Publications by authors named "Igor Karpov"

27 Publications

  • Page 1 of 1

Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory.

Tuberc Res Treat 2021 2;2021:6646239. Epub 2021 Apr 2.

International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.

Background: To cure drug-resistant (DR) tuberculosis (TB), the antituberculous treatment should be guided by drug-susceptibility testing (DST). In this study, we compared conventional DST performed in Minsk, Belarus, a TB DR high-burden country, with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, for TB/HIV coinfected patients. Subsequently, DST results were related to treatment regimen and outcome.

Methods: Thirty TB/HIV coinfected patients from Minsk were included and descriptive statistics applied.

Results: Based on results from Minsk, 10 (33%) TB/HIV patients had drug-sensitive TB. Two (7%) had isoniazid monoresistant TB, 8 (27%) had multidrug-resistant (MDR) TB, 5 (17%) preextensive drug-resistant (preXDR) TB, and 5 (17%) had extensive drug-resistant (XDR) TB. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For the second-line anti-TB drugs, discrepancies were more pronounced. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. Initially, all patients received standard anti-TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. However, this was only suitable for 40% of the patients based on DST. On average, DR-TB patients were changed to 4 (IQR 3-5) active drugs after 1.5 months (IQR 1-2). After treatment adjustment, the treatment duration was 8 months (IQR 2-11). Four (22%) patients with DR-TB received treatment for >18 months. In total, sixteen (53%) patients died during 24 months of follow-up.

Conclusions: We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed. This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Carefully designed individualized treatment regimens in accordance with DST patterns will likely improve patients' outcome and reduce transmission with drug-resistant strains.
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http://dx.doi.org/10.1155/2021/6646239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035031PMC
April 2021

Clinical efficacy of pneumococcal vaccination in multiple myeloma patients on novel agents: Results of a prospective clinical study.

Vaccine 2020 06 14;38(30):4713-4716. Epub 2020 May 14.

Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology, Belarus.

Introduction: Among the high risk groups, patients with multiple myeloma (MM) have one of the highest incidence of invasive pneumococcal disease, mainly pneumonias. Recent changes in MM treatment have now led to an increase of survival, while the infection-related mortality remains high. The question of efficacy of pneumococcal vaccination in patients receiving novel target agents has not been clinically investigated before.

Patients And Methods: We have introduced the 3-dose vaccination regimen by 13-valent pneumococcal conjugate (PCV13) vaccine between the treatment courses with novel target agents (bortezomib, lenalidomide, ixazomib) with a minimum of 1 month interval. The incidence of pneumonias during the one-year observation period was taken as a primary outcome in this registered clinical trial.

Results: From 2017 to 2020, we have prospectively included 18 adult patients who were vaccinated by PCV13 along with 18 patients of a control matched group. No adverse effects of vaccination were registered in the study. We have observed an independent effect of PCV13 vaccination on the incidence of pneumonias. The absolute risk reduction of pneumonias in patients received PCV13 vaccination was 33.3%. Number needed to treat for PCV13 vaccination in multiple myeloma patients receiving novel agents was 3.0; (95% CI 1.61-22.1; p = 0.0571).

Conclusion: Therefore, we have shown the clinical effectiveness of PCV13 vaccination schedule based on 3 doses given with a minimum 1 month interval between the courses of novel agents in multiple myeloma patients, despite the expected decrease in immunological response to vaccination during target and immunotherapy. ClinicalTrials.gov Identifier: NCT03619252.
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http://dx.doi.org/10.1016/j.vaccine.2020.05.024DOI Listing
June 2020

Diffusion processes modeling in magnetic resonance imaging.

Insights Imaging 2020 Apr 28;11(1):60. Epub 2020 Apr 28.

Central Institute of Traumatology and Orthopaedics named after N. N. Priorov, 10, ul. Priorova, Moscow, 127299, Russia.

Background: The paper covers modern approaches to the evaluation of neoplastic processes with diffusion-weighted imaging (DWI) and proposes a physical model for monitoring the primary quantitative parameters of DWI and quality assurance. Models of hindered and restricted diffusion are studied.

Material And Method: To simulate hindered diffusion, we used aqueous solutions of polyvinylpyrrolidone with concentrations of 0 to 70%. We created siloxane-based water-in-oil emulsions that simulate restricted diffusion in the intracellular space. To obtain a high signal on DWI in the broadest range of b values, we used silicon oil with high T: cyclomethicone and caprylyl methicone. For quantitative assessment of our phantom, we performed DWI on 1.5T magnetic resonance scanner with various fat suppression techniques. We assessed water-in-oil emulsion as an extracorporeal source signal by simultaneously scanning a patient in whole-body DWI sequence.

Results: We developed phantom with control substances for apparent diffusion coefficient (ADC) measurements ranging from normal tissue to benign and malignant lesions: from 2.29 to 0.28 mm/s. The ADC values of polymer solutions are well relevant to the mono-exponential equation with the mean relative difference of 0.91%.

Conclusion: The phantom can be used to assess the accuracy of the ADC measurements, as well as the effectiveness of fat suppression. The control substances (emulsions) can be used as a body marker for quality assurance in whole-body DWI with a wide range of b values.
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http://dx.doi.org/10.1186/s13244-020-00863-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188746PMC
April 2020

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions.

World J Gastroenterol 2019 Aug;25(29):3897-3919

Medical Affairs, Mylan Pharmaceuticals Private Limited, Kadubeesanahalli, Bengaluru 560103, India.

Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of region-specific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.
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http://dx.doi.org/10.3748/wjg.v25.i29.3897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689802PMC
August 2019

Combination of sepsis biomarkers may indicate an invasive fungal infection in haematological patients.

Biomarkers 2019 Jun 4;24(4):401-406. Epub 2019 Apr 4.

b Minsk Scientific Practical Center of Surgery, Transplantation and Hematology , Minsk , Belarus.

Invasive fungal infections are a major threat to a large cohort of immunocompromised patients, including patients with chemotherapy-associated neutropenia. Early differential diagnosis with bacterial infections is often complicated, which leads to a delay in empirical antifungal therapy and increases risk for adverse outcome. Accessibility and performance of specific fungal antigen and PCR-tests are still limited, while sepsis biomarkers are more broadly used in most settings currently. Haematological patients hospitalized to receive chemotherapy with proven or probable invasive fungal infection or microbiologically proven bacterial bloodstream infection were included in the study. C-reactive protein was assessed daily during the profound neutropenia period, while procalcitonin or presepsin were measured during the first 48 hours after the onset of febrile episode. There were totally 64 patients included in the study, 53 with bacterial bloodstream infections and 11 with invasive fungal infections. Combination of CRP >120 with PCT <1.25 or presepsin <170 was shown to be a possible combined biomarker for invasive fungal infections in immunocompromised patients, with areas under the ROC-curves: 0.962 (95% CI 0.868 to 0.995) for PCT-based combination and 0.907 (95% CI 0.692 to 0.990) for presepsin-based combination.
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http://dx.doi.org/10.1080/1354750X.2019.1600023DOI Listing
June 2019

People who inject drugs remain hard-to-reach population across all HIV continuum stages in Central, Eastern and South Eastern Europe - data from Euro-guidelines in Central and Eastern Europe Network.

Infect Dis (Lond) 2019 04 21;51(4):277-286. Epub 2019 Feb 21.

i Hospital for Infectious Diseases Medical University of Warsaw , Warsaw , Poland.

Background/objectives: Inadequate HIV care for hard-to-reach populations may result in failing the UNAIDS 90-90-90 goal. Therefore, we aimed to review the HIV continuum of care and hard-to-reach populations for each step of the continuum in Central, Eastern and South Eastern Europe.

Methods: Euro-guidelines in Central and Eastern Europe (ECEE) Network Group were created in February 2016. The aim of the network was to review the standards of HIV care in the countries of the region. Information about each stage of HIV continuum of care and hard-to-reach populations for each stage was collected through on-line surveys. Respondents were ECEE members chosen based on their expertise and involvement in national HIV care. Data sources (year 2016) used by respondents included HIV Clinics electronic databases, Institutes of Public Health, Centres for AIDS Prevention, and HIV Programme Reviews.

Results: The percentage of people living with HIV (PLHIV) linked to HIV care after HIV diagnosis was ranged between 80% and 96% in Central Europe, 51% and 92% in Eastern Europe and 80% and 100% in South-Eastern Europe. The percentage of PLHIV who are on ART was ranged from 80% to 93% in Central Europe, 18% to 92% in Eastern Europe and 80% to 100% in South-Eastern Europe. The percentage of people virologically suppressed while on ART was reported as 70-95%, 12-95% and 62-97% in Central, Eastern, and South Eastern Europe, respectively. All three regions reported people who inject drugs (PWID) as hard-to-reach population across all HIV continuum stages. Migrants were the second most reported hard-to-reach population. The proportion of late presenters among newly diagnosed ranged between 20% and 55%, 40% and 55% and 48% and 60% in Central, Eastern and South Eastern Europe, respectively. Four countries reported ARVs' delivery delays resulting in treatment interruptions in 2016: two (25%) in South-Eastern, one (20%) in Central and 1 (16.7%) in Eastern Europe.

Conclusion: Irrespective of the diversity in national HIV epidemics, countries from all three regions reported PWIDs as hard-to-reach population across all HIV continuum stages. Some countries are close to the UNAIDS 2020 goals, others need to strive for progress. However, differences in data sources and variations in definitions limit the utility of continuum of care as a comparative tool.
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http://dx.doi.org/10.1080/23744235.2019.1565415DOI Listing
April 2019

Persistent disparities in antiretroviral treatment (ART) coverage and virological suppression across Europe, 2004 to 2015.

Euro Surveill 2018 05;23(21)

The members of the EuroSIDA Study Group are acknowledged at the end of the article.

Background: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection.

Aim: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA < 500 copies/mL) across Europe and explored temporal trends.

Methods: In three cross-sectional analyses in 2004-05, 2009-10 and 2014-15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression.

Results: Overall, the percentage of people on ART increased from 2004-05 (67.8%) to 2014-15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004-05, 87.7% in 2014-15). However, the rate of improvement over time varied significantly between regions (p < 0.01). In 2014-15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014-15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13-0.21) in Eastern Europe.

Conclusions: Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.21.1700382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152212PMC
May 2018

Decolonization of Intestinal Carriage of MDR/XDR Gram-Negative Bacteria with Oral Colistin in Patients with Hematological Malignancies: Results of a Randomized Controlled Trial.

Mediterr J Hematol Infect Dis 2018 1;10(1):e2018030. Epub 2018 May 1.

City clinical hospital №9, Minsk, 220045, Semashko str., 8, Belarus.

Background: Intestinal colonization by MDR/XDR gram-negative bacteria leads to an increased risk of subsequent bloodstream infections (BSI) in patients receiving chemotherapy as a treatment for hematologic malignancies.

Objectives: The objective of this study was to evaluate the efficacy of oral colistin in eradicating the intestinal carriage of MDR/XDR Gram-negative bacteria in patients with hematological malignancies.

Methods: In a tertiary hematology center, adult patients with intestinal colonization by MDR/XDR Gram-negative bacteria were included in a randomized controlled trial (RCT) during a period from November 2016 to October 2017. Patients were treated with oral colistin for 14 days or observed with the primary outcome set as decolonization on day 21 post-treatment. Secondary outcomes included treatment safety and changes in MICs of isolated microorganisms. ClinicalTrials.gov Identifier: NCT02966457.

Results: Short-time positive effect (61.3% vs 32.3%; OR 3.32; 95% CI 1.17-9.44; p=0.0241) was demonstrated on the day 14 of colistin treatment, without any statistical difference on day 21 post-treatment. The incidence of BSI in decolonization group was lower in the first 30 days after the intervention (3.2% vs. 12.9%), but overall in the 90-day observation period, it did not show any advantages comparing to control group (log-rank test; p=0.4721). No serious adverse effects or increase in resistance to colistin was observed.

Conclusions: This study suggests that in hematological patients the strategy of selective intestinal decolonization by colistin may be beneficial to decrease the rate of MDR/XDR Gram-negative intestinal colonization and the risk of BSI in the short-term period, having no long-term sustainable effects.
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http://dx.doi.org/10.4084/MJHID.2018.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937973PMC
May 2018

Mesenchymal stem cells transplantation in hematological patients with acute graft-versus-host disease: characteristics and risk factors for infectious complications.

Ann Hematol 2018 May 29;97(5):885-891. Epub 2018 Jan 29.

City Clinical Hospital №9, Semashko Str., 8, 220045, Minsk, Belarus.

The role of MSCs in infection prevention and treatment is still discussed in transplant and hematological patients. The spectrum and risk factors for infections after MSCs transplantation in patients with acute GVHD have not been studied before. To determine the risk factors and spectrum of infectious complications in patients received mesenchymal stem cell transplantation as a treatment for acute GVHD. A prospective observational study was performed to evaluate the risk factors and characteristics of infectious complications after MSCs transplantation in adult patients having acute GVHD. Thirty-four episodes of MSCs transplantation in patients with acute GVHD after allogeneic HSCT were enrolled in the study. MSCs were given at a median dose of 1.32 (interquartile range 0.87-2.16) mln cells/kg per infusion at 91 days (interquartile range 31-131 days) after HSCT. Data relating to age, gender, date, and type of transplantation, characteristics of MSCs, infectious agents, and antimicrobial therapy and prevention regimens were prospectively collected in all of the enrolled patients. The episode of proven infectious complication was set as a primary outcome. There were totally 68 patients with acute GVHD in the study; among them there were 34 cases of MSCs transplantation performed. Among the registered infectious episodes were viral infections (CMV-associated disease, EBV-associated disease), invasive pulmonary aspergillosis, bacterial bloodstream infections, and pneumonia. MSCs transplantation has shown no statistically significant association with risk of infectious complications in patients with acute GVHD in a performed multivariate analysis. Among the most frequent infections in acute GVHD, we have described CMV, invasive aspergillosis, and bacterial infections (bloodstream infections or pneumonia). Among risk factors for infectious complications in patients with acute GVHD with/without MSCs transplantation are progression of main disease and neutropenia below 500 cells/mm (for aspergillosis) and unrelated HSCT in the past history and progression of main disease (for bacterial bloodstream infections and pneumonia).
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http://dx.doi.org/10.1007/s00277-018-3250-8DOI Listing
May 2018

Uptake of tenofovir-based antiretroviral therapy among HIV-HBV-coinfected patients in the EuroSIDA study.

Antivir Ther 2018 ;23(5):405-413

CHIP, Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

Background: According to guidelines all HIV-HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV-HBV patients in the EuroSIDA study.

Methods: All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events.

Results: 953 HIV-HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4 T-cell count <350 cells/mm decreased from 85% to 52% in the periods 2002-2006 to 2007-2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events (n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir.

Conclusions: Although use of tenofovir-based cART among HIV-HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.
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http://dx.doi.org/10.3851/IMP3218DOI Listing
September 2019

Ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin for treatment of chronic hepatitis C 1 genotype in the Republic of Belarus.

Clin Exp Hepatol 2017 Sep 25;3(3):164-168. Epub 2017 Sep 25.

Belarusian State Medical University, Belarus.

Aim Of The Study: Aim of the study is to evaluate real-world efficacy of the ombitasvir/ paritaprevir/ ritonavir + dasabuvir ± ribavirin for treatment of chronic hepatitis C 1 genotype.

Material And Methods: The study included 27 patients according to inclusion criteria. Main laboratory studies were performed in all patients at the baseline and during the treatment.

Results: Efficacy of the antiviral therapy was assessed by measuring the SVR12 and the SVR24 along with measuring of viral load during the treatment. The SVR12 and SVR24 rate was 100% (27/27).

Discussion: The results of the treatment were comparable to the results of pivotal, large-scale, randomized clinical trials. There were no serious adverse events during the treatment.
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http://dx.doi.org/10.5114/ceh.2017.70281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5649486PMC
September 2017

First report of ceftriaxone-resistant Streptococcus pneumoniae meningitis in Belarus.

J Glob Antimicrob Resist 2017 12 9;11:188-189. Epub 2017 Sep 9.

Department of Microbiology, Virology and Immunology, Belarusian State Medical University, Minsk, Belarus; Laboratory for Clinical and Experimental Microbiology, The Republican Research and Practical Center for Epidemiology and Microbiology, Minsk, Belarus; Department of Infectious Diseases, Belarusian State Medical University, Minsk, Belarus; Laboratory for Clinical and Experimental Microbiology, The Republican Research and Practical Center for Epidemiology and Microbiology, Minsk, Belarus; Department of Infectious Diseases, Belarusian State Medical University, Minsk, Belarus. Electronic address:

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http://dx.doi.org/10.1016/j.jgar.2017.09.003DOI Listing
December 2017

Association of TNF-α and CCL5 with response to interferon-based therapy in patients with HCV 1 genotype.

Clin Exp Hepatol 2017 Mar 20;3(1):16-22. Epub 2017 Jan 20.

Belarusian State Medical University, Minsk, Belarus.

Aim Of The Study: To evaluate the role of potential genetic predictors -308G/A TNF-α and -403G/A CCL5 in treatment for HCV 1 genotype.

Material And Methods: Treatment results of 130 patients with chronic hepatitis C 1 genotype according to different genotypes of IL28B, CCL5, and TNF-α were analysed using multiple logistic regression.

Results: IL28B genotypes CC/CT/TT were found in 27 (20.8%), 74 (56.9%), and 29 (22.3%) patients. Genotypes GG/GA/AA of -308G/A TNF-α were revealed in 98 (75.4%), 30 (23.1%), and 2 (1.5%) patients. Genotypes GG/GA/AA of -403G/A CCL5 were revealed in 86 (66.2%), 39 (30%), and 5 (3.8%) patients, respectively. The previously known effect of IL28B was observed. IL28B TT genotype decreased end of treatment response (EOTR) rates by a factor of 29.0 (95% CI: 6.4-183). The combination of CCL5 GG and IL28B CT genotypes increased the risk of failure to achieve EOTR by a factor of 28.5 (95% CI: 7.2-160). Genotypes GA and AA of TNF-α (-308) G/A SNP increased the risk of relapse in patients who achieved EOTR (OR = 9.4; 95% CI: 2.4-48).

Conclusions: Practitioners may benefit from using these predictors when considering indications for the antiviral therapy and deciding on the treatment regimen.
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http://dx.doi.org/10.5114/ceh.2017.65279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497450PMC
March 2017

Diagnostic value of sepsis biomarkers in hematopoietic stem cell transplant recipients in a condition of high prevalence of gram-negative pathogens.

Hematol Oncol Stem Cell Ther 2017 Mar 20;10(1):15-21. Epub 2016 Oct 20.

City Clinical Hospital No. 9, Minsk, Belarus.

Objective/background: A decision about the need for antimicrobial therapy in a patient with febrile neutropenia after hematopoietic stem cell transplantation (HSCT) is often complicated because of the low frequency of culture isolation and reduced clinical manifestation of infection. Usefulness and choice of sepsis biomarkers to distinguish bloodstream infection (BSI) from other causes of febrile episode is still argued in HSCT recipients in modern epidemiological situations characterized by the emergence of highly resistant gram-negative microorganisms. In this study a comparative analysis of diagnostic values of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) was performed as sepsis biomarkers in adult patients after HSCT in a condition of high prevalence of gram-negative pathogens.

Methods: A prospective observational clinical study was performed at the Center of Hematology and Bone Marrow Transplantation in Minsk, Republic of Belarus. The biomarkers (presepsin, PCT, and CRP) were assessed in a 4-hour period after the onset of febrile neutropenia episode in adult patients after HSCT. Microbiologically-confirmed BSI caused by a gram-negative pathogen was set as a primary outcome.

Results: Clinical and laboratory data were analyzed in 52 neutropenic patients after HSCT aged 18-79years. Out of the biomarkers assessed, the best diagnostic value was shown in presepsin (area under the curve [AUC]: 0.889, 95% confidence interval [CI]: 0.644-0.987, p<.0001) with 75% sensitivity and 100% specificity, then in PCT (AUC: 0.741, 95% CI: 0.573-0.869, p=.0037) with 62% sensitivity and 88% specificity. The optimal cut-off value for CRP was set as 165mg/L, while it had an average diagnostic value (AUC: 0.707, 95% CI: 0.564-0.825, p=.0049) with low sensitivity (40%) and should not be routinely recommended as a biomarker in adult patients with suspected BSI after HSCT.

Conclusion: Presepsin may be recommended in adult patients with suspected gram-negative BSI after HSCT as a possible additional supplementary test with a cut-off value of 218pg/mL. PCT is inferior to presepsin in terms of sensitivity and specificity, but still shows a good quality of diagnostic value with an optimal cut-off value of 1.5ng/mL. CRP showed an average diagnostic value with low sensitivity (40%) and should not be routinely recommended as a biomarker in adult patients with suspected BSI after HSCT in a condition of high prevalence of gram-negative pathogens.
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http://dx.doi.org/10.1016/j.hemonc.2016.09.002DOI Listing
March 2017

Risk factors for mortality in patients with bloodstream infections during the pre-engraftment period after hematopoietic stem cell transplantation.

Blood Res 2016 Jun 23;51(2):102-6. Epub 2016 Jun 23.

Department of Infectious Diseases, City Clinical Hospital №9, Minsk, Belarus.

Background: Bloodstream infections (BSI) remain a frequent complication during the pre-engraftment period after hematopoietic stem cell transplantation (HSCT), resulting in high mortality rates. This study evaluated risk factors for mortality in hematopoietic stem cell transplant recipients with BSI in the pre-engraftment period.

Methods: This prospective case control study was performed at the Center of Hematology and Bone Marrow Transplantation in Minsk, Republic of Belarus. Data relating to patient age and gender, date and type of transplantation, conditioning chemotherapy regimen, microorganisms isolated from blood, and antibacterial therapy were prospectively collected from all hematopoietic stem cell recipients with microbiologically proven cases of BSI in the pre-engraftment period. The primary outcome was all-cause 30-day mortality after onset of febrile neutropenia.

Results: A total of 135 adult patients with microbiologically proven BSI after HSCT were studied, with 65.2% of cases caused by gram-negative microorganisms and 21.5% by non-fermenting bacteria. Inadequate empiric antibacterial therapy and isolation of carbapenem-resistant non-fermenting gram-negative bacteria (Acinetobacter baumannii and Pseudomonas aeruginosa) were independently associated with increased all-cause 30-day mortality in these patients.

Conclusion: The risk factors for mortality in adult patients with BSI in the pre-engraftment period after HSCT were inadequacy of empirical antibacterial therapy and isolation of carbapenem-resistant A. baumannii or P. aeruginosa.
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http://dx.doi.org/10.5045/br.2016.51.2.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931927PMC
June 2016

Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals.

AIDS 2015 Jun;29(10):1205-15

aUCL, London, UK bCHIP, Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark cDepartment of Medicine I, University of Bonn, Bonn, Germany dBotkin Hospital of Infectious Diseases, St Petersburg eNovgorod Centre for AIDS, Novgorod, Russia fHospital Saint Antoine, Paris, France gBelarus State Medical University, Minsk, Belarus hSacco hospital, Milan, Italy iHospital de Sant Pau, Barcelona, Spain.

Background: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.

Methods: Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.

Results: LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively).

Conclusion: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.
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http://dx.doi.org/10.1097/QAD.0000000000000674DOI Listing
June 2015

Regional differences in self-reported HIV care and management in the EuroSIDA study.

J Int AIDS Soc 2014 2;17(4 Suppl 3):19504. Epub 2014 Nov 2.

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Introduction: EuroSIDA has previously reported a poorer clinical prognosis for HIV-positive individuals in Eastern Europe (EE) as compared with patients from other parts of Europe, not solely explained by differences in patient characteristics. We explored regional variability in self-reported HIV management at individual EuroSIDA clinics, with a goal of identifying opportunities to reduce the apparent inequalities in health.

Methods: A survey (www.chip.dk/eurosida/csurvey) on HIV management was conducted in early 2014 in all currently active EuroSIDA clinics. Responders in EE were compared with clinics in all other EuroSIDA regions combined (non-EE). Characteristics were compared between regions using Fishers exact test.

Results: A total of 80/97 clinics responded (82.5%, 12/15 in EE, 68/82 in non-EE). Participating clinics reported seeing a total of 133,532 patients [a median of 1300 per clinic (IQR 700-2399)]. The majority of clinics requested viral load and CD4 measurements at least every six months for patients on as well as off ART (EE 66.7%, non-EE 75%, p=0,72). Significantly fewer EE clinics performed resistance tests before ART as well as upon treatment failure (Figure 1). Half of the EE clinics indicated following WHO guidelines (EE 50%, non-EE 7.4%, p<0.0001), whereas most non-EE clinics followed EACS guidelines (non-EE 76.5%, EE 41.7%, p=0.017). The majority of EE clinics and ¼ non-EE clinics indicated deferral of ART initiation in asymptomatic individuals until CD4 ≤350 cells/mm(3) (Figure 1). There were no significant regional differences in screening haematology, liver or renal function, which the majority of clinics reported to do routinely. However, EE clinics reported screening significantly less for cardiovascular disease (CVD), and only about half screened for tobacco use, alcohol consumption and drug use (Figure 1). Screening for cervical cancer and for anorectal cancer was low in both regions (Figure 1).

Conclusions: We found significant regional variability in self-reported HIV management across Europe, with less resistance testing, screening for CVD and substance use in EE. EE clinics indicated deferral of ART initiation for longer than non-EE clinics. Adherence to international guidelines for cervical cancer screening was poor in both regions. Whether differences in HIV management are reflected in clinical outcomes deserves further investigation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224929PMC
http://dx.doi.org/10.7448/IAS.17.4.19504DOI Listing
January 2016

Carbapenem-resistant Acinetobacter baumannii in the Republic of Belarus.

J Glob Antimicrob Resist 2014 Sep 9;2(3):201-202. Epub 2014 May 9.

Institute of Antimicrobial Chemotherapy, 46A Kirova Street, Smolensk 214019, Russian Federation.

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http://dx.doi.org/10.1016/j.jgar.2014.04.001DOI Listing
September 2014

Multi-drug-resistant tuberculosis in HIV positive patients in Eastern Europe.

J Infect 2014 Mar 16;68(3):259-63. Epub 2013 Nov 16.

Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.

Observational data from Eastern Europe on the management and outcome of multi-drug-resistant tuberculosis (MDR TB) in HIV positive populations remain sparse in the English-language literature. We compared clinical characteristics and outcomes of 55 patients who were diagnosed with HIV and MDR TB in Eastern Europe between 2004 and 2006 to 89 patients whose Mycobacterium tuberculosis isolates were susceptible to isoniazid and rifampicin. Patients with HIV and MDR TB were young and predominantly male with high rates of intravenous drug use, imprisonment and hepatitis C co-infection. Eighty-four per cent of patients with MDR TB had no history of previous TB drug exposure suggesting that the majority of MDR TB resulted from transmission of drug-resistant M. tuberculosis. The use of non-standardized tuberculosis treatment was common, and the use of antiretroviral therapy infrequent. Compared to those with susceptible tuberculosis, patients with MDR TB were less likely to achieve cure or complete tuberculosis treatment (21.8% vs. 62.9%, p < 0.0001), and they were more likely to die (65.5% vs. 27.0%, p < 0.0001). Our study documents suboptimal management and poor outcomes in HIV positive patients with MDR TB. Implementation of WHO guidelines, rapid TB diagnostics and TB drug susceptibility testing for all patients remain a priority in this region.
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http://dx.doi.org/10.1016/j.jinf.2013.09.034DOI Listing
March 2014

Benchmarking HIV health care: from individual patient care to health care evaluation. An example from the EuroSIDA study.

BMC Infect Dis 2012 Sep 25;12:229. Epub 2012 Sep 25.

Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark.

Background: State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV patients based on four key indicators.

Methods: Four indicators of health care were assessed: Compliance with current guidelines on initiation of: 1) combination antiretroviral therapy (cART); 2) chemoprophylaxis; 3) frequency of laboratory monitoring; and 4) virological response to cART (proportion of patients with HIV-RNA < 500copies/ml for >90% of time on cART).

Results: 7097 EuroSIDA patients were included from Northern (n = 923), Southern (n = 1059), West Central (n = 1290) East Central (n = 1366), Eastern (n = 1964) Europe, and Argentina (n = 495). Patients in Eastern Europe with a CD4 < 200cells/mm(3) were less likely to initiate cART and Pneumocystis jiroveci-chemoprophylaxis compared to patients from all other regions, and less frequently had a laboratory assessment of their disease status. The proportion of patients with virological response was highest in Northern, 89% vs. 84%, 78%, 78%, 61%, 55% in West Central, Southern, East Central Europe, Argentina and Eastern Europe, respectively (p < 0.0001). Compared to Northern, patients from other regions had significantly lower odds of virological response; the difference was most pronounced for Eastern Europe and Argentina (adjusted OR 0.16 [95%CI 0.11-0.23, p < 0.0001]; 0.20[0.14-0.28, p < 0.0001] respectively).

Conclusions: This assessment of HIV health care utilization revealed pronounced regional differences in adherence to guidelines and can help to identify gaps and direct target interventions. It may serve as a tool for the assessment and benchmarking of the clinical management of HIV patients in any setting worldwide.
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http://dx.doi.org/10.1186/1471-2334-12-229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532324PMC
September 2012

Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study.

PLoS One 2012 23;7(7):e41673. Epub 2012 Jul 23.

Medical School, University College London, London, United Kingdom.

Background: Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina.

Methods: 13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death.

Findings: During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis.

Interpretations: There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0041673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402435PMC
February 2013

New equipment for microwave electric field visualization.

Rev Sci Instrum 2012 Jul;83(7):074704

Institute of Solid State Physics of RAS, Chernogolovka, Moscow District 142432, Russia.

We present the operation and design of newly developed, fully automatic equipment for the visualization of microwave electric fields. This equipment enables the observation of microwave field patterns around different objects including metamaterial prototypes and to study the field patterns of various microwave antennas and other objects that have been developed and that interact with a surrounding microwave electromagnetic field. Moreover, the developed prototypes whose interaction with an incident electromagnetic wave is crucial for practical applications can be investigated using size scaling, and hence our equipment can be used for the testing of antennas and other devices that interact with electromagnetic radiation, not only at microwave frequencies, but also at radio frequencies. The performance of our innovative equipment was demonstrated through the investigation of the metamaterial cloak. The frequency behavior of the metamaterial cloak revealed frequency bands with maximum cloaking efficiencies.
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http://dx.doi.org/10.1063/1.4737495DOI Listing
July 2012

Horizontal transmission of the Leningrad-Zagreb mumps vaccine strain: a report of six symptomatic cases of parotitis and one case of meningitis.

Vaccine 2012 Aug 28;30(36):5324-6. Epub 2012 Jun 28.

Belarusian State Medical University, Infectious Diseases Department, Hospital of Infectious Diseases, Kropotkina str., b.76, Minsk 220050, Belarus.

Here we report horizontal symptomatic transmission of the Leningrad-Zagreb (L-Zagreb) mumps vaccine virus. Children who were the source of transmission had been vaccinated with the MMR vaccine (Serum Institute of India) contained L-Zagreb mumps virus. This is the first report of horizontal symptomatic transmission of this vaccine. The etiology of all seven contact cases was confirmed by epidemiological linking, serology and by F, SH, NP and HN mumps virus genes sequencing.
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http://dx.doi.org/10.1016/j.vaccine.2012.06.055DOI Listing
August 2012

The EuroSIDA study: Regional differences in the HIV-1 epidemic and treatment response to antiretroviral therapy among HIV-infected patients across Europe--a review of published results.

Cent Eur J Public Health 2008 Sep;16(3):99-105

Copenhagen HIV Programme, University of Copenhagen, Denmark.

EuroSIDA is a pan-European observational study that follows 14,265 HIV-infected patients from 31 European countries, Israel and Argentina, of which 2,560 are patients from eastern Europe (EE). The study group has performed several analyses addressing regional differences in the HIV-epidemic across Europe, where all countries were divided into five regions: south, west central, north, east central Europe and EE. Significant regional differences in patients' characteristics and pattern of AIDS diagnoses were documented. More patients from EE were diagnosed with tuberculosis compared to other regions. Significantly fewer HIV-infected patients in EE, who fulfilled the criteria for starting combination antiretroviral therapy (cART), actually received cART as compared with other regions of Europe. Those, receiving cART in EE had a lower initial virologic response rate irrespectively of the regimen used, although it has improved within years. Besides, treatment failure was more common in this region. Thus, improvements in the clinical management of HIV patients in EE are urgently needed. Strategies include creating scientific collaborations for HIV clinicians as well as teaching clinicians about the most advanced HIV management at clinically oriented courses held in eastern Europe.
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http://dx.doi.org/10.21101/cejph.a3490DOI Listing
September 2008

Investigation of mumps vaccine failures in Minsk, Belarus, 2001-2003.

Vaccine 2007 Jun 25;25(24):4651-8. Epub 2007 Apr 25.

State Research Center of Virology and Biotechnology Vector, Koltsovo, Novosibirsk Region, Russia.

The purpose of this study was to investigate mumps vaccine failures (VF) in a highly vaccinated population of Minsk, Belarus, and to investigate a possible role for virus strain-specific immunity. During our 3-year study period, 22 adults were admitted to the Infectious Diseases Hospital in Minsk with a diagnosis of mumps. A genotype H1 mumps virus (MuV) strain was identified in all patients. Of 15 patients from whom the paired sera were collected, 9 were confirmed to have been previously vaccinated. Serological examinations indicated primary VF in seven of these cases and secondary VF in two. Despite almost all vaccinated patients possessing MuV specific IgG, few possessed neutralizing antibody to the vaccine strain and titers were nominal. Importantly, none of the sera were able to neutralize a genotype H MuV strain. Our results demonstrate the importance of assaying for neutralizing antibody and support the assertion that antigenic differences between wild type and vaccine MuV strains may play a role in cases of breakthrough infection in vaccinees.
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http://dx.doi.org/10.1016/j.vaccine.2007.04.020DOI Listing
June 2007

Hyperscanning: simultaneous fMRI during linked social interactions.

Neuroimage 2002 Aug;16(4):1159-64

Center for Theoretical Neuroscience, Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.

"Plain question and plain answer make the shortest road out of most perplexities." Mark Twain-Life on the Mississippi. A new methodology for the measurement of the neural substrates of human social interaction is described. This technology, termed "Hyperscan," embodies both the hardware and the software necessary to link magnetic resonance scanners through the internet. Hyperscanning allows for the performance of human behavioral experiments in which participants can interact with each other while functional MRI is acquired in synchrony with the behavioral interactions. Data are presented from a simple game of deception between pairs of subjects. Because people may interact both asymmetrically and asynchronously, both the design and the analysis must accommodate this added complexity. Several potential approaches are described.
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http://dx.doi.org/10.1006/nimg.2002.1150DOI Listing
August 2002
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