Current State of Knee Arthroplasty in Russia: Analysis of 36,350 Сases from the Register of the Vreden National Medical Research Center of Traumatology and Orthopedics

Background.Nowadays the knee arthroplasty register of the Vreden National Medical Research Center of Traumatology and Orthopedics (hereinafter referred to as the Vreden Center) contains clinical and statistical data on more than 39,000 primary and revision knee replacements, that mimics current state of this kind of surgery in Russia. Aimofthestudy to analyze the last decade trends in primary knee arthroplasty in largest Russian arthroplasty center. Methods.Data were obtained from the register of the Vreden Center for the period from 2011 to 2022. Information on knee arthroplasty included epidemiologic and numerous peri-operative data including type of surgery and implant, degree of constrain, primary patella resurfacing etc. Resultsanddiscussion.From 2011 to 2022, 36,350 (92.3%) primary arthroplasties performed at the Vreden Center. The number of interventions increased more than twice: from 1,678 in 2011 to 3,924 in 2022. Similar trends observed in Australia and Sweden, where the number of knee arthroplasties increased by 8.2% and 8% in 2021 compared to 2020, respectively. The frequency of primary patellar resurfacing at the Vreden Center was 2.2% over the entire period of observation. On the contrary, the rate of patella replacement increased from 41% in 2005 to 76.1% in 2021 in Australia and from 24.4% in 2015 to 31.9% in 2020 in Switzerland. The partial knee arthroplasty showed enormous growth more than 14 times: from 0.3% in 2011 to 4.3% in 2022 at the Vreden Center. Worldwide unicompartmental knee replacement is still less popular than total and its number widely varies: 4.2% in the USA, 6.9% in Australia, 9.2% in Canada, 11.9% in Norway, 12.8% in Sweden, and 18.4% in Switzerland. Posterior cruciate ligament (PCL) retaining total knee arthroplasties (TKA) prevailed at the Vreden Center: 68.3%, while in other countries it utilize even more widely: 70.5% in Norway, 75% in New Zealand and 93.5% in Sweden. The total length of hospital stay (LOS) decreased dramatically from 19.6 in 2011 to 8.6 in 2022 at the Vreden Center. Nevertheless, there are still opportunities to improve it: by the way in Canada the average LOS for TKA is 2.3 and the USA 0.8 and 1.7 for partial and total arthroplasty, respectively. Conclusion.The main current trends of knee arthroplasty in Russia are the following: increase the number of surgeries, reduced LOS, TKA without patella resurfacing and with PCL retention, finally the growth of partial knee arthroplasties

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB: HIV study

Objectives: Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods: In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results: A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5-74.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions: Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

Major Challenges in clinical management of TB/HIV coinfected patients in Eastern Europe compared with Western Europe and Latin America

Objectives: rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and methods: between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results: significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00-4.09), prior anti-TB treatment (3.42 (1.88-6.22)), and living in EE (7.19 (3.28-15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90-96% in other regions (p<0.0001). Conclusions: in EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART

Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America.

BACKGROUND: Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens. METHODS: HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients. RESULTS: Of 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72-1.78), virological suppression (aHR, 95%CI: 0.97, 0.76-1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81-1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens. CONCLUSION: In this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months

Major differences in organization and availability of health care and medicines for HIV/TB coinfected patients across Europe

Objectives: The aim of the study was to investigate the organization and delivery of HIV and tuberculosis (TB) health care and to analyse potential differences between treatment centres in Eastern (EE) and Western Europe (WE). Methods: Thirty‐eight European HIV and TB treatment centres participating in the TB:HIV study within EuroCoord completed a survey on health care management for coinfected patients in 2013 (EE: 17 respondents; WE:21; 76% of all TB:HIV centres). Descriptive statistics were obtained for regional comparisons. The reported data on health care strategies were compared with actual clinical practice at patient level via data derived from the TB:HIV study. Results: Respondent centres in EE comprised: Belarus (n = 3), Estonia (1), Georgia (1), Latvia (1), Lithuania (1), Poland (4), Romania (1), the Russian Federation (4) and Ukraine (1); those in WE comprised: Belgium (1), Denmark (1), France (1), Italy (7), Spain (2), Switzerland (1) and UK (8). Compared with WE, treatment of HIV and TB in EE are less often located at the same site (47% in EE versus 100% in WE; P < 0.001) and less often provided by the same doctors (41% versus 90%, respectively; P = 0.002), whereas regular screening of HIV‐infected patients for TB (80% versus 40%, respectively; P = 0.037) and directly observed treatment (88% versus 20%, respectively; P < 0.001) were more common in EE. The reported availability of rifabutin and second‐ and third‐line anti‐TB drugs was lower, and opioid substitution therapy (OST) was available at fewer centres in EE compared with WE (53% versus 100%, respectively; P < 0.001). Conclusions: Major differences exist between EE and WE in relation to the organization and delivery of health care for HIV/TB‐coinfected patients and the availability of anti‐TB drugs and OST. Significant discrepancies between reported and actual clinical practices were found in EE

Epithelial-Immune Cell Crosstalk Determines the Activation of Immune Cells In Vitro by the Human Cathelicidin LL-37 at Low Physiological Concentrations

The only human cathelicidin, LL-37, is a host defense antimicrobial peptide with antimicrobial activities against protozoans, fungi, Gram(+) and Gram(−) bacteria, and enveloped viruses. It has been shown in experiments in vitro that LL-37 is able to induce the production of various inflammatory and anti-inflammatory cytokines and chemokines by different human cell types. However, it remains an open question whether such cytokine induction is physiologically relevant, as LL-37 exhibited its immunomodulatory properties at concentrations that are much higher (>20 μg/mL) than those observed in non-inflamed tissues (1–5 μg/mL). In the current study, we assessed the permeability of LL-37 across the Caco-2 polarized monolayer and showed that this peptide could pass through the Caco-2 monolayer with low efficiency, which predetermined its low absorption in the gut. We showed that LL-37 at low physiological concentrations (<5 μg/mL) was not able to directly activate monocytes. However, in the presence of polarized epithelial monolayers, LL-37 is able to activate monocytes through the MAPK/ERK signaling pathway and induce the production of cytokines, as assessed by a multiplex assay at the protein level. We have demonstrated that LL-37 is able to fulfill its immunomodulatory action in vivo in non-inflamed tissues at low physiological concentrations. In the present work, we revealed a key role of epithelial-immune cell crosstalk in the implementation of immunomodulatory functions of the human cathelicidin LL-37, which might shed light on its physiological action in vivo

Healthcare delivery for HIV-positive people with tuberculosis in Europe

Background: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). Objectives: To verify the differences in TB and HIV services in EE vs. WE. Methods: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. Results: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. Conclusion: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites

New Hybrid Tetrahydropyrrolo[3,2,1-<i>ij</i>]quinolin-1-ylidene-2-thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluation

Despite extensive research in the field of thrombotic diseases, the prevention of blood clots remains an important area of study. Therefore, the development of new anticoagulant drugs with better therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein, we report the synthesis and evaluation of novel pyrroloquinolinedione-based rhodanine derivatives, which were chosen from 24 developed derivatives by docking as potential molecules to inhibit the clotting factors Xa and XIa. For the synthesis of new hybrid derivatives of pyrrolo[3,2,1-ij]quinoline-2-one, we used a convenient structural modification of the tetrahydroquinoline fragment by varying the substituents in positions 2, 4, and 6. In addition, the design of target molecules was achieved by alkylating the amino group of the rhodanine fragment with propargyl bromide or by replacing the rhodanine fragment with 2-thioxoimidazolidin-4-one. The in vitro testing showed that eight derivatives are capable of inhibiting both coagulation factors, two compounds are selective inhibitors of factor Xa, and two compounds are selective inhibitors of factor XIa. Overall, these data indicate the potential anticoagulant activity of these molecules through the inhibition of the coagulation factors Xa and XIa