Efficacy and safety of hyperbaric oxygen therapy monitored by fluorescein angiography in patients with retinal artery occlusion.

AIMS: To assess the efficacy and safety of a standardised hyperbaric oxygen therapy protocol (HBOT) monitored by fluorescein angiography (FA) in patients with retinal artery occlusion (RAO). METHODS: It is a prospective, non-comparative, monocentric study conducted between July 2016 and March 2022. All consecutive patients diagnosed with RAO within 7 days underwent visual acuity measurement, FA, macular optical coherence tomography (OCT) and OCT-angiography. They received two daily HBOT sessions (2.5 atmosphere absolute, 90 min) until revascularisation assessed by FA. Complete ophthalmic follow-up was scheduled at day 14, day 21 and at 1 month. The main outcome measure was a best-corrected visual acuity (BCVA) improvement defined as a decrease ≥0.3 logMAR at 1 month. RESULTS: Thirty-one patients were included and received a mean number of 33.9 (13-56) HBOT sessions. Retinal revascularisation was observed in 48.4% and 87.1% of patients at days 14 and 21, respectively. The mean BCVA on referral and at 1 month was 1.51 logMAR and 1.10 logMAR, respectively. Fifteen (48.4%) patients achieved the main outcome measure. Six (19.4%) patients experienced minor barotrauma that did not require HBOT discontinuation. The univariate analysis showed that antiplatelet-treated patients (p=0.044) and patients with a poor initial BCVA (p=0.008) were more likely to achieve a BCVA improvement. OCT-angiography was not sensitive enough to diagnose RAO or assess revascularisation. CONCLUSION: In RAO patients monitored by FA until spontaneous revascularisation of the central retinal artery, HBOT was effective and safe.

Lesson from the COVID-19 pandemic lockdown: A major change of hospital-diagnosed bacteremia epidemiology.

OBJECTIVES: When the COVID-19 pandemic reached France early in 2020, the enforced nationwide lockdown deeply altered lifestyle as well as hospital processes and modalities of care. The aim of the study was to evaluate the impact during the lockdown of the first epidemic wave on the epidemiology of bacteremia in one French University Hospital. PATIENTS AND METHODS: Retrospective cohort study including adult patients with positive blood culture between 23rd March to 24th May 2020. The clinical-microbiological characteristics were compared with those of the period from 25th March to 26th May 2019. The data were adjusted to the number of hospitalizations (h). RESULTS: In 2020, 189 bacteremia were diagnosed from 1939 vials (9658 hospitalizations, 10911 emergency room consultations) compared to 143 from 1976 vials (14797 hospitalizations, 16493 emergency room consultations) recorded in 2019. The incidence of bacteremia increased up to 19.7 per 1000h in 2020 vs 9.7 in 2019 (p < 0.001). The main differences (2020 vs 2019) were: Staphylococcus aureus bacteremia (2.4 vs 1.0/1000h, p = 0.012), polymicrobial bacteremia (2.2 vs 0.9/1000h p = 0.013) and Gram-negative bacteremia (8.9 vs 4.3/1000h, p < 0.01). Conversely, Streptococcus pneumoniae incidence decreased (0 vs 0.47/1000h, p = 0.047). The standardized incidence ratio calculation confirmed these results. CONCLUSION: The lockdown and the impact of the first wave of the Covid-19 pandemic on the health system resulted in increased hospital-diagnosed bacteremia and decreased pneumococcal bacteremia. Disruption and overload of ICUs, lockdown with preventive control measures, and decrease in human-to-human interaction may have been the main reasons.

[Medulloblastoma: The latest major advances]. / Le médulloblastome : les dernières avancées majeures.

Medulloblastoma (MB) is a malignant brain tumor that mainly affects children. It is rarely found in adults. Among the four groups of MB defined today according to molecular characteristics, group 3 is the least favorable with an overall survival rate of 50 %. Current treatments, based on surgery, radiotherapy, and chemotherapy, are not sufficiently adapted to the different characteristics of the four MB groups. However, the use of new cellular and animal models has opened new doors to interesting therapeutic avenues. In this review, we detail recent advances in MB research, with a focus on the genes and pathways that drive tumorigenesis, with particular emphasis on the animal models that have been developed to study tumor biology, as well as advances in new targeted therapies.

Accurate Detection of SARS-CoV-2 by Next-Generation Sequencing in Low Viral Load Specimens.

As new SARS-CoV-2 variants emerge, there is an urgent need to increase the efficiency and availability of viral genome sequencing, notably to detect the lineage in samples with a low viral load. SARS-CoV-2 genome next-generation sequencing (NGS) was performed retrospectively in a single center on 175 positive samples from individuals. An automated workflow used the Ion AmpliSeq SARS-CoV-2 Insight Research Assay on the Genexus Sequencer. All samples were collected in the metropolitan area of the city of Nice (France) over a period of 32 weeks (from 19 July 2021 to 11 February 2022). In total, 76% of cases were identified with a low viral load (Ct ≥ 32, and ≤200 copies/µL). The NGS analysis was successful in 91% of cases, among which 57% of cases harbored the Delta variant, and 34% the Omicron BA.1.1 variant. Only 9% of cases had unreadable sequences. There was no significant difference in the viral load in patients infected with the Omicron variant compared to the Delta variant (Ct values, p = 0.0507; copy number, p = 0.252). We show that the NGS analysis of the SARS-CoV-2 genome provides reliable detection of the Delta and Omicron SARS-CoV-2 variants in low viral load samples.

Plasmatic osteopontin and vascular access dysfunction in hemodialysis patients: a cross-sectional, case-control study (The OSMOSIS Study).

BACKGROUND AND AIMS: Despite close follow-up of patients with native arteriovenous fistulas (AVFs), up to 10% experience thrombosis each year. The OSMOSIS Study (Osteopontin as a Marker of Stenosis) tested the hypothesis that the systemic osteopontin level, a pro-inflammatory mediator related to vascular remodelling and intimal hyperplasia, increases in AVF stenosis, and may be used in clinical surveillance. METHODS: Our cross-sectional study compared the level of plasmatic osteopontin (pOPN) between patients with a well-functioning AVF (control group) and patients who required revision of their AVF due to stenosis (stenosis group). Blood samples were collected before dialysis (control group) or before intervention (stenosis group) from the AVF arm, and from the opposite arm as a within-subject control. pOPN level was measured by enzyme-linked immunosorbent assay. RESULTS: A total of 76 patients were included in the study. Baseline characteristics were similar between the groups (mean age, 70 years; men, 63%; AVF duration, 39 months), apart from prevalence of type 2 diabetes (T2D) (control group, 33%; stenosis group, 57%; p = 0.04). pOPN levels were similar between the AVF arm and the contralateral arm (551 ± 42 ng/mL vs. 521 ± 41 ng/mL, respectively, p = 0.11, paired t-test). Patients in the stenosis group displayed a higher pOPN level than patients in the control group (650.2 ± 59.8 ng/mL vs. 460.5 ± 61.2, respectively, p = 0.03; two-way ANOVA). T2D was not identified as an associated factor in a multivariate analysis (p = 0.50). CONCLUSIONS: The level of pOPN in hemodialysis patients was associated with the presence of AVF stenosis requiring intervention. Thus, its potential as a diagnostic biomarker should be assessed in a vascular access surveillance program.

COVID-19 patients age, comorbidity profiles and clinical presentation related to the SARS-CoV-2 UK-variant spread in the Southeast of France.

The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (Southeast of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this area. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. We performed an observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n = 1247) and those hospitalized in the infectious diseases ward or ICU (n = 232). The UK-variant was absent in this area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63 to 50% (p = 0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p < 0.001) while the proportion of patients without comorbidity increased from 16 to 42% (p = 0.007). Spread of the UK-variant in the Southeast of France affects younger and healthier patients.

Focal cardiac ultrasound learning with pocked ultrasound device: A bicentric prospective blinded randomized study.

PURPOSE: Point-of-care ultrasound using a pocket-ultrasound-device (PUD) is increasing in clinical medicine but the optimal way to teach focused cardiac ultrasound is not clear. We evaluated whether teaching using a PUD or a conventional-ultrasound-device (CUD) is different when the final exam was conducted on a PUD. The primary aim was to compare the weighted total quality scale (WTQS, out of 100) obtained by participants in the two groups (CUD and PUD) on a live volunteer 2-4 weeks after their initial training. The secondary aims were to compare examination time and students' confidence levels (out of 50). METHODS: This bicentric, prospective single-blind randomized trial included undergraduate medical students. After watching a 15 min video about echocardiography views, students had a 45 min hands-on training session with a live volunteer using a PUD or a CUD. The final examination was conducted with a PUD on a live volunteer. RESULTS: Eighty-six comparable students were included, with 4 ± 1 years of medical training. In the PUD group, the mean WTQS was 65 ± 16 versus 60 ± 15 in the CUD group [p = 0.22; in multivariate analysis, OR 0.8 95% CI (0.1;1.6), p = 0.34]. The examination time was 10.0 [6.2-12.4] min in the PUD group versus 11.4 [7.3-13.2] in the CUD group (p = 0.39), while the confidence level was 27.9 ± 7.7 in the PUD group versus 27.4 ± 7.2 in the CUD group (p = 0.76). CONCLUSION: There was no difference between teaching echocardiographic views using a PUD as compared to a CUD on the PUD image quality, exam time, or confidence level of students.

Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity.

Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient's evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

Hypoxia and hypoxia-inducible factors promote the development of neointimal hyperplasia in arteriovenous fistula.

KEY POINTS: Patients with end-stage renal failure need arteriovenous fistulas (AVF) to undergo dialysis. However, AVFs present a high rate of failure as a result of excessive venous thickness. Excessive venous thickness may be a consequence of surgical dissection and change in oxygen concentration within the venous wall. We show that venous cells adapt their metabolism and growth depending on oxygen concentration, and drugs targeting the hypoxic response pathway modulate this response in vitro. We used the same drugs on a mouse model of AVF and show that direct or indirect inhibition of the hypoxia-inducible factors (HIFs) help decrease excessive venous thickness. Hypoxia and HIFs can be targets of therapeutic drugs to prevent excessive venous thickness in patients undergoing AVF surgical creation. ABSTRACT: Because the oxygen concentration changes in the venous wall, surrounding tissue and the blood during surgical creation of arteriovenous fistula (AVF), we hypothesized that hypoxia could contribute to AVF failure as a result of neointimal hyperplasia. We postulated that modulation of the hypoxia-inducible factors (HIF) with pharmacological compounds could promote AVF maturation. Fibroblasts [normal human fibroblasts (NHF)], smooth muscle cells [human umbilical vein smooth muscle cells (HUVSMC)] and endothelial cells [human umbilical vein endothelial cells (HUVEC)], representing the three layers of the venous wall, were tested in vitro for proliferation, cell death, metabolism, reactive oxygen species production and migration after silencing of HIF1/2-α or after treatment with deferioxamine (DFO), everolimus (Eve), metformin (Met), N-acetyl-l-cysteine (NAC) and topoisomerase I (TOPO), which modulate HIF-α stability or activity. Compounds that were considered to most probably modify intimal hyperplasia were applied locally to the vessels in a mouse model of aortocaval fistula. We showed, in vitro, that NHF and HUVSMC can adapt their metabolism and thus their growth depending on oxygen concentration, whereas HUVEC appears to be less flexible. siHIF1/2α, DFO, Eve, Met, NAC and TOPO can modulate metabolism and proliferation depending on the cell type and the oxygen concentration. In vivo, siHIF1/2α, Eve and TOPO decreased neointimal hyperplasia by 32%-50%, 7 days after treatment. Within the vascular wall, hypoxia and HIF-1/2 mediate early failure of AVF. Local delivery of drugs targeting HIF-1/2 could inhibit neointimal hyperplasia in a mouse model of AVF. Such compounds may be delivered during the surgical procedure for AVF creation to prevent early AVF failure.

Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic.

Importance: Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown. Objective: To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic. Design, Setting, and Participants: In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included. Main Outcomes and Measures: Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis. Results: Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19. Conclusions and Relevance: Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy. Trial Registration: ClinicalTrials.gov Identifier: NCT04344119.

Evidences of a Direct Relationship between Cellular Fuel Supply and Ciliogenesis Regulated by Hypoxic VDAC1-ΔC.

Metabolic flexibility is the ability of a cell to adapt its metabolism to changes in its surrounding environment. Such adaptability, combined with apoptosis resistance provides cancer cells with a survival advantage. Mitochondrial voltage-dependent anion channel 1 (VDAC1) has been defined as a metabolic checkpoint at the crossroad of these two processes. Here, we show that the hypoxia-induced cleaved form of VDAC1 (VDAC1-ΔC) is implicated in both the up-regulation of glycolysis and the mitochondrial respiration. We demonstrate that VDAC1-ΔC, due to the loss of the putative phosphorylation site at serine 215, concomitantly with the loss of interaction with tubulin and microtubules, reprograms the cell to utilize more metabolites, favoring cell growth in hypoxic microenvironment. We further found that VDAC1-ΔC represses ciliogenesis and thus participates in ciliopathy, a group of genetic disorders involving dysfunctional primary cilium. Cancer, although not representing a ciliopathy, is tightly linked to cilia. Moreover, we highlight, for the first time, a direct relationship between the cilium and cancer cell metabolism. Our study provides the first new comprehensive molecular-level model centered on VDAC1-ΔC integrating metabolic flexibility, ciliogenesis, and enhanced survival in a hypoxic microenvironment.

High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019.

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.

Identification of a new aggressive axis driven by ciliogenesis and absence of VDAC1-ΔC in clear cell Renal Cell Carcinoma patients.

Rationale: Renal cell carcinoma (RCC) accounts for about 2% of all adult cancers, and clear cell RCC (ccRCC) is the most common RCC histologic subtype. A hallmark of ccRCC is the loss of the primary cilium, a cellular antenna that senses a wide variety of signals. Loss of this key organelle in ccRCC is associated with the loss of the von Hippel-Lindau protein (VHL). However, not all mechanisms of ciliopathy have been clearly elucidated. Methods: By using RCC4 renal cancer cells and patient samples, we examined the regulation of ciliogenesis via the presence or absence of the hypoxic form of the voltage-dependent anion channel (VDAC1-ΔC) and its impact on tumor aggressiveness. Three independent cohorts were analyzed. Cohort A was from PREDIR and included 12 patients with hereditary pVHL mutations and 22 sporadic patients presenting tumors with wild-type pVHL or mutated pVHL; Cohort B included tissue samples from 43 patients with non-metastatic ccRCC who had undergone surgery; and Cohort C was composed of 375 non-metastatic ccRCC tumor samples from The Cancer Genome Atlas (TCGA) and was used for validation. The presence of VDAC1-ΔC and legumain was determined by immunoblot. Transcriptional regulation of IFT20/GLI1 expression was evaluated by qPCR. Ciliogenesis was detected using both mouse anti-acetylated α-tubulin and rabbit polyclonal ARL13B antibodies for immunofluorescence. Results: Our study defines, for the first time, a group of ccRCC patients in which the hypoxia-cleaved form of VDAC1 (VDAC1-ΔC) induces resorption of the primary cilium in a Hypoxia-Inducible Factor-1 (HIF-1)-dependent manner. An additional novel group, in which the primary cilium is re-expressed or maintained, lacked VDAC1-ΔC yet maintained glycolysis, a signature of epithelial-mesenchymal transition (EMT) and more aggressive tumor progression, but was independent to VHL. Moreover, these patients were less sensitive to sunitinib, the first-line treatment for ccRCC, but were potentially suitable for immunotherapy, as indicated by the immunophenoscore and the presence of PDL1 expression. Conclusion: This study provides a new way to classify ccRCC patients and proposes potential therapeutic targets linked to metabolism and immunotherapy.

Co-culture of human fibroblasts, smooth muscle and endothelial cells promotes osteopontin induction in hypoxia.

Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end-stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure. Identification of new factors that participate in remodelling of AVFs is a challenge. Three cell lines representing the cells of the three layers of the walls of arteries and veins, fibroblasts, smooth muscle cells and endothelial cells, were tested in mono- and co-culture in vitro for OPN expression and secretion in normoxia compared to hypoxia after silencing the hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1/2α) with siRNA or after treatment with an inhibitor of NF-kB. None of the cells in mono-culture showed OPN induction in hypoxia, whereas cells in co-culture secreted OPN in hypoxia. The changes in oxygenation that occur during AVF maturation up-regulate secretion of OPN through cell-cell interactions between the different cell layers that form AVF, and in turn, these promote endothelial cell proliferation and could participate in neointimal hyperplasia.

Role of Hypoxia and Metabolism in the Development of Neointimal Hyperplasia in Arteriovenous Fistulas.

For patients with end-stage renal disease requiring hemodialysis, their vascular access is both their lifeline and their Achilles heel. Despite being recommended as primary vascular access, the arteriovenous fistula (AVF) shows sub-optimal results, with about 50% of patients needing a revision during the year following creation. After the AVF is created, the venous wall must adapt to new environment. While hemodynamic changes are responsible for the adaptation of the extracellular matrix and activation of the endothelium, surgical dissection and mobilization of the vein disrupt the vasa vasorum, causing wall ischemia and oxidative stress. As a consequence, migration and proliferation of vascular cells participate in venous wall thickening by a mechanism of neointimal hyperplasia (NH). When aggressive, NH causes stenosis and AVF dysfunction. In this review we show how hypoxia, metabolism, and flow parameters are intricate mechanisms responsible for the development of NH and stenosis during AVF maturation.

Presepsin versus other biomarkers to predict sepsis and septic shock in patients with infection defined by Sepsis-3 criteria: the PREDI study of diagnostic accuracy. / Capacidad diagnóstica de presepsina comparada con otros biomarcadores para predecir sepsis y shock séptico en pacientes con infección siguiendo la definición Sepsis-3 (estudio PREDI).

OBJECTIVES: An accurate diagnosis of sepsis in the emergency department must be made before appropriate treatment can be started. Many biomarkers that are potentially useful have been studied. The main aim of this study was to compare the diagnostic accuracy of blood levels of presepsin, lactate, C-reactive protein (CRP), and procalcitonin (PCT) for predicting sepsis as defined by the Sepsis-3 criteria. The secondary aim was to evaluate the diagnostic accuracy of these biomarkers for predicting bacteremia whether or not sepsis or septic shock was present. MATERIAL AND METHODS: Single-center, prospective, observational cohort study in the emergency department of a university hospital. Consecutive patients suspected of having infection were enrolled prospectively if they had at least 2 criteria for systemic inflammatory response syndrome. We measured presepsin, PCT, CRP, and lactate in blood extracted on admission. RESULTS: Blood samples from 359 patients were analyzed; 228 (63.5%) met the criteria for sepsis and 20 (5.6%) met the criteria for septic shock. PCT and presepsin levels were the best predictors of sepsis and septic shock with areas under the receiver operating characteristic curve (AUC) of 0.711 (95% CI, 0.660-0.758) and 0.709 (95% CI, 0.658- 0.756), respectively (P <.001, both comparisons). The AUCs for CRP and lactate concentrations were, respectively, 0.63 (95% CI, 0.58-0.69) and 0.61 (95% CI, 0.56-0.66) (P <.05, both comparisons). On applying the diagnostic cut points of 0.25 ng/mL for PCT and 500 pg/mL for presepsin, the odds ratios were 2.51 (95% CI, 1.53-4.12) for PCT and 3.19 (95% CI, 1.91-5.31) for presepsin. The diagnostic accuracy of the combination of presepsin and PCT results (AUC, 0.71; 95% CI 0.66-0.76; P <.001) was no better than the accuracy of PCT alone. The most accurate predictor of bacteremia was PCT (AUC, 0.835; 95% CI, 0.79-0.87; P <.001). CONCLUSION: Presepsin and PCT seem to be the best predictors of a diagnosis of sepsis or septic shock in emergency department patients.

OBJETIVO: El diagnóstico correcto de la sepsis en urgencias es clave para iniciar el tratamiento de forma adecuada. Para ello, se han estudiado múltiples biomarcadores que podrían ser de utilidad. El objetivo principal de este estudio fue evaluar la capacidad diagnóstica de presepsina en sangre, en comparación con procalcitonina (PCT), proteína C reactiva (PCR) y lactato, para predecir sepsis o shock séptico según la definición de Sepsis-3. El objetivo secundario fue valorar la capacidad de estos biomarcadores para predecir bacteriemia, independientemente del diagnóstico final de sepsis o shock séptico. METODO: Estudio prospectivo de cohorte observacional, realizado en un único servicio de urgencias (SU) de un hospital universitario. Se incluyeron pacientes con sospecha clínica de infección y al menos dos criterios de síndrome de respuesta inflamatoria sistémica. En todos los pacientes se determinó en sangre presepsina, PCT, PCR y lactato en el momento de la visita en el SU. RESULTADOS: Se analizaron 359 pacientes, de los que 228 (63,5%) presentaban criterios de sepsis y 20 (5,6%) de shock séptico. PCT y presepsina fueron los mejores biomarcadores para predecir la sepsis/shock séptico con un área bajo la curva (ABC) de la capacidad operativa del receptor (ROC) de 0,711 (IC 95% 0,660-0,758; p < 0,001) y 0,709 (IC 95% 0,658-0,756; p < 0,001). La PCR obtuvo una ABC de 0,635 (IC 95% 0,582-0,686; p < 0,05), y el lactato una ABC de 0,61 (IC 95% 0,556-0,661; p < 0,05). Se utilizó un punto de decisión de 0,25 ng/ml para PCT y de 500 pg/ ml para presepsina. La odds ratio de presepsina para predecir sepsis fue de 3,19 (IC 95% 1,91-5,31) y para PCT de 2,51 (IC 95% 1,53-4,12). El diagnóstico de sepsis/shock séptico no mejoró al combinar presepsina y PCT (el ABC-ROC fue de 0,714, IC 95% 0,66-0,76; p < 0,001) en comparación con PCT aislada. La PCT fue el predictor más preciso de bacteriemia en pacientes con infección con un ABC-ROC de 0,835 (IC 95% 0,79-0,87; p < 0,001). CONCLUSIONES: La presepsina y la PCT son los biomarcadores con mejor rendimiento para el diagnóstico de sepsis y shock séptico en el SU.

Intranasal sufentanil given in the emergency department triage zone for severe acute traumatic pain: a randomized double-blind controlled trial.

The goal of our study was to determine if an intranasal (IN) dose of sufentanil delivered in the ED triage zone would improve the management of severely painful patients. We performed a randomized, double blind and placebo-controlled trial on adult patients suffering from an acute severe pain (≥ 6/10) consecutive to an isolated limb injury. We compared 2 analgesic strategies: the usual pain treatment with IV-only multimodal analgesics (IVMA) including IV opioids if needed (control group) and another strategy (active group) based on a single dose of IN sufentanil (0.4 µg/kg) given at triage and followed by IV multimodal analgesia. Our primary outcome was the proportion of patients reaching pain-relief (≤ 3/10) 30 min after IN injection at triage. Secondary outcomes were rates of adverse events, frequency of clinical interventions required by these events, and satisfaction of patients. A total of 144 adult participants completed the study, 72 in each group. Compared with usual IV-only pain management, the analgesic strategy initiated in triage zone with a dose of IN sufentanil increased the proportion of patients reaching pain relief in 30 min: 72.2% versus 51.4%, in our trial (p = 0.01 and number needed to treat of 5). There was no serious adverse event (AE) in both groups. Patients who received IN sufentanil experienced more frequently minor opiate side effects. Proportion of respiratory AEs was higher in the active group (12.5% of bradypnea < 10 cycles per minute versus 1.4%) but these events were of mild severity, as only 2 participants (one in each group) received temporary low dose oxygen therapy, and none required naloxone. Lengths of stay in the ED were similar in both groups, as well as satisfaction of patients (above 9/10) and pain scores at discharge (< 2/10). We found that a single dose of IN sufentanil delivered in the ED triage zone significantly increases the proportion of severely painful patients reaching painrelief in 30 min, compared to usual analgesia with IV-only multimodal analgesia.

Blood lactate measurement within the emergency department: A two-year retrospective analysis.

We evaluate in this retrospective cohort, the clinical situations leading emergency physicians to take a blood lactate sample, the prevalence of hyperlactatemia and its impact on short-term adverse outcome. ED patients requiring a blood lactate measurement (BLM) during a two-year period were included. Early patients' outcomes were extracted and discharge diagnoses were classified into 12 diagnostic categories. A total of 118,737 patients were analyzed. A BLM was carried out in 13,089 of them. Surprisingly, the proportion of patients having a BLM was higher in those admitted for seizure (31.4%) than in those admitted for infection (27.9%). Ten percent of patients who had a blood lactate test had a lactate level >4 mmol/l (1,315). Among them, 23.2% were admitted for infections, 20% for seizures, and 11% for cardiovascular diseases. After excluding the patients older than 75 years from the analysis in order to prevent a selection bias, the patient's severity was independently associated to an age over 65 years (OR: 1.26), an arterial blood sampling (OR: 2.77) and the blood lactate level (OR: 1.31). The blood lactate level was very informative to detect the sicker patients in the infection group whereas its interest was poor in the group of patients admitted for seizures. In conclusion, blood lactate testing has become routine in emergency departments and a large proportion of patients have abnormal blood lactate levels. The most frequent causes of high blood lactate in the ED are infection and seizures but the prognostic value of blood lactate seems to be different from one diagnostic category to the other.