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| 2. |
- Andréasson, Kristofer, et al.
(författare)
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Disease Features and Gastrointestinal Microbial Composition in Patients with Systemic Sclerosis from Two Independent Cohorts
- 2022
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Ingår i: ACR Open Rheumatology. - : Wiley. - 2578-5745. ; 4:5, s. 417-425
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The study objective was to examine alterations in gastrointestinal (GI) microbial composition in patients with systemic sclerosis (SSc) and to investigate the relationship between SSc features and GI microbiota using two independent, international cohorts. Methods: Prospective patients with SSc from Lund University (LU), Sweden, from the University of California, Los Angeles (UCLA), United States, and control subjects provided stool specimens for 16S ribosomal RNA sequencing. Alpha and beta diversity analyses were performed. Multivariate negative binomial models identified differentially abundant genera between groups. Results: Patients from LU with SSc (n = 106) with recent SSc diagnosis (median disease duration 2.0 years) had lower abundance of commensal genera (eg, Faecalibacterium) and higher abundance of pathobiont genera (eg, Desulfovibrio) than LU-controls (n = 85). Patients from UCLA with SSc (n = 71) had a similar prevalence of females, a similar body mass index, and similar age but an increased disease duration (median 7.1 years) compared with patients from LU with SSc. Factors associated with beta diversity in patients with SSc from both LU and UCLA included disease duration (P = 0.0016), interstitial lung disease (P = 0.003), small intestinal bacterial overgrowth (P = 0.002), and immunosuppression use (P = 0.014). In multivariable analysis, the UCLA-SSc cohort had higher abundance of specific pathobiont genera (eg, Streptococcus) compared with the LU-SSc cohort. Conclusion: Enrichments and depletions in certain microbial genera were observed in patients recently diagnosed with SSc, suggesting that dysbiosis is present in early SSc. Specific disease features were independently associated with fecal microbial composition in both cohorts. After controlling for these factors, the abundance of several pathobiont bacteria differed between the cohorts, suggesting that environmental factors, along with disease manifestations, should be considered in future SSc studies.
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| 3. |
- Andréasson, Kristofer, et al.
(författare)
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Treatment for Rheumatoid Arthritis Associated With Alterations in the Gastrointestinal Microbiota
- 2024
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Ingår i: ACR Open Rheumatology. - 2578-5745.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Emerging research suggests that rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This prospective pilot study evaluates changes in intestinal microbial composition in patients with RA initiating treatment with either methotrexate (MTX) or a tumor necrosis factor inhibitor (TNFi). Methods: Consecutive patients, fulfilling the 2010 American College of Rheumatology/EULAR classification criteria for RA, who started treatment with either MTX or TNFi delivered a stool sample upon initiation of immunosuppression and 3 months later. A 16S ribosomal RNA gene-based validated microbiota test (GA-map Dysbiosis Index Score [DIS], Genetic Analysis, Oslo, Norway) was used to evaluate for the presence and degree of dysbiosis. Fecal levels of Prevotella copri (P. copri) were analyzed by custom-made quantitative polymerase chain reaction. Changes in microbial composition were analyzed in relation to changes in disease activity, as measured by the disease activity score based on 28-joint counts, using C-reactive protein. Results: At baseline, dysbiosis was present in 33 of 50 (66%) participants and more common in participants with more than 2 years of disease duration (P = 0.019). At the 3-month follow-up, 27 of 50 (54%) were good treatment responders and the DIS had improved in 14 of 50 (28%). Participants initiating TNFi more often exhibited improvement in the DIS compared with those initiating MTX (P = 0.031). P. copri was identified in 32 of 50 (64%) at baseline. An improvement in disease activity score based on 28-joint counts, using C-reactive protein was associated with a simultaneous decrease in P. copri abundance (rs = 0.30, P = 0.036). Conclusion: This study affirms that dysbiosis is a feature of RA. Although patients were not randomized to MTX or TNFi, the findings suggest that specific therapies may differentially modulate the gastrointestinal microbiota in RA. The association between P. copri and treatment response requires further study.
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| 4. |
- Denisov, Vladimir P., et al.
(författare)
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Kinetics of DNA hydration
- 1997
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 268:1, s. 118-136
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Tidskriftsartikel (refereegranskat)abstract
- The hydration of the d(CGCGAATTCGCG) B-DNA duplex in solution was studied by nuclear magnetic relaxation dispersion (NMRD) of the water nuclei 1H, 2H, and 17O, and by nuclear Overhauser effects (NOEs) in high-resolution two-dimensional 1H NMR spectra. By comparing results from the free duplex with those from its complex with netropsin, water molecules in the 'spine of hydration' in the AATT region of the minor groove could be distinguished from hydration water elsewhere in the duplex. The 2H and 17O relaxation dispersions yield a model-independent residence time of 0.9(±0.1) ns at 4°C for five highly ordered water molecules in the spine. When corrected for frequency offset effects, the NOE data yield the same residence time as the NMRD data, giving credence to both methods. At 27°C, the residence time is estimated to 0.2 ns, a factor of 40 shorter than the tumbling time of the duplex. The NMRD data show that all water molecules associated with the duplex, except the five molecules in the spine, have residence times significantly shorter than Ins at 4°C. There is thus no long-lived hydration structure associated with the phosphate backbone. In contrast to 2H and 17O, the 1H relaxation dispersion is dominated by labile DNA protons and therefore provides little information about DNA hydration.
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| 5. |
- Kuemmerli, Christoph, et al.
(författare)
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Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis
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Ingår i: Journal of Hepato-Biliary-Pancreatic Sciences. - 1868-6974.
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Forskningsöversikt (refereegranskat)abstract
- Background: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD). Methods: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70–79 years) and older patients (≥80 years). Results: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65–1.29], p =.596 and OR 1.22 [95% CI: 0.61–2.46], p =.508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (−0.14 days [95% CI: −0.29 to 0.01], p =.071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (−0.28 days [95% CI: −0.62 to 0.05], p =.069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (−0.36 days [95% CI: −0.71 to −0.004], p =.048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group. Conclusion: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.
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| 6. |
- Kuemmerli, Christoph, et al.
(författare)
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Impact of enhanced recovery protocols after pancreatoduodenectomy : meta-analysis
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 256-266
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.
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| 7. |
- Nguyen, Audrey D., et al.
(författare)
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Gastrointestinal tract involvement in systemic sclerosis : The roles of diet and the microbiome
- 2023
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Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype. Objectives: Our study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. Methods: Adult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet. Results: Of the 66 total SSc patients included, the majority were women (n = 56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N = 19) versus non-low (N = 16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus. Conclusion: SSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.
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| 8. |
- Sharma, Abhinav, et al.
(författare)
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Clinical Events Classification (CEC) in Clinical Trials : Report on the Current Landscape and Future Directions - Proceedings from the CEC Summit 2018
- 2022
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 246, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Clinical events adjudication is pivotal for generating consistent and comparable evidence in clinical trials. The methodology of event adjudication is evolving, but research is needed to develop best practices and spur innovation.Observations: A meeting of stakeholders from regulatory agencies, academic and contract research organizations, pharmaceutical and device companies, and clinical trialists convened in Chicago, IL, for Clinical Events Classification (CEC) Summit 2018 to discuss key topics and future directions. Formal studies are lacking on strategies to optimize CEC conduct, improve efficiency, minimize cost, and generally increase the speed and accuracy of the event adjudication process. Major challenges to CEC discussed included ensuring rigorous quality of the process, identifying safety events, standardizing event definitions, using uniform strategies for missing information, facilitating interactions between CEC members and other trial leadership, and determining the CEC's role in pragmatic trials or trials using real-world data. Consensus recommendations from the meeting include the following: 1) ensure an adequate adjudication infrastructure; 2) use negatively adjudicated events to identify important safety events reported only outside the scope of the primary endpoint; 3) conduct further research in the use of artificial intelligence and digital/mobile technologies to streamline adjudication processes; and 4) emphasize the importance of standardizing event definitions and quality metrics of CEC programs.Conclusions and Relevance: As novel strategies for clinical trials emerge to generate evidence for regulatory approval and to guide clinical practice, a greater understanding of the role of the CEC process will be critical to optimize trial conduct and increase confidence in the data generated.
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