| 1. |
- Gilg, Stefan, et al.
(författare)
-
The Molecular Adsorbent Recirculating System in Posthepatectomy Liver Failure : Results From a Prospective Phase I Study
- 2018
-
Ingår i: HEPATOLOGY COMMUNICATIONS. - : JOHN WILEY & SONS LTD. - 2471-254X. ; 2:4, s. 445-454
-
Tidskriftsartikel (refereegranskat)abstract
- Posthepatectomy liver failure (PHLF) represents the single most important cause of postoperative mortality after major liver resection, yet no effective treatment option is available. Extracorporeal liver support devices might be helpful, but systematic studies are lacking. Accordingly, we aimed to assess the safety and feasibility of the Molecular Adsorbent Recirculating System (MARS) in patients with PHLF. Between December 2012 and May 2015, a total of 206 patients underwent major or extended hepatectomy, and 10 consecutive patients with PHLF (according to the Balzan 50: 50 criteria) were enrolled into the study. MARS treatment was initiated on postoperative day 5-7, and five to seven consecutive treatment sessions were completed for each patient. In total, 59 MARS cycles were implemented, and MARS was initiated and completed without major complications in any patient. However, 1 patient developed an immense asymptomatic hyperbilirubinemia (without encephalopathy), 1 had repeated clotting problems in the MARS filter, and 2 patients experienced access problems with the central venous line. Otherwise, no adverse events were observed. In 9 patients, the bilirubin level and international normalized ratio decreased significantly (P < 0.05) during MARS treatment. The 60- and 90-day mortality was 0% and 10%, respectively. Among the 9 survivors, 4 still had liver dysfunction at 90 days postoperatively. Five patients were alive 1 year postoperatively without any signs of liver dysfunction or disease recurrence. Conclusion: The use of MARS in PHLF is feasible and safe and improves liver function in patients with PHLF. In the present study, 60- and 90-day mortality rates were unexpectedly low compared to a historical control group. The impact of MARS treatment on mortality in PHLF should be further evaluated in a randomized controlled clinical trial.
|
|
| 2. |
- Duraj, Frans, et al.
(författare)
-
Tarmtransplantation : Första svenska tunntarmstransplantationen till en vuxen patient med pseudoobstruktion
- 1998
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 95:28-29, s. 3172-3176
-
Tidskriftsartikel (refereegranskat)abstract
- Recent advances, first and foremost the development of new immunosuppressive agents, have markedly improved the outcome of intestinal transplantation, which is a treatment option for patients with serious intestinal diseases who have become dependent on total parenteral nutrition. The first small bowel transplantation in Sweden was performed at Huddinge Hospital in 1997, in the adult patient with intestinal pseudo-obstruction. The article reports the course of this patient and an update of international progress in intestinal transplantation.
|
|
| 3. |
- Michaëlsson, Erik, et al.
(författare)
-
Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF.
- 2023
-
Ingår i: JACC. Heart failure. - 2213-1787. ; 11:7, s. 775-87
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic microvascular dysfunction and inflammation are postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF).This study aimed to identify biomarker profiles associated with clinical outcomes in HFpEF and investigate how inhibition of the neutrophil-derived reactive oxygen species-producing enzyme, myeloperoxidase, affects these biomarkers.Using supervised principal component analyses, the investigators assessed the associations between baseline plasma proteomic Olink biomarkers and clinical outcomes in 3 independent observational HFpEF cohorts (n=86, n=216, and n=242). These profiles were then compared with the biomarker profiles discriminating patients treated with active drug vs placebo in SATELLITE (Safety and Tolerability Study of AZD4831 in Patients With HeartFailure), a double-blind randomized 3-month trial evaluating safety and tolerability of the myeloperoxidase inhibitor AZD4831 in HFpEF (n=41). Pathophysiological pathways were inferred from the biomarker profiles by interrogation of the Ingenuity Knowledge database.TNF-R1, TRAIL-R2, GDF15, U-PAR, and ADM were the top individual biomarkers associated with heart failure hospitalization or death, and FABP4, HGF, RARRES2, CSTB, and FGF23 were associated with lower functional capacity and poorer quality of life. AZD4831 downregulated many markers (most significantly CDCP1, PRELP, CX3CL1, LIFR, VSIG2). There was remarkable consistency among pathways associated with clinical outcomes in the observational HFpEF cohorts, the top canonical pathways being associated with tumor microenvironments, wound healing signaling, and cardiac hypertrophy signaling. These pathways were predicted to be downregulated in AZD4831 relative to placebo-treated patients.Biomarker pathways that were most strongly associated with clinical outcomes were also the ones reduced by AZD4831. These results support the further investigation of myeloperoxidase inhibition in HFpEF.
|
|
| 4. |
- Myhre, Peder L., et al.
(författare)
-
External validation of a deep learning algorithm for automated echocardiographic strain measurements
- 2024
-
Ingår i: EUROPEAN HEART JOURNAL - DIGITAL HEALTH. - 2634-3916. ; 5:1, s. 60-68
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Echocardiographic strain imaging reflects myocardial deformation and is a sensitive measure of cardiac function and wall-motion abnormalities. Deep learning (DL) algorithms could automate the interpretation of echocardiographic strain imaging.Methods and results We developed and trained an automated DL-based algorithm for left ventricular (LV) strain measurements in an internal dataset. Global longitudinal strain (GLS) was validated externally in (i) a real-world Taiwanese cohort of participants with and without heart failure (HF), (ii) a core-lab measured dataset from the multinational prevalence of microvascular dysfunction-HF and preserved ejection fraction (PROMIS-HFpEF) study, and regional strain in (iii) the HMC-QU-MI study of patients with suspected myocardial infarction. Outcomes included measures of agreement [bias, mean absolute difference (MAD), root-mean-squared-error (RMSE), and Pearson's correlation (R)] and area under the curve (AUC) to identify HF and regional wall-motion abnormalities. The DL workflow successfully analysed 3741 (89%) studies in the Taiwanese cohort, 176 (96%) in PROMIS-HFpEF, and 158 (98%) in HMC-QU-MI. Automated GLS showed good agreement with manual measurements (mean +/- SD): -18.9 +/- 4.5% vs. -18.2 +/- 4.4%, respectively, bias 0.68 +/- 2.52%, MAD 2.0 +/- 1.67, RMSE = 2.61, R = 0.84 in the Taiwanese cohort; and -15.4 +/- 4.1% vs. -15.9 +/- 3.6%, respectively, bias -0.65 +/- 2.71%, MAD 2.19 +/- 1.71, RMSE = 2.78, R = 0.76 in PROMIS-HFpEF. In the Taiwanese cohort, automated GLS accurately identified patients with HF (AUC = 0.89 for total HF and AUC = 0.98 for HF with reduced ejection fraction). In HMC-QU-MI, automated regional strain identified regional wall-motion abnormalities with an average AUC = 0.80.Conclusion DL algorithms can interpret echocardiographic strain images with similar accuracy as conventional measurements. These results highlight the potential of DL algorithms to democratize the use of cardiac strain measurements and reduce time-spent and costs for echo labs globally. Graphical Abstract
|
|
| 5. |
- Svedlund, Sara, et al.
(författare)
-
Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results.
- 2023
-
Ingår i: Journal of cardiac failure. - 1532-8414. ; 30:1, s. 104-10
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation is a key driver of heart failure (HF) with preserved left ventricular ejection fraction (LVEF). AZD4831 inhibits extracellular myeloperoxidase, reduces inflammation and improves microvascular function in preclinical disease models.In this double-blind phase 2a study (SATELLITE; NCT03756285), patients with symptomatic HF, LVEF ≥40%, and elevated B-type natriuretic peptides were randomized 2:1 to once-daily oral AZD4831 5 mg or placebo for 90 days. We aimed to assess target engagement (primary endpoint: myeloperoxidase specific activity) and safety of AZD4831.Due to COVID-19, the study was terminated early after randomizing 41 patients (median age, 74.0 years; 53.7% male). Myeloperoxidase activity was reduced by >50% from baseline to day 30 and 90 in the AZD4831 group, with a placebo-adjusted reduction of 75% (95% confidence interval: 48, 88; nominal P <0.001). No improvements were noted in secondary/exploratory endpoints, apart from a trend in Kansas City Cardiomyopathy Questionnaire overall summary score. No deaths or treatment-related serious adverse events occurred. AZD4831 treatment-related adverse events were generalized maculopapular rash, pruritus and diarrhoea (all n=1).AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.Few treatments are available for patients with the forms of heart failure known as 'heart failure with preserved or mildly reduced ejection fraction'. Current treatments do not target inflammation, which may play an important role in this condition. We tested a new drug called AZD4831 (mitiperstat), which reduces inflammation by inhibiting the enzyme myeloperoxidase. Among the 41 patients in our clinical trial, AZD4831 had a good safety profile and inhibited myeloperoxidase by the expected amount. Results mean we can conduct further trials to see whether AZD4831 reduces the symptoms of heart failure and improves patients' ability to take physical exercise.
|
|
| 6. |
|
|
| 7. |
- van der Oost, John, et al.
(författare)
-
Bacillus subtilis cytochrome oxidase mutants: biochemical analysis and genetic evidence for two aa3-type oxidases
- 1991
-
Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 5:8, s. 2063-2072
-
Tidskriftsartikel (refereegranskat)abstract
- The ctaBCDEF genes coding for cytochrome c oxidase were found to reside adjacent to a regulatory gene ctaA at 127-degrees on the Bacillus subtilis chromosome. The structural genes for subunits I and II, ctaD and ctaC, were deleted by gene-replacement using a phleomycin-resistance marker. The mutant was unable to oxidize N,N,N',N'-tetramethyl-p-phenylenediamine and oxidized cytochrome c at a significantly lower rate. Absorption spectra of the mutant and wild-type membranes confirmed the presence of two haem A-containing enzymes in B. subtilis. Another mutant, with a spontaneous deletion upstream from ctaC, was found to express neither of these enzymes. Radioactive haem-labelling was used to identify subunit 11, which contains a haem C, and cytochrome c-550 among the membrane-bound c-type cytochromes of B. subtilis.
|
|
| 8. |
- Venkateshvaran, Ashwin, et al.
(författare)
-
Association of Epicardial Adipose Tissue with Proteomics, Coronary Flow Reserve, Cardiac Structure and Function, and Quality of Life in Heart Failure with Preserved Ejection Fraction: Insights from the PROMIS-HFpEF study.
- 2022
-
Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:12, s. 2251-2260
-
Tidskriftsartikel (refereegranskat)abstract
- Epicardial Adipose Tissue (EAT) may play a role in the pathophysiology of Heart Failure with preserved Ejection Fraction (HFpEF). We investigated associations of EAT with proteomics, coronary flow reserve (CFR), cardiac structure and function, and quality of life (QoL) in the prospective multinational PROMIS-HFpEF cohort.EAT was measured by echocardiography in 182 patients and defined as increased if ≥9mm. Proteins were measured using high-throughput proximity extension assays. Microvascular dysfunction was evaluated with Doppler-based CFR, cardiac structural and functional indices with echocardiography and QoL by Kansas City Cardiomyopathy Questionnaire (KCCQ). Patients with increased EAT (n=54; 30%) had higher body mass index (BMI) [32 (28-40) vs. 27 (23-30) kg/m2; p <0.001], lower NT-proBNP [466 (193-1133) vs. 1120 (494-1990) pg/mL; p <0.001], smaller indexed left ventricular (LV) end-diastolic and left atrial (LA) volumes and tendency to lower KCCQ score. Non-indexed LV/LA volumes did not differ between groups. When adjusted for BMI, EAT remained associated with LV septal wall thickness [Coeff 1.02, 95% CI 1.00-1.04; p=0.018] and mitral E wave deceleration time [Coeff 1.03, 95% CI 1.01-1.05; p=0.005]. Increased EAT was associated with proteomic markers of adipose biology and inflammation, insulin resistance, endothelial dysfunction, and dyslipidemia but not significantly with CFR.Increased EAT was associated with cardiac structural alterations and proteins expressing adiposity, inflammation, lower insulin sensitivity and endothelial dysfunction related to HFpEF pathology, probably driven by general obesity. Potential local mechanical or paracrine effects mediated by EAT remain to be elucidated. This article is protected by copyright. All rights reserved.
|
|
