SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3 , and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

Where are we with pre-exposure prophylaxis use in Central and Eastern Europe? Data from the Euroguidelines in Central and Eastern Europe (ECEE) Network Group.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) for HIV infection is an important intervention for control of the HIV epidemic. The incidence of HIV infection is increasing in the countries of Central and Eastern Europe (CEE). Therefore, we investigated the change in PrEP use in CEE over time. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care for HIV and viral hepatitis infections in CEE. Data on access to PrEP were collected from 23 countries through online surveys in May-June 2017 (76 respondents) and in November 2018-May 2019 (28 respondents). RESULTS: About 34.2% of respondents stated that tenofovir/emtricitabine (TDF/FTC) was licensed for use in their country in 2017, and 66.7% that it was licensed for use in 2018 (P = 0.02). PrEP was recommended in national guidelines in 39.5% of responses in 2017 and 40.7% in 2018 (P = 0.378). About 70.7% of respondents were aware of "informal" PrEP use in 2017, while 66.6% were aware of this in 2018 (P = 0.698). In 2018, there were 53 centres offering PreP (the highest numbers in Poland and Romania), whereas six countries had no centres offering PreP. The estimated number of HIV-negative people on PreP in the region was 4500 in 2018. Generic TDF/FTC costs (in Euros) ranged from €10 (Romania) to €256.92 (Slovakia), while brand TDF/FTC costs ranged from €60 (Albania) to €853 (Finland). CONCLUSIONS: Although the process of licensing TDF/FTC use for PrEP has improved, this is not yet reflected in the guidelines, nor has there been a reduction in the "informal" use of PrEP. PrEP remains a rarely used preventive method in CEE countries.

The EuroSIDA study: 25 years of scientific achievements.

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

Increasing incidence of HIV- associated tuberculosis in Romanian injecting drug users.

BACKGROUND: A high prevalence of tuberculosis (TB) among HIV-positive injecting drug users (IDUs) may fuel the TB epidemic in the general population of Romania. We determined the frequency and characteristics of TB in HIV-infected IDUs referred to a national centre. METHODS: Prospective observational cohort study of all newly-diagnosed HIV-positive IDUs admitted to Victor Babes Hospital, Bucharest, between January 2009 and December 2014. Socio-demographics, clinical characteristics and outcomes of HIV/TB co-infected IDUs were compared to HIV-positive IDUs without TB. RESULTS: 170/598 (28.5%) HIV-infected IDUs were diagnosed with TB. The prevalence increased from 12.5% in 2009 to 32.1% in 2014 (P < 0.001). HIV/TB co-infected individuals had lower median CD4 cell counts 75 (vs. 450/mm3 , P < 0.0001) and higher median HIV viral loads 5.6 log10 (vs. 4.9 log10 , P < 0.0001) when presenting to healthcare services. 103/170 (60.6%) HIV/TB co-infected IDUs were diagnosed with pulmonary TB. Resistant Mycobacterium tuberculosis strains were common, with 18/105 (17.1%) of patients having Multi-Drug Resistant (MDR) disease. Higher mortality rate was associated with TB co-infection (P < 0.0001), extra-pulmonary TB (P = 0.0026) and extensively drug resistant TB (P = 0.024). CONCLUSIONS: Tuberculosis (TB) is an increasing problem in HIV-infected IDUs in Romania. Presentation is often with advanced HIV, significant TB drug resistance and consequent outcomes are poor.

European AIDS Clinical Society Second Standard of Care Meeting, Brussels 16-17 November 2016: a summary.

The European AIDS Clinical Society (EACS) organized a second meeting on Standard of Care in Europe on November 16-17 th, 2016. The aims of the meeting were to discuss and propose actions on three topics, namely: Adherence to guidelines for treatment initiation, treatment monitoring and outcomes, Retention in care and HIV and tuberculosis co-infection. Several actions need to be implemented in order to further improve quality of care and treatment of HIV in Europe. A common ground for standard of care, based on the EACS Guidelines should be established throughout Europe. EACS plans to interact with policy makers and other stakeholders to insure this common minimal level of standard of care, in particular for initiating of ART, accessibility of drugs and monitoring of ART with viral load. Progress should be made to monitor retention in care, prevent lost to follow and insure return to care. Improving integration of services and accessibility to care play a major role. Integration is also key for optimizing care of HIV-tuberculosis co-infection, as well as diagnosis and prevention of tuberculosis in population at risk. The Standard of Care meeting organized every other year by EACS provides a unique opportunity to monitor progresses and pitfalls in HIV patient care throughout Europe. It is also a forum for advocacy towards policy makers and other stakeholders to constantly improve HIV patient global management, aiming to provide the same level of quality on the whole continent.

Anatomic-imaging correlations of lumbar disk-vertebral morphometric indices / Correlaciones anatomopatológicas de los índices morfométricos disco-vertebral lumbar

SUMMARY: This study represents a morphometric assessment of the anterior segment of the lumbar spine, focused on the vertebral body - intervertebral disk assembly, calculating some specific indicators and then completing direct morphometry data with the data resulting from the imaging interpretation and subsequently correlating the same to map an anatomic-imaging model. The study was carried out with anatomic items from personal archive and images obtained from Computer Tomography (CT) and Magnetic Resonance Imaging (MRI) assessment. The morphometric assessment was carried out for intervertebral disks, the disk height in the anterior and posterior sections and correlated with the disk angle degree. Direct morphometric data was compared and correlated with the data resulting from the imaging interpretation. Direct morphometric assessment was carried out for 11 vertebral blocks; the vertebral blocks were sectioned and turned into 22 vertebral semi-blocks allowing easy access to absolutely all dimensional values pursued, including the ones covered by the posterior arc. The assessment of imaging data was made with CT, CT 3D and MRI investigations from the 120 subjects in the study. The disk sizes were assessed by direct measurements on the anatomic items and directly measured by means of the software for modern imaging examination. In case of significant differences between the vertebral bodies, the calculation of disk sizes was made indirectly, on grounds of the geometric interpretation of the vertebral body face sizes. The vertebral body / intervertebral disk (IVD) assembly represents a dynamic structure, permanently subject to changes and adaptation, IVD being capable of incurring changes for the entire life time, including growth changes; the growth, however, is not lineal, but a succession of thickening and getting thinner, in full concordance with the structural stresses and changes occurring inside.

RESUMEN: El estudio representa una evaluación morfométrica del segmento anterior de la columna lumbar, centrado en el conjunto del cuerpo vertebral - disco intervertebral, calculando algunos indicadores específicos y completando los datos morfométricos directos. El objetivo del trabajo fue mapear un modelo de imagen anatómica con los datos de la interpretación de la imagen, posteriormente correlacionando los datos. El estudio se llevó a cabo con artículos anatómicos de archivos personales y de las imágenes obtenidas de tomografía computarizada (TC) y resonancia magnética (RM) de evaluación. La evaluación morfométrica se realizó en los discos intervertebrales, la altura del disco en las secciones anterior y posterior y se correlacionó con el grado del ángulo del disco. Se compararon los datos morfométricos directos y se correlacionaron con los datos resultantes de la interpretación de la imagen. Se realizó una evaluación morfométrica directa de 11 bloques vertebrales; Los bloques vertebrales se seccionaron y se convirtieron en 22 semibloques vertebrales permitiendo el fácil acceso a todos los valores dimensionales, incluyendo aquellos cubiertos por el arco posterior. La evaluación de los datos de imagen se realizó en 120 sujetos con CT, CT 3D y MRI. Los tamaños de los discos se evaluaron mediante medidas directas de los elementos anatómicos y se midieron con el software para la examinación de imágenes. En caso de diferencias significativas entre los cuerpos vertebrales, el cálculo de los tamaños de los discos se realizó indirectamente, debido a la interpretación geométrica de los tamaños de la cara del cuerpo vertebral. El conjunto cuerpo vertebral / disco intervertebral (CVDV) representa una estructura dinámica, permanentemente sujeta a transformaciones y adaptación, siendo (CVDV) capaz de incurrir en cambios durante toda la vida, incluyendo aquellos relacionados con crecimiento. El crecimiento, sin embargo, no es lineal, sino una sucesión de engrosamiento y adelgazamiento, en plena concordancia con las tensiones estructurales y los cambios que se producen en su interior.

Euroguidelines in Central and Eastern Europe (ECEE) conference and the Warsaw Declaration - a comprehensive meeting report.

OBJECTIVES: The objective of this paper is to summarize the outcomes of the Euroguidelines in Central and Eastern Europe (ECEE) conference held in Warsaw in February 2016. The main aim of this conference was to facilitate a discussion on European AIDS Clinical Society (EACS) guidelines implementation across the region and neighbouring countries and to present the current obstacles in benchmarking HIV care in Europe. METHODS: During a 2-day meeting, there were country-based presentations using a predefined template so as to make the data comparable and focus the discussion. Areas covered were country epidemiology, surveillance, national strategy for treatment and prevention, standards of care, access to care and treatment availability. Each participant filled in a questionnaire investigating HIV guidelines usage per country. RESULTS: In total, 16 Central and Eastern Europe (CEE) and neighbouring countries were represented at the conference: Albania, Armenia, Belarus, Croatia, Czech Republic, Estonia, Georgia, Hungary, Lithuania, Moldova, Poland, Romania, Russia, Serbia, Slovakia and Turkey. EACS guidelines version 7.1 were used in 14 (87%) countries. In 11 (69%) countries, national guidelines were available, of which eight had been recently updated. Half of the countries declared that they use World Health Organization (WHO) and Department of Health and Human Services (DHHS) guidelines, over one-third the European Centre for Disease Prevention and Control (ECDC) HIV testing guidelines and one in five the International Antiviral Society-USA (IAS-USA) Panel guidelines from 2012. CONCLUSIONS: Participants declared their will to promote the widespread use of EACS guidelines for HIV infection in the CEE region and neighbouring countries by signing the Warsaw Declaration. They also emphasized the need to increase publishing of data from national cohorts in that region.

ADIPONECTIN CORRELATION WITH BIOCLINICAL BENEFITS OF USING NATURAL THERAPEUTIC FACTORS IN KNEE OSTEOARTHRITIS.

CONTEXT AND OBJECTIVE: The new insights in the pathogenesis of osteoarthritis (OA) reveal the implications of adipocytokines. This study aims to analyze the correlations between the serum value of adiponectin and the clinical rehabilitation effects in patients diagnosed with knee OA, admitted and treated in the complex balneal resort of Techirghiol lake. SUBJECTS AND METHODS: The prospective randomized clinical study included 23 patients in the study group, diagnosed with knee OA according to ACR criteria, and a matching control group of 23 subjects. Serum level of adiponectin (using ELISA technique), uric acid, triglycerides, cholesterol, HDL-cholesterol and clinical response using a visual analog scale (VAS) were evaluated in all patients on their admission day and after 10 days of balneal treatment. Control group benefited from the same procedures except for cold mud therapy and mineral water baths. RESULTS: Plasma adiponectin levels (23.73±6.44 ng/dL) were statistically higher (p<0.05) in the study group compared to the control group (18.15±6.49 ng/dL). The mean VAS in both groups was decreased (p<0.005) compared to the initial moment. CONCLUSIONS: Cold peloidotherapy combined with physical therapy and balneal factors induces serum adiponectin elevation and improves knee pain in OA. Therapeutic properties of Techirghiol mud still need further research.

European AIDS Clinical Society Standard of Care meeting on HIV and related coinfections: The Rome Statements.

OBJECTIVES: The objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future. METHODS: Data-driven presentations were given on specific topics followed by interactive panel discussions. RESULTS: In Eastern European countries, the epidemic is largely driven by injecting drug use, in contrast with Western Europe where the infection mainly occurs through heterosexual contact. A high proportion of people living with HIV remain unaware of their infection. Substantial differences exist in Eastern Europe and Central Asia with respect to treatment coverage, regimen availability and continuity of drug supply. In 2012, tuberculosis case notification rates were 5-10 times higher in Eastern Europe compared with Western Europe, with an alarming proportion of newly diagnosed multi-drug-resistant cases. Hepatitis C is widespread in selected geographical areas and risk groups. CONCLUSIONS: The key conclusion from the meeting was that a high-priority group of actions could be identified, including: increasing HIV awareness and testing, improving training for health care providers, ensuring equitable patient access to treatments and diagnostics for HIV and comorbidities, and implementing best practices in infection control and treatment of HIV-infected patients coinfected with tuberculosis and hepatitis C virus, for whom direct acting antiviral treatment. should be considered.

A phase I pharmacokinetic study of the vascular disrupting agent ombrabulin (AVE8062) and docetaxel in advanced solid tumours.

BACKGROUND: The vascular disrupting agent ombrabulin shows synergy with docetaxel in vivo. Recommended phase II doses were determined in a dose escalation study in advanced solid tumours. METHODS: Ombrabulin (30-min infusion, day 1) followed by docetaxel (1-h infusion, day 2) every 3 weeks was explored. Ombrabulin was escalated from 11.5 to 42 mg m(-2) with 75 mg m(-2) docetaxel, then from 30 to 35 mg m(-2) with 100 mg m(-2) docetaxel. Recommended phase II dose cohorts were expanded. RESULTS: Fifty-eight patients were treated. Recommended phase II doses were 35 mg m(-2) ombrabulin with 75 mg m(-2) docetaxel (35/75 mg m(-2); 13 patients) and 30 mg m(-2) ombrabulin with 100 mg m(-2) docetaxel (30/100 mg m(-2); 16 patients). Dose-limiting toxicities were grade 3 fatigue (two patients; 42/75, 35/100), grade 3 neutropaenic infection (25/75), grade 3 headache (42/75), grade 4 febrile neutropaenia (30/100), and grade 3 thrombosis (35/100). Toxicities were consistent with each agent; mild nausea/vomiting, asthaenia/fatigue, alopecia, and anaemia were common, as were neutropaenia and leukopaenia. Diarrhoea, nail disorders and neurological symptoms were frequent at 100 mg m(-2) docetaxel. Pharmacokinetic analyses did not show any relevant drug interactions. Ten patients had partial responses (seven at 30 mg m(-2) ombrabulin), eight lasting >3 months. CONCLUSIONS: Sequential administration of ombrabulin with 75 or 100 mg m(-2) docetaxel every 3 weeks is feasible.

Multivariate comparison of elemental concentrations in human teeth.

R-mode factor analysis was applied to characterize the chemical composition of human teeth investigated by particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and X-ray fluorescence (XRF) techniques. The approach developed in this study enabled the separation between essential mineral teeth components and the pollutants deposited in teeth tissues during the human life. The three independent sources of metals incorporated in human teeth were found. The first source, representing about 43% of the variance of the concentration data, was characterized by pollutant elements of power industry emissions. The second factor was loaded with toxic elements of general urban pollution. The third factor represented the tooth source as it contained mainly large fractions of the mineral components of the tooth tissue as Ca and K.

Primary diffuse large B-cell non-Hodgkin lymphoma of the paranasal sinuses: a report of 14 cases.

Sinonasal lymphoma (SL) is a rare form of extranodal lymphoma. Of 33 SL cases, 14 consecutive diffuse large B-cell lymphomas were treated with CHOP (adriamycin, cyclophosphamide, vincristine and prednisone) or CHOP-like chemotherapy regimen. Ten achieved complete remission (CR) and three achieved a partial remission. With a median follow-up period of 80 months, seven patients relapsed or progressed [one case including central nervous system (CNS) progression]. Four of the relapses involved the CNS. Eight patients were alive, including seven in CR and six patients had died of their lymphoma. This observation strongly suggests that CNS prophylaxis should be used in SL.

[Isolated neurologic disorders disclosing Biermer's disease in young subjects]. / Troubles neurologiques isolés révélant une maladie de Biermer chez le sujet jeune.

INTRODUCTION: In young subjects, the discovery of a cobalamine deficiency (Biermer's disease) at the time of neuropsychiatric disorders even of isolated MRI anomalies is a rare event (less than 0.01%). EXEGESIS: We report two observations of cobalamine deficiency, in patients 30 and 37 years old, revealed by acroparesthesia and spontaneous hypersignal in the T2 sequence of MRI and by a peripheral sensitive neuropathy respectively. CONCLUSION: The neuropsychiatric demonstrations of pernicious anemia are polymorphic with, sometimes, isolated spinothalamic attacks. The MRI can contribute to the diagnosis but more often leads to an erroneous diagnosis. Our observations are of special interest because symptoms occurred apart from supplementation of folates and recovered ad integrum with an early treatment by vitamin B12.

[Is there a place for interferon-alpha in the treatment strategy of multicentric Castleman's disease?]. / Y a-t-il une place pour l'interféron-alpha dans la stratégie thérapeutique de la maladie de Castleman multicentrique?

INTRODUCTION: Castleman's disease is an unusual condition of unknown cause, consisting of massive proliferation of lymphoid tissue. Two forms (localized and multicentric) have been described. Interleukin-6 (IL-6) is at the core of the disease, being responsible for most of the clinical and biological signs that may be observed. Despite the benignancy of this pre-lymphoma condition, its course is usually aggressive and of poor prognosis in regard to the multicentric form. No consensus regarding treatment has been defined. Available data on the multicentric form of the disease are to scarce to allow any conclusion about the treatment timing and type of chemotherapy best suited to this condition. We report the case of a patient in whom interferon alpha (IFN-alpha) was used as first line treatment. EXEGESIS: The case of a 52-year-old man with multicentric Castleman's disease combined with high IL-6, in whom, however, testing for human herpes virus-8 proved to be negative, is described. Interferon alpha (4.5 MU/m2 three times per week during 18 months) administered as first line treatment induced dramatic improvement in the patient's general condition and normalization of the tumoral syndrome. Moreover, biological parameters and IL-6 returned to normal. Two years after interferon disruption, complete remission is still present. CONCLUSION: On the basis of the present data and those of two previous observations, anti-IL-6 and anti-infective properties of IFN-alpha are discussed. Treatment of multicentric Castleman's disease is based on corticosteroids and drugs derived from those pertaining to treatment of malignant lymphomas. Our results indicate that IFN-alpha is truly directed against Castleman's disease and has less toxicity than drugs usually prescribed. This argues for early use of IFN-alpha in Castleman's disease, in association or not with corticosteroids.

Clinical manifestations in the West Nile virus outbreak.

During the summer of 1996 an unusual clustering of meningoencephalitis cases was recorded in the Capital City, Bucharest, and in some areas from South-East Romania. After an initial suspicion of an enteroviral etiology was discarded, the West Nile etiology was confirmed by specific antibodies demonstration through hemagglutination-inhibition and ELISA tests. This study included 251 patients with the diagnoses of West Nile acute encephalitis (166 cases), acute meningitis (57 cases) and acute febrile disease (33 cases). The patients' age ranged from 1 to 89 years (mean 51.1 years). The most frequent clinical manifestations were: fever (95.7% of cases), cephalalgia (92.6%), stiffness of the neck (89.1%), vomiting (62.5%), marked asthenia (46.5%), myalgia (28.9%). In addition, patients with encephalitis exhibited: alteration of consciousness (89.2% of cases), tremor of extremities (40.4%), ataxia (44%), paralysis (15.1%). The fatality rate was 15.1% in acute encephalitis, 1.8% in acute meningitis and 0% in the acute febrile disease.

[Changes in the antibacterial activity of nitrofurantoin preparations induced by peptone and hydrolysates]. / Modificari in activitatea antibacteriana a preparatului nitrofurantoin determinate de peptona si hidrolizate.

The determination of the activity of the product nitrofurantoin (10 and 100 mcg) versus 324 strains of Gram-negative bacteria showed that the diameter of the inhibition zones and the MIC values on a medium with a definite composition (7SG) are considerably larger than on the Mueller-Hinton (MH) medium, in the bacto-tryptose (BT) medium. An increase with 8-12 mm phi or with 2-4 binary dilutions changes the interpretation from resistant, on the MH and BT media into sensitive on the 7SG medium. The low results recorded on the conventional media reveal the existence of an antagonism between peptone and nitrofurantoin, similar to that known for sulfamides. The authors believe that the peptone antagonism has hindered the knowledge of the activity of the nitrofurfural derivatives and the correct assessment of the bacteria sensitivity. They also consider questionable the elimination tendency of the small dosage of microtablets of nitrofurantoin (10 mcg) and sulfamide (30 mcg), since their apparent insufficiency might be due less to the inadequate contraction of substances and more to the inadequate testing media. The results plead for the use of the media with definite chemical composition sulfamide and nitrofuran antagonists free and for reconsideration of several methodologic problems: use of the media with definite chemical composition; introduction of an intermediary dosage of maximum 100 mcg/microtablet; reassessment of the sensitivity categories for sulphafurazole and nitrofurantoin.