Microbiological efficiency of the combinations of two carbapenems against antibiotic resistant Klebsiella pneumoniae strains.

Combined antibiotic therapy is widely used for infections caused by carbapenem-resistant K. pneumoniae. The objective of this work was to identify the synergistic activity of combinations of two carbapenems against multidrug- and extensively drug-resistant K. pneumoniae strains producing various types of carbapenemases. For 60 antibiotic-resistant K. pneumoniae strains isolated in 8 cities of Belarus, the minimum inhibitory concentrations (MIC) of colistin and carbapenems were determined by subsequent broth microdilution method, and the genes of carbapenemases and phosphoethanolamine transferases were detected. The checkerboard method was used to determine the sensitivity to the combination of ertapenem and doripenem. High MIC values of carbapenems were revealed for NDM carbapenemase-producing strains (MIC50 of meropenem 64 mg/L, MIC50 of doripenem 64 mg/L). Doripenem was more active; MIC of doripenem ≤ 16 mg/L (low level of resistance) was determined in 28 (46.7%) strains, MIC of meropenem ≤ 16 mg/L - in 8 (13.3% of strains). The effect of potentiating the activity of doripenem with ertapenem at a fixed pharmacokinetic / pharmacodynamic concentration was observed for 20.0% of the strains producing KPC carbapenemase and 29.0% of the strains producing OXA-48 carbapenemase. The potentiating effect was independent of the presence of colistin resistance. Thus, the ability of ertapenem to potentiate the antimicrobial activity of doripenem and meropenem against some of the strains producing serine carbapenemases (KPC and OXA-48) was confirmed. The necessity of routine determination of the true MIC values of carbapenems was shown to optimize their dosage regimens and select the combination antibiotic therapy regimens.

[Open prosthetic repair of descending aortic aneurysm after its primary endoprosthetic repair]. / Otkrytaia operatsiia protezirovaniia anevrizmy niskhodiashchego otdela aorty posle ee pervichnogo éndoprotezirovaniia.

Presented in the article is a clinical case report regarding management of an 82-year-old female patient with late complications after staged treatment for an aneurysm of the descending and abdominal portions of the aorta, with the first stage consisting in endoprosthetic repair of the descending aortic portion and the second stage (after 4 months) in endoprosthetic repair of the abdominal aortic portion. Outpatient computed tomography performed 9 months after endoprosthetic repair of the abdominal aorta revealed an increase in aortic diameter over the distance between two stent grafts in the thoracic and abdominal aortic portions from 44 mm to 76 mm. In May 2019, a repeat operation was performed: resection of the aneurysm of the distal portion of the descending aorta on temporary subclavian-femoral and prosthesis-femoral shunts, with dissection of part of the thoracic stent graft, followed by formation of a proximal anastomosis between the endoprosthesis and a 30-mm linear Dacron prosthesis, and a distal anastomosis above the celiac trunk. The woman was discharged on POD 16. Follow-up computed tomography performed 8 months later demonstrated a type II endoleak from the inferior mesenteric artery and growth of the abdominal aortic aneurysm, thus requiring embolization of the ostium of the inferior mesenteric artery via the system of the superior mesenteric artery, with a good clinical effect and a decrease in the diameter of the aortic abdominal aneurysm.

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.

Abacavir usage patterns and hypersensitivity reactions in the EuroSIDA cohort.

OBJECTIVES: Five to eight per cent of HIV-positive individuals initiating abacavir (ABC) experience potentially fatal hypersensitivity reactions (HSRs). We sought to describe the proportion of individuals initiating ABC and to describe the incidence and factors associated with HSR among those prescribed ABC. METHODS: We calculated the proportion of EuroSIDA individuals receiving ABC-based combination antiretroviral therapy (cART) among those receiving cART after 1 January 2009. Poisson regression was used to identify demographic, and current clinical and laboratory factors associated with ABC utilization and discontinuation. RESULTS: Between 2009 and 2016, of 10 076 individuals receiving cART, 3472 (34%) had ever received ABC-based cART. Temporal trends of ABC utilization were also heterogeneous, with 28% using ABC in 2009, dropping to 26% in 2010 and increasing to 31% in 2016, and varied across regions and over time. Poisson models showed lower ABC utilization in older individuals, and in those with higher CD4 cell counts, higher cART lines, and prior AIDS. Higher ABC utilization was associated with higher HIV RNA and poor renal function, and was more common in Central-East and Eastern Europe and lowest during 2014. During 779 person-years of follow-up (PYFU) in 2139 individuals starting ABC after 1 January 2009, 113 discontinued ABC within 6 weeks of initiation for any reason [incidence rate (IR) 14.5 (95% confidence interval (CI) 12.1, 17.5) per 100 PYFU], 13 because of reported HSR [IR 0.3 (95% CI 0.1, 1.0) per 100 PYFU] and 35 because of reported HSR/any toxicity [IR 4.5 (95% CI 3.2, 6.3) per 100 PYFU]. There were no factors significantly associated with ABC discontinuation because of reported HSR/any toxicity. CONCLUSIONS: ABC remains commonly used across Europe and the incidence of discontinuation because of reported HSR was low in our study population.

Patterns of Cell-Matrix Interactions during Formation the Distraction Bone Regenerates.

Multiple-day distraction regenerate contains a number of foci or zones merging into one another with different structural organization of the fibrocellular basis that reflects successive stages of reparative regeneration. At the moment of the last traction, the central part of the regenerate represents a zone of fibrogenesis (growth zone), which is common for the proximal and distal parts of the distraction regenerate. The other zones are paired and symmetrical: zones of angiogenesis, fibrous osteogenesis (primary), and osteogenesis (secondary). The latter include subzones of resorption, secondary osteogenesis, and functional remodeling.

Adenocarcinoma of the lung with rare insertion mutation in EGFR exon 19 that had partial response to gefitinib: a case report.

AIM: Classic activating mutations L858R and deletions in exon 19 (19del) in the gene for epidermal growth factor receptor (EGFR) are associated with sensitivity of the non-small cell lung cancer (NSCLC) to therapy with tyrosine kinase inhibitors (TKI). Insertions in EGFR exon 19 (19ins) are rare mutations in NSCLC; response of cases with 19ins to TKI is not well studied. Here we report a case of NSCLC with 19ins in a Russian patient who was treated with gefitinib. We also overview cases of 19ins reported in the literature. CASE DESCRIPTION: A 48 years old female Russian patient was diagnosed with adenocarcinoma of the lung (T3N2M1, stage IV). Mutation 19ins was detected in the tumor biopsy by fragment analysis and genotyped by Sanger sequencing as p.I744_K745insKIPVAI. Treatment with gefitinib (250 mg/day) resulted in clinical and radiological improvements scored as partial response that lasted 12 months. CONCLUSION: Treatment with gefitinib of lung adenocarcinoma that carries mutation EGFR 19ins can result in durable response.

[Systemic Antimicrobials Consumption and Expenditures in Departments of Surgery of Multi-Profile Hospitals in the Russian Federation and the Republic of Belarus: Results of Multicentre Pharmacoepidemiological Study].

The results of the systemic antimicrobials (AM) consumption and expenditures assessment in the departments of surgery of multi-profile hospitals in different regions of the Russian Federation and the Republic of Belarus in 2009-2010 based on retrospective collection and analysis of the data from the hospital expenditure notes using ATC/DDD methodology are presented. The average AM consumption and expenditure rates in the above mentioned departments varied from 24.9 DDD/100 bed-days to 61.7 DDD/100 bed-days depending on the department profile, with beta-lactams (cephalosporins and penicillins) share in the consumption being as high as 70-90%, followed by fluoroquinolones and aminoglycosides. Only 55-70% of the consumed AM belonged to the drugs of choice, whereas the improper AM consumption and expenditure rates amounted up to 10-18%. The study outputs can be used for the budget allocation and AM distribution improvement in the departments of surgery, as well as for the development and efficacy control of the local antimicrobial stewardship programs.

Infection-related and -unrelated malignancies, HIV and the aging population.

OBJECTIVES: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. METHODS: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. RESULTS: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/µL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/µL], independent of age, while a CD4 count < 200 cells/µL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40-4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5-5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2-7.2) per 1000 person-years over the same period. CONCLUSIONS: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost-benefit of screening for IURMs in HIV-infected populations.

Detection of the insulating gap and conductive filament growth direction in resistive memories.

Filament growth is a key aspect in the operation of bipolar resistive random access memory (RRAM) devices, yet there are conflicting reports in the literature on the direction of growth of conductive filaments in valence change RRAM devices. We report here that an insulating gap between the filament and the semiconductor electrode can be detected by the metal-insulator-semiconductor bipolar transistor structure, and thus provide information on the filament growth direction. Using this technique, we show how voltage polarity and electrode chemistry control the filament growth direction during electro-forming. The experimental results and the nature of a gap between the filament and an electrode are discussed in light of possible models of filament formation.

Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in the EuroSIDA study.

OBJECTIVES: The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe. METHODS: Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in the study. cART was defined as d4T-containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T. RESULTS: A total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19-20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23-29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16-19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80-0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17-9.98) versus other European regions and HIV RNA > 400 copies/mL (aIRR 3.11; 95% CI 1.60-6.02) versus HIV RNA < 400 copies/mL. CONCLUSIONS: d4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV-positive patients are aware of the potential harmful effects associated with d4T.

Severe bacterial non-aids infections in HIV-positive persons: incidence rates and risk factors.

OBJECTIVES: This study aimed to determine incidence rates (IR) and identify risk factors for severe bacterial non-AIDS infections (SBnAI) requiring hospital admission. METHODS: Data from the prospective EuroSIDA cohort were utilized to determine IRs of first diagnosis of the following SBnAI requiring hospital admission: bacteremia, endocarditis, meningitis, peritonitis, pneumonia, osteitis, and pyolonephritis. Incidence rate-ratios (IRRs) and risk factors were assessed by Poisson regression. RESULTS: During 35,839 person-years of follow-up (PYFU), 275 patients were diagnosed with SBnAI (IR = 7.67 per 1000 PYFU, 95% confidence interval: 6.79-8.64). The most frequent infections were pneumonia (IR = 5.36, 4.63-6.17), bacteremia (IR = 1.14, 0.82-1.55), and pyelonephritis (IR = 0.67, 0.43-1.00). A strong risk factor for SBnAI was reduced estimated glomerular filtration rate [eGFR] (adjusted IRR = 5.07, 2.12-12.1 and IRR = 2.73, 1.63-4.56 for eGFR ≤ 60 and 60.1-90 compared to eGFR > 90, respectively). No current combined antiretroviral therapy (cART) compared with current cART use increased the risk of SBnAI (adjusted IRR = 2.96, 2.03-4.32). Other risk factors for SBnAI included current CD4+ count <350 cells/µL, female gender, age, infection with HIV through IDU, prior AIDS diagnosis, and anaemia. CONCLUSIONS: Enhanced attention directed towards people with comorbidity is warranted to limit the burden of these infections.

[Mumps vaccine virus transmission].

In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.

[Comparison of different methods of molecular-genetic analysis of somatic mutations in K-ras gene in patients with colorectal cancer].

Two approaches to somatic point mutations in 12 and 13 codones of K-ras gene were analyzed: PCR/SSCP/ACRS/sequencing and allele-specific PCR in the real-life regimen (Russian set "KRAS-7M"). The comparison was carried out on 62 examples of genomic DNA extracted from frozen colon carcinomas, which underwent manual dissection. The results obtained in two attempts were consistent in 95,2% (N=59). Specificity and sensitivity of K-ras mutations detection using "KRAS-7M" set were 100 and 96,4% respectively, and 94,1 and 100% respectievly using PCR/SSCP/ACRS/automatic sequencing. False positive results were absent when detecting with "KRAS-7M" and accounted for 2 cases (5,9%) when using PCR/SSCP/ ACRS/automatic sequencing. The only false negative response (3,6%) was obtained analyzing mutations using "KRAS-7M".

Measles in Minsk, Belarus, 2001-2003: clinical, virological and serological parameters.

BACKGROUND: A number of cases of measles have been reported in the Republic of Belarus despite vaccine coverage of 98%. The absence of information on measles virus genotypes circulating in the Republic of Belarus has made it difficult to asses the situation. OBJECTIVES: The purpose of this study was to isolate and sequence measles virus strains from clinical cases in Minsk, Belarus, and to estimate the role of vaccine failure in those cases. STUDY DESIGN: Between 2001 and 2003 years, 14 measles cases admitted to the Hospital of Infectious Diseases of Minsk were enrolled in our study. Clinical, routine laboratory, as well as serological and virological examinations were carried out. Detection of measles antibodies and IgG avidity testing was performed using commercial test kits. All measles cases were confirmed by RT-PCR and phylogenetically characterized. RESULTS: Only 42.9% of the cases met the WHO laboratory criteria for measles, however, all cases were confirmed by RT-PCR. Most of the measles cases were attributed to secondary vaccine failure (SVF). Phylogenetic analysis revealed the presence of genotype A virus strains in 2001 and 2002 with D6 and D7 genotypes in 2003. CONCLUSIONS: For the first time, MVs were genetically characterized in Belarus. Our results suggest that in a highly vaccinated population, most of measles cases represent vaccine failures and are vaccine-modified. Our results also indicate that confirmation of a clinical diagnosis of vaccine-modified measles requires a combination of serological and virological tests.

[Postoperative analgesia in abdominal surgery: a new look at an old problem]. / Posleoperatsionnoe obezbolivanie v abdominal'noi khirurgii: novyi vzgliad na staruiu problemu.

Analgesia in abdominal surgery is a sufficiently complicated problem. The extensive surgeries in the abdominal cavity are concomitant with massive tissue damages and are associated the systematic tissue inflammatory response to an intensity of the pain syndrome and of other postoperative complications. The modern understanding of surgical-trauma pathophysiology is indicative of the necessity to modulate the systemic inflammatory response whose severity is preconditioned not only by postoperative pain intensity but also by surgical results. With respect to the above stated, multi-model analgesia can be regarded as an optimal technique since it presupposes the long-term administration of local anesthetics (preferably 0.2% ropivakain) concurrently with non-steroid anti-inflammatory drugs used preoperatively (the most effective one is lornoxicam).

Effect of embryonic bone tissue on bone regeneration.

Fragmented embryonic bone tissue stimulates bone regeneration. Bone formation starts not from implanted embryonic fragments, but in intact periosteum and endosteum containing cambial cells of the osteodifferon. In rabbits, recovery of damaged radial bone after implantation of fragmented embryonic bone tissue into bone defect was associated with a pronounced periosteal reaction and focal resorption of intact ulnar bone. Consolidation of damaged radial bone without implantation of fragmented embryonic bone tissue was incomplete in all experimental animals.