| 1. |
- Alimohammadi, Mohammad, et al.
(författare)
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Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:11, s. 4396-4401
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.
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| 2. |
- Andreasson, Anna, et al.
(författare)
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The prediction of colorectal cancer using anthropometric measures : A Swedish population-based cohort study with 22 years of follow-up
- 2019
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Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 7:9, s. 1250-1260
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a risk factor for colorectal cancer (CRC).Objective: The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI).Methods: Data were analysed from the Malmo Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women.Results: None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men.Conclusions: Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.
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| 3. |
- Astuti, D, et al.
(författare)
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Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.
- 2001
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 69:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Recently, pheochromocytoma susceptibility has been associated with germline SDHD mutations. Germline SDHD mutations were originally described in hereditary paraganglioma, a dominantly inherited disorder characterized by vascular tumors in the head and the neck, most frequently at the carotid bifurcation. The gene products of two components of succinate dehydrogenase, SDHC and SDHD, anchor the gene products of two other components, SDHA and SDHB, which form the catalytic core, to the inner-mitochondrial membrane. Although mutations in SDHC and in SDHD may cause hereditary paraganglioma, germline SDHA mutations are associated with juvenile encephalopathy, and the phenotypic consequences of SDHB mutations have not been defined. To investigate the genetic causes of pheochromocytoma, we analyzed SDHB and SDHC, in familial and in sporadic cases. Inactivating SDHB mutations were detected in two of the five kindreds with familial pheochromocytoma, two of the three kindreds with pheochromocytoma and paraganglioma susceptibility, and 1 of the 24 cases of sporadic pheochromocytoma. These findings extend the link between mitochondrial dysfunction and tumorigenesis and suggest that germline SDHB mutations are an important cause of pheochromocytoma susceptibility.
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| 4. |
- Bratland, Eirik, et al.
(författare)
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Epitope mapping of human aromatic L-amino acid decarboxylase
- 2007
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 353:3, s. 692-698
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type I (APS I) is a rare hereditary condition considered a model disease for organ specific autoimmunity. A wide range of autoantibodies targeting antigens present in the affected organs have been identified. Autoantibodies against aromatic l-amino acid decarboxylase (AADC) are present in about 50% of APS I patients. In order to increase our understanding of autoantibody specificity in APS I, the aim of the present study was to localize target regions on AADC recognized by sera from APS I patients. Using several complementing strategies, we have shown that autoantibodies against AADC mainly recognize conformational epitopes. The major antigenic determinants were detected N-terminally to amino acid residue 237. Replacement of amino acids 227–230 (ERDK) with alanine residues reduced the reactivity towards AADC by >80% in all patient sera tested, suggesting that amino acids 227–230 are an important part of an immunodominant epitope.
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| 5. |
- Cameron, Raquel, et al.
(författare)
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Mortality risk increased in colonic diverticular disease : a nationwide cohort study
- 2022
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Ingår i: Annals of Epidemiology. - : Elsevier. - 1047-2797 .- 1873-2585. ; 76, s. 39-49
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: There are limited population cohort data on overall and cause-specific mortality in colonic diverticular disease.Objective: To measure overall and cause-specific mortality in colonic diverticular disease, compared to matched reference individuals and siblings.Methods: Population-based cohort study ("the ESPRESSO study") in Sweden. There were 97,850 cases with a medical diagnosis of diverticular disease (defined by international classification of disease codes) and colorectal histology identified in 1987-2017 from histopathology reports. The mortality risk between individuals with colonic diverticular disease and matched reference individuals ( n = 453/634) from the general population was determined. Cox regression models adjusted for comorbidity estimated hazard ratios (HRs) for all-cause mortality.
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| 6. |
- Enblad, Malin, et al.
(författare)
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Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
- 2016
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 23:4, s. 1149-1156
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Tidskriftsartikel (refereegranskat)abstract
- The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.
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| 7. |
- Fetissov, Sergueï O, et al.
(författare)
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Autoantibodies in autoimmune polyglandular syndrome type I patients react with major brain neurotransmitter systems.
- 2009
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Ingår i: The Journal of comparative neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 513:1, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L-amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff-man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain gamma-aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC-containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D-group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple-labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as, e.g., shown in previous studies in stiff-man syndrome.
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| 8. |
- Granlund, Johan, et al.
(författare)
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Mortality in patients hospitalised for diverticulitis in Sweden—A national population‐based cohort study
- 2021
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Ingår i: GastroHep. - : John Wiley & Sons. - 1478-1239 .- 1478-1239. ; 3:3, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMortality in diverticulitis patients is poorly documented.AimsTo determine short- and long-term mortality in diverticulitis patients compared to matched disease-free individuals.MethodsBy use of nation-wide registers, mortality among all individuals with a first-time hospital admission for diverticulitis 1990-2010 was compared to a disease-free cohort, matched for gender and age, with up to 21 years of follow-up. Hazard ratios (HR) for death within 0-100 days and 101 days–5 years from admission, respectively, were calculated using Cox regression, adjusting for prior comorbidity and social factors. Separate analyses were performed on diverticulitis treated conservatively and surgically.Results83 461 diverticulitis and 812 942 disease-free individuals were included. Among all diverticulitis patients, mortality within 100 days was four times higher than in disease-free individuals, HR 4.44 (95% confidence interval 4.26-4.63), and in surgically treated patients, a HR of 12.13 (11.03-13.34) was observed. Within 100 days, 11.4% of patients receiving surgical treatment died, compared to 3.2% after conservative treatment. From day 101 to 5 years, the HR was 1.40 (1.32-1.47) after surgical treatment and 1.08 (1.05-1.10) after conservative treatment. Relative mortality within 100 days was slightly more pronounced in females than males, whereas in the 101 days–5 years interval, HRs were similar between genders.ConclusionsIn patients initially admitted for diverticulitis, survival is significantly reduced, both in the short and the long-term. This highlights the need of further efforts for prevention and optimised treatment.
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| 9. |
- Gustafsson, Jan, et al.
(författare)
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APSI - svår autoimmun sjukdom med endokrina och icke-endokrina symtom
- 2004
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:24, s. 2096-2103
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.
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| 10. |
- Järbrink-Sehgal, M. Ellionore, et al.
(författare)
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Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization
- 2018
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 16:9, s. 1474-1480
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. METHODS: We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. RESULTS: Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007). CONCLUSIONS: In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later.
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| 11. |
- Kjärstad, Jan, 1956, et al.
(författare)
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Transforming the energy system in Västra Götaland and Halland – linking short term actions to long term goals
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This study analyzes pathways to meet EU, national and regional targets for CO2 emissions, energy efficiency and penetration of renewable energy in the Swedish part of the Kattegat-Skagerrak region (KASK-SE), i.e. more specifically in the counties of Västra Götaland (VGR) and Halland. Special focus is placed on four areas: The potential for energy savings in the building sector, energy savings and fuel shifting in the energy intensive industry, large-scale deployment of renewables in the electricity generation sector and greenhouse gas emission reductions in the transport sector. The energy savings are through the implementation of different energy efficiency measures.
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| 12. |
- Kollatos, Christos, et al.
(författare)
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Evaluation of laparoscopic peritoneal lavage for perforated diverticulitis : a national registry-based study
- 2024
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 111:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Laparoscopic lavage (LPL) has been suggested for treatment of non-feculent perforated diverticulitis. In this observational study, the surgical treatment of diverticular disease in Sweden outside prospective trials was investigated. Methods: This population-based study used the National Patient Register to identify all patients in Sweden with emergency admissions for diverticular disease, as defined by ICD codes from July 2014 to December 2020. Demographics, surgical procedures and outcomes were assessed. In addition, register data since 1997 were retrieved to assess co-morbidities, previous abdominal surgeries, and previous admissions for diverticular disease. Results: Among 47 294 patients with emergency hospital admission, 2035 underwent LPL (427 patients) or sigmoid resection (SR, 1608 patients) for diverticular disease. The mean follow-up was 30.8 months. Patients selected for LPL were younger, healthier and with less previous abdominal surgery for diverticular disease than those in the SR group (P < 0.01). LPL was associated with shorter postoperative hospital stay (mean 9.4 versus 14.9 days, P < 0.001) and lower 30-day mortality (3.5% versus 8.7%, P < 0.001). Diverticular disease-associated subsequent surgery was more common in the SR group than the LPL group except during the first year (P < 0.001). LPL had a lower mortality rate during the study period (stratified HR 0.70, 95% c.i. 0.53-0.92, P = 0.023). Conclusion: Laparoscopic lavage constitutes a safe alternative to sigmoid resection for selected patients judged clinically to require surgery.
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| 13. |
- Ma, Wenjie, et al.
(författare)
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Cancer risk in patients with diverticular disease : A nationwide cohort study
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105.
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are little data on diverticular disease and cancer development other than colorectal cancer.Methods: We conducted a population-based, matched cohort study with linkage of nationwide registers to the Epidemiology Strengthened by histoPathology Reports in Sweden histopathology cohort. We included 75 704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313 480 reference individuals from the general population matched on age, sex, calendar year, and county. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) for associations between diverticular disease and overall cancer and specific cancers.Results: Over a median follow-up of 6 years, we documented 12 846 incident cancers among patients with diverticular disease and 43 354 incident cancers among reference individuals from the general population. Compared with reference individuals, patients with diverticular disease had statistically significantly increased overall cancer incidence (24.5 vs 18.1 per 1000 person-years), equivalent to 1 extra cancer case in 16 individuals with diverticular disease followed-up for 10 years. After adjusting for covariates, having a diagnosis of diverticular disease was associated with a 33% increased risk of overall cancer (95% confidence interval [CI] = 1.31 to 1.36). The risk increases also persisted compared with siblings as secondary comparators (HR = 1.26, 95% CI = 1.21 to 1.32). Patients with diverticular disease also had an increased risk of specific cancers, including colon cancer (HR = 1.71, 95% CI = 1.60 to 1.82), liver cancer (HR = 1.72, 95% CI = 1.41 to 2.10), pancreatic cancer (HR = 1.62, 95% CI = 1.42 to 1.84), and lung cancer (HR = 1.50, 95% CI = 1.39 to 1.61). The increase in colorectal cancer risk was primarily restricted to the first year of follow-up, and especially early cancer stages.Conclusions: Patients with diverticular disease who have colorectal histopathology have an increased risk of overall incident cancer.
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| 14. |
- Moberger, Peter, et al.
(författare)
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Evaluation of the Swedish Colorectal Cancer Registry : an overview of completeness, timeliness, comparability and validity
- 2018
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:12, s. 1611-1621
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish Colorectal Cancer Registry (SCRCR) is a national registry established in 1995 for rectal cancer, and also including colon cancer since 2007. Knowledge of the quality of the registry is vital in order to draw correct conclusions from studies based on the registry. The aim of this study was to assess the completeness, timeliness, comparability and validity of the SCRCR. Material and methods: Completeness, timeliness and comparability of the registry were estimated. From the SCRCR year 2008, 500 cases were randomly selected to examine the validity of the registry and 486 cases were retrieved. Using hospital patient records as source documents, 130 variables in the SCRCR were reabstracted using the SCRCR registration forms and then compared with the original files. Result: During the period 2008-2015, the average completeness of the SCRCR was 98.5% for colon cancer and 98.8% for rectal cancer. Timeliness improved between the years 2008 and 2015, with 98% of the patients registered within 12 months for the year 2015. For most of the variables, comparability was estimated to be reproducible and comparable with other registries. Regarding the validity of the registry, when comparing reabstracted data with the original SCRCR data, average agreement was 90%. Conclusion: The SCRCR can be considered a reliable registry useful for quality assurance and research. Standardization and improvements in journal documentation are needed to improve future evaluation of the source documents.
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| 15. |
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| 16. |
- Sakari, Thorbjörn B.
(författare)
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Adhesive small bowel obstruction: aspects on epidemiology, treatment, costs and prevention
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small bowel obstruction (SBO) is a common and sometimes life-threatening clinical condition, usually caused by post-operative adhesions. The aims of this thesis were to investigate the outcome after SBO surgery (Paper I), cost of SBO surgery including follow-up (Paper II), incidence of SBO after colorectal cancer (CRC) surgery (Paper III), and to assess the safety of using the adhesion preventing substance icodextrin in CRC surgery (Paper IV).Paper I, a population-based retrospective study on all patients operated for adhesive SBO (n=402) in the Uppsala and Gävleborg counties between 2007 and 2012. The SBO mechanism was a fibrous band in 56%. Complications and reoperations were recorded in 48% and 10% of patients, respectively. Complications, ICU care and early mortality were associated with age and ASA class. Seventy two patients had a recurrence of SBO, 26 of whom were re-operated. Previous laparotomies, diffuse adhesions, and complicated surgery (bowel injury, longer operation times and bleeding) were predictors of recurrent SBO. Paper II used the same cohort as in Paper I with an extended follow-up (8 years in median). Mean total cost estimates per patients were €40,467 during the study period. Diffuse adhesions and complications were associated with increased costs for SBO in a multivariable analysis (p<0.001).Paper III is a population-based register study based on all CRC cancer patients in Sweden 2007–2017. Among 33,632 CRC patients operated for stage I–III disease, the 5-year cumulative incidence was 7.6% for SBO and 2.2% for SBO surgery. In 198,649 matched CRC-free comparators the corresponding incidences were 0.6% and 0.2%, respectively. Open surgery and radiotherapy were associated with an increased incidence of SBO and SBO surgery. Paper IV is an interim analysis regarding morbidity and mortality, of a randomized controlled multicenter study assessing whether the adhesion preventing substance icodextrin can reduce the risk of postoperative SBO in stage I–III CRC patients. Randomization, to standard treatment with or without icodextrin, was blinded to the authors. Demographic data and overall complications were similar in the groups. Mortality, ICU care, anastomotic leaks and reoperations did not differ.
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| 17. |
- Sakari, Thorbjörn, et al.
(författare)
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Economic Consequences of Surgery for Adhesive Small Bowel Obstruction : A Population-Based Study
- 2023
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Ingår i: Gastroenterology Research and Practice. - : Hindawi Publishing Corporation. - 1687-6121 .- 1687-630X. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims. Most patients develop adhesions after abdominal surgery, some will be hospitalized with small bowel obstruction (SBO), and some also require surgery. The operations and follow-up are expensive, but recent data of costs are scarce. The aim of this study was to describe the direct costs of SBO-surgery and follow-up, in a population-based setting. The association between cost of SBO and peri- and postoperative data was also studied.Methods. In a retrospective cohort study, all patients (n = 402) operated for adhesive SBO in Gävleborg and Uppsala counties (2007–2012) were studied. The median follow-up was 8 years. Costs were calculated according to the pricelist of Uppsala University Hospital, Uppsala, Sweden.Results. Overall total costs were €16.267 million, corresponding to a mean total cost per patient of €40,467 during the studied period. Diffuse adhesions and postoperative complications were associated with increased costs for SBO in a multivariable analysis (P < 0.001). Most costs, about €14 million (85%), arouse in conjunction with the SBO-index surgery period. In-hospital stay was the dominating cost, accounting for 70% of the total costs.Conclusion. Surgery for SBO generates substantial economic burden for healthcare systems. Measures that reduce the incidence of SBO, the frequency of postoperative complication, or the length of stay have the potential to reduce this economic burden. The cost estimates from this study may be valuable for future cost–benefit analyses in intervention studies.
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| 18. |
- Sakari, Thorbjörn, et al.
(författare)
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Incidence of adhesive small bowel obstruction after surgery for colorectal cancer in Sweden 2007-2016
- 2024
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Ingår i: Colorectal Disease. - : John Wiley & Sons. - 1462-8910 .- 1463-1318. ; 26:2, s. 300-308
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Tidskriftsartikel (refereegranskat)abstract
- AimPopulation-based data on incidence and risk factors of adhesive small bowel obstruction (SBO) are limited. The aims of this study were to assess the risk of SBO and SBO surgery after bowel resection for colorectal cancer (CRC) and to assess whether this risk is modified by minimally invasive surgery (MIS) and radiotherapy in a retrospective national study.MethodsCRCBaSe, a nationwide register linkage originating from the Swedish Colorectal Cancer Register, was used to identify Stage I–III CRC patients who underwent resection in 2007–2016, with follow-up throughout 2017. Matched CRC-free comparators (1:6) were included as a reference of SBO and SBO surgery incidence. The association between MIS and preoperative radiotherapy and the incidence rate of SBO was evaluated in adjusted multivariable Cox regression models.ResultsAmong 33 632 CRC patients and 198 649 comparators, the 5-year cumulative incidence of SBO and SBO surgery was 7.6% and 2.2% among patients and 0.6% and 0.2% among comparators, with death as a competing risk. In all patients, MIS was associated with a reduced incidence of SBO (hazard ratio [HR] 0.7, 95% CI 0.6–0.8) and SBO surgery (HR 0.5, 95% CI 0.3–0.7). In rectal cancer patients, radiotherapy was associated with an increased incidence of SBO (HR 1.6, 95% CI 1.4–1.8) and SBO surgery (HR 1.7, 95% CI 1.3–2.3).DiscussionColorectal cancer surgery is associated with a marked increase in risk of SBO, compared with the general population. The incidence is further increased if open surgery or radiotherapy is performed.
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| 19. |
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| 20. |
- Sköldberg, Filip, et al.
(författare)
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A population-based case-control study on statin exposure and risk of acute diverticular disease
- 2016
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 51:2, s. 203-210
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. Material and methods: A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed <= 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. Results: A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17-1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]). Conclusions: The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease.
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| 21. |
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| 22. |
- Sköldberg, Filip, et al.
(författare)
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Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:4, s. 1636-1640
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. Three of 83 patients (3.6%) with autoimmune polyendocrine syndrome type 1 (APS1) were anti-CSAD positive in a radioimmunoprecipitation assay. Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. Moreover, CSAD may be a useful mold for the construction of recombinant chimerical antigens in attempts to map conformational epitopes on other group II PLP-dependent amino acid decarboxylases.
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| 23. |
- Sköldberg, Filip, et al.
(författare)
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Appendectomy and Risk of Subsequent Diverticular Disease Requiring Hospitalization : A Population-Based Case-Control Study
- 2018
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Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 61:7, s. 830-839
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Appendicitis and acute diverticulitis share clinical features and are both influenced by genetic and environmental factors. Appendectomy has been positively associated with diverticular disease in hospital-based case-control studies. OBJECTIVE: The aim of the present study was to investigate, in a population-based setting, whether appendectomy, with or without appendicitis, is associated with an altered risk of hospitalization with diverticular disease. DESIGN: This was a population-based case-control study. SETTINGS: The study was based on national healthcare and population registers. PATIENTS: We studied 41,988 individuals hospitalized between 2000 and 2010 with a first-time diagnosis of colonic diverticular disease and 413,115 matched control subjects. MAIN OUTCOME MEASURES: The association between appendectomy with or without appendicitis and diverticular disease was investigated by conditional logistic regression, including a model adjusting for hospital use. RESULTS: A total of 2813 cases (6.7%) and 19,037 controls (4.6%) had a previous record of appendectomy (appendectomy with acute appendicitis: adjusted OR = 1.31 (95% CI, 1.24-1.39); without appendicitis: adjusted OR = 1.30 (95% CI, 1.23-1.38)). Appendectomy was most strongly associated with an increased risk of diverticular disease within 1 year (with appendicitis: adjusted OR = 2.26 (95% CI, 1.61-3.16); without appendicitis: adjusted OR = 3.98 (95% CI, 2.71-5.83)), but the association was still present 20 years after appendectomy (with appendicitis: adjusted OR = 1.22 (95% CI, 1.12-1.32); without appendicitis: adjusted OR = 1.19 (95% CI, 1.10-1.28)). LIMITATIONS: Detailed clinical information on the cases was not available. There were unmeasured potential confounders, such as smoking and dietary factors. CONCLUSIONS: The findings are consistent with a hypothesis of appendectomy causing an increased risk of diverticular disease, for example, by affecting the mucosal immune system or the gut microbiome. However, several other mechanisms may contribute to, or account for, the positive association, including a propensity for abdominal pain increasing the risk of both the exposure and the outcome. See Video Abstract at http://links.lww.com/DCR/A604.
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| 24. |
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| 25. |
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| 26. |
- Sköldberg, Filip, et al.
(författare)
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Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells
- 2003
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 88:4, s. 1445-1452
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune polyendocrine syndrome type 1 often have autoantibodies against neurotransmitter synthesizing enzymes, including the pyridoxal phosphate-dependent enzymes glutamic acid decarboxylase and aromatic L-amino acid decarboxylase. Using a candidate approach, we have identified the histamine-synthesizing enzyme histidine decarboxylase, also pyridoxal phosphate dependent, as an autoantigen in this disorder. Anti-histidine decarboxylase antibodies reacting with in vitro translated antigen were found in 36/97 (37%) of autoimmune polyendocrine syndrome type 1 patients studied. The antibodies also reacted with the native enzyme in HMC-1 cell lysates and did not cross-react with the highly homologous aromatic L-amino acid decarboxylase. Anti-histidine decarboxylase antibodies were associated with a history of intestinal dysfunction (P = 0.017). Gastric and duodenal biopsies from a patient with anti-histidine decarboxylase antibodies were studied by immunohistochemistry. The oxyntic mucosa was found to lack the histamine producing enterochromaffin-like cells, suggestive of an autoimmune destruction. To our knowledge, this is the first report of autoantibodies against histidine decarboxylase and absence of gastric enterochromaffin-like cells.
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| 27. |
- Sköldberg, Filip, et al.
(författare)
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Identification of AHNAK as a novel autoantigen in systemic lupus erythematosus.
- 2002
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 291:4, s. 951-8
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Tidskriftsartikel (refereegranskat)abstract
- To identify candidate autoantigens associated with arthritis, a rat chondrocyte cDNA library was immunoscreened with serum from a patient with rheumatoid arthritis. One isolated cDNA encoded part of AHNAK, a 700-kDa phosphoprotein with DNA binding properties, that appears to be involved in several signal transduction pathways. Immunoreactivity against an in vitro translated human AHNAK fragment was detected in 4.6% (5/109) of patients with rheumatoid arthritis, 29.5% (18/61) of patients with systemic lupus erythematosus (SLE), and 1.2% (2/172) of blood donors. Anti-AHNAK antibodies reacted with a recombinant human AHNAK fragment and with native AHNAK from C32 cell lysates. In vitro translated AHNAK fragment could be cleaved by granzyme B and caspase-3. Anti-AHNAK positive SLE patients had a higher frequency of homogeneous antinuclear antibody staining patterns and a lower frequency of recent mucosal ulcerations. This is the first report that AHNAK can be targeted by the immune system in autoimmune disease.
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| 28. |
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| 29. |
- Sköldberg, Filip, et al.
(författare)
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Incidence and lifetime risk of hospitalization and surgery for diverticular disease
- 2019
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:7, s. 930-939
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies on incidence rates of first-time colonic diverticular disease are few, and population-based estimates of lifetime risk are lacking. In this observational study, the incidence, admission rates and lifetime risks of hospitalization and surgery for diverticular disease were investigated.Methods: Considering the entire Swedish population as an open cohort, incidence and admission rates, and lifetime risk estimates (considering death as a competing risk) of hospitalization and surgery for diverticular disease were calculated using data from cross-linked national registers and population statistics from 1987 to 2010.Results: In total, there were 144 107 hospital admissions for diverticular disease in 95 049 individual patients. Of these, 17 599 were admissions with bowel resection or stoma formation in 16 824 patients. The total number of person-years in the population during the study period was 213 949 897. Age-standardized incidence rates were 47.4 (95 per cent c. i. 47.1 to 47.7) for first-time hospitalization with diverticular disease and 8.4 (8.2 to 8.5) per 100 000 person-years for diverticular disease surgery. The corresponding admission rates (including readmissions) were 70.8 (70.4 to 71.2) and 8.7 (8.6 to 8.9) per 100 000 person-years. Following an increase in 1990-1994, rates stabilized. Based on incidence and mortality rates from 2000 to 2010, the estimated remaining lifetime risk of hospitalization from 30 years of age was 3.1 per cent in men and 5.0 per cent in women. The corresponding risk of surgery was 0.5 per cent in men and 0.8 per cent in women.Conclusion: Diverticular disease is a common reason for hospital admission, particularly in women, but rates are stable and the lifetime risk of surgery is low.
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| 30. |
- Sköldberg, Filip
(författare)
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Studies of Autoantibodies in Systemic and Organ-Specific Autoimmune Disease
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease, whereas autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal disorder characterized by combinations of organ-specific autoimmune manifestations including hypoparathyroidism and intestinal dysfunction, and may serve as a model for organ-specific autoimmunity. Autoantibodies directed against proteins expressed in the affected tissues are found in both diseases. From a chondrocyte cDNA expression library, we identified the protein AHNAK as an autoantigen in SLE. Anti-AHNAK antibodies were found in 29.5% (18/61) of patients with SLE, 4.6% (5/109) of patients with rheumatoid arthritis, and 1.2% (2/172) of blood donors. Using a candidate approach, we analyzed the prevalence in APS1 and other organ-specific autoimmune diseases, of autoantibodies against the pyridoxal phosphate-dependent enzymes histidine decarboxylase (HDC) and cysteine sulfinic acid decarboxylase (CSAD), which are structurally closely related to known autoantigens. Anti-HDC and anti-CSAD reactivity was detected exclusively in APS1 patient sera. Anti-HDC antibodies were detected in 37.1% (36/97) of the APS1 sera, did not cross-react with aromatic L-amino acid decarboxylase, and were associated with intestinal dysfunction and loss of histamine-producing gastric enterochromaffin-like cells. In contrast, anti-CSAD reactivity was detected in 3.6% (3/83) of APS1 sera and cross-reacted with recombinant glutamic acid decarboxylase. From a parathyroid cDNA expression library, novel spliced transcripts of the CLLD4 gene on human chromosome 13q14, encoding 26 and 31 kDa isoforms recognized by autoantibodies in 3.4% (3/87) of APS1 patients, were identified and found to be preferentially expressed in lung and ovary. Both isoforms contain an N-terminal BTB/POZ domain, similarly to the TNF-alpha-regulated protein B12, localize both to the cytoplasm and nucleus in transfected COS cells, and form oligomers in vitro. The CLLD4 gene is located in a region frequently deleted in several forms of cancer, including lung and ovarian tumors. In conclusion, we have identified and partially characterized AHNAK and HDC as two common targets of autoantibodies in SLE and APS1, respectively. We have also identified CSAD and CLLD4 as two minor autoantigens in APS1, one of which is a novel protein with unknown function.
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| 31. |
- Sköldberg, Håkan, et al.
(författare)
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BIO-CCS I FJÄRRVÄRMESEKTORN – SYNTES
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den svenska fjärrvärmesektorn har stor potential att bidra med negativa koldioxidutsläpp genom bio-CCS, minst 10 Mton per år. Den största osäkerheten beträffande möjligheterna för bio-CCS gäller marknads förutsättningarna. Uppvärmningsbranschen har en vision om att år 2045 utgöra en kolsänka. Ett sätt att åstadkomma detta är genom att avskilja och lagra koldioxidutsläpp med biogent ursprung. Ett antal fjärrvärmeföretag har redan olika långt gångna planer på att satsa på bio-CCS. De har sett ett värde i att samarbeta kring hur detta kan åstadkommas. Ett led i detta är projektet Bio-CCS i fjärrvärmesektorn som består av ett gediget underlag baserat på forskning kring olika aspekter av frågan samt en strategi baserad på det underlaget. I denna rapport redovisas en syntes av detta forskningsarbete. Projektet visar att fjärrvärmesektorn har stor teoretisk potential att bidra med negativa koldioxidutsläpp, minst 10 Mton per år. I huvudsak är avskiljning, transport och lagring av koldioxid beprövad teknik även om tillämpningen i detta fall är ny. Även om bio-CCS är förknippad med energianvändning så bidrar tekniken sett ur ett systemperspektiv med stor nytta för att minska koldioxid[1]utsläppen. Bio-CCS är en relativt dyr teknik och det är angeläget att utnyttja samverkan och kluster för att exempelvis skapa ökad kostnadseffektivitet i transport och mellanlagring. Tillgång till lagringsplatser är en förutsättning för framgång och flera alternativ bedöms bli tillgängliga. Det kan dock uppstå konkurrens om tillgången till lagringsplatserna. De regelmässiga förutsättningarna för bio-CCS i Sverige har förbättrats avsevärt de senaste dryga decenniet. Flera regelmässiga hinder kvarstår dock. En del utgör mindre barriärer, andra är av mer betydande karaktär. Den största osäkerheten beträffande möjligheterna för bio-CCS gäller ekonomin. Flera potentiella finansieringsmetoder har studerats, både stöd, regleringar och frivilligmarknader. Det finns fortfarande oklarheter kring syftet med planerade stöd och det framtida ägandet av de negativa utsläppen. Det genomförda projektet har skapat ett forum för kunskapsuppbyggnad, erfarenhetsutbyte och nätverkande, vilket de deltagande företagen bedömt vara mycket värdefullt.
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| 32. |
- Winge, Ingeborg, et al.
(författare)
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Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression
- 2015
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Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 90, s. 173-184
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Tidskriftsartikel (refereegranskat)abstract
- Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have been proposed to be involved in the pyridoxa1-5'-phosphate (PLP)-dependent biosynthesis of taurine. In the present study, we compared the catalytic properties, inhibitor sensitivity and expression profiles of GADL1 and CSAD in brain tissue. In mouse and human brain we observed distinct patterns of expression of the PLP-dependent decarboxylases CSAD, GADL1 and glutamic acid decarboxylase 67 (GAD67). CSAD levels were highest during prenatal and early postnatal development; GADL1 peaked early in prenatal development, while GAD67 increased rapidly after birth. Both CSAD and GADL1 are being expressed in neurons, whereas only CSAD mRNA was detected in astrocytes. Cysteine sulfinic acid was the preferred substrate for both mouse CSAD and GADL1, although both enzymes also decarboxylated cysteic acid and aspartate. In silica screening and molecular docking using the crystal structure of CSAD and in vitro assays led to the discovery of eight new enzyme inhibitors with partial selectivity for either CSAD or GADL1. Lithium had minimal effect on their enzyme activities. In conclusion, taurine biosynthesis in vertebrates involves two structurally related PLP-dependent decarboxylases (CSAD and GADL1) that have partially overlapping catalytic properties but different tissue distribution, indicating divergent physiological roles. Development of selective enzyme inhibitors targeting these enzymes is important to further dissect their (patho)physiological roles.
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