Mpox across countries from Central and Eastern Europe - 2022 outbreak.

BACKGROUND: The aim of the study was to assess socio-demographical characteristics, clinical presentation, and outcomes in patients diagnosed with mpox. METHODS: A survey on patients diagnosed with mpox was performed in 14 countries from Central and Eastern Europe. Data was compared according to HIV status and country of origin (EU vs. non-EU). Mpox diagnosis was confirmed by RT-PCR from oropharyngeal swabs, skin lesions, and other body fluids. RESULTS: Out of 154 patients confirmed with mpox in 2022, 99.3% were males, with a median age (years) of 35 (IQR 30-39), 90.2% MSM and 48.7% PLWH. Compared to HIV-negative subjects, PLWH had more frequent high-risk behaviours:chemsex (p = 0.015), group sex (p = 0.027), and a history of sexually transmitted infections (STIs) (p = 0.004). Persons from EU were more often PLWH (p = 0.042), MSM (p < 0.0001), had multiple sexual partners (p = 0.025), practiced chemsex (p = 0.008) or group-sex (p = 0.005) and had more often history of STIs (p < 0.0001). The median CD4 cell count/mL at mpox diagnosis was 713 (IQR 486-996) and 73.5% had undetectable HIV VL. The commonest clinical features were fever (108 cases), lymphadenopathy (78), and vesiculo-pustular rash: penile (76), perianal (48), limbs (67). Fifty-one (31%) persons were hospitalized due to complications or epidemiological reasons. Three patients received tecovirimat or cidofovir. The outcome was favorable for all patients, including 4 with severe forms. CONCLUSIONS: Mpox was diagnosed predominantly in young MSM, with high-risk behaviors and history of STIs. Effective contact tracing and vaccination are important strategic pillars to control mpox outbreaks.

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review.

Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and has markedly improved the disease burden and life expectancy of people living with HIV. HIV enters the central nervous system (CNS) early in the course of infection, establishes latency, and produces a pro-inflammatory milieu that may affect cognitive functions, even in the cART era. Whereas severe forms of neurocognitive impairment (NCI) such as HIV-associated dementia have declined over the last decades, milder forms have become more prevalent, are commonly multifactorial, and are associated with comorbidity burdens, mental health, cART neurotoxicity, and ageing. Since 2007, the Frascati criteria have been used to characterize and classify HIV-associated neurocognitive disorders (HAND) into three stages, namely asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). These criteria are based on a comprehensive neuropsychological assessment that presupposes the availability of validated, demographically adjusted, and normative population data. Novel neuroimaging modalities and biomarkers have been proposed in order to complement NCI assessments, elucidate neuropathogenic mechanisms, and support HIV-associated NCI diagnosis, monitoring, and prognosis. By integrating neuropsychological assessments with biomarkers and neuroimaging into a holistic care approach, clinicians can enhance diagnostic accuracy, prognosis, and patient outcomes. This review interrogates the value of these modes of assessment and proposes a unified approach to NCI diagnosis.

Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Addition of macrolide antibiotics to ß-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from observational studies and meta-analyses rather than randomised clinical trials. We investigated if addition of the macrolide clarithromycin to treatment with a ß-lactam antibiotic in this population could improve early clinical response-the new regulatory endpoint for community-acquired pneumonia-and explored the possible contribution of modulation of the inflammatory host response to that outcome. METHODS: The ACCESS trial was a phase 3 prospective, double-blind, randomised controlled trial, in which adults in hospital with community-acquired pneumonia who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin 0·25 ng/mL or more were enrolled in 18 internal medicine departments of public Greek hospitals. Patients were randomly assigned (1:1) by computer-generated block randomisation to standard of care medication (including intravenous administration of a third-generation cephalosporin or intravenous administration of ß-lactam plus ß-lactamase inhibitor combination) plus either oral placebo or oral clarithromycin 500 mg twice daily for 7 days. Investigators, staff, and patients were masked to group allocation. The primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours (ie, day 4 of treatment): (1) decrease in respiratory symptom severity score of 50% or more as an indicator of early clinical response and (2) decrease in SOFA score of at least 30% or favourable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0·25 ng/mL), or both, as an indicator of early inflammatory response. Participants who were randomly assigned and received allocated treatment were included in the primary analysis population. This trial is complete and is registered with the EU Clinical Trials Register (2020-004452-15) and ClinicalTrials.gov (NCT04724044). FINDINGS: Patients were enrolled between Jan 25, 2021, and April 11, 2023, and 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the analysis of the primary endpoint. The primary endpoint was met in 91 (68%) patients in the clarithromycin group and 51 (38%) patients in the placebo group (difference 29·6% [95% CI 17·7-40·3]; odds ratio [OR] 3·40 [95% CI 2·06-5·63]; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 58 (43%) patients in the clarithromycin group and 70 (53%) patients in the placebo group (difference 9·4% [95% CI -2·6 to 20·9]; OR 0·67 [95% CI 0·42 to 1·11]; p=0·14). None of the serious TEAEs was judged to be related to treatment assignment. INTERPRETATION: Addition of clarithromycin to standard of care enhances early clinical response and attenuates the inflammatory burden of community-acquired pneumonia. The mechanism of benefit is associated with changes in the immune response. These findings suggest the importance of adding clarithromycin to ß-lactams for treatment of patients in hospital with community-acquired pneumonia to achieve early clinical response and early decrease of the inflammatory burden. FUNDING: Hellenic Institute for the Study of Sepsis and Abbott Products Operations.

Enterovirus-Rhinovirus-Induced Acute Respiratory Distress Syndrome in Adults: A Case Report and Short Literature Review.

Enteroviruses and rhinoviruses (EV-RV) are small RNA viruses that usually cause the common cold and asthma exacerbations. Although EV-RV-induced acute respiratory distress syndrome (ARDS) is common in children, only scattered reports of ARDS in adults have been published. The diagnosis has been greatly facilitated by the advent of molecular techniques, namely, real-time polymerase chain reaction (RT-PCR). EV-RV can cause ARDS by stimulating a cytokine cascade. No antiviral therapy has yet been approved, and treatment is entirely supportive. Herein, we report a rare case of EV-RV infection in an afebrile adult with dyspnea that rapidly progressed to acute lung injury and ARDS. EV-RV was isolated with multiple real-time PCR in nasopharyngeal and bronchial specimens, while no other pathogen was detected. We also present an up-to-date review of relevant literature, in an attempt to stress the importance of the early identification of viral culprits, which can minimize the use of invasive diagnostic procedures and antibiotic agents.

Cohesion and Adhesion Performance of Tannin-Glyoxal Adhesives at Different Formulations and Hardener Types for Bonding Particleboard Made of Areca (Areca catechu) Leaf Sheath.

The use of alternative raw materials, such as agricultural biomass and by-products, in particleboard (PB) production is a viable approach to address the growing global demand for sustainable wood-based materials. The purpose of this study was to investigate the effect of the type of hardener and tannin-glyoxal (TG) adhesive formulation on the cohesion and adhesion performance of TG adhesives for areca-based PB. Two types of hardeners were used, NH4Cl and NaOH, and three adhesive formulations with tannin:glyoxal ratios (i.e., F1 (1:2), F2 (1:1), and F3 (2:1)) were applied to improve the cohesion performance and adhesion for areca-based TG adhesive for PB. The basic, chemical, and mechanical properties of the TG adhesive were investigated using a Fourier transform infrared spectrometer, rotational rheometer, dynamic mechanical analyzer (DMA), and X-ray diffractometer. The results show that a high glyoxal percentage increases the percentage of crystallinity in the adhesive. This shows that the increase in glyoxal is able to form better polymer bonds. DMA analysis shows that the adhesive is elastic and the use of NH4Cl hardener has better mechanical properties in thermodynamic changes than the adhesive using NaOH hardener. Finally, the adhesion performance of the TG adhesives on various types of hardeners and adhesive formulations was evaluated on areca-based PB panels. Regardless of the type of hardener, the TG adhesive made with F1 had better cohesion and adhesion properties compared to F2 and F3. Combining F1 with NH4Cl produced areca-based PB panels with better physical and mechanical qualities than the adhesive formulations F2 and F3, and complied with Type 8 particleboard according to SNI 03-2105-2006 standard.

Endothelial Glycocalyx Integrity in Treatment-Naïve People Living with HIV before and One Year after Antiretroviral Treatment Initiation.

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed EG at baseline, 24 (±4) and 48 (±4) weeks, by measuring the perfused boundary region (PBR, inversely proportional to EG thickness), in sublingual microvessels. In total, 66 consecutive PLWH (60 (90.9%) males) with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40(60.6%) received INSTI-based regimens. The mean (standard deviation) PBR decreased significantly from 2.17 (0.29) µm at baseline to 2.04 (0.26) µm (p = 0.019), and then to 1.93 (0.3) µm (p < 0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. PLWH on INSTIs had a significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low levels of viremia experienced the greatest PBR reduction. This study is the first to report the benefit of antiretroviral treatment on EG improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH.

Foot Osteomyelitis Caused by Multidrug- and Extensively Drug-Resistant Gram-Negative Bacteria.

There are scarce data regarding foot osteomyelitis (FO) caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB). This study investigates the causative organisms, the diagnostic and therapeutic approach and the outcome of these infections. All patients with FO caused by MDR and/or XDR GNB who received treatment in the Department of osseous infectious diseases of the "Attikon" University Hospital of Athens, Greece, were recorded and evaluated during a six-year-period. Seventeen patients, of which 64.7% females, with a mean age of 54.06 years were studied. There were nine cases with diabetic (DFO), and 76.5% of patients reported previous use of antimicrobials. Pathogens were isolated from soft-tissue biopsies or intra-operative tissue samples (n=12) and/or affected bone samples (n=5). In most cases, E. coli and P. aeruginosa were isolated (each 29.4%), followed by P. mirabilis (11.7%), while polymicrobial infection was detected in nine patients (53%). Most cases were given antimicrobial monotherapy (88.2%) with a mean duration of 90.05 days, while surgery significantly promoted cure of the infection. Foot and DFO cases represent a challenging to treat disease, requiring a multidisciplinary approach. Surgical treatment remains the cornerstone of treatment, while it is of utmost importance to isolate the causative organisms. MDR and XDR GNB represent an emerging threat and more data are needed to better understand these infections.

NF-kappa-B essential modulator (NEMO) gene polymorphism in an adult woman with systemic lupus erythematosus and recurrent non-tuberculous mycobacterial disseminated infections.

Infections are among the most serious complications in patients with systemic lupus erythematosus (SLE), with bacterial and viral infections being the most common. Non-tuberculous mycobacterial (NTM) infections are quite rare and are typically seen in older patients with SLE with longstanding disease duration treated with corticosteroids. Here, we describe a 39-year-old woman with SLE and an unusual pattern of recurrent NTM disseminated infections. After excluding the presence of autoantibodies against interferon-γ, whole exome sequencing revealed a homozygous polymorphism in the NF-kappa-B essential modulator (NEMO) gene. Primary immunodeficiencies should be included in the differential diagnosis of patients with recurrent opportunistic infections, even in those with iatrogenic immunosuppression.

Vaccination against HBV and HAV as Mode of Hepatitis Prevention among People Living with HIV-Data from ECEE Network Group.

(1) Background: Viral hepatitis C (HCV) and viral hepatitis B (HBV) are common co-infections in people living with HIV (PLWH). All PLWH should be vaccinated against HBV and hepatitis A (HAV) and treated for HBV and HCV. We aimed to compare testing, prophylaxis and treatment of viral hepatitis in PLWH in Central and Eastern Europe (CEE) in 2019 and 2022. (2) Methods: Data was collected through two on-line surveys conducted in 2019 and 2022 among 18 countries of the Euroguidelines in CEE (ECEE) Network Group. (3) Results: In all 18 countries the standard of care was to screen all PLWH for HBV and HCV both years; screening of HAV was routine in 2019 in 54.5% and in 2022 47.4% of clinics. Vaccination of PLWH against HAV was available in 2019 in 16.7%, in 2022 in 22.2% countries. Vaccination against HBV was available routinely and free of charge in 50% of clinics both in 2019 and 2022. In HIV/HBV co-infected the choice of NRTI was tenofovir-based in 94.4% of countries in both years. All clinics that responded had access to direct-acting antivirals (DAAs) but 50% still had limitations for treatment. (4) Conclusions: Although testing for HBV and HCV was good, testing for HAV is insufficient. Vaccination against HBV and especially against HAV has room for improvement; furthermore, HCV treatment access needs to overcome restrictions.

Eco-Friendly Tannin-Based Non-Isocyanate Polyurethane Resins for the Modification of Ramie (Boehmeria nivea L.) Fibers.

This study aimed to develop tannin-based non-isocyanate polyurethane (tannin-Bio-NIPU) and tannin-based polyurethane (tannin-Bio-PU) resins for the impregnation of ramie fibers (Boehmeria nivea L.) and investigate their mechanical and thermal properties. The reaction between the tannin extract, dimethyl carbonate, and hexamethylene diamine produced the tannin-Bio-NIPU resin, while the tannin-Bio-PU was made with polymeric diphenylmethane diisocyanate (pMDI). Two types of ramie fiber were used: natural ramie without pre-treatment (RN) and with pre-treatment (RH). They were impregnated in a vacuum chamber with tannin-based Bio-PU resins for 60 min at 25 °C under 50 kPa. The yield of the tannin extract produced was 26.43 ± 1.36%. Fourier-transform infrared (FTIR) spectroscopy showed that both resin types produced urethane (-NCO) groups. The viscosity and cohesion strength of tannin-Bio-NIPU (20.35 mPa·s and 5.08 Pa) were lower than those of tannin-Bio-PU (42.70 mPa·s and 10.67 Pa). The RN fiber type (18.9% residue) was more thermally stable than RH (7.3% residue). The impregnation process with both resins could improve the ramie fibers' thermal stability and mechanical strength. The highest thermal stability was found in RN impregnated with the tannin-Bio-PU resin (30.5% residue). The highest tensile strength was determined in the tannin-Bio-NIPU RN of 451.3 MPa. The tannin-Bio-PU resin gave the highest MOE for both fiber types (RN of 13.5 GPa and RH of 11.7 GPa) compared to the tannin-Bio-NIPU resin.

Nanotechnology and Wood Science.

Nanotechnology, in a sense, is not entirely a new concept [...].

Low-Intensity Pulsed Ultrasound Treatment for Non-unions of Long Bone Fractures in a Scottish District General Hospital.

OBJECTIVE: Despite advances in treatment, the management of fracture non-union remains a challenging and complex problem in orthopaedics. Low-intensity pulsed ultrasound (LIPUS) treatment has been shown to be an effective, non-invasive, affordable treatment option. This treatment was evaluated in a Scottish district hospital over a nine-year period, which included the COVID-19 pandemic. MATERIALS AND METHODS: This submission describes a case series at Dr Gray's Hospital in Scotland, 18 patients in whom fracture non-union was treated using LIPUS. RESULTS: An overall healing rate of 94% was achieved. Exogen™ (Bioventus LLC, NC, USA) proved to be most successful in oligotrophic non-union. No observed patient demographic appeared predictive of outcome. LIPUS treatment failed in one case. No significant adverse effects of LIPUS were detected. CONCLUSION: LIPUS represents a useful, cost-effective potential alternative to revision surgery. LIPUS may therefore be the preferred treatment when surgical intervention and face-to-face interactions are to be minimised, as during the COVID-19 pandemic.

Cardiovascular disease and risk assessment in people living with HIV: Current practices and novel perspectives.

Human immunodeficiency virus (HIV) infection represents a major cardiovascular risk factor, and the cumulative cardiovascular disease (CVD) burden among aging people living with HIV (PLWH) constitutes a leading cause of morbidity and mortality. To date, CVD risk assessment in PLWH remains challenging. Therefore, it is necessary to evaluate and stratify the cardiovascular risk in PLWH with appropriate screening and risk assessment tools and protocols to correctly identify which patients are at a higher risk for CVD and will benefit most from prevention measures and timely management. This review aims to accumulate the current evidence on the association between HIV infection and CVD, as well as the risk factors contributing to CVD in PLWH. Furthermore, considering the need for cardiovascular risk assessment in daily clinical practice, the purpose of this review is also to report the current practices and novel perspectives in cardiovascular risk assessment of PLWH and provide further insights into the development and implementation of appropriate CVD risk stratification and treatment strategies, particularly in countries with high HIV burden and limited resources.

PrEP Scale-Up and PEP in Central and Eastern Europe: Changes in Time and the Challenges We Face with No Expected HIV Vaccine in the near Future.

With no expected vaccine for HIV in the near future, we aimed to define the current situation and challenges for pre- and post-exposure prophylaxis (PrEP and PEP) in Central and Eastern Europe (CEE). The Euroguidelines CEE Network Group members were invited to respond to a 27-item survey including questions on PrEP (response rate 91.6%). PrEP was licensed in 68.2%; 95 centers offered PrEP and the estimated number on PrEP was around 9000. It was available in daily (40.1%), on-demand (13.3%), or both forms (33.3%). The access rate was <1−80%. Three major barriers for access were lack of knowledge/awareness among people who are in need (59.1%), not being reimbursed (50.0%), and low perception of HIV risk (45.5%). Non-occupational PEP was available in 86.4% and was recommended in the guidelines in 54.5%. It was fully reimbursed in 36.4%, only for accidental exposures in 40.9%, and was not reimbursed in 22.72%. Occupational PEP was available in 95.5% and was reimbursed fully. Although PrEP scale-up in the region has gained momentum, a huge gap exists between those who are in need of and those who can access PrEP. Prompt action is required to address the urgent need for PrEP scale-up in the CEE region.

Switching from Tenofovir Disoproxil to Tenofovir Alafenamide Fumarate: Impact on Cardiovascular Risk and Lipid Profile in People Living with HIV, an Observational Study.

In the era of combination antiretroviral therapy (ART), people living with HIV (PLHIV) still face an increased risk of cardiovascular disease (CVD). Tenofovir alafenamide fumarate (TAF) is superior to its precursor tenofovir disoproxil fumarate (TDF) regarding bone and renal toxicity, but there are concerns about a negative effect on lipid profile. This observational, single-center study investigates the effects on lipid profile and cardiovascular (CVD) risk of the switch from TDF to TAF, in combination with emtricitabine/elvitegravir/cobicistat (FTC/EVG/c), in patients with no exposure to other antiretrovirals. Routine laboratory measurements, somatometric characteristics, and smoking status were analyzed for the assessment of CVD risk changes, using D:A:D and ATP III scores pre- and postswitch. A total of 62 patients with a mean age of 32.9 years were included in this study. Sixty-one patients (98.4%) were men, 38 (61.3%) late presenters, and 39 (62.9%) active smokers. A year after the switch, there was a significant increase in total cholesterol (178 ± 38 to 194 ± 40 mg/dL, p < .001), high-density lipoprotein (45 ± 12 to 48 ± 13 mg/dL, p = .001), and low-density lipoprotein (117 ± 32 to 137 ± 36 mg/dL, p < .001). Mean increase of the 10-year D:A:D score was 1.13% (95% confidence interval, 1.05-1.22, p = .002). Changes were more prominent in nonsmokers. Body mass index and average weight showed an upward trend. Switching from TDF to TAF caused significant changes in lipid profile at 14 months of follow-up, in young, otherwise healthy PLHIV. CVD risk, as measured by D:A:D, showed a statistically significant increase, but more data are needed to determine clinical significance. These results point toward a patient-centered approach when selecting an ART regimen.

HIV treatment strategies across Central, Eastern and Southeastern Europe: New times, old problems.

INTRODUCTION: In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region. RESULTS: In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons. CONCLUSIONS: In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries.

An Improved Optimization Model to Predict the MOR of Glulam Prepared by UF-Oxidized Starch Adhesive: A Hybrid Artificial Neural Network-Modified Genetic Algorithm Optimization Approach.

The purpose of the present article is to study the bending strength of glulam prepared by plane tree (Platanus Orientalis-L) wood layers adhered by UF resin with different formaldehyde to urea molar ratios containing the modified starch adhesive with different NaOCl concentrations. Artificial neural network (ANN) as a modern tool was used to predict this response, too. The multilayer perceptron (MLP) models were used to predict the modulus of rapture (MOR) and the statistics, including the determination coefficient (R2), root mean square error (RMSE), and mean absolute percentage error (MAPE) were used to validate the prediction. Combining the ANN and the genetic algorithm by using the multiple objective and nonlinear constraint functions, the optimum point was determined based on the experimental and estimated data, respectively. The characterization analysis, performed by FTIR and XRD, was used to describe the effect of the inputs on the output. The results indicated that the statistics obtained show excellent MOR predictions by the feed-forward neural network using Levenberg-Marquardt algorithms. The comparison of the optimal output of the actual values obtained by the genetic algorithm resulting from the multi-objective function and the optimal output of the values estimated by the nonlinear constraint function indicates a minimum difference between both functions.

Chronic Kidney Disease and Nephrology Care in People Living with HIV in Central/Eastern Europe and Neighbouring Countries-Cross-Sectional Analysis from the ECEE Network.

Chronic kidney disease (CKD) is a significant cause of morbidity and mortality among patients infected with human immunodeficiency virus (HIV). The Central and East Europe (CEE) region consists of countries with highly diversified HIV epidemics, health care systems and socioeconomic status. The aim of the present study was to describe variations in CKD burden and care between countries. The Euroguidelines in the CEE Network Group includes 19 countries and was initiated to improve the standard of care for HIV infection in the region. Information on kidney care in HIV-positive patients was collected through online surveys sent to all members of the Network Group. Almost all centres use regular screening for CKD in all HIV (+) patients. Basic diagnostic tests for kidney function are available in the majority of centres. The most commonly used method for eGFR calculation is the Cockcroft-Gault equation. Nephrology consultation is available in all centres. The median frequency of CKD was 5% and the main cause was comorbidity. Haemodialysis was the only modality of treatment for kidney failure available in all ECEE countries. Only 39% of centres declared that all treatment options are available for HIV+ patients. The most commonly indicated barrier in kidney care was patients' noncompliance. In the CEE region, people living with HIV have full access to screening for kidney disease but there are important limitations in treatment. The choice of dialysis modality and access to kidney transplantation are limited. The main burden of kidney disease is unrelated to HIV infection. Patient care can be significantly improved by addressing noncompliance.

Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock-inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors.

OBJECTIVES: HIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis. METHODS: Our nationwide sample included HIV-1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999-2015. Our analysis was based on the molecularly inferred HIV-1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B. RESULTS: Analysis of the determinants of LP was conducted using either CD4 counts or AIDS-defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age-dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks. CONCLUSIONS: We demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations.

Pan-Echinocandin Resistant C. parapsilosis Harboring an F652S Fks1 Alteration in a Patient with Prolonged Echinocandin Therapy.

The isolation of a pan-echinocandin-resistant Candida parapsilosis strain (anidulafungin, caspofungin, micafungin and rezafungin EUCAST MICs > 8 mg/L) from urine of a patient following prolonged exposure to echinocandins (38 days of micafungin followed by 16 days of anidulafungin) is described. The isolate harbored the novel alteration F652S in the hotspot 1 region of fks1. Isogenic C. parapsilosis bloodstream isolates collected up to 1.5 months earlier from the same patient were susceptible to echinocandins (anidulafungin, caspofungin and micafungin EUCAST MICs 1−2, 1 and 1 mg/L, respectively) and contained wild-type FKS1 sequences. This is the first report of pan-echinocandin resistance in C. parapsilosis associated with an aminoacid change in hotspot 1 region of fks1.