Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial.

BACKGROUND: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial. METHODS: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment. RESULTS: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013). CONCLUSION: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.

The impact of frailty and illness perceptions on quality of life among people living with HIV in Greece: A network analysis.

OBJECTIVE: Despite the significant advances in healthcare, people living with HIV still face challenges that affect their quality of life (QoL), both in terms of their physical state as represented by frailty and of their illness perceptions (IP). The aim of this study was to unravel the associations between these constructs (QoL, frailty, IP). METHODS: This multicenter, cross-sectional study included 477 people living with HIV (93% male; median age = 43 years, IQR = 51.7) from six HIV clinics in Greece. Frailty phenotype, QoL and IP were assessed using Fried's criteria, EuroQoL (EQ-5D-5L) and Brief Illness Perception Questionnaire (BIPQ), respectively. Network analysis model was utilized. RESULTS: Among frailty criteria, exhaustion had the highest expected influence, while the strongest correlation concerns exhaustion and weak grip strength (pr = 0.14). Regarding the QoL items, usual activities displayed the highest expected influence. The correlations of pain/discomfort with mobility (pr = 0.31), and usual activities with self-care (pr = 0.34) were the strongest. For the BIPQ items, the strongest correlation was found between illness concern and emotional response (pr = 0.45), whereas the latter item was the one that displayed the highest expected influence. Three communities were formed: 1) personal control, treatment control and coherence, 2) the frailty items with mobility, self-care, usual activities, and pain/discomfort, and 3) the rest BIPQ items with anxiety/depression. Identity displayed the highest bridge strength, followed by pain/discomfort, usual activities and consequences. CONCLUSIONS: The interplay between QoL, frailty, and IP in people living with HIV requires clinical attention. Self-reported exhaustion, slow walking speed, and low physical activity affect the physical QoL dimensions, while anxiety/depression is strongly associated with illness-related concern and perceived emotional effects, leading to psychological distress. Symptom management can improve QoL, and information on the disease and treatment can enhance control over the disease. Developing interventions to address QoL, frailty, and IP is crucial.

Innate Immune Gene Polymorphisms and COVID-19 Prognosis.

COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211, and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe, and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data support the notion that the host's genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708, and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.

Probable Three-Species In Vivo Transfer of blaNDM-1 in a Single Patient in Greece: Occurrence of NDM-1-Producing Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii.

NDM carbapenemase-encoding genes disseminate commonly among Enterobacterales through transferable plasmids carrying additional resistance determinants. Apart from the intra-species dissemination, the inter-species exchange of plasmids seems to play an additional important role in the spread of blaNDM. We here present the genetics related to the isolation of three species (Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii) harboring the blaNDM-1 gene from a single patient in Greece. Bacterial identification and antimicrobial susceptibility testing were performed using the Vitek2. Whole genome sequencing and bioinformatic tools were used to identify resistance genes and plasmids. BlaNDM-1 harboring plasmids were found in all three isolates. Moreover, the plasmid constructs of the respective incomplete or circular contigs showed that the blaNDM-1 and its neighboring genes form a cluster that was found in all isolates. Our microbiological findings, together with the patient's history, suggest the in vivo transfer of the blaNDM-1-containing cluster through three different species in a single patient.

Low pre-ART CD4 count is associated with increased risk of clinical progression or death even after reaching 500 CD4 cells/µL on ART.

INTRODUCTION: Clinical disadvantages of initiating ART at low CD4 counts have been clearly demonstrated but whether any excess risk remains even after reaching relatively high/safe CD4 levels remains unclear. We explore whether individuals starting ART with <500 CD4 cells/µL who increased their CD4 count above this level, have, from this point onwards, similar risk of clinical progression to serious AIDS/non-AIDS events or death with individuals starting ART with ≥500 CD4 cells/µL. METHODS: Data were derived from a multicenter cohort (AMACS). Adults, starting PI, NNRTI or INSTI based ART, in or after 2000 were eligible, provided they started ART with ≥500 ("High CD4") or started with CD4 <500 cells/µL but surpassed this threshold while on ART ("Low CD4"). Baseline was the date of ART initiation ("High CD4") or of first reaching 500 CD4 cells/µL ("Low CD4"). Survival analysis, allowing for competing risks, was used to explore the risk of progression to study's endpoints. RESULTS: The study included 694 persons in the "High CD4" and 3,306 in the "Low CD4" group. Median (IQR) follow-up was 66 (36, 106) months. In total, 257 events (40 AIDS related, 217 SNAEs) were observed. Rates of progression did not differ significantly between the two groups but the subgroup of those initiating ART with <200 CD4 cells/µL had significantly higher risk of progression after baseline, compared to those in the "High CD4" group. CONCLUSIONS: Individuals starting ART with <200 cells/µL remain on increased risk even after reaching 500 CD4 cells/µL. These patients should be closely followed.

Phase Angle and Handgrip Strength as Predictors of Clinical Outcomes in Hospitalized COVID-19 Patients.

Phase angle (PhA) and muscle strength are predictors of clinical outcomes in critically ill patients. Malnutrition may affect body composition measurements. The aim of this prospective study was to investigate the association between PhA and handgrip strength (HGS), and clinical outcomes in hospitalized COVID-19 patients. The study included a total of 102 patients. Both PhA and HGS were measured twice, within 48 h of hospital admission and on the 7th day of hospitalization. The primary outcome was the clinical status on the 28th day of hospitalization. Secondary outcomes included the hospital length of stay (LOS), the concentrations of ferritin, C-reactive protein and albumin, oxygen requirements and the severity of pneumonia. A one-way analysis of variance (ANOVA) test and Spearman rS correlation coefficient were used for statistical analysis. No differences were found for PhA [on day 1 (p = 0.769) and day 7 (p = 0.807)] and the primary outcome. A difference was found between HGS on day 1 and the primary outcome (p = 0.008), while no difference was found for HGS on day 7 (p = 0.476). Body mass index was found to be associated with the oxygen requirement on day 7 (p = 0.005). LOS was correlated neither with PhA (rs = -0.081, p = 0.422) nor with HGS (rs = 0.137, p = 0.177) on the first day. HGS could be a useful indicator of clinical outcomes in COVID-19 patients, while PhA does not seem to have a clinical impact. However, further research is needed to validate the results of our study.

Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: A subgroup analysis of the SAVE-MORE randomised trial.

Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22-0.50; CCI < 2, OR: 0.38, 95% CI 0.21-0.68; suPAR > 9 ng/mL, OR: 0.35, 95% CI 0.19-0.66; suPAR 6-9 ng/mL, OR: 0.35, 95% CI 0.24-0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25-0.66; and patients <65 years, OR: 0.29, 95% CI 0.19-0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28-0.57) and 0.46 (95% CI 0.32-0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90. Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB.

Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.

Mapping frailty in people living with HIV: A nationwide study in Greece.

OBJECTIVES: Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data. METHODS: Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored. RESULTS: The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/µl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty. CONCLUSIONS: Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.

The Implementation of a Health Care Worker Screening Program Based on the Advanta RT-qPCR Saliva Assay in a Tertiary Care Referral Hospital in Northern Greece.

Health care workers are at increased risk of acquiring SARS-CoV-2 infection due to different exposures in the community and in hospital settings. Interventions implemented to avoid nosocomial outbreaks include preventive testing strategies. In this report, we present results from the mass screening program applied in our hospital to all professionals, irrespective of symptoms or risk of exposure. We processed saliva specimens with real-time reverse transcription polymerase chain reaction. The total number of samples received was 43,726. Positive results were 672 and average positivity rate was 1.21%. The average positivity rate was similar to the positivity rate in the community in Greece and EU. More specifically, 80.5% of the positive participants care for patients in their daily activities, 31% experienced no symptoms before receiving the positive result, 46.1% reported a close contact with a patient or infected coworkers and 32.8% reported a close contact with infected family members. We believe that the identification of asymptomatic carriers has proved the effectiveness of the screening program by preventing the putative nosocomial spread of the virus and the depletion of workforce. In conclusion, in times of high incidence in the community, the periodic testing of health care personnel is wise and relevant for implementation costs.

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.

Changes in Body Mass Index after Initiation of Antiretroviral Treatment: Differences by Class of Core Drug.

Recent research on antiretroviral treatment (ART) for HIV suggests that integrase strand transfer inhibitors (INSTIs) cause faster weight gain compared to other drug classes. Here, we investigated changes in body mass index (BMI) and obesity prevalence after treatment initiation and corresponding differences between drug classes. Data were derived from a large collaborative cohort in Greece. Included individuals were adults who started ART, in or after 2010, while previously ART naïve and achieved virologic response within the first year of ART. Data were analysed using mixed fractional polynomial models. INSTI regimens led to the more pronounced BMI increases, followed by boosted PI and NNRTI based regimens. Individuals with normal initial BMI are expected to gain 6 kg with an INSTI regimen compared to 4 kg with a boosted PI and less than 3 kg with a NNRTI regimen after four years of treatment. Prevalence of obesity was 5.7% at ART initiation and 12.2%, 14.2% and 18.1% after four years of treatment with NNRTIs, PIs, and INSTIs, respectively. Dolutegravir or Raltegravir were associated with marginally faster BMI increase compared to Elvitegravir. INSTIs are associated with faster weight gain. INSTIs' increased risk of treatment emergent obesity and, possibly, weight-related co-morbidities should be judged against their improved efficacy and tolerability but increased clinical attention is required.

Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

The COVID-19 pandemic as inspiration to reconsider epidemic models: A novel approach to spatially homogeneous epidemic spread modeling.

Epidemic spread models are useful tools to study the spread and the effectiveness of the interventions at a population level, to an epidemic. The workhorse of spatially homogeneous class models is the SIR-type ones comprising ordinary differential equations for the unknown state variables. The transition between different states is expressed through rate functions. Inspired by -but not restricted to- features of the COVID-19 pandemic, a new framework for modeling a disease spread is proposed. The main concept refers to the assignment of properties to each individual person as regards his response to the disease. A multidimensional distribution of these properties represents the whole population. The temporal evolution of this distribution is the only dependent variable of the problem. All other variables can be extracted by post-processing of this distribution. It is noteworthy that the new concept allows an improved consideration of vaccination modeling because it recognizes vaccination as a modifier of individuals response to the disease and not as a means for individuals to totally defeat the disease. At the heart of the new approach is an infection age model engaging a sharp cut-off. This model is analyzed in detail, and it is shown to admit self-similar solutions. A hierarchy of models based on the new approach, from a generalized one to a specific one with three dominant properties, is derived. The latter is implemented as an example and indicative results are presented and discussed. It appears that the new framework is general and versatile enough to simulate disease spread processes and to predict the evolution of several variables of the population during this spread.

An exploration of the quality of life of people living with HIV in Greece: Challenges and opportunities.

OBJECTIVE: Improving the quality of life (QoL) of people living with HIV (PLWH) has been proposed as a new priority in HIV care. The objective of this cross-sectional, qualitative study was to explore the perspectives of PLWH in Greece regarding their QoL. DESIGN: Twenty-four semi-structured interviews were conducted with PLWH receiving care across six HIV clinics in Greece. The thematic analysis of the transcribed interviews resulted in four themes and eleven subthemes. RESULTS: First, fear of repercussions (e.g., stigmatization) makes PLWH reluctant to disclose their diagnosis in public settings or disclose accounting for factors like the confidant's discretion. Second, participants are challenged by HIV's unique biopsychosocial facets (e.g., uncertainty about symptoms) and fear for the future (e.g., a confidant revealing their HIV status without consent). Third, support received by specialist services is satisfactory in contrast to non-HIV specialist services, where significant improvements are needed to reduce stigmatization. Finally, the experiences of PLWH include contrasting elements of post-traumatic growth and an inability to accept their seropositivity (e.g., avoiding social interactions). CONCLUSIONS: Empowering PLWH in these QoL areas is greatly needed. Increasing the life expectancy of PLWH is only the initial step; their QoL needs to be secured as the next priority in HIV care.

Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Prevalence, recurrence and seasonal variation of hyperkalemia among patients on hemodialysis.

PURPOSE: Observational studies have shown that among patients on hemodialysis, hyperkalemia is strongly associated with excess risk for cardiovascular-related hospitalizations and sudden cardiac death. However, the actual burden of hyperkalemia, the rates of its recurrence and seasonality in its variation still remain unclear. METHODS: Between June 2020 and May 2021, 1786 mid-week pre-dialysis serum potassium (sK) measurements were retrospectively recorded from 149 patients receiving thrice-weekly hemodialysis in a single-center in Thessaloniki, Greece. The prevalence, recurrence and seasonal variation of hyperkalemia were assessed using three pre-specified sK thresholds (≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L). RESULTS: At baseline, 60.4%, 42.2% and 13.4% of patients had sK levels ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. At any time-point during follow-up, 85.2%, 69.8% and 38.9% of patients experienced at least one hyperkalemic event ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. Of the 104 patients experiencing an initial sK elevation ≥ 5.5 mmol/L, hyperkalemia at the same threshold reoccurred in 60.6% at month 1, in 47.1% at month 2 and in 46.1% at month 3 of follow-up. Seasonal variation was also observed, with the prevalence of hyperkalemia to be significantly higher in summer. Shorter delivered hemodialysis < 4 h/session (OR: 2.568; 95% CI 1.045-6.313) and the use of a high dialysate K concentration (OR: 14.646; 95% CI 2.727-78.647) were the 2 factors that were independently associated with hyperkalemia. CONCLUSION: The present study shows that among hemodialysis patients, the rates of hyperkalemia prevalence and recurrence are very high, reflecting the large unmet need to identify more effective potassium-lowering therapeutic interventions in this high-risk population.

Polyclonal Endemicity of Carbapenemase-Producing Klebsiella pneumoniae in ICUs of a Greek Tertiary Care Hospital.

Carbapenemase-producing Klebsiella pneumoniae (CPKP) emerged in Greece in 2002 and became endemic thereafter. Driven by a notable variability in the phenotypic testing results for carbapenemase production in K. pneumoniae isolates from the intensive care units (ICUs) of our hospital, we performed a study to assess the molecular epidemiology of CPKP isolated between 2016 and 2019 using pulse-field gel electrophoresis (PFGE) including isolates recovered from 165 single patients. We investigated the molecular relatedness among strains recovered from rectal surveillance cultures and from respective subsequent infections due to CPKP in the same individual (48/165 cases). For the optimal interpretation of our findings, we carried out a systematic review regarding the clonality of CPKP isolated from clinical samples in ICUs in Europe. In our study, we identified 128 distinguishable pulsotypes and 17 clusters that indicated extended dissemination of CPKP within the hospital ICU setting throughout the study period. Among the clinical isolates, 122 harbored KPC genes (74%), 2 harbored KPC+NDM (1.2%), 38 harbored NDM (23%), 1 harbored NDM+OXA-48 (0.6%), 1 harbored NDM+VIM (0.6%) and 1 harbored the VIM (0.6%) gene. Multiple CPKP strains in our hospital have achieved sustained transmission. The polyclonal endemicity of CPKP presents a further threat for the selection of pathogens resistant to last-resort antimicrobial agents.

Dating the Origin and Estimating the Transmission Rates of the Major HIV-1 Clusters in Greece: Evidence about the Earliest Subtype A1 Epidemic in Europe.

Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infections/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV-1 outbreak ten years ago in Athens, Greece. Transmission rate can be considered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs.

SARS-CoV-2 adsorption on suspended solids along a sewerage network: mathematical model formulation, sensitivity analysis, and parametric study.

Accounting for SARS-CoV-2 adsorption on solids suspended in wastewater is a necessary step towards the reliable estimation of virus shedding rate in a sewerage system, based on measurements performed at a terminal collection station, i.e., at the entrance of a wastewater treatment plant. This concept is extended herein to include several measurement stations across a city to enable the estimation of spatial distribution of virus shedding rate. This study presents a pioneer general model describing the most relevant physicochemical phenomena with a special effort to reduce the complicated algebra. This is performed both in the topology regime, introducing a discrete-continuous approach, and in the domain of independent variables, introducing a monodisperse moment method to reduce the dimensionality of the resulting population balance equations. The resulting simplified model consists of a large system of ordinary differential equations. A sensitivity analysis is performed with respect to some key parameters for a single pipe topology. Specific numerical techniques are employed for the integration of the model. Finally, a parametric case study for an indicative-yet realistic-sewerage piping system is performed to show how the model is applied to SARS-CoV-2 adsorption on wastewater solids in the presence of other competing species. This is the first model of this kind appearing in scientific literature and a first step towards setting up an inverse problem to assess the spatial distribution of virus shedding rate based on its concentration in wastewater.