Immune Disorders in HIV-Infected Patients Coinfected with Hepatitis C Virus

In Russia, more than half of HIV-infected people are coinfected with hepatitis C. Both viruses interact with the immune system compounding the disease course. HIV infection accelerates the onset of hepatitis-mediated liver fibrosis and cirrhosis. Hepatitis C slows down the recovery of CD4+ T-lymphocytes during antiretroviral treatment and fuels the already intense chronic inflammation. In the present review, we discuss coinfection prevalence and reasons for its abundance, provide extensive coverage of the known mechanisms that give rise to the detrimental health effects in HIV/hepatitis C-coinfected patients, and report our own data on the double infection consequences in people with discordant immunologic response to treatment

Regulatory T cell subsets in peripheral blood of HIV-infected patients with discordant response to antiretroviral therapy

The discordant immunologic response to antiretroviral therapy in HIV-infected patients is characterized by ineffective recovery of CD4+T cell counts. The role of regulatory T cells in discordant response to the treatment remains poorly understood both due to the lack of specific and reliable markers of regulatory T cells and their subset’s heterogeneity. In the present work, we studied two groups of HIV-infected patients receiving antiretroviral therapy for more than two years and thus having their viral load suppressed (less than 50 copies of HIV per ml of blood): those who responded (n = 22) and did not respond (n = 19) to the treatment with an increase in their CD4+T cell counts. The control group consisted of uninfected volunteers (n = 23). The CD4+T lymphocyte subset composition was examined by flow cytometry. It was shown that in HIV-infected patients with ineffective immune recovery compared with subjects having a standard response to antiretroviral therapy, the absolute counts of regulatory T cells, as well as CD4+T lymphocytes, was reduced in all maturational subsets: naive cells, central memory, effector memory, and terminally differentiated effectors. That differed immunological nonresponders from patients with a standard response to the treatment, which had a shortage only in naive and central memory regulatory T cell subsets. It is important to note that in HIV-infected patients with a discordant response to therapy, the proportion of effector memory regulatory T cells, that posses the most prominent suppressive capacity, was significantly increased compared with that in other CD4+T lymphocyte subsets. Apparently, despite of regulatory T cell deficiency, in HIV-infected patients with a discordant response to the treatment, the regulatory T cell pool size is big enough to control CD4+T lymphocyte activation. Nevertheless, the number of regulatory T cells may not be sufficient to suppress the over-activation of immunocompetent cells that are not in the CD4+T lymphocyte subset. This can partly explain the increased cell activation level in patients with a discordant response to therapy as compared with those who have a standard respond to the treatment

Субпопуляционный состав регуляторных Т-лимфоцитов у пациентов с ВИЧ-инфекцией при эффективной антиретровирусной терапии

Background. The reason why HIV-infected patients receiving highly active antiretroviral therapy (HAART) suffer from the increased immune activation remains elusive. Regulatory T-cells (Treg) are able to control immune activation, but their quantity may vary due to the infection. The aim of this work was to estimate the number and subsets of Tregs in HIV-positive patients receiving virologically effective HAART.Materials and methods. The CD4+ T-lymphocyte (CD3+CD4+) and Treg (CD3+CD4+FOXP3+) quantities were determined by flow cytometry. Treg subsets were assessed based on the FOXP3 expression level. The state of T-cell activation was established according to the simultaneous expression of CD38 and HLA-DR molecules.Results. It was shown that HIV-positive patients compared to healthy people have reduced CD4+ T-lymphocyte counts despite virologically effective HAART. At the same time in HIV-infected people, Treg absolute numbers were only slightly decreased. Moreover, the major part of Treg pool in their blood consisted of lymphocytes with a high level of FOXP3 expression that corresponded to the phenotype of cells with the highest suppressor activity. However, an increased relative amount of activated CD4+ T-lymphocytes was retained in the HIV-infected individuals’ blood.Conclusion. In HIV-infected patients who received HAART in time and whose treatment resulted in an effective HIV viral load suppression and a satisfactory CD4+ T-cell counts increase, a relatively large pool of peripheral Tregs is maintained. However, these lymphocytes are not enough to fully control immune activation that develops against the background of chronic lentivirus infection. Актуальность. Причина, по которой у инфицированных вирусом иммунодефицита человека (ВИЧ) пациентов, получающих высокоактивную антиретровирусную терапию (АРТ), сохраняется повышенный уровень активации иммунной системы, остается не до конца понятной. Регуляторные Т-лимфоциты способны контролировать иммунную активацию, однако под влиянием инфекционного процесса их количество может изменяться.Цель. Оценка численности и субпопуляционного состава регуляторных Т-лимфоцитов ВИЧпозитивных пациентов, принимающих эффективную АРТ.Материалы и методы. Количество CD4+ Т-лимфоцитов (CD3+CD4+) и регуляторных Т-клеток (Treg; CD3+CD4+FOXP3+) определяли методом проточной цитофлюориметрии. Субпопуляционный состав регуляторных Т-лимфоцитов оценивали по уровню экспрессии FOXP3. Состояние активации Т-клеток устанавливали по одновременной экспрессии молекул CD38 и HLA-DR.Результаты. Показано, что по сравнению со здоровыми людьми у ВИЧ-позитивных больных наблюдается дефицит CD4+ Т-лимфоцитов: их численность остается сниженной, несмотря на эффективную АРТ. Вместе с тем абсолютное количество регуляторных CD4+ Т-клеток у зараженных ВИЧ людей падает незначительно. Более того, основная доля Treg в их крови представлена лимфоцитами с высоким уровнем экспрессии FOXP3, что соответствует фенотипу клеток, обладающих наибольшей супрессорной активностью. Однако на этом фоне в крови ВИЧ-инфицированных лиц сохраняется повышенное относительное количество активированных CD4+ Т-лимфоцитов.Заключение. У ВИЧ-инфицированных пациентов, которым была своевременно назначена терапия и у которых лечение привело кэффективному подавлению вирусной нагрузки ВИЧ и удовлетворительному приросту числа периферических CD4+ Т-лимфоцитов, поддерживается сравнительно большой пул периферических регуляторных Т-клеток. Однако этих лимфоцитов оказывается недостаточно для полного контроля над иммунной активацией, развивающейся на фоне хронической лентивирусной инфекции

MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Objectives To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) phase 2b/3 upadacitinib clinical programmes. Methods Data were analysed and summarised from clinical trials of RA, PsA and AS treated with upadacitinib 15 mg once daily (QD) and 30 mg QD (as of 30 June 2021). Data from adalimumab (RA and PsA) and methotrexate (RA) arms were included as comparators. Adjudicated MACEs and VTE events were presented as exposure-adjusted rates per 100 patient-years (E/100 PY). Univariable Cox proportional hazard regression analyses assessed potential associations of risk factors for MACE and VTE. Results In total, 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907 and AS n=182) and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). In patients with RA and PsA, rates of MACE (0.3–0.6 E/100 PY) and VTE (0.2–0.4 E/100 PY) were similar across upadacitinib doses; in patients with AS, no MACEs and one VTE event occurred. Most patients experiencing MACEs or VTE events had two or more baseline cardiovascular risk factors. Across RA and PsA groups, rates of MACEs and VTE events were similar. Conclusions Rates of MACEs and VTE events with upadacitinib were consistent with previously reported data for patients receiving conventional synthetic and biologic disease-modifying anti-rheumatic drugs and comparable with active comparators adalimumab and methotrexate. Associated patient characteristics are known risk factors for MACEs and VTE events

КЛИНИКО-ЭПИДЕМИОЛОГИЧЕСКИЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ГЕМОРРАГИЧЕСКОЙ ЛИХОРАДКИ С ПОЧЕЧНЫМ СИНДРОМОМ В ПЕРМСКОМ КРАЕ

The results of retrospective analysis of hemorrhagic fever with renal syndrome (HFRS) incidence in the Perm region for 1995–2009 are shown in the article. There are highly active natural foci of infection on the territory of the region, mainly in the subzone of mixed coniferous-deciduous forests. Factors supporting the morbidity are high numbers of small mammals, in particular, the bank vole, with a large circulation of the HFRS virus and active population visit of natural foci in summer-autumn period. Analysis of clinical features of HFRS in 338 patients living in the Perm region, revealed some peculiarities of its course. Among surveyed contingent men (72,4%) prevailed. Most of the patients (80,4%) were of working age (16 to 60 years). More frequently mild and moderate forms (92,8%) of HFRS were observed. A typical picture of the disease with the development of all specific syndromes occurred mainly in patients with severe and moderate forms. Mild cases occurred blurry in the absence of pathognomonic symptoms. Notable was the frequent lesion of liver, with the development of acute anicteric hepatitis (51,2%). Among the complications dominated: pneumonia (4,7%) and acute renal  ailure (4,4%). Manifestations of DIC syndrome with recurrent bleeding were registered in 0,6% of patients, toxic shock – at 0,3%. Case fatality rate was 0,6%.В статье представлены результаты ретроспективного анализа заболеваемости геморрагической лихорадкой с почечным синдромом (ГЛПС) в Пермском крае за 1995–2009 гг. На территории края, преимущественно в подзоне хвойно-широколиственных лесов, имеются высокоактивные природные очаги инфекции. Факторами, поддерживающими заболеваемость, являются: высокая численность мелких млекопитающих, в частности, рыжей полевки, с значительной циркуляцией вируса ГЛПС и активное посещение населением природных очагов в летне-осенний период. Анализ клинической характеристики ГЛПС у 338 больных, проживающих в Пермском крае, позволил выявить некоторые особенности ее течения. Среди обследуемого контингента преобладают мужчины (72,4%). Большинство пациентов (80,4%) находятся в трудоспособном возрасте (от 16 до 60 лет). Чаще наблюдаются легкие и среднетяжелые формы (92,8%) ГЛПС. Типичная картина заболевания с развитием всех характерных синдромов имеет место, в основном, у пациентов с тяжелой и среднетяжелой формами. Легкие случаи протекают стерто, в отсутствии патогномоничных симптомов. Примечательным является частое поражение печени, с развитием острого безжелтушного гепатита (51,2%). Из осложнений доминируют: пневмонии (4,7%) и ОПН (4,4%). Проявления ДВС-синдрома с рецидивирующими кровотечениями зарегистрированы у 0,6% больных, инфекционно-токсический шок – у 0,3%. Летальность составляет 0,6%

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153772/1/acr24131.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153772/2/acr24131_am.pd

Prevalence of Therapeutic use of Opioids in Chronic non-Cancer Pain Patients and Associated Factors: A Systematic Review and Meta-Analysis

Objectives: To determine the prevalence and factors associated with the use of opioids among patients with chronic non-cancer pain (CNCP). Methods: A systematic review and meta-analysis. Comprehensive literature searches in Medline-PubMed, Embase and SCOPUS databases. Original studies published between 2009 and 2019 with a cross-sectional design were included. The quality of the studies was assessed with Critical Appraisal Checklist for Studies Reporting Prevalence Data from the Joanna Briggs Institute. Protocol registered in the International Prospective Register of Systematic Reviews with reference number: CRD42019137990. Results: Out of the 1,310 potential studies found, 25 studies fulfilled the inclusion criteria. Most of the studies were of high quality. High levels of heterogeneity were found in the studies included. In the general population, the prevalence of long-term opioid use was 2.3% (95% CI: 1.5-3.6%), the prevalence of short-term opioid use was 8.1% (95% CI: 5.6-11.6%), and among people with chronic low back pain it was 5.8% (95% CI: 0.5-45.5%). The prevalence of opioid use among patients from the health records or medical surveys was 41% (95% CI: 23.3-61.3%). Finally, in patients with musculoskeletal pain, the prevalence was 20.5% (95% CI: 12.9-30.9%) and in patients with fibromyalgia, 24.5% (95% CI: 22.9-26.2%). A higher prevalence of opioid use was observed among men, younger people, patients receiving prescriptions of different types of drugs, smokers and patients without insurance or with noncommercial insurance. In addition, non-white and Asian patients were less likely to receive opioids than non-Hispanic white patients. Conclusions: The prevalence of opioid use among patients with CNCP was higher in subjects with short or occasional use compared to those with long-term use. Men, younger people, more chronic pain conditions, and patients without insurance or with noncommercial insurance were most related to opioid use. However, non-white and Asian patients, and those treated by a physician trained in complementary medicine were less likely to use opioids