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- Silfvenius, Annie U.K., et al.
(författare)
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Laparoscopic ventral hernia repair : early follow-up of a randomized controlled study of primary fascial closure before mesh placement
- 2024
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 111:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Suturing of the hernia aperture in laparoscopic ventral hernia repair has increased during the past decade. The primary aim of this is to restore the anatomy of the abdominal wall. Closure of the aperture, however, may cause additional tension in the abdominal wall which could increase postoperative pain. The aim of this study was to investigate whether suturing of the hernia aperture affects postoperative pain and hernia-site complications, including seroma, infection, pseudohernia, and mesh migration, 3 months after repair.Methods: Some 192 patients with a midline hernia between 2 and 8 cm in transverse diameter were included in a randomized controlled double-blinded multicentre study. Patients were randomized to mesh repair with (intervention) or without (control) suturing of the hernia aperture before mesh placement. Patients completed the Ventral Hernia Pain Questionnaire before and 3 months after surgery. Abdominal wall pain and hernia-site complications were assessed 3 months after surgery.Results: Ninety-seven patients were randomized to the intervention group and 95 to the control group. Among all patients, median age and BMI was 56 years and 31 kg/m2 respectively. Overall pain experienced decreased by 3 months after operation (P < 0.001). There was no difference between groups regarding hernia-site complications or pain experienced during the past week (13 versus 23 patients; P = 0.111). Seroma and pseudohernia occurred in 13 and 11 patients in the intervention and control groups respectively (P = 0.975 and P = 0.977).Conclusion: Restoration of the abdominal wall anatomy by suturing the hernia aperture before mesh placement does not increase the risk of hernia-site complication or pain 3 months after surgery. This implies that fascial suturing of the aperture can be justified if there are potential long-term benefits such as lower recurrence and/or complication rates.Registration number: ISRCTN51495042 (http://www.controlled-trials.com).
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- Becker, K., et al.
(författare)
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Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis
- 2021
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Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 73
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Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, preclinical evidence for its utility in other disease indications has yet to be provided. Here we studied the therapeutic potential of EBL-1003 in the treatment of complicated urinary tract infection and acute pyelonephritis (cUTI/AP). Methods: A combination of data-base mining, antimicrobial susceptibility testing, time-kill experiments, and four murine infection models was used in a comprehensive assessment of the microbiological coverage and efficacy of EBL-1003 against Gram-negative uropathogens. The pharmacokinetics and renal toxicology of EBL-1003 in rats was studied to assess the therapeutic window of EBL-1003 in the treatment of cUTI/AP. Findings: EBL-1003 demonstrated broad-spectrum activity and rapid multi-log CFU reduction against a phenotypic variety of bacterial uropathogens including aminoglycoside-resistant clinical isolates. The basicity of amines in the apramycin molecule suggested a higher increase in positive charge at urinary pH when compared to gentamicin or amikacin, resulting in sustained drug uptake and bactericidal activity, and consequently in potent efficacy in mouse infection models. Renal pharmacokinetics, biomarkers for toxicity, and kidney histopathology in adult rats all indicated a significantly lower nephrotoxicity of EBL-1003 than of gentamicin. Interpretation: This study provides preclinical proof-of-concept for the efficacy of EBL-1003 in cUTI/AP. Similar efficacy but lower nephrotoxicity of EBL-1003 in comparison to gentamicin may thus translate into a higher safety margin and a wider therapeutic window in the treatment of cUTI/API. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. © 2021 The Author(s)
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| 5. |
- Jernberg, T., et al.
(författare)
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Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction
- 2018
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 138:24, s. 2754-2762
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure. METHODS: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of >= 90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air. RESULTS: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84-1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0-3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88-1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87-1.33; P=0.52). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up.
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- Karason, Kristjan, 1962, et al.
(författare)
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Randomized trial of a left ventricular assist device as destination therapy versus guideline-directed medical therapy in patients with advanced heart failure. Rationale and design of the SWEdish evaluation of left Ventricular Assist Device (SweVAD) trial
- 2020
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:2, s. 739-50
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Tidskriftsartikel (refereegranskat)abstract
- Aims Patients with advanced heart failure (AdHF) who are ineligible for heart transplantation (HTx) can become candidates for treatment with a left ventricular assist device (LVAD) in some countries, but not others. This reflects the lack of a systematic analysis of the usefulness of LVAD systems in this context, and of their benefits, limitations and cost-effectiveness. The SWEdish evaluation of left Ventricular Assist Device (SweVAD) study is a Phase IV, prospective, 1:1 randomized, non-blinded, multicentre trial that will examine the impact of assignment to mechanical circulatory support with guideline-directed LVAD destination therapy (GD-LVAD-DT) using the HeartMate 3 (HM3) continuous flow pump vs. guideline-directed medical therapy (GDMT) on survival in a population of AdHF patients ineligible for HTx. Methods A total of 80 patients will be recruited to SweVAD at the seven university hospitals in Sweden. The study population will comprise patients with AdHF (New York Heart Association class IIIB-IV, INTERMACS profile 2-6) who display signs of poor prognosis despite GDMT and who are not considered eligible for HTx. Participants will be followed for 2 years or until death occurs. Other endpoints will be determined by blinded adjudication. Patients who remain on study-assigned interventions beyond 2 years will be asked to continue follow-up for outcomes and adverse events for up to 5 years. Conclusion The SweVAD study will compare survival, medium-term benefits, costs and potential hazards between GD-LVAD-DT and GDMT and will provide a valuable reference point to guide destination therapy strategies for patients with AdHF ineligible for HTx.
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| 7. |
- Lindmark, G, et al.
(författare)
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Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer : relation to survival.
- 1993
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 19:1, s. 50-60
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Tidskriftsartikel (refereegranskat)abstract
- The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA-ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator.
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- Wiklund, Fredrik E, et al.
(författare)
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Macrophage inhibitory cytokine-1 (MIC-1/GDF15) : a new marker of all-cause mortality
- 2010
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 9:6, s. 1057-1064
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Tidskriftsartikel (refereegranskat)abstract
- Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the TGF-b superfamily, previously studied in cancer and inflammation. In addition to regulating body weight, MIC-1/GDF15 may be used to predict mortality and/or disease course in cancer, cardiovascular disease (CVD), chronic renal and heart failure, as well as pulmonary embolism. These data suggested that MIC-1/GDF15 may be a marker of all-cause mortality. To determine whether serum MIC-1/GDF15 estimation is a predictor of all-cause mortality, we examined a cohort of 876 male subjects aged 35-80 years, selected from the Swedish Population Registry, and followed them for overall mortality. Serum MIC-1/GDF15 levels were determined for all subjects from samples taken at study entry. A second (independent) cohort of 324 same-sex twins (69% female) from the Swedish Twin Registry was similarly examined. All the twins had telomere length measured and 183 had serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) available. Patients were followed for up to 14 years and had cause-specific and all-cause mortality determined. Serum MIC-1/GDF15 levels predicted mortality in the all-male cohort with an adjusted odds ratio (OR) of death of 3.38 (95%CI 1.38-8.26). This finding was validated in the twin cohort. Serum MIC-1/GDF15 remained an independent predictor of mortality when further adjusted for telomere length, IL-6 and CRP. Additionally, serum MIC-1/GDF15 levels were directly correlated with survival time independently of genetic background. Serum MIC-1/GDF15 is a novel predictor of all-cause mortality.
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| 17. |
- Zervos, T., et al.
(författare)
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The influence of MIMO terminal user's hand on channel capacity
- 2006
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Konferensbidrag (refereegranskat)abstract
- In this paper the impact of user's hand holding a Multiple-Input-Multiple- Output (MIMO) terminal on the system performance is investigated. A 4×4 MIMO system is considered with a Personal Digital Assistant (PDA) terminal equipped with a compact array of 4 patch elements. The radiation patterns of the antenna elements are simulated in the presence of the other elements and in the presence of a user's hand. The obtained patterns are used to evaluate the covariance matrix of the receive antenna which is incorporated in a correlation-based MIMO channel model. MIMO channel capacity is calculated to demonstrate the capacity degradation caused by the user's hand.
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| 18. |
- Alexander, S, et al.
(författare)
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Maternal health outcomes in Europe.
- 2003
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Ingår i: European Journal of Obstet & Gynecol and Repro. Biol.. ; 111, s. 78-
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Tidskriftsartikel (refereegranskat)
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| 19. |
- Barlind, Jonas G, et al.
(författare)
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Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687)
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:23, s. 10610-10629
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Tidskriftsartikel (refereegranskat)abstract
- A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.
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- Duchemin, Sandrine, et al.
(författare)
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Genetic parameters for noncoagulating milk, milk coagulation properties, and detailed milk composition in Swedish Red Dairy Cattle
- 2020
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Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 103:9, s. 8330-8342
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Tidskriftsartikel (refereegranskat)abstract
- The rennet-induced coagulation ability of milk is important in cheese production. For Swedish Red Dairy Cattle (RDC), this ability is reduced because of a high prevalence of noncoagulating (NC) milk. In this study, we simultaneously combined genetic parameters for NC milk, milk coagulation properties, milk composition, physical traits, and milk protein composition. Our aim was to estimate heritability and genetic and phenotypic correlations for NC milk and 24 traits (milk coagulation properties, milk composition, physical traits, and milk protein composition). Phenotypes and ~7,000 SNP genotypes were available for all 600 Swedish RDC. The genotypes were imputed from ~7,000 SNP to 50,000 SNP. Variance components and genetic parameters were estimated with an animal model. In Swedish RDC, a moderate heritability estimate of 0.28 was found for NC milk. For the other 24 traits, heritability estimates ranged from 0.12 to 0.77 (standard errors from 0.08 to 0.18). A total of 300 phenotypic and genetic correlations were estimated. For phenotypic and genetic correlations, 172 and 95 were significant, respectively. In general, most traits showing significant genetic correlations also showed significant phenotypic correlations. In this study, phenotypic and genetic correlations with NC milk suggest that many correlations between traits exist, making it difficult to predict the real consequences on the composition of milk, if selective breeding is applied on NC milk. We speculate that some of these consequences may lead to changes in the composition of milk, most likely affecting its physical and organoleptic properties. However, our results suggest that κ-casein could be used as an indicator trait to predict the occurrence of NC milk at the herd level.
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