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Background and Objectives: Selecting the most appropriate blood tests is crucial for the management of patients with amyotrophic lateral sclerosis (ALS). This study evaluates the diagnostic and prognostic performance of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (pTau181) biomarkers in ALS to establish their clinical relevance and cutoff values., Methods: In a cohort of patients from the ALS center in Montpellier, we conducted a head-to-head comparison of 4 different technologies and 3 distinct serum analytes: NfL was tested using the ultrasensitive Simoa and the microfluidic Ella platforms, along with 2 assays recently set up on clinical-grade platforms: Lumipulse and Elecsys. We also used Elecsys to assess serum GFAP and pTau181., Results: Our cohort included 139 patients with ALS and 70 non-ALS patients, with a mean age of 66.1 ± 11.4 years and 47.4% of women. The mean follow-up was 42 ± 26.3 months for patients with ALS and 141.6 ± 106.3 months for non-ALS patients, with a mortality rate of 85.5% vs 7.7%. There was a high correlation between all methods tested for serum NfL quantification (R 2 = 0.939 to 0.963). The area under the curve (AUC) for ALS diagnosis was 0.889 (0.827-0.932) for NfL Simoa, 0.906 (0.847-0.944) for Ella, 0.912 (0.853-0.948) for Lumipulse, and 0.910 (0.851-0.946) for Elecsys. Serum pTau181 and GFAP showed poor diagnostic performance with AUCs of 0.565 (0.472-0.649) and 0.546 (0.461-0.636), respectively. Kaplan-Meier survival analysis revealed significant hazard ratios (4.4-5.4) for blood NfL. Patients with ALS had a 40%-50% chance of surviving 50 weeks below the prognostic cutoff values while survival rates dropped to near zero above. NfL and GFAP levels were associated with age and body mass index, considered confounding factors. pTau181 levels varied significantly in patients with ALS depending on the site of onset., Discussion: This study demonstrates the consistent performance of 4 immunoassays for serum NfL quantification in ALS. NfL showed high diagnostic and prognostic accuracy, making it suitable for individual assessment, unlike GFAP or pTau181. We propose diagnostic and prognostic cutoff values for serum NfL, providing a basis for wider implementation, especially with the clinically accredited Lumipulse and Elecsys platforms, which are becoming standard practice., Classification of Evidence: This study provides Class II evidence that serum NfL levels are useful in identifying over 80% of patients with ALS and predicting survival in patients with ALS compared with pTau181 and GFAP levels.

Bariatric surgery induces a decrease in areal BMD (aBMD), but the long-term effect on trabecular and cortical volumetric BMD (vBMD) has not been well assessed. The main aim of this 5-yr longitudinal study was to investigate the changes following sleeve gastrectomy (SG) in aBMD, bone turnover markers, and trabecular and cortical vBMD. Forty-five patients with obesity were assessed before and 1, 2, and 5 yr after SG. Trabecular and cortical vBMD, cortical thickness, and structural parameters were assessed by 3D-Shaper software at the hip. Values of bone turnover markers peaked after 1 yr and decreased after 2 and 5 yr, but without returning to baseline values. aBMD decreased mostly at the femoral neck (-9.7%) and total hip (-10.7%) over the 5 yr, with the greatest loss occurring at 1 yr (-5.9% and -6.3%, respectively). A similar profile of decrease was observed for integral hip vBMD with significant decreases of 6.6%, 7.7%, and 10.7% after 1, 2, and 5 yr, mainly due to a reduction in the trabecular (10.5%, 12.0%, and 17.2%, respectively) rather than cortical (1.4%, 1.9%, and 2.9%, respectively) component. A modest decrease in mean cortical thickness (2.5%, 2.8%, and 3.9%, respectively) and an alteration in the structural parameters were concomitantly observed. Older age and greater body weight loss were the factors most associated with an increased loss of aBMD and vBMD. In conclusion, the study demonstrates that SG induces not only an alteration in bone turnover and aBMD, but also a reduction in vBMD at the hip, predominantly due to trabecular component deterioration as determined by 3D-Shaper software. The maintenance of bone deterioration for at least 5 yr-ie, after 4 yr of relative body weight stabilization or minimal weight regain-suggests the need for a therapeutic approach to preserve bone health in patients who undergo SG., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Methylmalonic aciduria and homocystinuria, cobalamin C type (cblC), constitute the most common inborn error of intracellular cobalamin metabolism. Here, we report the case of a 6-month-old child, presenting severe subacute neurological decline associated with failure to thrive. Biochemical tests indicated a disorder of intracellular cobalamin metabolism, with elevated urinary and plasma methylmalonic acid levels associated with high plasma homocysteine concentrations, with normal plasma vitamin B12 concentrations. Diagnosis was later confirmed by genetic analysis which identified two pathogenic variants on the MMACHC gene: c.271dupA (p.Arg91lysfs∗14) paternal allele and c.388T > C (p.Tyr130His) maternal allele. The patient responded well to hydroxocobalamin treatment, with a rapid recovery of symptoms and a normal growth at 2.8 years of follow-up. This case illustrates the importance of early diagnosis of cobalamin metabolism disorders by prescribing adequate biochemical tests., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Importance: Early detection of brain amyloidosis (Aβ+) is pivotal for diagnosing Alzheimer's disease (AD) and optimizing patient management, especially in light of emerging treatments. While plasma biomarkers are promising, their combined diagnostic value through specific ratios remains underexplored., Objective: To evaluate the diagnostic accuracy of plasma pTau isoform (pTau181 and pTau217) to Aβ42 ratios in detecting Aβ+ status., Design Setting and Participants: This study included 423 participants from the multicenter prospective ALZAN cohort, recruited for cognitive complaints. Aβ+ status was determined using cerebrospinal fluid (CSF) biomarkers. Validation of the key findings was performed in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, where Aβ+ status was determined using PET imaging., Exposures: Plasma biomarkers (pTau181, pTau217, Aβ40, Aβ42) were measured using immunoassays and mass spectrometry, with specific ratios calculated. In the ALZAN cohort, the impact of confounding factors such as age, renal function, ApoE4 status, body mass index, and the delay between blood collection and processing was also evaluated to assess their influence on biomarker concentrations and diagnostic performance., Main Outcomes and Measures: The primary outcome was the diagnostic performance of plasma biomarkers and their ratios for detecting Aβ+ status. Secondary outcomes included the proportion of patients classified as low, intermediate, or high risk for Aβ+ using a two-cutoff approach., Results: The pTau181/Aβ42 ratio matched the diagnostic performance of pTau217 with AUC of 0.911 (0.880-0.936). The pTau217/Aβ42 ratio demonstrated the highest diagnostic accuracy in the ALZAN cohort, with an AUC of 0.927 (0.898-0.950), outperforming individual biomarkers. Both ratios effectively mitigated confounding factors, such as variations in renal function, and were particularly excellent in identifying Aβ+ status in individuals with early cognitive decline. Validation in the ADNI cohort confirmed these findings, with consistent performance across different measurement methods. The two-cutoff workflow using pTau217/Aβ42 reduced the intermediate-risk zone from 16% to 8%, enhancing stratification for clinical decision-making., Conclusions and Relevance: The pTau217/Aβ42 ratio offers superior diagnostic accuracy for detecting Aβ+ compared to individual biomarkers and reduces diagnostic uncertainty. These findings highlight the clinical utility of plasma biomarker ratios for early AD detection, paving the way for broader implementation in clinical and research settings.

Introduction: Cardiovascular (CV) diseases persist as the foremost cause of morbidity/mortality among chronic kidney disease (CKD) patients. This paper examines the values of coronary artery calcification (CAC) and biomarkers of CV on major adverse CV events (MACE)/CV death in a sample of 425 non-dialysis CKD patients., Methods: At inclusion, patients underwent chest multidetector computed tomography for CAC scoring and biomarkers of CV risk including CRP, mineral metabolism markers, fibroblast growth factor-23 (FGF-23), α-Klotho, osteoprotegerin, tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, matrix gla protein (both dephosphorylated uncarboxylated [dp-ucMGP] and total uncarboxylated), and growth differentiation factor-15 (GDF-15) were measured. Patients were followed for a median of 3.61 years (25th-75th percentiles = 1.92-6.70)., Results: Our results reported that CAC was a major independent factor of MACE/CV mortality showing a hazard ratio of 1.71 95% (confidence interval = 1.00-2.93) after adjustment for age, gender, diabetes, and history of CV events for patients with CAC >300. Interestingly, CAC effect was further enhanced in the presence of low levels of 25(OH) vitamin D3 or α-Klotho and high levels of intact parathyroid hormone (PTH), high-sensitive C reactive protein, FGF-23, osteoprotegerin, sclerostin, dp-ucMGP, or GDF-15., Conclusion: CAC constitutes a significant CV risk, further exacerbated by inflammation, hyperparathyroidism, and regulation of bone molecules implicated in calcification progression. This finding aligns with the original concept of multiple hits. Consequently, addressing the detrimental environment that fosters plaque vulnerability, reducing chronic low-grade inflammation, and normalizing mineral metabolism markers (such as vitamin D and PTH) and bone-regulating molecules may emerge as a viable therapeutic strategy., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Hemodialysis (HD) can lead to left ventricular (LV) transient regional wall motion abnormalities (RWMAs), due to segmental hypoperfusion, better known as myocardial stunning. Repeated episodes of HD-induced ischemia contribute directly to the development of heart failure and increased mortality in patients receiving HD. Intradialytic exercise (IDE) training is capable of exerting favorable effects on the cardiovascular system. However, its impact on HD-induced myocardial stunning remains currently unknown., Methods: In this prospective controlled study, 31 patients participating in an intradialytic aerobic and resistance training program (3/week for 16 weeks) were compared with 30 patients receiving usual care. Two-dimensional echocardiography was performed at baseline and follow-up both just before HD onset (T 0 ) and at peak stress of HD (T peak ). LV longitudinal strain from an 18-segment model were used to assess the presence of RWMAs., Results: Training resulted in a significant reduction of RWMAs at T peak between groups [-2.22 segments; 95% confidence interval (CI) -0.49/-3.96; P  = .01]. Compared with usual care, trained patients demonstrated also a greater reduction in the decline of global longitudinal strain during HD (-1.45%; 95% CI -0.24/-2.66; P  = .01). There were significant reductions in LV mass (-23.3 g; 95% CI -8.7/-37.9; P  = .002) and improvements in LV ejection fraction (4%; 95% CI 1.5/6.6; P  = .002) between groups favoring IDE. Correlations were found between change in RWMAs with change in LV mass and ejection fraction over the study period., Conclusion: IDE training is cardioprotective, improving LV remodeling and reducing HD-induced myocardial stunning., Competing Interests: None., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Frailty, characterized by vulnerability, reduced reserves and increased susceptibility to severe events, is a significant concern in chronic haemodialysis (HD) patients. Sarcopenia, corresponding to the progressive loss of muscle mass and strength, may contribute to frailty by reducing functional capacity, mobility and autonomy. However, consensus lacks on the optimal bedside frailty index for chronic HD patients. This study investigated the influence of frailty on chronic HD patient survival and explored the associated factors., Methods: A total of 135 patients were enrolled from January to April 2019 and then followed up prospectively until April 2022. At inclusion, frailty was assessed by the Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests including gait speed, standing balance and lower limb muscle strength., Results: From a total of 114 prevalent chronic HD patients (66% men, age 67.6 ± 15.1 years), 30 died during the follow-up period of 23.7 months (range 16.8-34.3). Deceased patients were older, had more comorbidities and a higher sarcopenia prevalence ( P  < .05). The TUG and SPPB test scores were significantly reduced in patients who had died [SPPB total score: 7.2 ± 3.3 versus 9.4 ± 2.5; TUG time 8.7 ± 5.8 versus 13.8 ± 10.5 ( P  < .05)]. Multivariate analysis showed that a higher SPPB score (total value >9) was associated with a lower mortality risk [hazard ratio 0.83 (95% confidence interval 0.74-0.92); P  < .03). Each component of the SPPB test was also associated with mortality in univariate analysis, but only the SPPB balance test remained protective against mortality in multivariate analysis. Older age, lower handgrip strength and lower protein catabolic rate were associated with SPPB total scores <9, SPPB balance score and TUG time >10 s., Conclusions: Screening for frailty is crucial in chronic HD patients, and incorporating SPPB, especially the balance test, provides valuable insights. Diminished muscle strength and inadequate protein intake negatively influence the SPPB score and balance in chronic HD patients. Effective identification and management of frailty can therefore improve outcomes., Clinical Trial Registration Clinicaltrialsgov: NCT03845452., Competing Interests: All authors declare they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Left atrial (LA) function plays a pivotal role in cardiac performance by modulating left ventricular (LV) function. Impairments in LV function are commonly reported during hemodialysis (HD), but available data describing changes in LA function are limited. There is growing evidence of the cardioprotective effect of intradialytic exercise (IDE) on LV function, but studies analyzing its effect on LA function are scarce. Our aim was to evaluate whether IDE can limit the severity of HD-induced impairment in LA myocardial function. In this prospective, open-label, two-center randomized crossover trial, 56 stable individuals receiving HD participated in 2 HD sessions in random order: standard HD and a session incorporating 30 min of aerobic exercise. LA and LV global longitudinal strains (GLSs) were obtained before and at peak stress of HD (i.e., 30 min before the HD ending). IDE totally eradicated the decline in LA reservoir strain observed during HD (estimated difference: 3.1%, 95% confidence interval: 0.4/5.8, P = 0.02), whereas it did not affect the other components of LA mechanics. A similar result favoring IDE intervention was also demonstrated on GLS changes over the HD procedure ( P < 0.001). Between-session differences of changes in GLS and LA reservoir strain were correlated ( r = -0.32, P = 0.03). The cardioprotective effect of IDE disappeared in patients with LA enlargement (i.e., LA volume index >34 mL/m 2 ). In conclusion, even a short duration of IDE at moderate intensity is effective in preventing HD-associated decline in LA reservoir function. Further research is needed to explore the long-term benefits of IDE on LA function. NEW & NOTEWORTHY A single bout of intradialytic exercise (IDE) at moderate intensity can prevent the hemodialysis-associated decline in left atrial (LA) function. This was partially explained by the relative preservation of left ventricular systolic function with IDE. Benefits of IDE on LA function were lost in patients with LA dilation. Further studies are needed to explore the mechanisms behind IDE-induced cardioprotection and evaluate the clinical impacts of the repetitive cardioprotective effects of IDE on LA function.

Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments.

Background : Acute heart failure (AHF) represents a leading cause of unscheduled hospital stays, frequent rehospitalisations, and mortality worldwide. The aim of our study was to develop a bedside prognostic tool, a multivariable predictive risk score, that is useful in daily practice, thus providing an early prognostic evaluation at admission and an accurate risk stratification after discharge in patients with AHF. Methods : This study is a subanalysis of the STADE HF study, which is a single-centre, prospective, randomised controlled trial enrolling 123 patients admitted to hospital for AHF. Here, 117 patients were included in the analysis, due to data exhaustivity. Regression analysis was performed to determine predictive variables for one-year mortality and/or rehospitalisation after discharge. Results : During the first year after discharge, 23 patients died. After modellisation, the variables considered to be of prognostic relevance in terms of mortality were (1) non-ischaemic aetiology of HF, (2) elevated creatinine levels at admission, (3) moderate/severe mitral regurgitation, and (4) prior HF hospitalisation. We designed a linear model based on these four independent predictive variables, and it showed a good ability to score and predict patient mortality with an AUC of 0.84 (95%CI: 0.76-0.92), thus denoting a high discriminative ability. A risk score equation was developed. During the first year after discharge, we observed as well that 41 patients died or were rehospitalised; hence, while searching for a model that could predict worsening health conditions (i.e., death and/or rehospitalisation), only two predictive variables were identified: non-ischaemic HF aetiology and previous HF hospitalisation (also included in the one-year mortality model). This second modellisation showed a more discrete discriminative ability with an AUC of 0.67 (95% C.I. 0.59-0.77). Conclusions : The proposed risk score and model, based on readily available predictive variables, are promising and useful tools to assess, respectively, the one-year mortality risk and the one-year mortality and/or rehospitalisations in patients hospitalised for AHF and to assist clinicians in the management of patients with HF aiming at improving their prognosis.

Importance: Minor head trauma (HT) is one of the most common causes of hospitalization in children. A diagnostic test could prevent unnecessary hospitalizations and cranial computed tomographic (CCT) scans., Objective: To evaluate the effectiveness of serum S100B values in reducing exposure to CCT scans and in-hospital observation in children with minor HT., Design, Setting, and Participants: This multicenter, unblinded, prospective, interventional randomized clinical trial used a stepped-wedge cluster design to compare S100B biomonitoring and control groups at 11 centers in France. Participants included children and adolescents 16 years or younger (hereinafter referred to as children) admitted to the emergency department with minor HT. The enrollment period was November 1, 2016, to October 31, 2021, with a follow-up period of 1 month for each patient. Data were analyzed from March 7 to May 29, 2023, based on the modified intention-to-treat and per protocol populations., Interventions: Children in the control group had CCT scans or were hospitalized according to current recommendations. In the S100B biomonitoring group, blood sampling took place within 3 hours after minor HT, and management depended on serum S100B protein levels. If the S100B level was within the reference range according to age, the children were discharged from the emergency department. Otherwise, children were treated as in the control group., Main Outcomes and Measures: Proportion of CCT scans performed (absence or presence of CCT scan for each patient) in the 48 hours following minor HT., Results: A total of 2078 children were included: 926 in the control group and 1152 in the S100B biomonitoring group (1235 [59.4%] boys; median age, 3.2 [IQR, 1.0-8.5] years). Cranial CT scans were performed in 299 children (32.3%) in the control group and 112 (9.7%) in the S100B biomonitoring group. This difference of 23% (95% CI, 19%-26%) was not statistically significant (P = .44) due to an intraclass correlation coefficient of 0.32. A statistically significant 50% reduction in hospitalizations (95% CI, 47%-53%) was observed in the S100B biomonitoring group (479 [41.6%] vs 849 [91.7%]; P < .001)., Conclusions and Relevance: In this randomized clinical trial of effectiveness of the serum S100B level in the management of pediatric minor HT, S100B biomonitoring yielded a reduction in the number of CCT scans and in-hospital observation when measured in accordance with the conditions defined by a clinical decision algorithm., Trial Registration: ClinicalTrials.gov Identifier: NCT02819778.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The authors report the relevance of using a point of care test (Helge ® ) for free hemoglobin determination and concordance of the values the with Cobas ® 8000 and spectrophotometer methods. Results: The within-run of the point of care test was <3%. Good correlations among the three methods were observed and an acceptable concordance for hemolysis index values from 50 mg/dl. An excellent agreement between the Cobas 8000 and the spectrophotometer was found. Conclusion: Automated methods represent methods of choice for free hemoglobin determination. An advantage of the Helge system is that it can be applied to samples experiencing a delay in evaluation due to the long distance between the collection site and the central laboratory. Another advantage is its use at the bedside, in the monitoring of extracorporeal membrane oxygenation patients.

Background and Aims: The dialysate magnesium (Mg) concentration is a major determinant of Mg balance in hemodialysis. This study aimed to assess the systemic variations of total (tMg) and ionized Mg (iMg) during a dialysis session using acetate or citrate fluids and 0.5 or 0.75 mM Mg., Materials and Methods: 134 patients in maintenance hemodialysis were assigned to a dialysis session with 4 different dialysates: acetate fluid with 0.5 mM Mg (1) or 0.75 mM Mg (2), citrate fluid with 0.5 mM Mg (3) or 0.75 mM Mg (4). Ionized form was measured by direct ion-selective electrode., Results: A Mg loss was observed in both acetate (0.12 and 0.08 mmol/L) and citrate (0.13 and 0.14 mmol/L for tMg and iMg, respectively) fluid groups containing 0.5 mM Mg. The use of acetate and citrate dialysates with 0.75 mM Mg led to a significant median intra-dialytic increase of 0.15 and 0.08 mmol/L for tMg, respectively. A significant augmentation in iMg concentration with acetate (0.11 mmol/L) but not with citrate dialysate (0.02 mmol/L) was observed., Conclusion: While a dialysate Mg concentration at 0.5 mM leads to a negative balance, increasing the concentration to 0.75 mM significantly raises post-dialysis circulating Mg. Monitoring of iMg should allow a personalized prescription in dialysate Mg., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cardiac alteration due to chronic kidney disease is described by tissue fibrosis. This remodeling involves myofibroblasts of various origins, including epithelial or endothelial to mesenchymal transitions. In addition, obesity and insulin resistance together or separately seem to exacerbate cardiovascular risk in chronic kidney disease (CKD). The main objective of this study was to assess if pre-existing metabolic disease exacerbates CKD-induced cardiac alterations. In addition, we hypothesised that endothelial to mesenchymal transition participates in this enhancement of cardiac fibrosis. Rats fed cafeteria type diet for 6 months underwent a subtotal nephrectomy at 4 months. Cardiac fibrosis was evaluated by histology and qRT-PCR. Collagens and macrophages were quantified by immunohistochemistry. Endothelial to mesenchymal transitions were assessed by qRT-PCR (CD31, VE-cadherin, α-SMA, nestin) and also by CD31 immunofluorescence staining. Rats fed with cafeteria type regimen were obese, hypertensive and insulin resistant. Cardiac fibrosis was predominant in CKD rats and was highly majored by cafeteria regimen. Collagen-1 and nestin expressions were higher in CKD rats, independently of regimen. Interestingly, in rats with CKD and cafeteria diet we found an increase of CD31 and α-SMA co-staining with suggest an implication of endothelial to mesenchymal transition during heart fibrosis. We showed that rats already obese and insulin resistant had an enhanced cardiac alteration to a subsequent renal injury. Cardiac fibrosis process could be supported by a involvement of the endothelial to mesenchymal transition phenomenon., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The prognostic value of vitamin B12 blood levels remains controversial. An association between elevated vitamin B12 and mortality has been reported, particularly among elderly patients with cancers and liver or blood diseases. The present study explored the relationship between mortality and elevated vitamin B12 levels in a population of unscheduled inpatients in an internal medicine unit., Methods: This retrospective observational analysis was conducted between August 2014 and December 2018. We compared 165 patients with elevated plasma vitamin B12 levels (>600 pmol/l) with a random sample of 165 patients with normal B12 levels who were hospitalized during the same period. Demographic, clinical, and biological characteristics were assessed during hospitalization. The primary endpoint was all-cause death at 1 year., Results: Patients with elevated B12 were younger, with a lower body mass index and lower plasma albumin than those with normal B12 (75 ± 16 years vs 79 ± 13 years, p  = 0.047; 23 ± 5 vs 26 ± 7 kg/m 2 , p   <  0.001; and 33 ± 5 vs 35 ± 5 g/l, p   <  0.001, respectively). The prevalence of auto-immune disease and referral from an intensive care unit was higher among patients with elevated B12 (11% vs 5%, p  = 0.043 and 36% vs 10%, p   <  0.001, respectively). After 1 year of follow-up, 64 (39%) patients with elevated B12 had died compared to 43 (26%) patients with normal B12 ( p  = 0.018). Multivariate analysis using the Cox proportional hazards regression model adjusted for age, gender, body mass index, intensive care unit hospitalization, albumin level, and the presence of solid cancer or autoimmune disease revealed elevated B12 to be associated with a significant risk of death in the first year of follow-up (hazard ratio: 1.71 [1.08-2.7], p  = 0.022)., Conclusion: Elevated B12 is an early warning indicator of increased short-term mortality, such as independently of age, cancer, or comorbidities, in patients hospitalized in an internal medicine department., Competing Interests: C.R. reports personal fees from Servier and Pfizer unrelated to this work. P.F. has received travel and accommodation fees from Actelion, Johnson and Johnson, BMS, Pfizer, and Servier unrelated to this work. The remaining authors declare no conflicts of interest., (Copyright © 2023 Benjamin Eduin et al.)

Objectives: Blood microsampling, particularly dried blood spots (DBSs), is an attractive minimally-invasive approach that is well suited for home sampling and predictive medicine associated with longitudinal follow-up of the elderly. However, in vitro diagnostic quantification of biomarkers from DBS poses a major challenge. Clinical mass spectrometry can reliably quantify blood proteins in various research projects. Our goal here was to use mass spectrometry of DBS in a real-world clinical setting and compared it to the standard immunoassay method. We also sought to correlate DBS mass spectrometry measurements with clinical indices., Methods: A clinical trial of diagnostic equivalence was conducted to compare conventional venous samples quantified by immunoassay and DBSs quantified by mass spectrometry in an elderly population. We assayed three protein biomarkers of nutritional and inflammatory status: prealbumin (transthyretin), C-reactive protein, and transferrin., Results: The analysis of DBSs showed satisfactory variability and low detection limits. Statistical analysis confirmed that the two methods give comparable results at clinical levels of accuracy. In conclusion, we demonstrated, in a real-life setting, that DBSs can be used to measure prealbumin, CRP and transferrin, which are commonly used markers of nutritional status and inflammation in the elderly. However, there was no correlation with patient frailty for these proteins., Conclusions: Early detection and regular monitoring of nutritional and inflammatory problems using DBS appear to be clinically feasible. This could help resolve major public health challenges in the elderly for whom frailty leads to serious risks of health complications., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Faced with the pandemic viral circulation of SARS-CoV-2, healthcare establishments have had to maintain an effective screening strategy in order to prevent nosocomial clusters. Automated antigenic tests appear to be a reliable and complementary alternative to RT-PCR (reverse transcriptase polymerase chain reaction) in order to optimize patient care in the emergency department. We report our experience of the deployment of the LumiraDx antigen tests on the LumiraDx platform, as well as the comparison of these tests' results with the RT-PCR results on a population of patients sampled in the emergency department.

Despite significant progress in dialysis modalities, intermittent renal replacement therapy remains an "unphysiological" treatment that imperfectly corrects uremic disorders and may lead to low-grade chronic inflammation, neutrophil activation, and oxidative stress due to repetitive blood/membrane interactions contributing to the "remaining uremic syndrome" and cardiovascular disease burden of hemodialysis patients. Understanding dialysis bioincompatibility pathways still remains a clinical and biochemical challenge. Indeed, surrogate biomarkers of inflammation including C-reactive protein could not discriminate between all components involved in these complex pathways. A few examples may serve to illustrate the case. Cytokine release during dialysis sessions may be underestimated due to their removal using high-flux dialysis or hemodiafiltration modalities. Complement activation is recognized as a key event of bioincompatibility. However, it appears as an early and transient event with anaphylatoxin level normalization at the end of the dialysis session. Complement activation is generally assumed to trigger leukocyte stimulation leading to proinflammatory mediators' secretion and oxidative burst. In addition to being part of the innate immune response involved in eliminating physically and enzymatically microbes, the formation of Neutrophil Extracellular Traps (NETs), known as NETosis, has been recently identified as a major harmful component in a wide range of pathologies associated with inflammatory processes. NETs result from the neutrophil degranulation induced by reactive oxygen species overproduction via NADPH oxidase and consist of modified chromatin decorated with serine proteases, elastase, bactericidal proteins, and myeloperoxidase (MPO) that produces hypochlorite anion. Currently, NETosis remains poorly investigated as a sensitive and integrated marker of bioincompatibility in dialysis. Only scarce data could be found in the literature. Oxidative burst and NADPH oxidase activation are well-known events in the bioincompatibility phenomenon. NET byproducts such as elastase, MPO, and circulating DNA have been reported to be increased in dialysis patients more specifically during dialysis sessions, and were identified as predictors of poor outcomes. As NETs and MPO could be taken up by endothelium, NETs could be considered as a vascular memory of intermittent bioincompatibility phenomenon. In this working hypothesis article, we summarized the puzzle pieces showing the involvement of NET formation during hemodialysis and postulated that NETosis may act as a disease modifier and may contribute to the comorbid burden associated with dialysis bioincompatibility., Competing Interests: BC was employed by the MTX Consulting Int. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Cristol, Thierry, Bargnoux, Morena-Carrere and Canaud.)

It is well documented that lean tissue mass (LTM) decreases with aging in patients with obesity, but there is no information available regarding muscle strength changes, a parameter that may be better associated with sarcopenic obesity (SO). The objectives of this study were to analyze the changes in LTM and fat mass (FM), muscle strength and muscle function with aging in women with obesity and to determine the prevalence of SO. LTM and FM were determined by DXA, muscle strength with the hand-grip test and muscle function with the 6 min walk test (6MWT) in 383 women with obesity. A redistribution of the LTM and FM occurred with age, characterized by a gain at the trunk to the detriment of the lower limbs, thus reducting in appendicular LTM indices. The physical performances evaluated by the muscle strength and muscle function decreased concomitantly, and the prevalence of low values for both these parameters was 22.8% and 13.4%, respectively, in the older patients. In summary, although a reduction in appendicular LTM and muscle performances occurred with age and resulted in an increase in the prevalence of SO, the number of women with obesity affected by SO remained low ( n ≤ 15), even in those older than 60 years.

Bariatric surgery induces bone loss, but the exact mechanisms by which this process occurs are not fully known. The aims of this 2-year longitudinal study were to (i) investigate the changes in areal bone mineral density (aBMD) and bone turnover markers following sleeve gastrectomy (SG) and (ii) determine the parameters associated with the aBMD variations. Bone turnover markers, sclerostin, periostin and semaphorin 4D were assessed before and 1, 12 and 24 months after SG, and aBMD was determined by DXA at baseline and after 12 and 24 months in 83 patients with obesity. Bone turnover increased from 1 month, peaked at 12 months and remained elevated at 24 months. Periostin and sclerostin presented only modest increases at 1 month, whereas semaphorin 4D showed increases only at 12 and 24 months. A significant aBMD decrease was observed only at total hip regions at 12 and 24 months. This demineralisation was mainly related to body weight loss. In summary, reduced aBMD was observed after SG in the hip region (mechanical-loading bone sites) due to an increase in bone turnover in favour of bone resorption. Periostin, sclerostin and semaphorin 4D levels varied after SG, showing different time lags, but contrary to weight loss, these biological parameters did not seem to be directly implicated in the skeletal deterioration.

Introduction: Misuse of inhaled nitrous oxide is a growing concern in France. It is known to alter concentrations of vitamin B 12, which is required as a cofactor for methionine synthase and methylmalonyl-CoA mutase activity. Hence, measurement of the concentrations of cobalamin metabolism biomarkers, including vitamin B 12 , homocysteine, and methylmalonic acid, could assist in the management of patients with a complex clinical presentation or in those who deny the consumption of nitrous oxide. Methods: We retrospectively collected clinical and biological data in patients hospitalized for nitrous oxide use in a university hospital in southern France between January 2020 and October 2022. Results: Thirty-one patients were identified during 34 months; 79% were men with a median age of 23.7 years. Most (97%) presented with peripheral polyneuropathy and/or myelopathy. The median vitamin B 12 concentration was 134.6 pmol/L, with 17 of 31 patients having values less than 145 pmol/L (the lower limit of the normal range). The median plasma folate concentration was 20.1 nmol/L, which is within the normal range. The median plasma homocysteine concentration was 87.7 µmol/L (normal range <15 µmol/L), and the median plasma methylmalonic acid concentration was 3.8 µmol/L (normal range <0.5 µmol/L). Conclusion: Nitrous oxide use is an emerging public health problem in France, as shown by the number of patients admitted to our hospital. The presence of a functional vitamin B 12 deficiency was a consistent feature that could be helpful in diagnosis in complex cases.

Significance Statement: Hemodialysis (HD) can lead to acute left ventricular (LV) myocardial wall motion abnormalities (myocardial stunning) due to segmental hypoperfusion. Exercise during dialysis is associated with favorable effects on central hemodynamics and BP stability, factors considered in the etiology of HD-induced myocardial stunning. In a speckle-tracking echocardiography analysis, the authors explored effects of acute intradialytic exercise (IDE) on LV regional myocardial function in 60 patients undergoing HD. They found beneficial effects of IDE on LV longitudinal and circumferential function and on torsional mechanics, not accounted for by cardiac loading conditions or central hemodynamics. These findings support the implementation of IDE in people with ESKD, given that LV transient dysfunction imposed by repetitive HD may contribute to heart failure and increased risk of cardiac events in such patients., Background: Hemodialysis (HD) induces left ventricular (LV) transient myocardial dysfunction. A complex interplay between linear deformations and torsional mechanics underlies LV myocardial performance. Although intradialytic exercise (IDE) induces favorable effects on central hemodynamics, its effect on myocardial mechanics has never been comprehensively documented., Methods: To evaluate the effects of IDE on LV myocardial mechanics, assessed by speckle-tracking echocardiography, we conducted a prospective, open-label, two-center randomized crossover trial. We enrolled 60 individuals with ESKD receiving HD, who were assigned to participate in two sessions performed in a randomized order: standard HD and HD incorporating 30 minutes of aerobic exercise (HDEX). We measured global longitudinal strain (GLS) at baseline (T0), 90 minutes after HD onset (T1), and 30 minutes before ending HD (T2). At T0 and T2, we also measured circumferential strain and twist, calculated as the net difference between apical and basal rotations. Central hemodynamic data (BP, cardiac output) also were collected., Results: The decline in GLS observed during the HD procedure was attenuated in the HDEX sessions (estimated difference, -1.16%; 95% confidence interval [95% CI], -0.31 to -2.02; P = 0.008). Compared with HD, HDEX also demonstrated greater improvements from T0 to T2 in twist, an important component of LV myocardial function (estimated difference, 2.48°; 95% CI, 0.30 to 4.65; P = 0.02). Differences in changes from T0 to T2 for cardiac loading and intradialytic hemodynamics did not account for the beneficial effects of IDE on LV myocardial mechanics kinetics., Conclusions: IDE applied acutely during HD improves regional myocardial mechanics and might warrant consideration in the therapeutic approach for patients on HD., (Copyright © 2023 by the American Society of Nephrology.)

Tunneled central venous catheters (CVC) are mainly considered as a rescue vascular access option in dialysis but are still used on approximately one quarter of prevalent patients worldwide even though they are associated with poor performances and higher risks., Study Design: in this retrospective single-center study, we aimed to report on the clinical performances achieved with high-flow tunneled CVCs (DualCath or DCath) and compared them with arteriovenous accesses (AVAs, e.g., AV fistula, AV graft, and Thomas Shunt) in a hospital-based dialysis unit., Methods: Sixty-eight stage 5 chronic kidney disease dialysis-dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up with for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-ups of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V, total Kt, ultrafiltration volume, and percent reduction in β2-M were measured monthly as part of quality control in our unit., Results: At baseline, the effective blood flow using a DCath was close to 400 mL/min, similar to an AVA. Recirculation with a DCath (7%, 6-13%) was higher than with an AVA. The diffusive dialysis dose delivered with a DCath (spKt and eKt/V) and convective dialysis dose achieved with a DCath were slightly lower than those achieved with AVAs, but they were still much higher than is recommended by guidelines. The percent reduction in β2-M achieved with a DCath was also 4 to 10% lower than that achieved with an AVA. On longitudinal follow-up, the main clinical performance indicators of DCaths (total Kt and total ultrafiltration volume, L/session) were maintained as very stable over time and close to those achieved with AVAs., Conclusions: As shown in this study, high-flow DualCath tunneled two-single-lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performance. These results relied on the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Background and Aims: Mobility and migration flows are growing from different countries of the world to European countries, including France and in particular the Mediterranean basin. This study aimed to investigate the presence of hemoglobin (Hb) variants in outpatients/inpatients of the Montpellier Hospital (France) in whom an HbA1c assay had been performed and for which the country of birth had been informed., Methods: This is a retrospective study from January 2016 to December 2020 based on all high-performance liquid chromatography (HPLC) chromatograms (Tosoh Bioscience HLC-723G8) having an alarm of suspected Hb variant during HbA1c measurement. The corresponding samples were systematically sent to the hematology laboratory for confirmation and identification of Hb variant. Patient's medical history, clinical and demographic data were extracted from each medical chart. Statistical analyses were performed using XLSTAT® software, version 2016.06.35661., Results: Three hundred sixty-three patients were confirmed with Hb variant exhibiting 17 different Hb profiles, highlighting the pivotal role of glycated hemoglobin (HbA1c) as a detection step. The prevalence of Hb variant in this southern French population was 0.71%, with the highest frequency for the beta-globin variants ( n  = 342/363; i.e., 94.2%), including the most common: S, C, E, and D in 200/342 (58.5%), 83/342 (24.3%), 29/342 (8.5%), and 11/342 (3.2%), respectively. Among patients with Hb variants, almost half (165/363; i.e., 45.4%) were born in the African continent with a predominance for Morocco (32/165; i.e., 19.3%) and Algeria (29/165; i.e., 17.5%)., Conclusion: HbA1c assay is a useful tool to detect Hb variants. Hemoglobinopathies are a public health issue in the current French population which is a multiethnic society. Despite the monocentric nature of our study, we note a high frequency of Hb variants in the south of France, which underlines the importance of screening for Hb variants in the whole population., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF)., Methods: Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145., Results: Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions., Conclusions: During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Purpose: This study aimed to evaluate feasibility and early effects of moderate intensity bed-cycling eccentric training on healthy individuals, and establish whether this training modality could be implemented into bedridden patients' routine care., Methods: Longitudinal study with prepost exercise intervention measurements. The development of a bed-adapted eccentric ergometer allowed to conduct five training sessions during 3 weeks at increasing intensity on 11 healthy individuals. Force-speed relationship, maximal voluntary knee extension force and neural activation of subjects were evaluated before and after the programme., Results: Five training sessions were sufficient to decrease the rate of perceived exertion whereas eccentric power output increased (+40%). After training, maximal voluntary isometric contraction force measured during knee extension had significantly improved in all subjects, with a mean increase of 17%. Maximal cycling power was also significantly higher (+7%) after the training programme., Conclusion: Taken together, these results show that moderate load eccentric bed cycling (i) was feasible and efficient, (ii) did not generate excessive individual perception of effort during exercise nor develop major muscular or joint pain after training and (iii) allowed early force and power gains in healthy subjects., (© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Factitious hypoglycemia is a factitious disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), referring to intentionally covertly induced hypoglycemia, with potentially severe consequences. Knowledge of factitious hypoglycemia relies on case reports, and evidence-based information and guidelines are lacking. Diagnosing factitious hypoglycemia in insulin-treated diabetic persons is therefore challenging and often requires a long and costly process. Moreover, the typical metrics proposed to differentiate insulin-induced factitious hypoglycemia from insulinoma (i.e., high insulin and low C-peptide versus high insulin and high C-peptide, respectively) are not always applicable, depending on whether the insulin quantification method can detect the insulin analog. When factitious hypoglycemia is suspected, an emerging trend from recent publications advocates a combination of two insulin quantification methods with different cross-reactivity for insulin analogs, early on in the diagnostic process., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Cardiovascular disease (CVD) is a major burden in dialysis-dependent chronic kidney disease (CKD5D) patients. Several factors contribute to this vulnerability including traditional risk factors such as age, gender, life style and comorbidities, and non-traditional ones as part of dialysis-induced systemic stress. In this context, it appears of utmost importance to bring a closer attention to CVD monitoring in caring for CKD5D patients to ensure early and appropriate intervention for improving their outcomes. Interestingly, new home-used, self-operated, connected medical devices offer convenient and new tools for monitoring in a fully automated and ambulatory mode CKD5D patients during the interdialytic period. Sensoring devices are installed with WiFi or Bluetooth. Some devices are also available in a cellular version such as the Withings Remote Patient Monitoring (RPM) solution. These devices analyze the data and upload the results to Withings HDS (Hybrid data security) platform servers. Data visualization can be viewed by the patient using the Withings Health Mate application on a smartphone, or with a web interface. Health Care Professionals (HCP) can also visualize patient data via the Withings web-based RPM interface. In this narrative essay, we analyze the clinical potential of pervasive wearable sensors for monitoring ambulatory dialysis patients and provide an assessment of such toolkit digital medical health devices currently available on the market. These devices offer a fully automated, unobtrusive and remote monitoring of main vital functions in ambulatory subjects. These unique features provide a multidimensional assessment of ambulatory CKD5D patients covering most physiologic functionalities, detecting unexpected disorders (i.e., volume overload, arrhythmias, sleep disorders) and allowing physicians to judge patient's response to treatment and recommendations. In the future, the wider availability of such pervasive health sensing and digital technology to monitor patients at an affordable cost price will improve the personalized management of CKD5D patients, so potentially resulting in improvements in patient quality of life and survival., Competing Interests: DC, ER are employees and/or stockholder from Withings. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Canaud, Kooman, Davenport, Campo, Carreel, Morena-Carrere and Cristol.)

Blood microsampling combined with large panels of clinically relevant tests are of major interest for the development of home sampling and predictive medicine. The aim of the study was to demonstrate the practicality and medical utility of microsamples quantification using mass spectrometry (MS) in a clinical setting by comparing two types of microsamples for multiplex MS protein detection. In a clinical trial based on elderly population, we compared 2 µL of plasma to dried blood spot (DBS) with a clinical quantitative multiplex MS approach. The analysis of the microsamples allowed the quantification of 62 proteins with satisfactory analytical performances. A total of 48 proteins were significantly correlated between microsampling plasma and DBS ( p < 0.0001). The quantification of 62 blood proteins allowed us to stratify patients according to their pathophysiological status. Apolipoproteins D and E were the best biomarker link to IADL (instrumental activities of daily living) score in microsampling plasma as well as in DBS. It is, thus, possible to detect multiple blood proteins from micro-samples in compliance with clinical requirements and this allows, for example, to monitor the nutritional or inflammatory status of patients. The implementation of this type of analysis opens new perspectives in the field of diagnosis, monitoring and risk assessment for personalized medicine approaches.

Background and Aims: Muscle mass (MM) impairment observed in facioscapulohumeral muscular dystrophy (FSHD) may bias estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcreat). eGFR based on cystatin C (eGFRcys), produced by all nucleated cells, should be an interesting alternative. Main objectives were to compare eGFRcreat and eGRFcys for chronic kidney disease (CKD) staging and for annual eGFR evolution. Secondary objective was to analyse creatinine, cystatin C with measured MM., Material and Methods: During 4 years, 159 FSHD patients having one or more creatinine and cystatin C measurements (total samples: n = 379), with MM determination by bio-impedancemetry during their follow-up were included. eGFR were determined with CKD-Epi and EKFC equations., Results: On first examination samples, mean eGFRcys was significantly lower than mean eGFRcreat of 25.5 and 17.9 ml/min/1.73 m 2 using CKD-Epi and EKFC equations, respectively. 53.5% (CKD-Epi) and 59.1% (EKFC) of agreement were obtained when using eGFRcys instead of eGFRcreat with reclassifications occurring mainly towards more severe stages. Age was correlated with cystatin C but not with creatinine, MM was correlated with creatinine but not with cystatin C. eGFR decreases > 1 ml/min/1.73 m 2 were more important when using eGFRcys instead of eGFRcreat (CKD-Epi: 37.5 vs 15.4%, p < 0.001; EKFC: 34.6 vs 20.2%, p < 0.01)., Conclusion: Cystatin C which is independent of MM appears as a promising candidate biomarker for CKD diagnosis and follow-up in FSHD patient., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In patients with facioscapulohumeral muscular dystrophy (FSHD), a rare genetic neuromuscular disease, reduced physical performance is associated with lower blood levels of vitamin C, zinc, selenium, and increased oxidative stress markers. Supplementation of vitamin C, vitamin E, zinc, and selenium improves the quadriceps' physical performance. Here, we compared the nutritional status of 74 women and 85 men with FSHD. Calorie intake was lower in women with FSHD than in men. Moreover, we assessed vitamin C, vitamin E, zinc, copper, and selenium intakes in diet and their concentrations in the plasma. Vitamin E, copper, and zinc intake were lower in women with FSHD than in men, whereas plasma vitamin C, copper levels, and copper/zinc ratio were higher in women with FSHD than in men. The dietary intake and plasma concentrations of the studied vitamins and minerals were not correlated in both sexes. A well-balanced and varied diet might not be enough in patients with FSHD to correct the observed vitamin/mineral deficiencies. A low energy intake is a risk factor for suboptimal intake of proteins, vitamins, and minerals that are important for protein synthesis and other metabolic pathways and that might contribute to progressive muscle mass loss. Antioxidant supplementation and higher protein intake seem necessary to confer protection against oxidative stress and skeletal muscle mass loss.

A HIV-infected female treated with a combination of emtricitabine/elvitegravir/tenofovir since 2017 presented an acute renal failure during her hospitalization for a SARS-CoV2 pneumonia. A computed tomography demonstrated left ureterohydronephrosis and ureteral stone. Fragments extracted by ureteroscopy showed a calculus composed of atazanavir and calcium oxalate. The patient's medical history showed atazanavir intake during ten years and then discontinued in 2017. This case report emphasizes that drug-induced urolithiasis should be considered when renal function declines, even far from discontinuation of atazanavir and without clinical signs of renal colitis. Moreover, identification of risk factors should alert to the possibility of drug-induced nephrolithiasis., Competing Interests: The authors declare that they have no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Maëlle Plawecki et al.)

Objective: To compare the estimated glomerular filtration rate (eGFR) using the creatinine equation (eGFRcreat) or the cystatin C equation (eGFRcys) in people with HIV (PWH) under antiretroviral drugs. We specifically included patients with an eGFRcreat around 60 ml/min per 1.73 m2 to evaluate agreement on stage 2 and 3 chronic kidney disease (CKD) classification., Design: eGFRcreat, eGFRcys and resulting CKD staging were determined in 262 consecutive patients with HIV-1 (PWH) with a suppressed viral load (<200 copies/ml) under antiretroviral drugs and having impaired renal function (eGFRcreat between 45 and 80 ml/min per 1.73 m2). Antiretroviral drugs regimens were classified into eight groups: cobicistat (COBI)+elvitegravir (EVG), ritonavir (RTV)+protease inhibitor, dolutegravir (DTG), DTG+rilpivirine (RPV), RPV, raltegravir (RAL), bictegravir (BIC), and other antiretroviral drugs., Results: Mean eGFRcys was higher than mean eGFRcreat (77.7 ± 0.5 vs. 67.9  ± 7.9 ml/min per 1.73 m2, P < 0.0001). The differences were significant in five treatment groups with COBI/EVG; DTG; DTG+RPV; RPV; RAL. CKD classification was modified for 51% of patients when using eGFRcys instead of eGFRcreat, with reclassification to less severe stages in 37% and worse stages in 14%., Conclusion: This study highlighted significant differences in eGFR depending on the renal marker used in PWH, having a significant impact on CKD classification. eGFRcys should be an additive tool for patients having eGFRcreat around 60 ml/min per 1.73 m2 for better identification of renal impairment., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The RECAP study reports results and outcomes (clinical performances, patient acceptance, cardiac outcomes, and technical survival) achieved with the S 3 system used as an intensive home hemodialysis (HHD) platform over a three-year French multicenter study. Ninety-four dialysis patients issued from ten dialysis centers and treated more than 6 months (mean follow-up: 24 months) with S 3 were included. A two-hour treatment time was maintained in 2/3 of patients to deliver 25 L of dialysis fluid, while 1/3 required up to 3 h to achieve 30 L. The additional convection volume produced by means of the SeCoHD tool (internal filtration backfiltration) was 3 L/session, and the net ultrafiltration produced to achieve dry weight was 1.4 L/session. On a weekly basis, an average 156 L of dialysate corresponding to 94 L of urea clearance when considering 85% dialysate saturation under low flow conditions was delivered. Such urea clearance was equivalent to 9.2 [8.0-13.0] mL/min weekly urea clearance and a standardized Kt/V of 2.5 [1.1-4.5]. The predialysis concentration of selected uremic markers remained remarkably stable over time. Fluid volume status and blood pressure were adequately controlled by means of a relatively low ultrafiltration rate (7.9 mL/h/kg). Technical survival on S 3 was 72% and 58% at 1 and 2 years, respectively. The S 3 system was easily handled and kept by patients at home, as indicated by technical survival. Patient perception was improved, while treatment burden was reduced. Cardiac features (assessed in a subset of patients) tended to improve over time. Intensive hemodialysis relying on the S 3 system offers a very appealing option for home treatment with quite satisfactory results, as shown in the RECAP study throughout a two-year follow-up time, and offers the best bridging solution to kidney transplantation.

Objectives: The objective of this prospective, single-center study was to explore the mid-term outcomes 6 to 9 months after hospitalization in an Intensive Care Unit (ICU) for severe COVID-19 infection., Methods: Patients systematically underwent biological tests, pulmonary function tests, chest computed tomography (CT) scan, and psychological tests., Results: Among 86 patients, including 71 (82.6%) men, median age of 65.8 years (56.7; 72.4), 57 (71.3%) patients presented post-COVID-19 asthenia, 39 (48.1%) muscle weakness, and 30 (36.6%) arthralgia. Fifty-two (64.2%) patients had a decreased diffusion capacity for carbon monoxide (DLCO) <80% and 16 (19.8%) had DLCO <60%. Chest CT-scans showed ground glass opacities in 35 (40.7%) patients, and reticular changes in 28 patients (33.7%), including fibrosis-like changes in 18 (21.7%) patients. Reticular changes and DLCO <60% were associated with length of stay in ICU, and reticular changes with higher maximal CRP level. The psychological questionnaires found 37.7% suffered from depression, 23.5% from anxiety, 42.4% from insomnia, and 9.4% from post-traumatic stress. Being female was associated with a higher frequency of depression and anxiety, with depression scores being associated with obesity., Conclusions: Many patients hospitalized in ICU for severe COVID-19 infection have mid-term sequelae. Additional studies on the prognostic factors seem necessary.

Many Point-of-Care devices have been released over the past decade. However, data regarding their analytical performances in real-world situations remains scarce. Herein, we aimed to assess the analytical performances of the i-STAT Alinity system. We conducted an analytical performances study with the i-STAT Alinity device using cartridges CG4+ (pH, Pco2, Po2, lactate, bicarbonate and base excess); CHEM8+ (Na, K, Cl, ionized Ca, urea, creatinine, glucose, hematocrit and hemoglobin) and PT/INR (prothrombin time and international normalized ratio). We assessed the imprecision and compared the results to those obtained on existing instruments in the central laboratory. We found that the within-lab coefficients of variation (CV) were very low (<2%) or low (2−5%), except for creatinine and PT (CV = 5.2% and CV = 6.3%, respectively). For almost all the parameters, the results were strongly (R2 = 90−95%) or very strongly (R2 > 95%) correlated with those of the existing laboratory instruments, and the biases were very low (<2%) or low (2−5%). However, correlations of the PT and INR measurements with existing instruments were lower (R2 = 86.0% and 89.7%), and biases in the Po2 (7.9%), creatinine (5.4%) and PT (−6.6%) measurements were higher. The i-STAT Alinity appeared as a convenient device for measurements of numerous parameters. However, clinicians should interpret Po2, creatinine and PT results with caution.

Acute heart failure (AHF) due to acute myocardial infarction (AMI) is likely to involve cardiogenic shock (CS), with neuro-hormonal activation. A relationship between AHF, CS and vasopressin response is suspected. This study aimed to investigate the implication of vasopressin on hemodynamic parameters and tissue perfusion at the early phase of CS complicating AMI. Experiments were performed on male Wistar rats submitted or not to left coronary artery ligation (AMI and Sham). Six groups were studied Sham and AMI treated or not with either a vasopressin antagonist SR-49059 (Sham-SR, AMI-SR) or agonist terlipressin (Sham-TLP, AMI-TLP). Animals were sacrificed one day after surgery (D 1 ) and after hemodynamic parameters determination. Vascular responses to vasopressin were evaluated, ex vivo, on aorta. AHF was defined by a left ventricular ejection fraction below 40%. CS was defined by AHF plus tissue hypoperfusion evidenced by elevated serum lactate level or low mesenteric oxygen saturation (SmO 2 ) at D 1 . Mortality rates were 40% in AMI, 0% in AMI-SR and 33% in AMI-TLP. Immediately after surgery, a sharp decrease in SmO 2 was observed in all groups. At D 1 , SmO 2 recovered in Sham and in SR-treated animals while it remained low in AMI and further decreased in TLP-treated groups. The incidence of CS among AHF animals was 72% in AMI or AMI-TLP while it was reduced to 25% in AMI-SR. Plasma copeptin level was increased by AMI. Maximal contractile response to vasopressin was decreased in AMI (32%) as in TLP- and SR- treated groups regardless of ligation. Increased vasopressin secretion occurring in the early phase of AMI may be responsible of mesenteric hypoperfusion resulting in tissue hypoxia. Treatment with a vasopressin antagonist enhanced mesenteric perfusion and improve survival. This could be an interesting therapeutic strategy to prevent progression to cardiogenic shock.

In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate postacute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and IGFBP7 product ([TIMP-2]•[IGFBP7]), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and [TIMP-2]•[IGFBP7] in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan-Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55-74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22-47) and median BMI: 25.7 kg/m 2 (IQR, 23.3-30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491-0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535-0.826), as compared to PTD and [TIMP-2]•[IGFBP7] (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01-1.06, p  = 0.005) and BMI (HR = 1.07, 95%CI: 1.00-1.14, p  = 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00-1.06, p  = 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20-12.5, p  = 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.

Protein energy malnutrition is recognized as a leading cause of morbidity and mortality in dialysis patients. Protein-energy-wasting process is observed in about 45% of the dialysis population using common biomarkers worldwide. Although several factors are implicated in protein energy wasting, inflammation and oxidative stress mechanisms play a central role in this pathogenic process. In this in-depth review, we analyzed the implication of sodium and water accumulation, as well as the role of fluid overload and fluid management, as major contributors to protein-energy-wasting process. Fluid overload and fluid depletion mimic a tide up and down phenomenon that contributes to inducing hypercatabolism and stimulates oxidation phosphorylation mechanisms at the cellular level in particular muscles. This endogenous metabolic water production may contribute to hyponatremia. In addition, salt tissue accumulation likely contributes to hypercatabolic state through locally inflammatory and immune-mediated mechanisms but also contributes to the perturbation of hormone receptors (i.e., insulin or growth hormone resistance). It is time to act more precisely on sodium and fluid imbalance to mitigate both nutritional and cardiovascular risks. Personalized management of sodium and fluid, using available tools including sodium management tool, has the potential to more adequately restore sodium and water homeostasis and to improve nutritional status and outcomes of dialysis patients., Competing Interests: BC is scientific consultant for FMC, MM-C, HL-M, J-PC have no conflict of interest.

Background and Objective: A clinician was intrigued about HbA1c upper 9% (75 mmol/mol) in a 76 year-old women with normal glycemia. Further explorations were performed in order to understand this discordance., Methods: First HbA1c test was performed on a HLC -723 G11 apparatus (Tosoh Bioscience) and thereafter compared to the HLC-723-G8 (Tosoh Bioscience), the Capillaris 3 Tera (Sebia) and the DCA Vantage point of care testing (POCT) (Siemens) apparatus. In addition, study of Hemoglobin (Hb) fraction and mutation analysis of HBB gene was realized due to the suspicion of an Hb variant., Results: Twice high results of HbA1c (9.3%, 78 mmol/mol and 10%, 86 mmol/mol) on the HLC-723 G11 was not confirmed with other instruments. HbA1c result for the same sample was 5.2% (33 mmol/mol) for the HLC-723 G8, 5.3% (34 mmol/mol) for the Capillaris and 6.2% (44 mmol/mol) for the DCA Vantage POCT. The subject had normal glycemia and none signs of diabetes mellitus. An abnormal Hb fraction was visualized on the graphs for the HLC-723 G11 and Capillaris but not for the HLC-723 G8 analyzer. Study of Hb fraction confirmed the presence of an abnormal Hb fraction that was identifed as an Hb G-Copenhagen through mutation analysis of HBB gene., Conclusion: This case evidenced an interference on HbA1c test in presence of Hb G-Copenhagen depending to the analyzer used. This report help to alert of such possibility and to remain that a discordance between HbA1c and glycemia can be due to an Hb variant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by progressive muscle weakness. Adenine nucleotide translocator 1 (ANT1), the only 4q35 gene involved in mitochondrial function, is strongly expressed in FSHD skeletal muscle biopsies. However, its role in FSHD is unclear. In this study, we evaluated ANT1 overexpression effects in primary myoblasts from healthy controls and during Xenopus laevis organogenesis. We also compared ANT1 overexpression effects with the phenotype of FSHD muscle cells and biopsies. Here, we report that the ANT1 overexpression-induced phenotype presents some similarities with FSHD muscle cells and biopsies. ANT1-overexpressing muscle cells showed disorganized morphology, altered cytoskeletal arrangement, enhanced mitochondrial respiration/glycolysis, ROS production, oxidative stress, mitochondrial fragmentation and ultrastructure alteration, as observed in FSHD muscle cells. ANT1 overexpression in Xenopus laevis embryos affected skeletal muscle development, impaired skeletal muscle, altered mitochondrial ultrastructure and led to oxidative stress as observed in FSHD muscle biopsies. Moreover, ANT1 overexpression in X. laevis embryos affected heart structure and mitochondrial ultrastructure leading to cardiac arrhythmia, as described in some patients with FSHD. Overall our data suggest that ANT1 could contribute to mitochondria dysfunction and oxidative stress in FSHD muscle cells by modifying their bioenergetic profile associated with ROS production. Such interplay between energy metabolism and ROS production in FSHD will be of significant interest for future prospects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)