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- Andersson, Manne, et al.
(författare)
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Structured Management of Patients with Suspected Acute Appendicitis Using a Clinical Score and Selective Imaging (STRAPPSCORE)
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe management of patients with suspected appendicitis is highly variable with implications for the rate of diagnostic errors, unnecessary admissions and resource consumption. We hypothesise that a structured management algorithm based on the Appendicitis Inflammatory Response (AIR) score can improve diagnostic accuracy, limit the use of diagnostic imaging, and reduce the number of hospital admissions for patients with suspected appendicitis.MethodsProspective interventional multicentre study. Patients at 25 Swedish hospitals over the age of five, presenting with suspected appendicitis at the emergency department were considered for inclusion. After an initial period of routine management and registration of the AIR score parameters (baseline period), an AIR-score-based management algorithm was implemented (intervention period). The study analyses the discriminating capacity and predictive value of the AIR score and the impact of implementing the AIR-score-based algorithm.ResultsIn total, 3791 patients were included. Advanced appendicitis is unlikely at an AIR score <5 points (sensitivity 0.96), and appendicitis is likely at an AIR score >8 (specificity 0.98). The implementation of the AIR-score-based algorithm resulted in fewer negative explorations and operations for phlegmonous appendicitis (1.6% vs 3.4%, p=0.019 and 5.5% vs 9.4%, p=0.003, respectively), a reduction in admissions to hospital and use of imaging (29.5% vs 42.8%, p<0.001 and 19.2% vs 34.5%, respectively), and no difference with regard to advanced appendicitis in the low-risk group, and a decrease in the use of diagnostic imaging in the high-risk group (38.5% vs 53.1%, p=0.021).ConclusionsThe AIR score has high discriminating capacity. Implementing an AIR-score-based algorithm increased diagnostic accuracy and lowered the use of diagnostic imaging and in-hospital observation.
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| 2. |
- Andersson, Manne, et al.
(författare)
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Validation of the Appendicitis Inflammatory Response (AIR) Score
- 2021
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 45:7, s. 2081-2091
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with suspicion of appendicitis present with a wide range of severity. Score-based risk stratification can optimise the management of these patients. This prospective study validates the Appendicitis Inflammatory Response (AIR) score in patients with suspicion of appendicitis. Method Consecutive patients over the age of five with suspicion of appendicitis presenting at 25 Swedish hospitals emergency departments were prospectively included. The diagnostic properties of the AIR score are estimated. Results Some 3878 patients were included, 821 with uncomplicated and 724 with complicated appendicitis, 1986 with non-specific abdominal pain and 347 with other diagnoses. The score performed better in detecting complicated appendicitis (ROC area 0.89 (95% confidence interval (CI) 0.88-0.90) versus 0.83 (CI 0.82-0.84) for any appendicitis, p < 0.001), in patients below age 15 years and in patients with >47 h duration of symptoms (ROC area 0.93, CI 0.90-0.95 for complicated and 0.87, CI 0.84-0.90 for any appendicitis in both categories). Complicated appendicitis is unlikely at AIR score <4 points (Negative Predictive Value 99%, CI 98-100%). Appendicitis is likely at AIR score >8 points, especially in young patients (positive predictive value (PPV) 96%, CI 90-100%) and men (PPV 89%, CI 84-93%). Conclusions The AIR score has high sensitivity for complicated appendicitis and identifies subgroups with low probability of complicated appendicitis or high probability of appendicitis. The discriminating capacity is high in children and patients with long duration of symptoms. It performs equally well in both sexes. This verifies the AIR score as a valid decision support.
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| 3. |
- Dimberg, Jan, et al.
(författare)
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Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:9, s. 4933-4940
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.
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| 4. |
- Shamoun, Levar, 1979-
(författare)
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Investigation of immune cell-derived factors as potential biomarkers in patients with colorectal cancer
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related death. It is a heterogeneous disease involving multiple molecular pathways that result in differing phenotypes. Individual variability in CRC susceptibility is influenced by genetic variation, such as single nucleotide polymorphisms (SNPs). Changes in genetics and epigenetics can disrupt intact signalling pathways involved in metabolism, proliferation, differentiation, and apoptosis. Inflammatory factors such as cytokines and chemokines, as well as their receptors, play important roles in immune regulation.In Papers I, II and III, selected SNPs in the genes of interleukin (IL)-4, IL-13, IL-2 or chemokine C-C motif ligand (CCL) 4 in patients with CRC were investigated to determine their prognostic significance by identifying associations with various clinicopathological parameters and long-term survival. The investigated IL-13 and IL-4 SNPs were found to be risk factors for CRC and could be useful potential prognostic markers in CRC patient follow-up and clinical management. The investigated IL-2 SNPs were significantly associated with an increased risk of CRC and worse cancer-specific survival in patients with stage II or stage III CRC.In Paper III, levels of CCL4 protein were measured in CRC patients to investigate their prognostic significance for CRC. The data showed that CRC tissue had a higher protein expression than normal paired tissue, and plasma CCL4 levels were higher in patients than in controls, being positively correlated with CRC tissue levels. Further, higher levels of tissue CCL4 protein were linked to a lower disease stage and a better prognosis.Paper IV was an investigation of the expression of zinc finger MYND-type containing 15 (zmynd15) and its roles in CRC. In CRC tissue, protein expression was found primarily in cluster of differentiation (CD) 68 positive cells. Zmynd15 messenger ribonucleic acid expression was lower in CRC tissue than in non-cancerous tissue. When zmynd15 was silenced in CRC cell lines, it caused alteration in genes known to be important in CRC, indicating that zmynd15-regulated genes are involved in CRC. Furthermore, tumour development in the colon was higher in zmynd15 knockout mice than in wild-type mice.In conclusion, the work presented in this thesis contributes to an understanding of the association of inflammatory markers in CRC with risk and survival, and their potential use as tools for monitoring CRC patients. In addition, it showed that zmynd15, a transcriptional suppressor, plays an important role in the development of CRC.
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| 5. |
- Shamoun, Levar, et al.
(författare)
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Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients
- 2018
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:1, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility.Materials and Methods: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-a (TNFa) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331).Results: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNFa, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. Conclusion. Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.
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