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High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival. 高iNOS和IL-1β免疫反应是结肠炎相关结直肠癌肿瘤的特征,但不能预测5年生存率。
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-01-02 eCollection Date: 2023-01-01 DOI: 10.48101/ujms.v128.10241
Kajsa Björner, Wei-Na Chen, Venkata Ram Gannavarapu, Fredrik Axling, Miklos Gulyas, Mohammad Abdul Halim, Dominic-Luc Webb, Per M Hellström

Background: 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.

Aim: 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.

Methods: Immunohistochemistry was performed on tissue sections as follows: CAC (n = 59); sporadic CRC (sCRC) (n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (n = 22); paracancerous IBD (pIBD) (n = 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.

Results: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (P < 0.01) and IL-1β (P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (P < 0.001), whereas IL-1β was higher (P < 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.

Conclusion: 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.

背景:炎症性肠病(IBD,主要是溃疡性结肠炎和克罗恩病)与结直肠癌(CRC)的发生有关,被称为结肠炎相关性结直肠癌(CAC)。在 IBD 炎症发作时,由于炎症组织中的诱导型一氧化氮合酶(iNOS)活性增加,管腔一氧化氮(NO)的产生也随之增加。据认为,iNOS 与促炎症的白细胞介素-1β(IL-1β)相似。目的:本研究的主要目的是研究 iNOS 和 IL-1β 在 CAC 肿瘤中的免疫反应,并与 CRC 和正常结肠粘膜进行比较;次要目的是确定免疫反应是否与 CAC 的 5 年生存率相关:方法:对以下组织切片进行免疫组化:方法:对以下组织切片进行免疫组化:CAC(n = 59);散发性 CRC(sCRC)(n = 12);sCRC 边缘外大于 2 厘米的结肠粘膜(正常粘膜)(n = 22);癌旁 IBD(pIBD)(n = 12)。iNOS和IL-1β的表达分别在上皮和基质中量化。数据采用 Mann-Whitney U 检验和 5 年 Kaplan-Meier 生存曲线的 log-rank 检验进行评估。结果与在线 mRNA 数据库进行了比较:结果:免疫反应主要发生在上皮细胞,其次是基质。与正常粘膜相比,CAC上皮细胞中iNOS(P < 0.01)和IL-1β(P < 0.005)的免疫反应性更高。在CAC基质中,iNOS的免疫oreactivity低于正常粘膜(P < 0.001),而IL-1β则高于正常粘膜(P < 0.05)。CAC患者的iNOS或IL-1β免疫活性差异与5年生存率无关。这些发现得到了在线 mRNA 数据库的支持:结论:与 IBD 中产生大量 NO 的情况一致,CAC 上皮细胞中有更多的 iNOS,但基质中没有。上皮细胞和基质中的 IL-1β 也存在这种免疫反应差异。精氨酸或 iNOS 活性对 CAC 化疗的干预并不直接。
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引用次数: 0
A temporary regulation to manage an impending shortage due to extraordinary prescribing patterns of chloroquines observed during early phase of COVID-19 epidemic. 由于在 COVID-19 流行病早期阶段观察到氯喹的特殊处方模式,为管理即将出现的短缺而制定的临时条例。
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-12-31 eCollection Date: 2023-01-01 DOI: 10.48101/ujms.v128.10033
Karl-Mikael Kälkner, Anders Sundström, Maria Juhasz Haverinen, Kenneth Nordback, Veronica Arthurson, Björn Zethelius, Rickard Ljung

Background: 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.

Methods: 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.

Results: 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%).

Conclusion: 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.

背景:由于COVID-19的预期治疗效果,氯喹和羟氯喹(C/HC)受到了国际媒体的广泛关注。我们评估了一项临时法规的效果,该法规规定药店只能配发由特定专业医生开具的 C/HC 处方:我们使用了斯德哥尔摩地区的数据,该地区的人口占瑞典 1,000 万人口的 2.4%。方法:使用斯德哥尔摩地区的数据,该地区包括瑞典 1,000 万人口中的 240 万人,并跟踪调查了 2020 年 1 月至 4 月期间按处方者工作地点分列的 C/HC 处方和申购的每周时间趋势:结果:从 1 月到 3 月,开出氯喹处方的人数增加了 10 倍,开出羟氯喹处方的人数增加了 3 倍多。4 月份的第一周,已开具的氯喹/羟氯喹处方数量有所下降。在 4 月的后几周,已配处方的数量恢复到了与 SARS-CoV-2 爆发前相似的水平。在 1 月和 2 月期间,风湿病专科医生开出的 979 张 C/HC 处方中,有 686 张(占 70.1%)是由风湿病专科医生开出的。三月份,大部分处方来自通常不开具 C/HC 处方的专科医生,在所有 1,639 张处方中,风湿病科占 628 张(38.3%)。四月份,风湿病专科医生开出的处方占所有 641 张处方中的 386 张(60.0%):结论:在观察到 C/HC 处方增加后,2020 年 4 月 2 日出台了一项临时规定,减少通常不开 C/HC 处方的专科医生的处方,以避免批准适应症内的患者用药短缺。随后,配药处方从 4 月份开始减少,之后保持在 COVID-19 前的水平。
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引用次数: 0
Dose-dependent regulation of kidney mitochondrial function by angiotensin II 血管紧张素 II 对肾线粒体功能的剂量依赖性调节
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-12-21 DOI: 10.48101/ujms.v128.10312
Ebba Sivertsson, Amanda Balboa, Tomas A. Schiffer, P. Hansell, M. Friederich‐Persson, P. Persson, Fredrik Palm
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. Methods: 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. Results: 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. Conclusions: 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.
背景:肾小球内缺氧被认为是慢性肾脏病(CKD)的一个统一途径,线粒体漏式呼吸增加,线粒体耗氧量增加,是导致缺氧发生的一个重要机制。先前的研究表明,血管紧张素 II(Ang II)对线粒体功能的影响可能与剂量有关。我们研究了中等和高浓度的 Ang II 如何影响肾脏线粒体功能和泄漏呼吸途径。研究方法用低剂量(400 纳克/千克/分钟)或高剂量(1,000 纳克/千克/分钟)的药物或 Ang II 治疗 C57 black 6 小鼠 4 周。通过高分辨率呼吸测定法测量肾皮质线粒体的功能。血管紧张素 II 对肾脏组织基因表达的影响通过实时定量 PCR 进行测量。测定硫代巴比妥酸活性物质作为氧化应激的标志,测定尿蛋白排泄量作为肾损伤的标志。结果小剂量 Ang II 可诱导线粒体的整体呼吸,但不影响 ATP 的生成能力。线粒体漏呼吸增加,氧化应激水平保持不变。然而,大剂量 Ang II 降低了线粒体的整体呼吸,并降低了线粒体产生 ATP 的能力。在肾组织中,线粒体泄漏呼吸减少,氧化应激增加。此外,刺激血管收缩和 ROS 生成的介质基因表达增加,而抵消途径的成分减少。结论总之,Ang II 会对线粒体功能和泄漏呼吸产生剂量依赖性影响。因此,在 Ang II 信号改变的条件下,Ang II 有可能直接影响细胞代谢。
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引用次数: 0
Reference values of serum total IgE in Uppsala – comparison over four decades 乌普萨拉的血清总 IgE 参考值 - 四十年间的比较
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-12-08 DOI: 10.48101/ujms.v128.9892
R. Movérare, Eilif Persson, A. Malinovschi, Christer Janson
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.
背景总免疫球蛋白E (IgE)分析是过敏症诊断的常用工具。建议的IgE参考值存在分歧,有时是基于过时的检测方法。我们的目的是验证发表的参考值(几何平均值[GM]: 13.2 kU/L,正常上限[ULN], 114 kU/L)在1974年乌普sala队列中使用Phadebas IgE PRIST显示,以及建议的临床阈值为100 kU/L (Zetterström和Johansson 1981)。方法采用ImmunoCAP™总IgE检测1997年(血库)和2011 - 2013年(欧洲共同体呼吸健康调查第三部分[ECRHS III])两个乌普萨拉队列的免疫球蛋白E。对于参考值计算,排除标准是特应性(两个队列)、医生诊断的哮喘和自我报告的过敏(花粉热、鼻炎、皮疹)(仅ECRHS III)。正常的上限定义为平均值+ 2标准差(SD),使用对数转换值和就诊前ULN的反向转换计算。评估了低于测定范围的结果的常见归算方法。结果平均GM为14.2 kU/L(血库,n = 63;估算方法范围:16.9-17.4 kU/L;ECRHS III, n = 113: 10.7-11.6 kU/L),总体平均ULN为118 kU/L(血库:113 - 130 kU/L;ECRHS III: 104-128 kU/L)。100 kU/L IgE阈值对特应性的临床敏感性和特异性分别为37.8和94.3%,对医生诊断的哮喘的临床敏感性和特异性分别为34.9和89.5%,对任何自报告过敏的临床敏感性和特异性分别为24.5和97.3% (ECRHS III)。结论各队列间计算的ULN值相似。我们得出结论,1974年乌普萨拉受试者的总IgE参考值仍然有效,也适用于免疫cap总IgE测定。100 kU/L的总IgE阈值对特应性、哮喘和过敏敏感性低,但特异性高。
{"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}
引用次数: 0
Recreational use of nitrous oxide causes seizure, pneumothorax, pneumomediastinum, and pneumopericardium: nitrous oxide and its harm, a case report 娱乐性使用一氧化二氮导致癫痫发作、气胸、气胸和心包积气:一氧化二氮及其危害,病例报告
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-12-08 DOI: 10.48101/ujms.v128.10281
Lee Ti Davidson
Nitrous oxide, commonly known as ‘laughing gas’, has become a popular recreational drug. Whippets, small canisters containing gas in pressurized form, can be easily obtained from a food store. However, inhaling nitrous oxide from these canisters, which contain a 100% concentration, can lead to hypoxia, resulting in seizures or even death. Inhalation of nitrous oxide rarely causes pneumothorax, pneumomediastinum, and pneumopericardium. This case study highlights the potential dangers of recreational abuse of nitrous oxide.
一氧化二氮,俗称“笑气”,已经成为一种流行的娱乐性毒品。Whippets是一种装有加压形式气体的小罐,可以很容易地从食品商店获得。然而,从这些含有100%浓度的氧化亚氮罐中吸入氧化亚氮会导致缺氧,导致癫痫发作甚至死亡。吸入一氧化二氮很少引起气胸、纵隔气和心包气。这个案例研究强调了娱乐性滥用一氧化二氮的潜在危险。
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引用次数: 0
A light at the end of the tunnel - from mutation identification to a potential treatment for Alzheimer's disease. 隧道尽头的曙光--从突变鉴定到阿尔茨海默病的潜在治疗方法。
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-11-28 eCollection Date: 2023-01-01 DOI: 10.48101/ujms.v128.10316
Lars Lannfelt

Recent advances have driven the development of immunotherapies that act by either promoting or suppressing a patient's immune system to treat inflammation, autoimmune disease, cardiovascular disease, infectious diseases, and several cancers. In addition, research conducted over the past 25 years has identified therapeutic targets and indicated that immunotherapy could be used to treat Alzheimer's disease (AD). Despite a number of setbacks, this approach has now led to the development of the first disease-modifying treatments for this devastating disease. A key neuropathological feature of AD is the accumulation of a ~40-amino acid peptide known as amyloid β (Aβ) in the brain and cerebrovasculature. Our detection of an Aβ precursor protein mutation that caused early-onset AD in a Swedish family by enhancing Aβ protofibril formation sharpened the focus on soluble Aβ aggregates (oligomers and protofibrils) as viable therapeutic targets. Initial studies developed and tested a mouse monoclonal antibody (mAb158) with specific conformation-dependent binding to these soluble Aβ aggregates. Treatment with mAb158 selectively reduced Aβ protofibrils in the brain and cerebrospinal fluid of a transgenic mouse model of AD. A humanized version of mAb158 (lecanemab) subsequently entered clinical trials. Based on promising Phase 2 data showing plaque clearance and reduced cognitive decline, a Phase 3 trial found that lecanemab slowed decline on the primary cognitive endpoint by 27% over 18 months and also produced positive effects on secondary clinical endpoints and key biomarkers. In July 2023, the FDA granted lecanemab a full approval, and this therapeutic antibody will be marketed as Leqembi®. This represents a significant advance for patients with AD, although many challenges remain. In particular, it is now more important than ever to identify individuals who are vulnerable to AD, so that treatment can be initiated at an early stage in the disease process.

免疫疗法通过促进或抑制患者的免疫系统来治疗炎症、自身免疫性疾病、心血管疾病、传染病和多种癌症。此外,过去 25 年的研究已经确定了治疗目标,并表明免疫疗法可用于治疗阿尔茨海默病(AD)。尽管遇到了一些挫折,但这种方法现在已经开发出了治疗这种毁灭性疾病的第一种疾病改变疗法。阿尔茨海默病的一个主要神经病理学特征是一种约40个氨基酸的肽在大脑和脑血管中积聚,这种肽被称为淀粉样β(Aβ)。我们发现一种 Aβ 前体蛋白突变会增强 Aβ 原纤维的形成,从而导致一个瑞典家庭出现早发性注意力缺失症,这使我们更加关注作为可行治疗靶点的可溶性 Aβ 聚集体(低聚物和原纤维)。最初的研究开发并测试了一种小鼠单克隆抗体(mAb158),该抗体与这些可溶性 Aβ 聚集体的结合具有特异性构象依赖性。用 mAb158 治疗可选择性地减少 AD 转基因小鼠模型大脑和脑脊液中的 Aβ 原纤维。mAb158 的人源化版本(lecanemab)随后进入临床试验阶段。基于显示斑块清除和认知能力下降的良好 2 期数据,3 期试验发现 lecanemab 在 18 个月内将主要认知终点的下降速度减缓了 27%,并对次要临床终点和关键生物标志物产生了积极影响。2023 年 7 月,美国食品和药物管理局全面批准了 lecanemab,这种治疗性抗体将作为 Leqembi® 上市销售。这对注意力缺失症患者来说是一个重大进步,尽管仍存在许多挑战。特别是,现在比以往任何时候都更需要识别易患注意力缺失症的个体,以便在疾病进程的早期阶段开始治疗。
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引用次数: 0
Vitamin D status in longstanding type 1 diabetes and controls. Association with upper extremity impairments. 长期1型糖尿病患者和对照组的维生素D状况。与上肢损伤的关系
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-11-22 eCollection Date: 2023-01-01 DOI: 10.48101/ujms.v128.9888
Hans J Arnqvist, Per Leanderson, Anna Spångeus

Background: Patients with type 1 diabetes have a high prevalence of upper extremity impairments (UEIs), such as frozen shoulder, carpal tunnel syndrome, and trigger finger. The UEIs are strongly associated with activity limitations and impaired quality of life. The etiology of the UEI is not clear. Vitamin D deficiency has been considered to play a role in the pathogenesis of type 1 diabetes and in the development of macro- and microvascular complications in diabetes.

Aim: To characterize vitamin D status in a large population of patients with type 1 diabetes, if vitamin D deficiency is associated with metabolic factors and possible association with UEI.

Material and methods: Patients who diagnosed before 35 years of age, whose diabetes duration >20 years, and who are not older than 65 years were invited to participate in this cross-sectional case-control, multicenter study. Controls matched for age and sex were obtained from the national population registry. Fasting blood samples were collected and stored at -80°C until analyzed regarding 25-hydroxy-vitamin D (25(OH)D3) by a liquid chromatographic-mass spectrometric method (LC-MS/MS).

Results: Vitamin D levels varied with season as expected in the northern hemisphere. The association between 25(OH)D3 and clinical variables was analyzed in a univariate general linear model, which indicated no difference in 25(OH)D3 in men with and without diabetes but higher values in women with diabetes. About 30% of both patients and controls had vitamin D deficiency (≤50 nmol/L). Analyzed by binary logistic regression UEIs was not associated with 25(OH)D3 levels. In both patients and controls, 25(OH)D3 was correlated to apolipoprotein A1 (r = 0.153; 0.220, P < 0.001).

Conclusion: In patients with type 1 diabetes and a duration of 20 years or more, vitamin D level is not lower than in nondiabetic controls and is not associated with UEIs.

背景:1 型糖尿病患者的上肢损伤(UEIs)发病率很高,如肩周炎、腕管综合征和扳机指。上肢损伤与活动受限和生活质量受损密切相关。UEI 的病因尚不清楚。维生素 D 缺乏被认为在 1 型糖尿病的发病机制以及糖尿病大血管和微血管并发症的发生中起着一定的作用:这项横断面病例对照多中心研究邀请了 35 岁之前确诊、糖尿病病程超过 20 年且年龄不超过 65 岁的患者。年龄和性别匹配的对照组来自全国人口登记处。研究人员采集空腹血样,并将其保存在零下 80 摄氏度的环境中,直至采用液相色谱-质谱法(LC-MS/MS)对 25- 羟基维生素 D(25(OH)D3)进行分析:结果:在北半球,维生素 D 水平随季节变化。在单变量一般线性模型中分析了 25(OH)D3 与临床变量之间的关系,结果表明男性糖尿病患者和非糖尿病患者的 25(OH)D3 没有差异,但女性糖尿病患者的 25(OH)D3 值较高。约30%的患者和对照组都存在维生素D缺乏症(≤50 nmol/L)。通过二元逻辑回归分析,UEIs与25(OH)D3水平无关。在患者和对照组中,25(OH)D3均与脂蛋白A1相关(r = 0.153; 0.220, P < 0.001):结论:在病程长达 20 年或更长时间的 1 型糖尿病患者中,维生素 D 水平并不比非糖尿病对照组低,也与 UEI 无关。
{"title":"Vitamin D status in longstanding type 1 diabetes and controls. Association with upper extremity impairments.","authors":"Hans J Arnqvist, Per Leanderson, Anna Spångeus","doi":"10.48101/ujms.v128.9888","DOIUrl":"10.48101/ujms.v128.9888","url":null,"abstract":"<p><strong>Background: </strong>Patients with type 1 diabetes have a high prevalence of upper extremity impairments (UEIs), such as frozen shoulder, carpal tunnel syndrome, and trigger finger. The UEIs are strongly associated with activity limitations and impaired quality of life. The etiology of the UEI is not clear. Vitamin D deficiency has been considered to play a role in the pathogenesis of type 1 diabetes and in the development of macro- and microvascular complications in diabetes.</p><p><strong>Aim: </strong>To characterize vitamin D status in a large population of patients with type 1 diabetes, if vitamin D deficiency is associated with metabolic factors and possible association with UEI.</p><p><strong>Material and methods: </strong>Patients who diagnosed before 35 years of age, whose diabetes duration >20 years, and who are not older than 65 years were invited to participate in this cross-sectional case-control, multicenter study. Controls matched for age and sex were obtained from the national population registry. Fasting blood samples were collected and stored at -80°C until analyzed regarding 25-hydroxy-vitamin D (25(OH)D3) by a liquid chromatographic-mass spectrometric method (LC-MS/MS).</p><p><strong>Results: </strong>Vitamin D levels varied with season as expected in the northern hemisphere. The association between 25(OH)D3 and clinical variables was analyzed in a univariate general linear model, which indicated no difference in 25(OH)D3 in men with and without diabetes but higher values in women with diabetes. About 30% of both patients and controls had vitamin D deficiency (≤50 nmol/L). Analyzed by binary logistic regression UEIs was not associated with 25(OH)D3 levels. In both patients and controls, 25(OH)D3 was correlated to apolipoprotein A1 (<i>r</i> = 0.153; 0.220, <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>In patients with type 1 diabetes and a duration of 20 years or more, vitamin D level is not lower than in nondiabetic controls and is not associated with UEIs.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809802","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}
引用次数: 0
Distribution of cup-disc ratio in a Swedish population. 瑞典人群中杯盘比的分布。
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-13 eCollection Date: 2023-01-01 DOI: 10.48101/ujms.v128.9805
Edvin Svedberg, Curt Ekström

Background: Increased cup-disc ratio (CDR) is a hallmark of open-angle glaucoma (OAG), an age-related neurodegenerative disease of significant importance for public health. There are few studies on the distribution of CDR in the Nordic populations.

Methods: The distribution of CDR was studied in 749 subjects aged 65-74 years in a population survey in the rural district of Tierp, Sweden, from 1984 to 86. The optic discs were assessed with binocular ophthalmoscopy at a slit lamp. Drawings of the discs were made in the protocol and used for the calculation of vertical CDRs. Odds ratios, adjusted for age and sex, according to Mantel-Haenszel (ORMH), were determined to estimate predictors of increased CDR, defined as a ratio in the upper quartile. For these analyses, the eye with the most advanced OAG or the highest pressure was chosen. Automated perimetry was used to identify OAG.

Results: The distribution of vertical CDR was fairly close to that of other European-derived populations. The mean CDR was 0.45 in both eyes, with no difference between women and men. An increased ratio was associated with the age ≥70 years, a positive family history of OAG and intraocular pressure ≥20 mmHg. OAG increased the risk 8-fold (ORMH 8.06; 95% CI 4.12-15.8).

Conclusions: In this study, the distribution of CDR was fairly close to that of other European-derived populations. As expected, OAG increased the risk of having a CDR in the upper quartile. The CDR increased with age.

背景:杯盘比(CDR)增加是开角型青光眼(OAG)的标志,OAG是一种与年龄相关的神经退行性疾病,对公众健康具有重要意义。很少有关于CDR在北欧人群中分布的研究。方法:1984年至86年在瑞典蒂尔普农村地区进行的一项人口调查中,对749名年龄在65-74岁之间的受试者的CDR分布进行了研究。在裂隙灯下用双眼检眼镜对视盘进行评估。在方案中绘制了光盘的图纸,并用于计算垂直CDR。根据Mantel Haenszel(ORMH)的说法,根据年龄和性别调整的比值比是为了估计CDR增加的预测因素,CDR定义为上四分位数的比值。在这些分析中,选择了OAG最先进或压力最高的眼睛。结果:垂直CDR的分布与其他欧洲来源人群相当接近。双眼的平均CDR为0.45,女性和男性之间没有差异。年龄≥70岁、有OAG阳性家族史和眼压≥20mmHg与比值增加有关。OAG使风险增加了8倍(ORMH 8.06;95%CI 4.12-15.8)。结论:在本研究中,CDR的分布与其他欧洲来源人群的分布相当接近。正如预期的那样,OAG增加了上四分位数CDR的风险。CDR随着年龄的增长而增加。
{"title":"Distribution of cup-disc ratio in a Swedish population.","authors":"Edvin Svedberg,&nbsp;Curt Ekström","doi":"10.48101/ujms.v128.9805","DOIUrl":"10.48101/ujms.v128.9805","url":null,"abstract":"<p><strong>Background: </strong>Increased cup-disc ratio (CDR) is a hallmark of open-angle glaucoma (OAG), an age-related neurodegenerative disease of significant importance for public health. There are few studies on the distribution of CDR in the Nordic populations.</p><p><strong>Methods: </strong>The distribution of CDR was studied in 749 subjects aged 65-74 years in a population survey in the rural district of Tierp, Sweden, from 1984 to 86. The optic discs were assessed with binocular ophthalmoscopy at a slit lamp. Drawings of the discs were made in the protocol and used for the calculation of vertical CDRs. Odds ratios, adjusted for age and sex, according to Mantel-Haenszel (OR<sub>MH</sub>), were determined to estimate predictors of increased CDR, defined as a ratio in the upper quartile. For these analyses, the eye with the most advanced OAG or the highest pressure was chosen. Automated perimetry was used to identify OAG.</p><p><strong>Results: </strong>The distribution of vertical CDR was fairly close to that of other European-derived populations. The mean CDR was 0.45 in both eyes, with no difference between women and men. An increased ratio was associated with the age ≥70 years, a positive family history of OAG and intraocular pressure ≥20 mmHg. OAG increased the risk 8-fold (OR<sub>MH</sub> 8.06; 95% CI 4.12-15.8).</p><p><strong>Conclusions: </strong>In this study, the distribution of CDR was fairly close to that of other European-derived populations. As expected, OAG increased the risk of having a CDR in the upper quartile. The CDR increased with age.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427253","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}
引用次数: 0
Persistent SARS-CoV-2 infection in patients with B-cell deficiency: a case series of successful antiviral treatment of four patients. B细胞缺乏症患者的持续性严重急性呼吸系统综合征冠状病毒2型感染:四名患者成功抗病毒治疗的一系列病例。
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-10-11 eCollection Date: 2023-01-01 DOI: 10.48101/ujms.v128.9807
Lisa Faxén, Marie Edvinsson

Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised patients remains a major medical challenge. Diagnosing the syndrome is difficult as symptoms may mimic other diseases and treatment guidelines are lacking. We describe a case series of four patients with persistent SARS-CoV-2 infection that all had an underlying B-cell deficiency due to rituximab treatment (in one case in combination with epcoritamab). In all four patients, it was initially difficult to recognize the persistent disease, leading to a duration of illness between 45 and 242 days. Two patients were only positive for SARS-CoV-2 by polymerase chain reaction (PCR) in the nasopharynx at the beginning of the disease but were later repeatedly negative. However, when bronchoalveolar lavage was performed, a positive SARS-CoV-2 PCR was revealed from the lower airways in both patients. The difficulties establishing diagnosis contributed to these two patients' long disease course. The longest disease duration was in the patient treated with rituximab and epcoritamab, who also responded poorly to single standard antiviral treatment. This patient ultimately cleared the infection after administering a combination treatment with remdesivir and nirmatrelvir/ritonavir. After a confirmed diagnosis, the other three patients cleared the infection when they were finally treated with antivirals. Increasing clinicians' awareness of this condition is important as it might be treatable once diagnosed. Further studies are warranted to define the condition and treatment strategy with greater precision.

免疫功能受损患者持续感染严重急性呼吸综合征冠状病毒2型(严重急性呼吸系统综合征冠状病毒)仍然是一个重大的医学挑战。诊断该综合征很困难,因为症状可能与其他疾病相似,而且缺乏治疗指南。我们描述了一个由四名持续感染严重急性呼吸系统综合征冠状病毒2型的患者组成的病例系列,他们都因利妥昔单抗治疗而存在潜在的B细胞缺乏症(其中一例与epcoritamab联合治疗)。在所有四名患者中,最初很难识别出持续的疾病,导致疾病持续时间在45至242天之间。两名患者在疾病开始时仅通过鼻咽聚合酶链式反应(PCR)检测出严重急性呼吸系统综合征冠状病毒2型呈阳性,但后来多次呈阴性。然而,当进行支气管肺泡灌洗时,两名患者的下呼吸道均显示出严重急性呼吸系统综合征冠状病毒2型聚合酶链式反应阳性。确定诊断的困难导致这两名患者的病程很长。疾病持续时间最长的患者是接受利妥昔单抗和依普利塔单抗治疗的患者,他们对单一标准抗病毒治疗的反应也很差。该患者在接受瑞德西韦和尼马特雷韦/利托那韦联合治疗后,最终清除了感染。在确诊后,其他三名患者在最终接受抗病毒药物治疗时清除了感染。提高临床医生对这种情况的认识很重要,因为一旦诊断出来,它可能是可以治疗的。需要进一步的研究来更精确地确定病情和治疗策略。
{"title":"Persistent SARS-CoV-2 infection in patients with B-cell deficiency: a case series of successful antiviral treatment of four patients.","authors":"Lisa Faxén,&nbsp;Marie Edvinsson","doi":"10.48101/ujms.v128.9807","DOIUrl":"10.48101/ujms.v128.9807","url":null,"abstract":"<p><p>Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised patients remains a major medical challenge. Diagnosing the syndrome is difficult as symptoms may mimic other diseases and treatment guidelines are lacking. We describe a case series of four patients with persistent SARS-CoV-2 infection that all had an underlying B-cell deficiency due to rituximab treatment (in one case in combination with epcoritamab). In all four patients, it was initially difficult to recognize the persistent disease, leading to a duration of illness between 45 and 242 days. Two patients were only positive for SARS-CoV-2 by polymerase chain reaction (PCR) in the nasopharynx at the beginning of the disease but were later repeatedly negative. However, when bronchoalveolar lavage was performed, a positive SARS-CoV-2 PCR was revealed from the lower airways in both patients. The difficulties establishing diagnosis contributed to these two patients' long disease course. The longest disease duration was in the patient treated with rituximab and epcoritamab, who also responded poorly to single standard antiviral treatment. This patient ultimately cleared the infection after administering a combination treatment with remdesivir and nirmatrelvir/ritonavir. After a confirmed diagnosis, the other three patients cleared the infection when they were finally treated with antivirals. Increasing clinicians' awareness of this condition is important as it might be treatable once diagnosed. Further studies are warranted to define the condition and treatment strategy with greater precision.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238906","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}
引用次数: 0
Associations of spleen volume with markers of blood count and lipid profile in a large population-based study. 一项基于人群的大型研究中脾脏体积与血细胞计数和脂质分布标志物的相关性。
IF 3.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2023-09-15 eCollection Date: 2023-01-01 DOI: 10.48101/ujms.v128.9785
Muhammad Naeem, Till Ittermann, Marcello Ricardo Paulista Markus, Mohammed Farah Mahmoud Mousa, Laura von Heder, Robin Bülow, Marcus Dörr, Matthias Nauck, Ali Agdassi, Florian H Heidel, Henry Völzke

Background: The aim of our study was to investigate associations of spleen volume with blood count markers and lipid profile in the general population.

Materials & methods: Cross-sectional data from 1,106 individuals aged 30-90 years from the population-based Study of Health in Pomerania (SHIP-START-2) were analyzed. Blood count markers included red blood cell (RBC) counts, hemoglobin, platelet count, and white blood cell (WBC) counts. Lipid profile included total-cholesterol, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) as well as triglycerides. Linear regression models adjusted for age, sex, body height, and weight were used to associate standardized spleen volume with blood counts and lipid profile markers.

Results: Spleen volume was positively associated with RBC (β = 0.05; 95% confidence interval [CI] = 0.03 to 0.08) and hemoglobin (β = 0.05; 95% CI = 0.01 to 0.09) but inversely with platelet count (β = -16.3; 95% CI = -20.5 to -12.1) and WBC (β = -0.25; 95% CI = -0.37 to -0.14). Furthermore, spleen volume showed inverse associations with total cholesterol (β = -0.17; 95% CI = -0.24 to -0.09), HDL-C (β = -0.08; 95% CI = -0.10 to -0.05), and LDL-C (β = -0.12; 95% CI = -0.17 to -0.06). There was no significant association of spleen volume with triglycerides.

Conclusion: Our study showed that the spleen volume is associated with markers of the blood count and lipid profile in the general population.

背景:我们研究的目的是调查普通人群中脾脏体积与血细胞计数标志物和脂质状况的关系。材料与方法:分析来自波美拉尼亚基于人群的健康研究(SHIP-START-2)的1106名30-90岁个体的横断面数据。血液计数标志物包括红细胞(RBC)计数、血红蛋白、血小板计数和白细胞(WBC)计数。脂质概况包括总胆固醇、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白蛋白胆固醇(LDL-C)以及甘油三酯。使用经年龄、性别、身高和体重调整的线性回归模型,将标准化脾脏体积与血细胞计数和脂质分布标志物相关联。结果:脾容量与红细胞(β=0.05;95%可信区间[CI]=0.03-0.08)和血红蛋白(β=0.005;95%CI=0.01-0.09)呈正相关,但与血小板计数(β=-16.3;95%CI=-20.5-12.1)和白细胞(β=-0.25;95%CI=-0.37--0.14)呈负相关。此外,脾容量与总胆固醇呈负相关(β=-0.17;95%CI=-0.14-0.09),HDL-C(β=-0.08;95%CI=-0.10至-0.05)和LDL-C(β=-0.12;95%CI=-0.17至-0.06)。脾脏体积与甘油三酯没有显著相关性。结论:我们的研究表明,在普通人群中,脾脏体积与血细胞计数和脂质分布的标志物有关。
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引用次数: 0
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Upsala journal of medical sciences
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