Upsala journal of medical sciences最新文献

{"title":"Anatomical and subcortical invasiveness in diffuse low-grade astrocytomas differ between IDH status and provide prognostic information.","authors":"Maria Zetterling, Markus Fahlström, Francesco Latini","doi":"10.48101/ujms.v129.10799","DOIUrl":"10.48101/ujms.v129.10799","url":null,"abstract":"<p><strong>Background: </strong>Diffuse astrocytomas preferentially infiltrate eloquent areas affecting the outcome. A preoperative understanding of isocitrate dehydrogenase (IDH) status may offer opportunities for specific targeted therapies impacting treatment management. The aim of this study was to analyze clinical, topographical, radiological in WHO 2 astrocytomas with different IDH status and the long-term patient's outcome.</p><p><strong>Methods: </strong>A series of confirmed WHO 2 astrocytoma patients (between 2005 and 2015) were retrospectively analyzed. MRI sequences (FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations into the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was used as an overlay for infiltration analysis of each tumor. Long-term follow-up was used to perform a survival analysis.</p><p><strong>Results: </strong>Forty patients with confirmed IDH status (26 IDH-mutant, IDHm/14 IDH-wild type, IDHwt) according to WHO 2021 classification were included with a mean follow-up of 7.8 years. IDHm astrocytomas displayed a lower number of BG-voxels (<i>P</i> < 0.05) and were preferentially located in the anterior insular region. IDHwt group displayed a posterior insular and peritrigonal location. IDHwt group displayed a shorter OS compared with IDHm (<i>P</i> < 0.05), with the infiltration of 7 or more BG-voxels as an independent factor predicting a shorter OS.</p><p><strong>Conclusions: </strong>IDHm and IDHwt astrocytomas differed in preferential location, number of BG-voxels and OS at long follow-up time. The number of BG-voxels affected the OS in IDHwt was possibly reflecting higher tumor invasiveness. We encourage the systematic use of alternative observational tools, such as gradient maps and the Brain-Grid analysis, to better detect differences of tumor invasiveness in diffuse low-grade gliomas subtypes.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"129 ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central obesity and fat-free mass are associated with a larger spleen volume in the general population.","authors":"Mohammed Farah Mahmoud Mousa, Muhammad Naeem, Saima Bibi, Robin Bülow, Martin Bahls, Ulrike Siewert-Markus, Philipp Töpfer, Ali Aghdassi, Muhammad Nasir Khan Khattak, Henry Völzke, Marcello Rp Markus, Till Ittermann","doi":"10.48101/ujms.v129.10465","DOIUrl":"10.48101/ujms.v129.10465","url":null,"abstract":"<p><strong>Background and aim: </strong>As the spleen plays a significant role in immunity, the aim was to investigate the associations of different body composition markers derived from various sources with spleen volume in a general population sample.</p><p><strong>Materials and methods: </strong>Cross-sectional data of 1095 individuals (570 women; 52%) aged between 30 and 90 years were collected in the Study of Health in Pomerania (SHIP-START-2). We measured spleen volume by magnetic resonance imaging (MRI).Body composition markers were derived from classic anthropometry, bioelectrical impedance analysis, including absolute fat mass (FM) and fat-free mass (FFM), as well as from MRI, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat content. Sex-stratified-adjusted linear regression models were used to analyze the associations of body composition markers with spleen volumes.</p><p><strong>Results: </strong>We observed positive associations of body mass index, body weight, waist circumference, hip circumference, waist-to-height ratio, absolute FM, absolute FFM, and VAT and SAT with spleen volume in men and women. An 8.12 kg higher absolute FFM was associated with a 38.4 mL (95% confidence interval [CI]: 26.7-50.1) higher spleen volume in men and a 5.21 kg higher absolute FFM with a 42.6 mL (95% CI: 26.2-59.0) higher spleen volume in women.</p><p><strong>Conclusion: </strong>Our findings indicate that obesity-related body composition markers and FFM are associated with a higher spleen volume. Particularly, higher absolute FFM showed a strong association with a larger spleen volume in both men and women. Further studies are warranted to understand the clinical significance of body composition markers on large spleen volume.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"129 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic targeting of <i>TP53</i> nonsense mutations in cancer.","authors":"Charlotte Strandgren, Klas G Wiman","doi":"10.48101/ujms.v129.10719","DOIUrl":"10.48101/ujms.v129.10719","url":null,"abstract":"<p><p>Mutations in the <i>TP53</i> tumor suppressor gene occur with high prevalence in a wide range of human tumors. A significant fraction of these mutations (around 10%) are nonsense mutations, creating a premature termination codon (PTC) that leads to the expression of truncated inactive p53 protein. Induction of translational readthrough across a PTC in nonsense mutant <i>TP53</i> allows the production of full-length protein and potentially restoration of normal p53 function. Aminoglycoside antibiotics and a number of novel compounds have been shown to induce full-length p53 in tumor cells carrying various <i>TP53</i> nonsense mutations. Full-length p53 protein generated by translational readthrough retains the capacity to transactivate p53 target genes and trigger tumor cell death. These findings raise hopes for efficient therapy of <i>TP53</i> nonsense mutant tumors in the future.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"129 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions between cancer-associated fibroblasts and T-cells: functional crosstalk with targeting and biomarker potential.","authors":"Vladan Milosevic, Arne Östman","doi":"10.48101/ujms.v129.10710","DOIUrl":"10.48101/ujms.v129.10710","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population recognized as a key component of the tumour microenvironment (TME). Cancer-associated fibroblasts are known to play an important role in maintaining and remodelling the extracellular matrix (ECM) in the tumour stroma, supporting cancer progression and inhibiting the immune system's response against cancer cells. This review aims to summarize the immunomodulatory roles of CAFs, particularly focussing on their T-cell suppressive effects. Cancer-associated fibroblasts have several ways by which they can affect the tumour's immune microenvironment (TIME). For example, their interactions with macrophages and dendritic cells (DCs) create an immunosuppressive milieu that can indirectly affect T-cell anticancer immunity and enable immune evasion. In addition, a number of recent studies have confirmed CAF-mediated direct suppressive effects on T-cell anticancer capacity through ECM remodelling, promoting the expression of immune checkpoints, cytokine secretion and the release of extracellular vesicles. The consequential impact of CAFs on T-cell function is then reflected in affecting T-cell proliferation and apoptosis, migration and infiltration, differentiation and exhaustion. Emerging evidence highlights the existence of specific CAF subsets with distinct capabilities to modulate the immune landscape of TME in various cancers, suggesting the possibility of their exploitation as possible prognostic biomarkers and therapeutic targets.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"129 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in rectal cancer treatment - are we on the right track?","authors":"Bengt Glimelius","doi":"10.48101/ujms.v129.10537","DOIUrl":"10.48101/ujms.v129.10537","url":null,"abstract":"<p><strong>Background: </strong>Staging and treatment of rectal cancer have evolved over several decades with considerably fewer locoregional recurrences but no marked improved survival since systemic recurrence risks remain virtually unchanged. This development will briefly be summarised followed by a thorough discussion of two recent developments.</p><p><strong>Methods: </strong>A systematic approach towards the literature is aimed at focusing on organ preservation and the delivery of all non-surgical treatments prior to surgery or total neoadjuvant treatment (TNT).</p><p><strong>Results: </strong>Organ preservation, that is to defer surgery if the tumour happens to disappear completely after any pre-treatment given to locally advanced tumours to decrease recurrence risks has increased in popularity and is, if not universally, widely accepted. To give neo-adjuvant treatment to intentionally obtain a clinically complete remission to avoid surgery is practised in some environments but is mostly still experimental. TNT, that is to provide both radiotherapy and chemotherapy aimed at killing microscopic disease in the pelvis or elsewhere has been subject to several trials. Collectively, they show that the chance of achieving a complete response, pathologically or clinically, has approximately doubled, increasing the chance for organ preservation, and the risk of distant metastasis has decreased at least in some trials. The best schedule remains to be established.</p><p><strong>Conclusions: </strong>To obtain substantial progress and also improve survival, the systemic treatments need to be improved even if preoperative delivery is more effective and better tolerated than postoperative. The locoregional treatment may be further optimised through better risk prediction.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"129 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective nationwide analysis of evolocumab use in Sweden and its effect on low-density lipoprotein cholesterol levels.","authors":"Maria K Svensson, Stefan James, Annica Ravn-Fischer, Guillermo Villa, Lovisa Schalin, Thomas Cars, Stefan Gustafsson, Emil Hagström","doi":"10.48101/ujms.v129.9618","DOIUrl":"10.48101/ujms.v129.9618","url":null,"abstract":"<p><strong>Background: </strong>Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduces low-density lipoprotein cholesterol (LDL-C) levels and decreases the incidence of major ischaemic events in clinical trials. However, less is known about the efficacy of PCSK9 inhibition in clinical practice. This study aimed to describe the change in LDL-C levels over time and LDL-C goal achievement in patients with/without atherosclerotic cardiovascular disease (ASCVD), who were prescribed evolocumab in clinical practice, and to describe adherence to and persistence with treatment.</p><p><strong>Methods: </strong>Patients in Sweden with at least one evolocumab prescription filled between July 2015 and May 2020 were included. Medical history and lipid-lowering therapy (LLT) were sourced from national registries. LDL-C levels before and after treatment initiation were assessed using medical records. Persistence with and adherence to evolocumab and oral LLT were assessed up to 12 months after treatment initiation using the refill-gap method and proportion of days covered, respectively.</p><p><strong>Results: </strong>Of the 2,360 patients with at least one prescription for evolocumab, 2,341 were included; 1,858 had ASCVD. Persistence with (76%) and adherence to (86%) evolocumab were high throughout the 12 months following initiation. Mean LDL-C levels decreased by 53% (95% confidence interval [CI]: 51-55%) in patients adherent to evolocumab (<i>n</i> = 567) and 59% (95% CI: 55-63%) in patients adherent to evolocumab and oral LLT (<i>n</i> = 186). Similar reductions in LDL-C were observed in patients with/without ASCVD. Reduced LDL-C levels remained stable during follow-up. Amongst patients adherent to evolocumab and those adherent to evolocumab and oral LLT, 23 and 55% achieved the LDL-C goal of <1.4 mmol/L, respectively.</p><p><strong>Conclusions: </strong>The evolocumab LDL-C-lowering effect observed in clinical trials was confirmed in clinical practice in Sweden, particularly in patients also treated with oral LLT. During follow-up, adherence to and persistence with evolocumab were high, with stable reduced levels of LDL-C during observation.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"129 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.","authors":"Kajsa Björner, Wei-Na Chen, Venkata Ram Gannavarapu, Fredrik Axling, Miklos Gulyas, Mohammad Abdul Halim, Dominic-Luc Webb, Per M Hellström","doi":"10.48101/ujms.v128.10241","DOIUrl":"10.48101/ujms.v128.10241","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown.</p><p><strong>Aim: </strong>The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC.</p><p><strong>Methods: </strong>Immunohistochemistry was performed on tissue sections as follows: CAC (<i>n</i> = 59); sporadic CRC (sCRC) (<i>n</i> = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (<i>n =</i> 22); paracancerous IBD (pIBD) (<i>n =</i> 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases.</p><p><strong>Results: </strong>Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (<i>P</i> < 0.01) and IL-1β (<i>P</i> < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (<i>P</i> < 0.001), whereas IL-1β was higher (<i>P</i> < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases.</p><p><strong>Conclusion: </strong>Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"28 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A temporary regulation to manage an impending shortage due to extraordinary prescribing patterns of chloroquines observed during early phase of COVID-19 epidemic.","authors":"Karl-Mikael Kälkner, Anders Sundström, Maria Juhasz Haverinen, Kenneth Nordback, Veronica Arthurson, Björn Zethelius, Rickard Ljung","doi":"10.48101/ujms.v128.10033","DOIUrl":"10.48101/ujms.v128.10033","url":null,"abstract":"<p><strong>Background: </strong>Chloroquine and hydroxychloroquine (C/HC) received considerable international media attention due to anticipated treatment effect in COVID-19. This led to increased prescriptions threatening to generate product shortages for patients prescribed within approved indications.We evaluated effects of a temporary regulation mandating pharmacies to only dispense C/HC prescribed by physicians with defined specialties.</p><p><strong>Methods: </strong>Data from Region Stockholm, which include 2.4 out of 10 million Sweden's population, were used. Weekly time trends of prescriptions and requisitions of C/HC by prescriber's workplace during January to April 2020 were followed.</p><p><strong>Results: </strong>Numbers of unique individuals with filled prescriptions of chloroquine increased tenfold and of hydroxychloroquine more than threefold from January to March. In the first week of April, filled prescriptions of C/HC dropped. In the later weeks of April, the number of filled prescriptions was back at similar levels as before the SARS-CoV-2 outbreak.During January and February, specialists in rheumatology accounted for 686 out of all 979 prescriptions dispensed (70.1%) of C/HC. In March, a large proportion of prescriptions dispensed were from specialists not usually prescribing C/HC, and rheumatology accounted for 628 out of all 1,639 prescriptions (38.3%). In April, specialists in rheumatology accounted for 386 out of all 641 prescriptions dispensed (60.0%).</p><p><strong>Conclusion: </strong>After an observed increase in prescriptions of C/HC, a temporary regulation was introduced on 2nd April 2020 to reduce prescriptions from specialists not usually prescribing C/HC to avoid shortages for patients within approved indications. Subsequently, dispensed prescriptions decreased from April and remained at pre-COVID-19 levels thereafter.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-dependent regulation of kidney mitochondrial function by angiotensin II","authors":"Ebba Sivertsson, Amanda Balboa, Tomas A. Schiffer, P. Hansell, M. Friederich‐Persson, P. Persson, Fredrik Palm","doi":"10.48101/ujms.v128.10312","DOIUrl":"https://doi.org/10.48101/ujms.v128.10312","url":null,"abstract":"Background: Intrarenal hypoxia has been suggested a unifying pathway to chronic kidney disease (CKD) and increased mitochondria leak respiration, which increases mitochondrial oxygen usage and is one important mechanism contributing to the development of the hypoxia. Previous studies indicate that angiotensin II (Ang II) effects on mitochondria function could be dose dependent. We investigated how moderate and high levels of Ang II affect kidney mitochondria function and pathways of leak respiration. \u0000Methods: C57 black 6 mice were treated with either vehicle or Ang II in low dose (400 ng/kg/min) or high dose (1,000 ng/kg/min) for 4 weeks. The function of kidney cortex mitochondria was measured by high-resolution respirometry. Ang II effects on gene expression in kidney tissue were measured by quantitative real-time PCR. Thiobarbituric acids reactive substances were determined as a marker of oxidative stress, and urinary protein excretion was measured as a maker of kidney injury. \u0000Results: Low-dose Ang II induced overall mitochondria respiration, without compromising capacity of ATP production. Mitochondrial leak respiration was increased, and levels of oxidative stress were unchanged. However, high-dose Ang II decreased overall mitochondria respiration and reduced mitochondrial capacity for ATP production. Mitochondrial leak respiration was decreased, and oxidative stress increased in kidney tissue. Furthermore, gene expression of mediators that stimulate vasoconstriction and ROS production was increased, while components of counteracting pathways were decreased. \u0000Conclusions: In conclusion, Ang II dose-dependently affects mitochondrial function and leak respiration. Thus, Ang II has the potential to directly affect cellular metabolism during conditions of altered Ang II signaling.","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"8 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reference values of serum total IgE in Uppsala – comparison over four decades","authors":"R. Movérare, Eilif Persson, A. Malinovschi, Christer Janson","doi":"10.48101/ujms.v128.9892","DOIUrl":"https://doi.org/10.48101/ujms.v128.9892","url":null,"abstract":"Background Total immunoglobulin E (IgE) analysis is a common tool in allergy diagnosis. Suggested reference values for IgE are divergent and sometimes based on outdated assay methods. We aimed to validate the published reference values (geometric mean [GM]: 13.2 kU/L, upper limit of normal [ULN], 114 kU/L) shown in an Uppsala cohort from 1974 using Phadebas IgE PRIST, and the suggested clinical threshold of 100 kU/L (Zetterström and Johansson 1981). Methods Immunoglobulin E was measured in two Uppsala cohorts from 1997 (Blood bank) and 2011 to 2013 (the European community respiratory health survey part III [ECRHS III]) using ImmunoCAP™ Total IgE. For the reference value calculations, exclusion criteria were atopy (both cohorts), doctor’s diagnosis of asthma and self-reported allergy (hay fever, rhinitis, rash) (only ECRHS III). Upper limit of normal was defined as mean + 2 standard deviations (SD) calculated using log-transformed values and back-transformation of the ULN prior to presentation. Common imputation methods for results below the assay range were evaluated. Results The average GM was 14.2 kU/L (Blood bank, n = 63; imputation method range: 16.9–17.4 kU/L; ECRHS III, n = 113: 10.7–11.6 kU/L) and the overall mean ULN was 118 kU/L (Blood bank: 113–130 kU/L; ECRHS III: 104–128 kU/L). The clinical sensitivity and specificity of the 100 kU/L IgE threshold were 37.8 and 94.3% for atopy, 34.9 and 89.5% for doctor’s diagnosis of asthma, and 24.5 and 97.3% for any self-reported allergy (ECRHS III). Conclusion The calculated ULN values were similar between the cohorts. We conclude that the total IgE reference values shown for Uppsala subjects from 1974 are still valid and suitable also for the ImmunoCAP Total IgE assay. The 100 kU/L threshold for total IgE had a low sensitivity but high specificity for atopy, asthma, and allergy.","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"40 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138588489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}