| 1. |
- Alkaissi, Lina Y., et al.
(författare)
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Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease
- 2021
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Ingår i: Inflammatory Bowel Diseases. - : OXFORD UNIV PRESS INC. - 1078-0998 .- 1536-4844. ; 27:7, s. 1116-1127
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Tidskriftsartikel (refereegranskat)abstract
- Background: The first visible signs of Crohns disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human alpha-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods: An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results: There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions: Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.
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| 2. |
- Biskou, Olga, et al.
(författare)
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Increased Numbers of Enteric Glial Cells in the Peyers Patches and Enhanced Intestinal Permeability by Glial Cell Mediators in Patients with Ileal Crohns Disease
- 2022
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Ingår i: Cells. - Basel, Switzerland : MDPI. - 2073-4409. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Enteric glial cells (EGC) are known to regulate gastrointestinal functions; however, their role in Crohns disease (CD) is elusive. Microscopic erosions over the ileal Peyers patches are early signs of CD. The aim of this work was to assess the localization of EGC in the follicle and interfollicular region of the Peyers patches and in the lamina propria and study the effects of EGC mediators on barrier function in CD patients and non-inflammatory bowel disease (non-IBD) controls. EGC markers, glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β) were quantified by immunofluorescence and Western blotting. Both markers showed significantly more EGC in the Peyers patches and lamina propria of CD patients compared to the non-IBD controls. In CD patients there were significantly more EGC in Peyers patches compared to lamina propria, while the opposite pattern was seen in controls. Barrier function studies using Ussing chambers showed increased paracellular permeability by EGC mediators in CD patients, whereas permeability decreased by the mediators in controls. We show the accumulation of EGC in Peyers patches of CD patients. Moreover, EGC mediators induced barrier dysfunction in CD patients. Thus, EGC might have harmful impacts on ongoing inflammation and contribute to the pathophysiology of the disease.
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| 3. |
- Dalby, Helene R., et al.
(författare)
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Management of acute uncomplicated diverticulitis and adherence to current guidelines : a multicentre SNAPSHOT study
- 2024
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 39:1
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo explore whether previous participation in clinical studies increases adherence to management guidelines in acute uncomplicated diverticulitis (AUD).MethodsThis retrospective cohort study was designed to give a SNAPSHOT of the management of AUD at six hospitals, three of which had participated in the AVOD trial comparing antibiotic versus non-antibiotic treatment of AUD. Patients with AUD were included from March 2019 through June 2020 and followed for 90 days. The primary outcome was treatment of AUD categorised by antibiotic treatment and inpatient or outpatient management compared between AVOD and non-AVOD hospitals. Descriptive statistics were compiled, and differences between hospitals were assessed with Pearson’s chi-squared test.ResultsThe cohort included 449 patients with AUD of which 63% were women and the median age was 63 (IQR: 52–73) years. Patient characteristics were comparable across the hospitals. Antibiotics were administered to 84 (19%) patients and 113 (25%) patients were managed as inpatients. Management varied significantly between AVOD and non-AVOD hospitals. The mean proportion of patients treated with antibiotics was 7% at AVOD hospitals compared to 38% at non-AVOD hospitals (p < 0.001). The mean proportion of in-hospital management was 18% at AVOD hospitals versus 38% at non-AVOD hospitals (p < 0.001).ConclusionMost patients with AUD were managed according to current guidelines. However, the management varies between hospitals and previous participation in clinical studies may increase knowledge of and adherence to guidelines.
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| 4. |
- Gnosa, Sebastian, et al.
(författare)
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MTDH genetic variants in colorectal cancer patients
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the second most common cancer worldwide and accounts for around 8.5% of all cancer related death. The colorectal carcinogenesis is a complex process of genetic alterations. For better prognosis it is very important to understand the composition of genetic alterations in a tumor. Astrocyte elevated gene-1 (AEG-1) has been shown to be overexpressed in CRC and had prognostic significance. The aim of this study was to determine the frequency and the spectrum of MTDH variants, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. We detected 42 intronic variants, whereby 25 were novel. Furthermore, we found eight exonic variants of which four, one missense (c.977C>G) and three frameshift mutations (c.533delA, c.1731delA, c.1340dupA), were novel. In silico prediction analyses revealed that four variants c.232G>T, c.533delA, c.1340dupA and c.1731delA were deleterious. There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. The detection of pathogenic mutations and alterations in functional protein domains suggest their involvement in tumorigenesis, although none of the variants had prognostic potential.
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| 5. |
- Haapaniemi, Staffan, et al.
(författare)
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Mortality after elective and emergency surgery for inguinal and femoral hernia
- 1999
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Ingår i: Hernia. - 1265-4906 .- 1248-9204. ; 3:4, s. 205-208
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate mortality following elective and emergency groin hernia surgery. Information concerning 17 591 inguinal and 579 femoral hernia operations, including death of patients within 30 days of surgery, were prospectively recorded in the Swedish Hernia Register over a period of six years. Elective surgery for groin hernia is known to be a low-risk procedure. Mortality within 30 days of surgery was compared with the mortality of the general Swedish population using the standard mortality rate (SMR). Of all inguinal and femoral hernia repairs 5.1 % and 35.2 % respectively, were performed as an emergency. Following elective inguinal hernia repair the SMR for men fell significantly below unity. No significant differences between observed and expected mortality were observed following inguinal hernia surgery on females or following elective femoral hernia surgery on either gender. The reduced SMR found after elective hernia repair in men is most likely attributable to patient selection. After elective surgery on patients 70 years or older there is a tendency towards a reduction in SMR of the same order of size as for patients analysed as one group which, however, did not reach statistical significance. Mortality following both inguinal and femoral emergency procedures is increased five- to ten-fold compared to the 30-day mortality in the general population. A further increase in postoperative mortality is noted following emergency surgery with bowel resection.
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| 6. |
- Haapaniemi, Staffan
(författare)
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Quality assessment in groin hernia surgery : the role of a register
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ever since the Romans 2000 years ago the management of hernia surgery has remained a challenge to surgeons. Modern groin hernia treatment started with the Italian, Eduardo Bassini, around 1890 when he presented his method of repair. The most important innovations after Bassini are the Shouldice repair and introduction of prosthetic materials.The last century has witnessed a continuous gap between, on the one hand excellent results repmted from dedicated hernia centres, and on the other outcome following hernia surgery in general surgical practice, in Sweden and elsewhere. One obstacle to quality assessment is the magnitude of hernia surgery. It is the most commonly performed procedure in Swedish general surgical practice with an incidence of around 17,000 to 20,000 repairs annually.In 1992 a national quality register for hernia surgery was started, the Swedish Hernia Register (SHR). The general aim of this thesis is to study to what extent a quality register can be used for describing and analysing hernia surgery and can serve as a tool in the improvement process in non-specialised hospitals. Prospectively registered data in the SHR from 1992 to 1998 are the source of information for the six papers included.The number of units participating in the SHR has increased from eight in 1992 to 65 in 2001, covering approximately 80% of units performing hernia surgery in Sweden. In January 2001 the database comprised almost 50,000 hernia repairs. Coverage of hernia operations in the SHR among participating units was high, 98%. Register participation, per se, improved the outcome of hernia surgery at aligned units during the early phase of the SHR.In the studies forming the basis of this thesis we found that the use of mesh increased from 6 to 61% from 1992 to 1996-1998 and that the cumulative incidence of reoperation for recurrence decreased significantly during the same period. Recurrent hernia, absorbable suture, direct hernia and postoperative complication were identified as factors carrying an enhanced risk for reoperation.SHR data show that femoral hernia is more common in females and associated with an enhanced risk for emergency operation. Mortality within 30 days of surgery, for men, was lower than that of the background population after elective inguinal hernia repair but increased after emergency operations, especially if bowel resection was undertaken.Recurrent groin hernia still constitutes a significant quantitative problem for the surgical community, 15% of all repairs registered in 1996-1998 being repairs for recurrence. Anterior mesh repair according to Lichtenstein and laparoscopic methods were associated with a lower risk for reoperation following recurrent hernia repair.In one hospital cohort from 1994, the recurrence rate was 10.5-14.6% 44 months after surgery, exceeding the reoperation rate by 1.7-2.3 times depending on definition of recurrence and method of follow-up. Fifteen per cent of patients in this cohort had pain related to previous hernia surgery, pain intensity being moderate or severe in 5 % of all patients followed-up.The SHR, with reoperation as its main endpoint, may be used to describe and analyse hernia surgery and to stimulate local improvement. It has to be supplemented by questionnaire and/or physical examination in order to estimate rates of recurrence and chronic pain.
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| 7. |
- Haapaniemi, Staffan, et al.
(författare)
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Recurrence and pain three years after groin hernia repair : Validation of postal questionnaire and selective physical examination as a method of follow-up
- 2002
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Ingår i: European Journal of Surgery. - : Oxford University Press (OUP). - 1102-4151 .- 1741-9271. ; 168:1, s. 22-28
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:To evaluate recurrence rate and chronic groin pain three years after hernia repair and to validate a postal questionnaire with selective physical examination as a method of follow-up.Design:Prospective cohort study.Setting:County hospital, Sweden.Patients:Prospective data were retrieved from the Swedish Hernia Register for patients aged 15–80 years at the time of groin hernia repair, operated on during 1994.Interventions:Three years after operation patients were mailed a three-item questionnaire and invited to have a physical examination. Those examined answered a detailed questionnaire about pain and functional impairment. When appropriate an extended physical examination was undertaken to find out the probable cause of the pain.Main outcome measures:Recurrence, pain, and functional impairment.Results:272 hernias were repaired in 264 patients. 24 patients had died and 16 had a recurrence before the follow-up examination. After a median observation time of 44 months, 218 patients with 223 repairs (96%) were examined. Depending on the definition of recurrence and completeness of physical examination (selective or all patients) the recurrence rate varied between 10% (25/239) and 15% (35/239) including recurrences diagnosed before follow-up. 40 patients (18%) reported groin pain at follow-up, which was considered to be caused by a previous hernia repair in 34 (15%), 12 of whom (5%) had moderate or severe pain. Postoperative complications were associated with an increased risk of chronic pain, whereas type of hernia and use of mesh had no influence.Conclusions:The incidence of recurrence and chronic pain after hernia repair requires continuous audit in non-specialised units. Participation in a register and follow-up by a three-item questionnaire and selective physical examination provides a solid basis for quality control.
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| 8. |
- Haapaniemi, Staffan, et al.
(författare)
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Reoperation after recurrent groin hernia repair
- 2001
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Ingår i: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 234:1, s. 122-126
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyze reoperation rates for recurrent and primary groin hernia repair documented in the Swedish Hernia Register from 1996 to 1998, and to study variables associated with increased or decreased relative risks for reoperation after recurrent hernia.Methods: Data were retrieved for all groin hernia repairs prospectively recorded in the Swedish Hernia register from 1996 to 1998. Actuarial analysis adjusted for patients' death was used for calculating the cumulative incidence of reoperation. Relative risk for reoperation was estimated using the Cox proportional hazards model.Results: From 1996 to 1998, 17,985 groin hernia operations were recorded in the Swedish Hernia Register, 15% for recurrent hernia and 85% for primary hernia. At 24 months the risk for having had a reoperation was 4.6% after recurrent hernia repair and 1.7% after primary hernia repair. The relative risk for reoperation was significantly lower for laparoscopic methods and for anterior tension-free repair than for other techniques. Postoperative complications and direct hernia were associated with an increased relative risk for reoperation. Day-case surgery and local infiltration anesthesia were used less frequently for recurrent hernia than for primary hernia.Conclusions: Recurrent groin hernia still constitutes a significant quantitative problem for the surgical community. This study supports the use of mesh by laparoscopy or anterior tension-free repair for recurrent hernia operations.
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| 9. |
- Koch Frisén, Angelica, et al.
(författare)
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Prospective evaluation of 6895 groin hernia repairs in women
- 2005
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 92:12, s. 1553-1558
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although 8 per cent of groin hernia repairs are performed in women, there is little published literature relating specifically to women. This study compared differences in outcome between women and men after groin hernia repair.Methods: Data collected prospectively in the Swedish Hernia Register between 1992 and 2003 were analysed, including 6895 groin hernia repairs in women and 83 753 in men.Results: A higher proportion of emergency operations was carried out in women (16.9 per cent) than men (5.0 per cent), leading to bowel resection in 16.6 and 5.6 per cent respectively. During reoperation femoral hernias were found in 41.6 per cent of the women who were diagnosed with a direct or indirect inguinal hernia at the primary operation. The corresponding proportion for men was 4.6 per cent. The hernia repair was not classified as a standard operation (e.g. Shouldice, Lichtenstein, Plug/Mesh, TAPP/TEP) in 38.2 per cent of women and 11.2 per cent of men. Women had a significantly higher risk of reoperation for recurrence than men, and techniques associated with the lowest risk for reoperation in men had the highest risk in women.Conclusion: A greater proportion of women than men require emergency groin hernia repair, with consequently higher rates of bowel resection, complications and death. Surgical techniques developed for use in men may put women at unnecessary risk. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.
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| 10. |
- Kokkinou, Efthymia, et al.
(författare)
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CD45RA(+)CD62L(-) ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs
- 2022
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Ingår i: Science immunology. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2470-9468. ; 7:70
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Tidskriftsartikel (refereegranskat)abstract
- Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The discovery of naive-like ILCs suggests an ILC differentiation process that is akin to naive T cell differentiation. Delineating the mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here, we showed that tonsillar ILCs expressing CD45RA lacked proliferative activity, indicative of cellular quiescence. CD62L distinguished two subsets of CD45RA(+) ILCs. CD45RA(+)CD62L(+) ILCs (CD62L(+) ILCs) resembled circulating naive ILCs because they lacked the transcriptional, metabolic, epigenetic, and cytokine production signatures of differentiated ILCs. CD45RA(+)CD62L(-) ILCs (CD62L(-) ILCs) were epigenetically similar to CD62L(+) ILCs but showed a transcriptional, metabolic, and cytokine production signature that was more akin to differentiated ILCs. CD62L(+) and CD62L(-) ILCs contained uni- and multipotent precursors of ILC1s/NK cells and ILC3s. Differentiation of CD62L(+) and CD62L(-) ILCs led to metabolic reprogramming including up-regulation of genes associated with glycolysis, which was needed for their effector functions after differentiation. CD62L(-) ILCs with preferential differentiation capacity toward IL-22-producing ILC3s accumulated in the inflamed mucosa of patients with inflammatory bowel disease. These data suggested distinct differentiation potential of CD62L(+) and CD62L(-) ILCs between tissue microenvironments and identified that manipulation of these cells is a possible approach to restore tissue-immune homeostasis.
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