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Glyphosate (GP) and its derivatives are present in almost all environments and suspected to induce acute and chronic kidney injuries. This public health issue is relatively underexplored. We therefore conducted an investigation on rats and tubular HK2 cells cultured for 24 h to determine whether GP’s and Roundup’s® (RU) potential renal toxicity might be related to mitochondrial respiration impairment and the increased production of hydrogen peroxide (H2O2) in both the renal cortex and medulla (involved in filtration and reabsorption, respectively) using a high-resolution oxygraph (Oxygraph-2K, Oroboros instruments). GP alone decreased maximal uncoupled mitochondrial respiration in the medulla (−14.2%, p = 0.02). RU decreased mitochondrial respiratory chain complexes I and I + II and the maximal respiratory capacity both in the renal cortex (−13.5%, p = 0.04; −20.1%, p = 0.009; and −14.7%, p = 0.08, respectively) and in the medulla for OXPHOS I + II (80.82 ± 7.88 vs. 61.03 ± 7.67 pmol/(s·mL), −24.5%, p = 0.003). Similarly, in HK2 cells, the decrease in OXPHOS CI + II was greater after RU (65.87 ± 1.30 vs. 51.82 ± 3.50 pmol/(s·mL), −21.3%, p = 0.04) compared to GP. Increased H2O2 production was mainly observed after RU in the medulla (+14.3% in OXPHOS CI + II, p = 0.04) and in HK2 cells (+19% in OXPHOS CI + II, p = 0.02). In conclusion, although the medulla might be more prone to GP-related mitochondrial damage, RU toxicity was greater in both the renal cortex and medulla and in cultured tubular HK2 cells. Enhancing mitochondrial respiration and reducing oxidative stress might favor the prevention of or reduction in such worldwide-used herbicides’ deleterious effects on the kidneys.

Herbicides, used worldwide to improve agricultural yields, are associated with pollution and significant health problems. Cardiac damage is a major concern, and the respective contributions of glyphosate (GP) and its commercial formulation, Roundup® (RU), warrant investigation. We studied the specific effects of GP and RU on isolated rat cardiac mitochondria and on H9c2 cardiomyocytes cultured for 6 and 24 h to determine whether the potential cardiotoxicity of GP and/or RU are linked to impaired mitochondrial respiration and increased hydrogen peroxide (H2O2) production. To this end, we used various mitochondrial complex substrates and a high-resolution oxygraphy. Unlike the GP alone which demonstrated no significant effect, the RU decreased cardiac mitochondrial respiration (21.90 ± 2.99 vs. 41.23 ± 7.09 pmol/s/mL, −46.9%, p = 0.007) for OXPHOS CI in respectively the RU and the control groups. RU also impaired OXPHOS CI+II (−51.5%, p = 0.003), maximal mitochondrial respiration (ETS CI+II, −46.7%, p = 0.001) and coupling (−35.4%, p = 0.0003). Similarly, 24 h exposure to RU decreased H9c2 cell number (−48.59%, p = 0.0023) but increased their mitochondrial respiration (+38.2%, p = 0.03, +37.6%, p = 0.03, +43.2%, p = 0.03 for OXPHOS CI, OXPHOS CI+II and ETS CI+II respectively). We observed a similar trend (NS) after 24 h exposure to GP. In conclusion, these results support an enhanced cardiac toxicity of the Roundup® as compared to the glyphosate. Both decreased mitochondrial respiration and increased hydrogen peroxide production were involved in isolated mitochondria impairment. After 24 h exposure to Roundup®, a compensatory mechanism potentially counterbalanced the decreased H9c2 cell number. These data support future studies aiming to reduce Roundup®-associated cardiac alterations not only by reducing its use but also by investigating the effectiveness of antioxidant and mitochondria-focused therapy.

COVID-19 is a public health issue with a significant mortality rate and potential long-lasting disabling symptoms responsible for the long-COVID syndrome. Mitochondrial dysfunction is a key mechanism but whether peripheral blood mononuclear cell (PBMC) mitochondrial respiration changes might be associated with mortality and/or occurrence and severity of long-COVID syndrome remains to be investigated. We determined mitochondrial respiratory chain oxygen consumption in twenty COVID-19 patients hospitalized in the intensive care unit and analyzed their remaining symptoms at the third year after hospital release. PBMC mitochondrial respiration was decreased in COVID-19 patients compared to the control group (14.13 ± 2.35 vs. 6.21 ± 0.88 pmol/s/106 cell, p = 0.0006 for the OXPHOS state by CII). Considering COVID severity, such a decrease was greater in long-COVID patients and in patients who deceased (4.91 ± 0.75, p = 0.008 and 4.94 ± 1.11 pmol/s/106 cell, p = 0.04, respectively). PBMC markers of inflammation also increased with the severity of COVID (1.0 ± 0.08 vs. 14.45 ± 2.07, p = 0.02 for ISG15 in patients who died) and ISG15 negatively correlated with PBMC mitochondrial respiration (r = −0.67, p = 0.02 for CII). In conclusion, this study shows that the greater the impairment in PBMC mitochondrial respiration in patients hospitalized in the intensive care unit for COVID-19, the greater the mortality rate and the more severe the long-COVID symptoms—three years after hospital discharge. Further, PBMC markers of inflammation also increased with the severity of COVID and ISG15 negatively correlated with PBMC mitochondrial respiration. These results support that PBMC mitochondrial respiration might be a biomarker of COVID severity and further studies investigating whether modulation of PBMC mitochondrial respiration might improve COVID-19 patients’ prognosis.

Anaphylaxis, an allergic reaction caused by the massive release of active mediators, can lead to anaphylactic shock (AS), the most severe and potentially life-threatening form of anaphylactic reaction. Nevertheless, understanding of its pathophysiology to support new therapies still needs to be improved. We performed a systematic review, assessing the role and the complex cellular interplay of mitochondria and oxidative stress during anaphylaxis, mast cell metabolism and degranulation. After presenting the main characteristics of anaphylaxis, the oxidant/antioxidant balance and mitochondrial functions, we focused this review on the involvement of mitochondria and oxidative stress in anaphylaxis. Then, we discussed the role of oxidative stress and mitochondria following mast cell stimulation by allergens, leading to degranulation, in order to further elucidate mechanistic pathways. Finally, we considered potential therapeutic interventions implementing these findings for the treatment of anaphylaxis. Experimental studies evaluated mainly cardiomyocyte metabolism during AS. Cardiac dysfunction was associated with left ventricle mitochondrial impairment and lipid peroxidation. Studies evaluating in vitro mast cell degranulation, following Immunoglobulin E (IgE) or non-IgE stimulation, revealed that mitochondrial respiratory complex integrity and membrane potential are crucial for mast cell degranulation. Antigen stimulation raises reactive oxygen species (ROS) production from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and mitochondria, leading to mast cell degranulation. Moreover, mast cell activation involved mitochondrial morphological changes and mitochondrial translocation to the cell surface near exocytosis sites. Interestingly, antioxidant administration reduced degranulation by lowering ROS levels. Altogether, these results highlight the crucial role of oxidative stress and mitochondria during anaphylaxis and mast cell degranulation. New therapeutics against anaphylaxis should probably target oxidative stress and mitochondria, in order to decrease anaphylaxis-induced systemic and major organ deleterious effects.

PurposeThrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO.MethodsThis retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT.ResultsA total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21–0.52]). Fourteen of 39 patients (35.9% [20.8–50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2–53.5] in Confirmed and 50% [23.8–76.2] in Excluded HIT (p = 0.48).ConclusionsPrevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.

Propofol and sevoflurane are two anesthetic agents widely used to induce and maintain general anesthesia (GA). Their intrinsic antinociceptive properties remain unclear and are still debated. To determine whether propofol presents stronger antinociceptive properties than sevoflurane using intraoperative clinical and experimental noxious stimulations and evaluating postoperative pain outcomes. A prospective randomized monocentric trial. Perioperative care. 60 adult patients with ASA status I to III who underwent elective abdominal laparoscopic surgery under GA were randomized either in propofol or sevoflurane group to induce and maintain GA. We used clinical and experimental noxious stimulations (intubation, tetanic stimulation) to assess the antinociceptive properties of propofol and sevoflurane in patients under GA and monitored using the NOL index, BIS index, heart rate, and mean arterial blood pressure. We measured the difference in the NOL index alterations after intubation and tetanic stimulation during either intravenous anesthesia (propofol) or inhaled anesthesia (sevoflurane). We also intraoperatively measured the NOL index and remifentanil consumption and recorded postoperative pain scores and opioid consumption in the post-anesthesia care unit. Intraoperative management was standardized by targeting similar values of depth of anesthesia (BIS index), hemodynamic (HR and MAP), NOL index values (below the threshold of 20), same multimodal analgesia and type of surgery. We found the antinociceptive properties of propofol and sevoflurane similar. The only minor difference was after tetanic stimulation: the delta NOL was higher in the sevoflurane group (39 ± 13 for the propofol group versus 47 ± 15 for sevoflurane; P = 0.04). Intraoperative and postoperative pain outcomes and opioid consumption were similar between groups. Despite a precise intraoperative experimental and clinical protocol using the NOL index, propofol does not provide a higher level of antinociception during anesthesia or analgesia after surgery when compared to sevoflurane. Anesthesiologists may prefer propofol over sevoflurane to reduce PONV or anesthesia-related pollution, but not for superior antinociceptive properties. •Propofol and sevoflurane's intrinsic antinociceptive properties are not yet clear.•Objective measurement of intraoperative nociception using the multiparametric NOL index helps precisely evaluate noxious stimulations.•Propofol and sevoflurane intraoperative antinociceptive properties were found to be similar.•No difference was observed in postoperative pain scores and consumption of analgesics.

Background Residual neuromuscular blockade (rNMB) after surgery can lead to complications such as respiratory distress, increased length of hospital stay, and higher healthcare costs. Sugammadex, a selective relaxant-binding agent, has shown efficacy in reversing rocuronium-induced neuromuscular blockade more rapidly than neostigmine. This study aimed to evaluate the effectiveness of a low dose of sugammadex (0.5 mg.kg −1 ) compared to standard neostigmine with glycopyrrolate for the reversal of moderate rocuronium-induced neuromuscular blockade. Methods This randomized, double-blind, controlled trial included adult patients undergoing surgery with rocuronium-induced moderate neuromuscular blockade. Participants were randomized to receive either low-dose sugammadex or standard-dose neostigmine with glycopyrrolate at the end of surgery. The primary outcome was the time to achieve a Train-of-Four (TOF) ratio of ≥ 0.9 after administration of the reversal agent. Secondary outcomes included extubation time, incidence of sugammadex rescue therapy for incomplete reversal, and postoperative complications. Statistical analysis used t-tests and Mann–Whitney-Wilcoxon tests for continuous variables and chi-square tests for categorical variables, with significance set at p  < 0.05. Results The median time to reach TOF ratio of ≥ 0.9 was significantly shorter in the sugammadex group (4.3 min, IQR: 3.2–6) compared to the neostigmine group (20.6 min, IQR: 10.1–21.3, p  < 0.001). Extubation times were also reduced with sugammadex, with a median of 11.6 (IQR: 8.6–15.1) minutes versus 25.9 (IQR: 17.7–29.7) minutes in the neostigmine group ( p  < 0.001). Only 4.8% of patients in the sugammadex group required rescue therapy to reverse the neuromuscular block with TOF ratio of ≥ 0.9, compared to 60.6% in the neostigmine group ( p  < 0.001). No significant differences were observed in postoperative respiratory complications or PACU length of stay. Conclusions Low-dose sugammadex provides a faster and more reliable reversal of moderate neuromuscular blockade than standard-dose neostigmine, with implications for improved operating room efficiency and patient safety. Continuous neuromuscular monitoring remains essential, as a small proportion of patients may still require additional intervention. Trial registration Registered retrospectively at ClinicalTrials.gov with registration number NCT05718934 on 2023–02-08.

Infective endocarditis (IE) is an uncommon but life‐threatening disease, most frequently caused by Staphylococcus aureus , streptococci, and enterococci. Vagococcus fluvialis is a Gram‐stain positive coccus, phenotypically close to enterococci, and rarely identified in human infections due to diagnostic challenges. We present a case report of a patient with a prosthetic valve endocarditis caused by V . fluvialis, along with details of the treatment initiated in a 63‐year‐old man with a history of mitral valve bioprosthesis for prior IE. He presented with fever, confusion, asthenia, and myalgia. Echocardiography identified a large vegetation on the mitral prosthesis. Blood cultures grew V. fluvialis , confirmed by MALDI‐TOF mass spectrometry and 16S RNA sequencing. Antibiotic therapy with intravenous amoxicillin led to rapid clinical and microbiological improvement. However, despite this favorable initial clinical response, follow‐up echocardiography demonstrated progression of the vegetation, ultimately necessitating a redo mitral valve replacement on Day 20. Intraoperative findings confirmed extensive vegetation without paravalvular complications. Although the prosthesis cultures were negative, sequencing identified V. fluvialis again. Postoperative recovery was uneventful, and the patient was discharged in good condition. V. fluvialis is increasingly recognized in human infections but remains difficult to distinguish from enterococci using conventional methods. Accurate diagnosis requires advanced tools such as 16S RNA sequencing. Unlike previous cases, this prosthetic valve IE progressed more slowly, characterized by persistent vegetation rather than acute valve destruction. Successful management was achieved through amoxicillin therapy combined with surgical intervention. This case highlights V. fluvialis as a rare but emerging cause of IE, emphasizes the need for precise microbiological identification, and suggests that amoxicillin monotherapy may contribute to initial clinical stabilization. Further reports are required to specify V. fluvialis ‐related IE prognosis and to establish the most effective treatment.

In the intensive care unit (ICU), many patients are unable to communicate their pain through self-reporting or behaviors due to their critical care condition, mechanical ventilation, and medication (eg, heavily sedated or chemically paralyzed). Therefore, alternative pain assessment methods are urgently needed for this vulnerable patient population. The Nociception Level (NOL) index is a multiparameter technology initially developed for the monitoring of nociception and related pain in anesthetized patients, and its use in the ICU is new. This study aims to validate the NOL for the assessment of nociception and related pain in critically ill adults in the ICU. Specific objectives are to examine the ability of the NOL to: (1) detect pain using standard criteria (ie, self-report and behavioral measures), (2) discriminate between nociceptive and nonnociceptive procedures, and (3) generate consistent values when patients are at rest. The NOL will be monitored in three ICU patient groups: (1) Group A, participants able to self-report their pain (the reference standard criterion using the 0-10 Faces Pain Thermometer) and express behaviors; (2) Group B, participants unable to self-report but able to express behaviors (the alternative standard criterion using the Critical-Care Pain Observation Tool); and (3) Group C, participants unable to self-report and express behaviors. The NOL will be tested before, during, and after two types of standard care procedures: (1) nonnociceptive (eg, cuff inflation to measure blood pressure, soft touch) and (2) nociceptive (eg, tube or drain removal, endotracheal or tracheal suctioning). Receiver operating characteristic curve analysis of the NOL will be performed for Groups A and B using pain standard measures as reference criteria. Mixed linear models for repeated measures will be used to compare time points, procedures, and their interaction in each group (A, B, and C). Based on power analyses and considering an attrition rate of 25%, a total sample size of 146 patients (68 in Group A, 62 in Group B, and 16 in Group C) is targeted. This study was funded in April 2020 but could not be launched until 2022 due to the COVID-19 pandemic. Recruitment and data collection began at the primary site in July 2022 and has been implemented at the secondary sites in 2023 and 2024 and is planned to continue until 2026. The primary strength of this study protocol is that it is based on rigorous validation strategies with the use of pain standard criteria (ie, self-report and behavioral measures). If found to be valid, the NOL could be used as an alternative physiologic measure of pain in critically ill adults for whom no other pain assessment methods are available. ClinicalTrials.gov NCT05339737; https://clinicaltrials.gov/study/NCT05339737. DERR1-10.2196/60672.

Background and Objectives: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. Methods: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). Results: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18–79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. Conclusion: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.