Intervention and Technology CLINTEC

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Intervention and Technology CLINTEC

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Fischler B.,Intervention and Technology CLINTEC | Nemeth A.,Intervention and Technology CLINTEC | Strom S.C.,Karolinska University Hospital
Journal of Internal Medicine | Year: 2012

Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation. Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic. © 2012 The Association for the Publication of the Journal of Internal Medicine.


Carrero J.J.,Center for Gender Medicine | Heimburger O.,Divisions of Renal Medicine | Lindholm B.,Baxter Novum | Hammarqvist F.,Intervention and Technology CLINTEC | Stenvinkel P.,Divisions of Renal Medicine
Journal of Internal Medicine | Year: 2011

Objectives. Low-grade systemic inflammation, oxidative stress and peripheral insulin resistance are intimately associated and contribute to the increased risk of cardiovascular complications in advanced chronic kidney disease (CKD). Because altered adipose tissue activities have previously been linked to pathophysiological processes in various inflammatory and metabolic diseases we hypothesized that the uraemic milieu in patients with CKD may interact with the adipose tissue, provoking an unfavourable shift in its transcriptional output. Design. Twenty-one adipokine mRNAs were quantified in abdominal subcutaneous adipose tissue (SAT) biopsies and serum/plasma concentrations of inflammatory markers and related protein products were measured. Setting. The study was conducted at the Karolinska University Hospital, Huddinge, and Karolinska Institutet, Stockholm, Sweden. Subjects. Thirty-seven patients with CKD [15 women, median 58 (interquartile range 49-65) years] and nine nonuraemic individuals [four women, age 62 (45-64) years] were recruited prior to initiation of peritoneal dialysis catheter insertion or elective hernia repair/laparoscopic cholecystectomy, respectively. Results. Even after correction for body mass index, SAT from patients showed a significant upregulation of inflammatory pathway genes interleukin 6 (3.0-fold, P=0.0002) and suppressor of cytokine signalling 3 (2.5-fold, P=0.01), as well as downregulation of leptin (2.0-fold, P=0.03) and the oxidative stress genes uncoupling protein 2 (1.5-fold, P=0.03) and cytochrome b-245, alpha polypeptide (1.5-fold, P=0.005), in relation to controls. Conclusions. These gene expression differences suggest that inflammatory and oxidative stress activities may be important features of the intrinsic properties of uraemic adipose tissue, which may have significant effects on the uraemic phenotype. © 2010 The Association for the Publication of the Journal of Internal Medicine.


Sjoqvist S.,Advanced Center for Translational Regenerative Medicine | Jungebluth P.,Karolinska University Hospital | Ling Lim M.,Karolinska Institutet | Haag J.C.,University of Rome Tor Vergata | And 20 more authors.
Nature Communications | Year: 2014

A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial-And muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi. © 2014 Macmillan Publishers Limited. All rights reserved.


PubMed | Intervention and Technology CLINTEC ., Uppsala University, c Karolinska Institute and Karolinska University Hospital
Type: Journal Article | Journal: Acta orthopaedica | Year: 2016

Hip fracture patients usually have low body mass index (BMI), and suffer further postoperative catabolism. How BMI relates to outcome in relatively healthy hip fracture patients is not well investigated. We investigated the association between BMI, survival, and independent living 1 year postoperatively.This prospective multicenter study involved 843 patients with a hip fracture (mean age 82 (SD 7) years, 73% women), without severe cognitive impairment and living independently before admission. We investigated the relationship between BMI and both 1-year mortality and ability to return to independent living.Patients with BMI>26 had a lower mortality rate than those with BMI<22 and those with BMI 22-26 (6%, 16%, and 18% respectively; p=0.006). The odds ratio (OR) for 1-year survival in the group with BMI>26 was 2.6 (95% CI: 1.2-5.5) after adjustment for age, sex, and physical status. Patients with BMI>26 were also more likely to return to independent living after the hip fracture (OR=2.6, 95% CI: 1.4-5.0). Patients with BMI<22 had similar mortality and a similar likelihood of independent living to those with BMI 22-26.In this selected group of patients with hip fracture, the overweight and obese patients (BMI>26) had a higher survival rate at 1 year, and returned to independent living to a higher degree than those of normal (healthy) weight. The obesity paradox and the recommendations for optimal BMI need further consideration in patients with hip fracture.


Sundin M.,Intervention and Technology CLINTEC | Sundin M.,Karolinska Institutet | Remberger M.,Astrid Lindgren Childrens Hospital | Remberger M.,Karolinska University Laboratory | And 7 more authors.
Pediatric Blood and Cancer | Year: 2015

Background: Hypogammaglobulinemia (hypo-IgG) is common early post-HSCT in children, occasionally necessitating long-term immunoglobulin (Ig) G replacement therapy. IgG replacement may not reduce mortality, although infectious complications are decreased Procedure: Clinical data and samples from 86 children were analyzed retrospectively with the aim to identify risk factors for developing long-term hypo-IgG (i.e., requiring ≥3 months IgG replacement) post-HSCT and studying the underlying biology. Laboratory studies covered serum cytokines, IGHG2 genotyping and routine laboratory investigations. Results were analyzed statistically. Results: Forty-eight percent of the children developed long-term hypo-IgG. These children were younger (<5 years) and had higher acute GvHD incidence, but had better overall survival (88% vs. 69%, P=0.036). Significantly lower Ig levels post-HSCT but equal immune cell recovery were seen in patients with long-term hypo-IgG compared with those of transient or no hypo-IgG. Pre-HSCT IL-6 and -7 and post-HSCT BAFF and APRIL levels were significantly higher in the long-term hypo-IgG group. Conclusions: Findings suggests an unfavorable cytokine milieu for graft-derived immune recovery, possibly inducing Ig isotype class switch arrest. Younger age, acute GvHD, and higher pre-HSCT IL-6 levels were identified as significant risk factors for long-term hypo-IgG. Long-term hypo-IgG post-HSCT does not need to be unfavorable and could be an effect of deteriorated cytokine signaling. Pediatr Blood Cancer 2015;62:890-896. © 2015 Wiley Periodicals, Inc.


Flodin L.,Karolinska University Hospital | Flodin L.,Karolinska Institutet | Laurin A.,Karolinska Institutet | Lokk J.,Karolinska University Hospital | And 6 more authors.
Acta Orthopaedica | Year: 2016

Background and purpose - Hip fracture patients usually have low body mass index (BMI), and suffer further postoperative catabolism. How BMI relates to outcome in relatively healthy hip fracture patients is not well investigated. We investigated the association between BMI, survival, and independent living 1 year postoperatively.Patients and methods - This prospective multicenter study involved 843 patients with a hip fracture (mean age 82 (SD 7) years, 73% women), without severe cognitive impairment and living independently before admission. We investigated the relationship between BMI and both 1-year mortality and ability to return to independent living.Results - Patients with BMI > 26 had a lower mortality rate than those with BMI < 22 and those with BMI 22-26 (6%, 16%, and 18% respectively; p = 0.006). The odds ratio (OR) for 1-year survival in the group with BMI > 26 was 2.6 (95% CI: 1.2-5.5) after adjustment for age, sex, and physical status. Patients with BMI > 26 were also more likely to return to independent living after the hip fracture (OR = 2.6, 95% CI: 1.4-5.0). Patients with BMI < 22 had similar mortality and a similar likelihood of independent living to those with BMI 22-26.Interpretation - In this selected group of patients with hip fracture, the overweight and obese patients (BMI > 26) had a higher survival rate at 1 year, and returned to independent living to a higher degree than those of normal (healthy) weight. The obesity paradox and the recommendations for optimal BMI need further consideration in patients with hip fracture. © 2016 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation.


Del Chiaro M.,Intervention and Technology CLINTEC | Blomberg J.,Intervention and Technology CLINTEC | Segersvard R.,Intervention and Technology CLINTEC | Rangelova E.,Intervention and Technology CLINTEC | And 2 more authors.
Journal of the Pancreas | Year: 2014

Context LigaSureTM is considered safe in performing pancreatoduodenectomy (PD). However, no data are available regarding the possible damage of tissues at the resection margins and the impact thereof on histologic margin assessment.Objective This study compares the degree of histologic damage to the resection margins when using LigaSureTM (group 1) or traditional ligature (group 2).Methods Both groups included 8 consecutive patients who underwent PD at Karolinska Institute in December 2013 (group 1) or earlier (group 2) by the same surgeon (MDC). The quality of tissues at the circumferential margins was compared between both groups by scoring for three different kinds of damage: tissue fragmentation, hemorrhage, and cell damage.Results The mean score for fragmentation was 1.3 (group 1) versus 1.7 (group 2; p=0.1). For hemorrhage the mean score was 0.8 (group 1) versus 1.5 (group 2; p=0.04). The mean score for cell damage was 1.4 (group 1) compared to 1.2 (group 2; p=0.1).Conclusions LigaSureTM does not cause tissue damage that could affect histologic margin assessment in PD specimens. © 2014, E.S. Burioni Ricerche Bibliografiche. All rights reserved.


Watanabe M.,Intervention and Technology CLINTEC | Zemack H.,Intervention and Technology CLINTEC | Johansson H.,Intervention and Technology CLINTEC | Hagbard L.,BioLamina AB | And 3 more authors.
PLoS ONE | Year: 2016

Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms-111,-211,-221,-332,-411,-421,-511, and-521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-Antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-Associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human hepatocytes, and that recombinant laminin is a promising xenofree and chemical defined strategy for preservation of hepatocyte specific function in vitro. © 2016 Watanabe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Agustsson T.,Intervention and Technology CLINTEC | Wikrantz P.,Intervention and Technology CLINTEC | Ryden M.,Karolinska University Hospital | Brismar T.,Intervention and Technology CLINTEC | Isaksson B.,Intervention and Technology CLINTEC
Nutrition | Year: 2012

Objective: Approximately 50% of patients with cancer develop cachexia. The aim of the present study was to determine if there were differences in the amount of visceral and subcutaneous adipose tissues at the time of the diagnosis among patients with cancer cachexia (CC), patients with cancer and a stable weight (WS), and patients with cancer and weight loss because of gastrointestinal obstruction (GO). Methods: Patients with recently diagnosed cancer were divided into the CC, WS, and GO groups. Body composition was determined by bioimpedance. Basal metabolic rate and energy expenditure were estimated by indirect calorimetry. Visceral and subcutaneous white adipose tissues (WATs) were quantified by the segmentation of a 10-mm-thick computed tomographic slice obtained through the central part of the third lumbar vertebra. Results: The body mass index and body fat were decreased in the CC and GO groups compared with the WS group, but there were no significant differences between the two weight-losing groups. Lean body mass, total body water, and energy expenditure were similar among the groups. The visceral WAT volume was decreased in the CC but not in the GO group compared with the WS group (P < 0.05). The subcutaneous WAT was decreased in the CC and GO groups compared with the WS group (P < 0.001). Conclusion: The WAT was decreased in the CC and GO groups compared with the WS group. Furthermore, patients with CC exhibited a selective decrease in visceral WAT. This may be new information regarding the WAT distribution in CC. © 2012 Elsevier Inc.


PubMed | Affinity Technology, Karolinska University Hospital, Gothenburg University and Intervention and Technology CLINTEC
Type: Journal Article | Journal: PloS one | Year: 2015

Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

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