| 1. |
- Danielson, Johan, 1975-, et al.
(författare)
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Percutaneous Hernia Repair in Children : Safe to introduce
- 2021
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 110:3, s. 380-385
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective:In 2014 we introduced percutaneous internal ring suture as an alternative to open surgery for the treatment of inguinal hernia. This study aims to evaluate the introduction of the procedure at our institution.Methods:In total, 100 consecutive patients operated with percutaneous internal ring suture were compared with 100 consecutive patients operated with open surgery. The patients were operated from August 2014 until November 2017. Patient demographics, clinical history, operative time, time in theater, and postoperative complications were extracted from charts.Results:The mean operative time for percutaneous internal ring suture was 26.54 min and for open surgery 39.94 min, P < 0.0001. The total mean operative theater time for percutaneous internal ring suture was 108.95 min and for open surgery 118.4 min, P = 0.0343. During follow-up, two percutaneous internal ring sutures were operated for recurrent hernia. In the open surgery-group, three patients were operated for recurrent hernia, three for secondary testicular retention, and three for metachronous contralateral hernia.Conclusions:Even when established as a new technique, the percutaneous internal ring suture procedure is safe and results in shorter operative time and shorter theater time compared to open surgery.
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| 2. |
- Gaziano, Liam, et al.
(författare)
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Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
- 2021
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19. Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
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| 3. |
- Högberg, Niclas, 1979-
(författare)
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Experimental and Clinical Necrotizing Enterocolitis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Necrotizing enterocolitis (NEC), a severe inflammatory disorder of the gastrointestinal tract with high morbidity and mortality, affects primarily preterm infants. The diagnosis represents a challenging task, and no biomarker has been found to aid early diagnosis with high accuracy. Microdialysis has been widely used to detect metabolites of anaerobic metabolism, enabling a local and early detection of ischemia. This thesis aims to evaluate the possibility of detecting intestinal ischemic stress in experimental and clinical NEC, by use of rectal intraluminal microdialysis.Intraluminal rectal microdialysis was performed on rats subjected to total intestinal ischemia. Metabolites of ischemia were detectable in both ileum and rectum, with raised glycerol concentrations and lactate/pyruvate ratios. Elevated concentrations of glycerol correlated to increasing intestinal histopathological injury.Experimental early NEC was induced in newborn rat pups, by hypoxia/re-oxygenation treatment. Development of NEC was confirmed by histopathology. Elevated glycerol concentrations were detected by rectal microdialysis.The genetic alterations following experimental NEC in rat pups were studied with microarray. Immunohistochemistry staining was performed for tight junction proteins claudin-1 and claudin-8. Several genes were altered in experimental NEC, mainly genes regulating tight junctions and cell adhesion. Immunohistochemistry revealed reduced expression of claudin-1.A prospective study was conducted on preterm infants with a gestational age of less than 28 weeks. The infants were admitted to a neonatal intensive care unit, and observed during a 4-week period. Rectal microdialysis was performed twice a week, and blood was drawn for analysis of I-FABP. A total of 15 infants were included in the study, whereof four infants developed NEC, and 11 served as controls. Rectal glycerol and I-FABP displayed high concentrations, which varied considerably during the observation periods, both in NEC and controls. No differences in either glycerol or I-FABP concentrations were seen in the NEC-group vs. the controls.In conclusion, rectal microdialysis can detect metabolites of intestinal ischemia, both in experimental and clinical NEC. Rectal microdialysis is safe and could provide a valuable non-invasive aid to detect hypoxia-induced intestinal damage or ischemic stress in extremely preterm infants. In this study however, it was not possible to predict the development of clinical NEC using microdialysis or I-FABP.
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| 4. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis
- 2013
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 48:11, s. 2308-2312
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose:Necrotizing enterocolitis (NEC) represents one of the gravest complications in preterm infants and carries significant morbidity and mortality. Increased intestinal permeability may play an important role in the pathogenesis of NEC. In this study we investigated the genes regulating structural proteins such as tight junctions (TJ) and cell adhesion in a neonatal rat model of early NEC, as well as the expression of TJ proteins by immunohistochemistry staining.Methods:The studies were performed on Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment on day 1 after birth. Intestinal specimens from the ileum were obtained, mRNA was purified and the transcriptome was analyzed using microarray. Immunohistochemistry staining was performed for TJ proteins.Results:We found several TJ genes such as claudins 1, 8, 14, 15 and gap junction protein to be affected. Immunohistochemistry staining for TJ protein claudin-1 revealed decreased levels in experimental NEC compared to controls. Alterations in genes involved in the inflammatory response was confirmed, along with several genes regulating proteins used as biomarkers for NEC.Conclusion:This study indicates that tight junctions and cell adhesion may play a critical role in the pathogenesis of early experimental NEC. Better understanding of the pathogenesis of NEC may lead to novel strategies for the prevention and treatment of NEC.
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| 5. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Intestinal intraluminal glycerol and plasma I-FABP levels in preterm infants with necrotizing enterocolitis
- 2016
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Ingår i: Clinics in Surgery. ; 1:1085, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: Necrotizing enterocolitis (NEC) is highly associated with prematurity and is characterized by bowel necrosis and multi-organ failure. There is a strong need for improved diagnostic methods to reduce the significant morbidity and mortality associated with NEC. The aim of this single centre prospective study was to investigate the possibility to detect early signs of NEC, by using rectal intraluminal microdialysis and plasma intestinal fatty acid binding protein (I-FABP) in preterm infants admitted to a level III neonatal intensive care unit.Methods: The study was performed on extremely preterm infants with a gestational age of less than 28 weeks. During a 4-week period after birth, rectal intraluminal microdialysate levels of glucose, lactate, pyruvate and glycerol were measured, and plasma was collected for I-FABP analysis. Infants not developing NEC served as controls. Results: Microdialysis revealed signs of intestinal hypoxic or ischemic damage and cell membrane degradation, with a marked increase of both intraluminal glycerol and plasma I-FABP in infants developing NEC, as well as in infants suffering from other complications. The microdialysate levels of glucose, lactate and pyruvate were too low to be evaluated in this setting. All infants tolerated the microdialysis well without any complications.Conclusion: Elevated levels of intraluminal glycerol and plasma I-FABP suggests mucosal cell membrane degradation and hypoxic or ischemic damage in preterm infants developing NEC, as well as in preterm infants suffering from other complications such as volvulus, sepsis or respiratory distress. However, it was not possible to predict development of NEC before clinical diagnosis using these markers.
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| 6. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Intestinal ischemia measured by intraluminal microdialysis
- 2012
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 72:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon. Methods. The studies were performed on male Sprague-Dawley rats. In the fi rst part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation. Results. Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage. Conclusion. Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and ay prove to be a valuable clinical tool for diagnosing intestinal ischemia.
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| 7. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis
- 2012
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 47:9, s. 1646-1651
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/PURPOSE:Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants and carries significant morbidity and mortality. There is a great need for improved diagnostic methods to reduce the severity and incidence of NEC. The aim of the study was to investigate if intraluminal microdialysis can detect intestinal ischemia in newborn rats with induced experimental NEC.METHODS:The studies were performed on 1-day-old Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment. Microdialysis catheters were rectally inserted and placed in the rectosigmoid part of the colon. Microdialysate levels of glucose, lactate, pyruvate, and glycerol were measured. Intestinal specimens were collected at the end of the experiments for microscopic evaluation.RESULTS:Intraluminal microdialysis revealed signs of intestinal hypoxia and cellular damage, with a marked increase of lactate and glycerol. Microscopic evaluation confirmed intestinal damage in the NEC group.CONCLUSION:Intraluminal microdialysis can detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model of NEC. Intestinal intraluminal microdialysis is easily accessible through the rectum and may be a useful noninvasive complement to other methods in the assessment of NEC.
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