskriftsartikel (refereegranskat)
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| 63. |
- Heil, J., et al.
(författare)
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Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis
- 2021
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Ingår i: British Journal of Surgery. - : OXFORD UNIV PRESS. - 0007-1323 .- 1365-2168. ; 108:7, s. 834-842
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Tidskriftsartikel (refereegranskat)abstract
- Y Background: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. Methods: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. Results: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P=0.020) and resectability (90 versus 68 per cent; P=0.007). Major complications (26 versus 34 per cent; P=0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. Conclusion: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.
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| 64. |
- Herrera, M, et al.
(författare)
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Prognostic Interactions between FAP+ Fibroblasts and CD8a+ T Cells in Colon Cancer
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Inter-case variations in immune cell and fibroblast composition are associated with prognosis in solid tumors, including colon cancer. A series of experimental studies suggest immune-modulatory roles of marker-defined fibroblast populations, including FAP-positive fibroblasts. These studies imply that the fibroblast status of tumors might affect the prognostic significance of immune-related features. Analyses of a population-based colon cancer cohort demonstrated good prognosis associations of FAP intensity and CD8a density. Notably, a significant prognostic interaction was detected between these markers (p = 0.013 in nonadjusted analyses and p = 0.003 in analyses adjusted for cofounding factors) in a manner where the good prognosis association of CD8 density was restricted to the FAP intensity-high group. This prognostic interaction was also detected in an independent randomized trial-derived colon cancer cohort (p = 0.048 in nonadjusted analyses). In the CD8-high group, FAP intensity was significantly associated with a higher total tumor density of FoxP3-positive immune cells and a higher ratio of epithelial-to-stromal density of CD8a T cells. The study presents findings relevant for the ongoing efforts to improve the prognostic performance of CD8-related markers and should be followed by additional validation studies. Furthermore, findings support, in general, earlier model-derived studies implying fibroblast subsets as clinically relevant modulators of immune surveillance. Finally, the associations between FAP intensity and specific immune features suggest mechanisms of fibroblast-immune crosstalk with therapeutic potential.
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| 65. |
- Karyotaki, Eirini, et al.
(författare)
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Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
- 2021
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
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Forskningsöversikt (refereegranskat)abstract
- IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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| 66. |
- Klein, V, et al.
(författare)
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Changes of Infant- and Family-Centered Care Practices Administered to Extremely Preterm Infants During Implementation of the NIDCAP Program
- 2021
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Ingår i: Frontiers in pediatrics. - : Frontiers Media SA. - 2296-2360. ; 9, s. 718813-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Many studies have evaluated the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP), but few studies have assessed changes in infant- and family-centered developmental care (IFCDC) practices during its implementation.Objectives:The primary objective of this single center study was to investigate the impact of the implementation of the NIDCAP program on IFCDC practices used for management of extremely preterm infants (EPIs). The secondary objective was to determine during implementation the impact of this program on the short-term medical outcomes of all EPIs hospitalized at our center.Methods:All EPIs (<28 weeks gestational age) who were hospitalized at Strasbourg University Hospital from 2007 to 2014 were initially included. Outborn infants were excluded. The data of EPIs were compared for three time periods: 2007 to 2008 (pre-NIDCAP), 2010 to 2011, and 2013 to 2014 (during-NIDCAP implementation) using appropriate statistical tests. The clinical and caring procedures used during the first 14 days of life were analyzed, with a focus on components of individualized developmental care (NIDCAP observations), infant pain management (number of painful procedures, clinical pain assessment), skin-to-skin contact (SSC; frequency, day of initiation, and duration), and family access and involvement in the care of their children (duration of parental presence, parental participation in care). The short-term mortality and morbidity at discharge were evaluated.Results:We examined 228 EPIs who received care during the three time periods. Over time, painful procedures decreased, but pain evaluations, parental involvement in care, individualized observations, and SSC increased (allp< 0.01). In addition, the first SSC was performed earlier (p= 0.03) and lasted longer (p< 0.01). There were no differences in mortality and morbidity, but there were reductions in the duration of mechanical ventilation (p= 0.02) and the time from birth to first extubation (p= 0.02), and an increase of weight gain at discharge (p= 0.02).Conclusion:NIDCAP implementation was accompanied by progressive, measurable, and significant changes in IFCDC strategies. There were, concomitantly, moderate but statistically significant improvements in multiple important outcome measures of all hospitalized EPI.
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| 67. |
- Lietzau, G, et al.
(författare)
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A High-Fat Diet Increases Activation of the Glucagon-Like Peptide-1-Producing Neurons in the Nucleus Tractus Solitarii: an Effect that is Partially Reversed by Drugs Normalizing Glycemia
- 2022
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Ingår i: Cellular and molecular neurobiology. - : Springer Science and Business Media LLC. - 1573-6830 .- 0272-4340. ; 42:6, s. 1995-2002
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1) is a peripheral incretin and centrally active peptide produced in the intestine and nucleus tractus solitarii (NTS), respectively. GLP-1 not only regulates metabolism but also improves cognition and is neuroprotective. While intestinal GLP-1-producing cells have been well characterized, less is known about GLP-1-producing neurons in NTS. We hypothesized that obesity-induced type 2 diabetes (T2D) impairs the function of NTS GLP-1-producing neurons and glycemia normalization counteracts this effect. We used immunohistochemistry/quantitative microscopy to investigate the number, potential atrophy, and activation (cFos-expression based) of NTS GLP-1-producing neurons, in non-diabetic versus obese/T2D mice (after 12 months of high-fat diet). NTS neuroinflammation was also assessed. The same parameters were quantified in obese/T2D mice treated from month 9 to 12 with two unrelated anti-hyperglycemic drugs: the dipeptidyl peptidase-4 inhibitor linagliptin and the sulfonylurea glimepiride. We show no effect of T2D on the number and volume but increased activation of NTS GLP-1-producing neurons. This effect was partially normalized by both anti-diabetic treatments, concurrent with decreased neuroinflammation. Increased activation of NTS GLP-1-producing neurons could represent an aberrant metabolic demand in T2D/obesity, attenuated by glycemia normalization. Whether this effect represents a pathophysiological process preceding GLP-1 signaling impairment in the CNS, remains to be investigated.
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| 68. |
- Martinello, K. A., et al.
(författare)
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Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia
- 2022
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 91:6, s. 1416-1427
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Perinatal inflammation combined with hypoxia-ischemia (HO exacerbates injury in the developing brain. Therapeutic hypothermia (HT) is standard care for neonatal encephalopathy; however, its benefit in inflammation-sensitized HI (IS-HI) is unknown. METHODS: Twelve newborn piglets received a 2 mu g/kg bolus and 1 mu g/kg/h infusion over 52 h of Escherichia coli lipopolysaccharide (LPS). HI was induced 4 h after LPS bolus. After HI, piglets were randomized to HT (33.5 degrees C 1-25 h after HI, n = 6) or normothermia (NT, n = 6). Amplitude-integrated electroencephalogram (aEEG) was recorded and magnetic resonance spectroscopy (MRS) was acquired at 24 and 48 h. At 48 h, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive brain cell death, microglial activation/proliferation, astrogliosis, and cleaved caspase-3 (CC3) were quantified. Hematology and plasma cytokines were serially measured. RESULTS: Two HT piglets died. aEEG recovery, thalamic and white matter MRS lactate/N-acetylaspartate, and TUNEL-positive cell death were similar between groups. HT increased microglial activation in the caudate, but had no other effect on glial activation/ proliferation. HT reduced CC3 overall. HT suppressed platelet count and attenuated leukocytosis. Cytokine profile was unchanged by HT. CONCLUSIONS: We did not observe protection with HT in this piglet IS-HI model based on aEEG, MRS, and immunohistochemistry. immunosuppressive effects of HT and countering neuroinflammation by LPS may contribute to the observed lack of HT efficacy. Other immunomodulatory strategies may be more effective in IS-HI.
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