Different features in Wegener's granulomatosis: Report of five cases

Wegener's granulomatosis (WG) is an autoimmune inflammatory condition. It is often a rapidly progressive and potentially fatal disease. The clinical presentation of WG can be so diverse that the list of its differential diagnosis is vast, ranging from infectious diseases to other vasculitis (e.g. Behcet's disease), as well as malignancies. The exact aetiology of WG remains unclear. The upper airway diseases including sinusitis, oral lesions and otitis media are the most common presenting features of WG. In this paper, we have described 5 WG cases. They had different presentations and chief complaints. Some of them presented with upper airways diseases, while the others mainly suffered from the manifestations of pulmonary involvement. Although all of them were finally diagnosed as WG cases, the processes of the work up for the diagnosis as well as the outcome of the disease were not the same. So, the diversities in the presentation should be mentioned in the management of the WG suspected patients

Association between CTLA-4 gene polymorphism and the risk of systemic lupus erythematosus: Brief report

Background: Cytotoxic lymphocyte antigen-4 (CTLA-4) plays an important role in regulating T cell activation. CTLA-4 gene polymorphisms are related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). We analyzed the role of CTLA-4 polymorphisms at positions -318CT in patients who suffer from SLE. Methods: This study was performed on 180 SLE patients referred to 5th Azar University Hospital in Gorgan, Iran. Three hundred and four ethnically-and age-matched healthy controls with no history of autoimmune diseases entered the study between 5th May 2008 and 23rd October 2009. DNA was extracted from blood samples according to the standard procedure. Polymerase chain reaction- restriction fragments length polymorphism (PCR-RFLP) was used to analyze the genotype and allele frequencies of this polymorphism. PCR was carried out using the following primers: forward 5′- AAATGAATTGGACTGGATGGT-3′ and reverse 5′-TTACGAGAAAGGAAGCCGT G-3′. The frequency of alleles and genotypes were assessed using direct counting. Chisquare test and Fisher’s exact test were used to compare the association between the alleles and genotype frequencies and SLE. P<0.05 were considered statistically significant. Results: The CC genotype was observed in 94.5% of the SLE patients and 82.4% of the controls; the difference was statistically significant (P=0.0001, OR=3.51, CI95%=1.77- 7.53). The CT genotype, on the other hand, was more frequently observed in the control group (17.1% vs. 5.5%, P=0.0001, OR=0.28). T allele was significantly more common in the controls compared to SLE patients (P=0.0001, OR=0.26, CI95%=0.13-0.53). Conclusion: Our results suggest that the -318C/T polymorphism of CTLA-4 gene might play a significant role in the genetic susceptibility to SLE. Therefore, further studies on populations, especially from other Middle East countries, are needed to confirm our results. © 2015, Tehran University of Medical Sciences. All Rights Reserved

No evidence of association between CTLA-4 polymorphisms and systemic lupus erythematosus in Iranian patients

Aim: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an important negative regulator of T-cell responses. CTLA-4 polymorphisms have been confirmed to be associated with several autoimmune diseases such as systemic lupus erythematosus (SLE). We analyzed the role of CTLA-4 polymorphism at positions -1661 and -1722 in Iranian patients suffering from SLE. Methods: One hundred and eighty SLE patients and 304 ethnically and age-matched healthy controls were studied. Polymerase chain reaction restriction fragments length polymorphism (PCR-RFLP) was used to analyze the genotype and allele frequencies of these polymorphisms. Results: There was no significant association between the studied genotypic and allelic frequencies between SLE patients and the controls. Although the TC genotype in 1722TC polymorphism was more common among the control group, the correlation was not statistically significant. Conclusion: Our results suggest that the -1661AG and -1722TC polymorphisms in the promoter region of the CTLA-4 gene does not play any role in genetic susceptibility to SLE. However, further studies on larger sample sizes are needed to approve our results. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

Association between 318C/T polymorphism of the CTLA-4 gene and systemic lupus erythematosus in Iranian patients

Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an important negative regulator of T-cell response. It is a functional candidate gene connected with susceptibility to systemic lupus erythematosus (SLE). We analyzed the role of -318C/T polymorphism in the promoter region of the CTLA-4 gene in Iranian patients suffering from SLE. Methods: A total of 180 SLE patients and 304 healthy ethnically matched controls were enrolled in the study. DNA was extracted from blood samples according to the standard procedure. Polymerase chain reaction restriction fragments length polymorphism (PCR-RFLP) was used to analyze the genotype and allele frequencies of these polymorphisms. Results: The CC genotype was observed in 170 (94.5%) of the SLE patients, which was significantly different compared to the controls (251 [82.4%]; P = 0.0001, OR = 3.51 95%CI = 1.77-7.53). T allele was significantly more common in the controls (9.2%) compared to SLE patients 2.8% (P = 0.0001, OR = 0.26, 95%CI = 0.13-0.53). There was no significant correlation between different genotypes and age, gender or family history of SLE in the studied population. Conclusion: It can be concluded that -318C/T polymorphism of CTLA-4 gene might play a significant role in the development of SLE in the Iranian patients. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

The CanOE Strategy: Integrating Genomic and Metabolic Contexts across Multiple Prokaryote Genomes to Find Candidate Genes for Orphan Enzymes

Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes), a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short). The first step locates “genomic metabolons”, i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12

Effect of primary care physicians' use of estimated glomerular filtration rate on the timing of their subspecialty referral decisions

<p>Abstract</p> <p>Background</p> <p>Primary care providers' suboptimal recognition of the severity of chronic kidney disease (CKD) may contribute to untimely referrals of patients with CKD to subspecialty care. It is unknown whether U.S. primary care physicians' use of estimated glomerular filtration rate (eGFR) rather than serum creatinine to estimate CKD severity could improve the timeliness of their subspecialty referral decisions.</p> <p>Methods</p> <p>We conducted a cross-sectional study of 154 United States primary care physicians to assess the effect of use of eGFR (versus creatinine) on the timing of their subspecialty referrals. Primary care physicians completed a questionnaire featuring questions regarding a hypothetical White or African American patient with progressing CKD. We asked primary care physicians to identify the serum creatinine and eGFR levels at which they would recommend patients like the hypothetical patient be referred for subspecialty evaluation. We assessed significant improvement in the timing [from eGFR < 30 to ≥ 30 mL/min/1.73m²) of their recommended referrals based on their use of creatinine versus eGFR.</p> <p>Results</p> <p>Primary care physicians recommended subspecialty referrals later (CKD more advanced) when using creatinine versus eGFR to assess kidney function [median eGFR 32 versus 55 mL/min/1.73m², p < 0.001]. Forty percent of primary care physicians significantly improved the timing of their referrals when basing their recommendations on eGFR. Improved timing occurred more frequently among primary care physicians practicing in academic (versus non-academic) practices or presented with White (versus African American) hypothetical patients [adjusted percentage(95% CI): 70% (45-87) versus 37% (reference) and 57% (39-73) versus 25% (reference), respectively, both p ≤ 0.01).</p> <p>Conclusions</p> <p>Primary care physicians recommended subspecialty referrals earlier when using eGFR (versus creatinine) to assess kidney function. Enhanced use of eGFR by primary care physicians' could lead to more timely subspecialty care and improved clinical outcomes for patients with CKD.</p

A systematic review of sarcopenia prevalence and associated factors in people living with human immunodeficiency virus

People living with human immunodeficiency virus (HIV) (PLWH) appear to be at an increased risk of sarcopenia, which can have a devastating effect on their life due to consequences such as physical disability, poor quality of life, and finally death. This systematic review examined sarcopenia prevalence and its associated factors in PLWH. A systematic search was conducted using the keywords in the online databases including Scopus, PubMed, Web of Science, Embase and Cochrane databases from the dates of inception up to May 2022. The retrieved articles underwent a two-step title/abstract and full-text review process, and the eligible papers were selected and included in the qualitative synthesis. Data relating to the study population, purpose of study, gender, age, race, body mass index, medical history, paraclinical results and antiretroviral therapy as associated factors of sarcopenia were extracted. In addition, the prevalence of sarcopenia in PLWH and its promoting and reducing factors were also extracted. We reviewed the 14 related studies for identifying of sarcopenia prevalence and its associated factors in PLWH. The total number of PLWH in all the reviewed studies was 2592. There was no criterion for the minimum number of people with HIV and the lowest number of PLWH was 27, and the highest number was 860. Some studies reported a significantly higher prevalence of sarcopenia in HIV-infected individuals compared with HIV-negative controls as follows: 24.2–6.7%, 15–4% and 10–6%, respectively. We showed that, age (30–50 years), being female, >5 years post-HIV diagnosis, multiple vertebral fractures, cocaine/heroin use and lower gamma-glutamyl transferase level were the main promoting factors of sarcopenia. Higher educational level, employment, physical exercise, calf circumference >31 cm, and gait speed >0.8 m/s were also factors to reduce sarcopenia. Sarcopenia prevalence in PLWH is higher than HIV-negative population. Given the importance and prevalence of sarcopenia among PLWH and its associated consequences (i.e., mortality and disability), determining its risk factors is of great importance. © 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. Findings: There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Funding: Bill &amp; Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe