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Abstract BackgroundSodium-23 magnetic resonance imaging (23Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na+]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na+] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na+] compared to healthy controls.MethodsThis was a case–control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg 23Na MRI for tissue [Na+] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients’ tissue [Na+] was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na+] and kidney function.ResultsA total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na+] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na+] Z-scores. Reduced whole-leg [Na+] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal–distal renal tubular acidosis). All tissue [Na+] measures were significantly associated with proteinuria and hypoalbuminemia.ConclusionsDepending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na+] compared with healthy controls.A higher resolution version of the Graphical abstract is available as Supplementary information.

ObjectivesTo study the effects of abatacept on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM).MethodsTwenty patients with DM (n=9) or PM (n=11) with refractory disease were enrolled in a randomised treatment delayed-start trial to receive either immediate active treatment with intravenous abatacept or a 3 month delayed-start. The primary endpoint was number of responders, defined by the International Myositis Assessment and Clinical Studies Group definition of improvement (DOI), after 6 months of treatment. Secondary endpoints included number of responders in the early treatment arm compared with the delayed treatment arm at 3 months. Repeated muscle biopsies were investigated for cellular markers and cytokines.Results8/19 patients included in the analyses achieved the DOI at 6 months. At 3 months of study, five (50%) patients were responders after active treatment but only one (11%) patient in the delayed treatment arm. Eight adverse events (AEs) were regarded as related to the drug, four mild and four moderate, and three serious AEs, none related to the drug. There was a significant increase in regulatory T cells (Tregs), whereas other markers were unchanged in repeated muscle biopsies.ConclusionsIn this pilot study, treatment of patients with DM and PM with abatacept resulted in lower disease activity in nearly half of the patients. In patients with repeat muscle biopsies, an increased frequency of Foxp3+ Tregs suggests a positive effect of treatment in muscle tissue.

BACKGROUND: Sodium-23 magnetic resonance imaging ((23)Na MRI) allows the measurement of skin sodium concentration ([Na(+)]). In patients requiring dialysis, no data are available relating to the clinical outcomes associated with skin sodium accumulation or the determinants of increasing deposition. METHODS: This was an exploratory, observational study of adult hemodialysis (HD) and peritoneal dialysis (PD) patients. Participants underwent skin [Na(+)] quantification with leg (23)Na MRI at the study's beginning. Outcomes of interest were all-cause mortality and composite all-cause mortality plus major adverse cardiovascular events. Cumulative total and event-free survival were assessed using the Kaplan-Meier survival function after stratification into skin [Na(+)] quartiles. Cox proportional hazards regression was used to model the association between skin [Na(+)] and outcomes of interest. Multiple linear regression was used to model the predictors of skin [Na(+)]. RESULTS: A total of 52 participants (42 HD and 10 PD) underwent the study procedures. The median follow-up was 529 days (interquartile range: 353-602). Increasing skin [Na(+)] quartiles were associated with significantly shorter overall and event-free survival (log-rank χ(2)(1) = 3.926, log-rank χ(2)(1) = 5.685; P for trend \\textless0.05 in both instances). Skin [Na(+)] was associated with all-cause mortality \\hazard ratio (HR) 4.013, [95% confidence interval (95% CI) 1.988-8.101]; P \\textless 0.001\\ and composite events [HR 2.332 (95% CI 1.378-3.945); P \\textless 0.01], independently of age, sex, serum [Na(+)] and albumin. In multiple regression models, dialysate [Na(+)], serum albumin and congestive heart failure were significantly associated with skin [Na(+)] in HD patients (R(2) (adj) = 0.62). CONCLUSIONS: Higher skin [Na(+)] was associated with worse clinical outcomes in dialysis patients and may represent a direct therapeutic target.

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (−37%, p  = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p  = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.

Background:Systemic lupus erythematosus (SLE) is inherently discriminatory, with a higher incidence in females and in those of African ancestry. Longitudinal data has helped to explore the association of damage and mortality across ethnic groups; however, most studies report low numbers of patients from Black ethnicities.Objectives:The primary aim was to describe the survival of a tertiary centre SLE cohort by ethnicity, the majority of whom identified as Black. Our secondary objectives were to describe the association of clinic attendance, medication concordance and hospital admissions with all-cause mortality.Methods:We examined the electronic health records for patients known to our centre with a clinician-recorded diagnosis of SLE between 1st June 2012 and 15th June 2023. We excluded those not seen in the previous 2 years and that died more than 5 years after their most recent appointment. Variables included ethnicity, index of multiple deprivation (IMD), diagnosis date, outpatient attendances, hospital admissions, end-stage renal failure and date of death. The collection of hospital-ordered prescriptions for disease modifying therapy was used as a surrogate for medication concordance. Individuals diagnosed during the study period formed our incident cohort. Cox regression models were used where appropriate.Results:We identified 328 eligible patients with 3494 person-years (py) of follow up during the study period, of which 83 were newly diagnosed during that time with 472 py of follow up (our incident cohort). In total, 31 patients died during this period (mortality rate 8.90/1000 py [6.24 - 12.62]) with 4 deaths in the incident cohort. These 4 patients had a mean time from diagnosis to death of 2.78 years (± 1.46) at an average age of 37.47 years old (± 13.35). Interestingly, there was no significant difference in the risk of death between Black and White ethnicities in the adjusted regression model (Figure 1).Age at diagnosis had no impact on the hazard rate of death in the multivariate model (adjusting for sex and ethnicity). However, 10 out of the 15 patients who died with a recorded SLE diagnosis date were diagnosed at <40 years old. Rheumatology clinic attendance was consistent across all ethnic groups (Table 1). Poor clinic attendance (<80%) was associated with an increased risk of death (HR 3.71 [1.21 – 11.36]) in the adjusted model. Furthermore, higher rates of hospital admissions per year were associated with an increased risk of death (HR 2.57 [1.57 - 4.22]). Two or more hospital admissions per year were seen in 10.79% of Black patients (84.62% of whom were from the lowest 2 IMD quintiles), 0% of White patients and 50% of those <40 years old.Medication collection percentages were recorded for 221 patients (Table 1) with no significant relationship to mortality.16 patients reached end-stage renal failure, 3 within our incident cohort (incidence rate 6.33/1000 py) with a mean time from diagnosis to ESRF of 3.91 years (± 5.14).Conclusion:Overall, there was no association between ethnicity and survival in our entire nor incident cohort. However, patients of Black ethnicity had higher rates of hospital admissions and ESRF compared to those of White ethnicity. Expectedly, poor clinic attendance and higher hospital admission rates were associated with an increased risk of death. However, there was no discernible association between medication collection and death in our study, likely due to assumptions in our methods.Our cohort is unique within the UK with a high proportion of patients from Black ethnicities. Additionally, we demonstrated a lower mortality rate than previously seen by Rees et al. [1]; however, they examined a large incident cohort and prior to the regular use of biologic agents. These findings emphasise the need to optimise clinic attendance and reduce hospital admissions in order to improve survival. Further qualitative work is planned to investigate any barriers to care, with an emphasis on bridging the cultural differences for our ethnically diverse cohort.REFERENCES:[1] Rees F, Doherty M, Grainge MJ, Lanyon P, Davenport G, Zhang W. Mortality in SLE in the United Kingdom 1999-2012. Rheumatology. 2016 May;55(5):854-60.Acknowledgements:NIL.Disclosure of Interests:Samir Patel: None declared, Maryam A. Adas: None declared, Rosaria Salerno: None declared, Deepak Nagra: None declared, Zijing Yang: None declared, Kate Bramham Research grant support from Astrazeneca, Chris Wincup: None declared, Patrick Gordon: None declared.

Cardio-kidney-metabolic (CKM) syndrome is defined by the American Heart Association as the intersection between metabolic, renal and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality and recent trends in the US is essential for developing targeted public interventions. We collected state-level and county-level CKM-associated age-adjusted premature cardiovascular mortality (aaCVM) (2010–2019) rates from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER). We linked the county-level aaCVM with a multi-component social deprivation metric: the Social Deprivation Index (SDI: range 0–100) and grouped them as follows: I: 0–25, II: 26–50, III: 51–75, and IV: 76–100. We conducted pair-wise comparison of aaCVM between SDI groups with the multiplicity adjusted Wilcoxon test; we compared aaCVM in men versus women, metropolitan versus nonmetropolitan counties, and non-hispanic white versus non-hispanic black residents. In 3101 analyzed counties in the US, the median CKM associated aaCVM was 61 [interquartile range (IQR): 45, 82]/100 000. Mississippi (99/100 000) and Minnesota (33/100 000) had the highest and lowest values respectively. CKM associated aaMR increased across SDI groups [I – 45 (IQR: 36, 55)/100 000, II- 61 (IQR: 49, 77)/100 000, III- 77 (IQR: 61, 94)/100 000, IV- 89 (IQR: 70, 110)/100 000; all pair-wise p-values < 0.001]. Men had higher rates [85 (64, 91)/100 000] than women [41 (28, 58)/100 000](p-value < 0.001), metropolitan counties [54 (40, 72)/100 000] had lower rates than non-metropolitan counties [66 (49, 90)/100 000](p-value < 0.001), and non-Hispanic Black [110 (86, 137)/100 000] had higher aaMR than non-Hispanic White residents [59 (44, 78)/100 000](p-value < 0.001). In the US, CKM mortality remains high and disproportionately occurs in more socially deprived counties and non-metropolitan counties. Our inability to reduce CKM mortality rates over the study period highlights the need for targeted policy interventions to curb the ongoing high burden.

Background and aimsAntimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori-infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy.Methods375 patients who were infected with H pylori and naïve to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group.ResultsEradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy.ConclusionIn an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

In recent years frequent periods of water scarcity have enhanced the need to use water more carefully, even in European areas which traditionally have an abundant supply of water, such as the Po Valley in northern Italy. In dry periods, water shortage problems can be enhanced by conflicting uses of water, such as irrigation, industry and power production (hydroelectric and thermoelectric). Furthermore, in the last decade the social perspective in relation to this issue has been increasing due to the possible impact of climate change and global warming scenarios which emerge from the IPCC Fifth Assessment Report (IPCC, 2013). Hence, the increased frequency of drought periods has stimulated the improvement of irrigation and water management. In this study we show the development and implementation of the PREGI real-time drought forecasting system; PREGI is an Italian acronym that means \"hydro-meteorological forecast for irrigation management\". The system, planned as a tool for irrigation optimization, is based on meteorological ensemble forecasts (20 members) at medium range (30 days) coupled with hydrological simulations of water balance to forecast the soil water content on a maize field in the Muzza Bassa Lodigiana (MBL) consortium in northern Italy. The hydrological model was validated against measurements of latent heat flux acquired by an eddy-covariance station, and soil moisture measured by TDR (time domain reflectivity) probes; the reliability of this forecasting system and its benefits were assessed in the 2012 growing season. The results obtained show how the proposed drought forecasting system is able to have a high reliability of forecast at least for 7–10 days ahead of time.

Disparities exist in the cardiovascular mortality rates among people with type 2 diabetes (T2D). Research has established that these disparities are often related to the environmental and social determinations of health. This study explores the spatial variation between air pollution, social determinants of health and T2D related age-adjusted cardiovascular mortality (aa-CVM) in the United States. We obtained county-level T2D related to aa-CVM (per 100,000 residents) from Centers for Disease Control and Prevention WONDER (Wide-ranging Online Data for Epidemiologic Research) (2010 to 2019). We fit a geographically weighted linear regression with aa-CVM as the outcome and the following covariates (ambient air pollution [particulate matter of 2.5 µm size], median annual household income, racial/ethnic minorities, higher education, rurality, food insecurity, and primary health care access) were included. Overall, the median aa-CVM rate was 92.9 and highest in the South (102.2). In the West, aa-CVM was significantly associated with particulate matter of 2.5 µm size, annual median household income, racial minority status and primary health care access. Food insecurity was the most significant exposure in the Midwest and Northeast, while in the South, annual median household income and food insecurity were significant. In conclusion, this study demonstrated a substantial regional variation of exposure to determinants of T2D related aa-CVM in the United States. These findings should be considered in policy frameworks and interventions as part of community-level approaches to addressing T2D related aa-CVM, and within broader state and national discussions of the importance of population health.

A short-term forecast of energy consumption is affected by different factors related to the demand in residential, commercial, thermoelectric, and industrial sectors. This demand can be strongly constrained by weather variables, especially temperatures, whose forecast may be very useful to predict the balances between supply and demand, minimizing the risk of price volatility. Energy companies use the relationship between meteorological forecast output and energy request to provide an effective scheduling of national gas and power grids and reduce operational costs in critical periods. This work reports a comparison analysis for short- and medium-term daily temperature forecasts during the period 2013-2014 by using the weather model e-kmf™ (eni-kassandra meteo forecast), currently adopted in gas and power applications where meteorological output has a key role. This weather forecast system uses different models and initial data to develop probabilistic predictions from a perspective of eleven days ahead. In particular, a set of model runs with horizontal grid spacing of 5.5, 8, 13, and 18 km with the same domain size are undertaken to assess the sensitivity of temperature to horizontal resolutions. A nonlinear Kalman filter has been also applied to postprocess forecasted data in eight European cities (Milano, Roma, Torino, Napoli, Munich, Paris, Brussels, and London). Filtered forecasts over these cities have been compared to local observations taken from SYNOP (surface synoptic observations) and METAR (meteorological Aerodrome Report) stations. Skill scores of performance have been used to generally assess the forecast reliability up to day +11. In order to understand the sensitivity to the horizontal resolution, investigations have been carried out even during four specific periods of two weeks with stable and unstable weather conditions.