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Abstract Background The objective was to assess the agreement between therapeutic proposals derived from basic critical care echocardiography performed by novice operators in ultrasonography after a limited training (residents) and by experts considered as reference. Secondary objectives were to assess the agreement between operators’ answers to simple clinical questions and the concordance between basic two-dimensional measurements. Methods This observational, prospective, single-center study was conducted over a 3-year period in a medical-surgical intensive care unit. Adult patients with acute circulatory and/or respiratory failure requiring a transthoracic echocardiography (TTE) examination were studied. In each patient, a TTE was performed by a resident novice in ultrasonography after a short training program and by an expert, independently but within 1 h and in random order. Each operator addressed standardized simple clinical questions and subsequently proposed a therapeutic strategy based on a predefined algorithm. Results Residents performed an average of 33 TTE studies in 244 patients (156 men; age: 63 years [52–74]; SAPS2: 45 [34–59]; 182 (75%) mechanically ventilated). Agreement between the therapeutic proposals of residents and experienced operators was good-to-excellent. The concordance was excellent for suggesting fluid loading, inotrope or vasopressor support (all Kappa values > 0.80). Inter-observer agreement was only moderate when considering the indication of negative fluid balance (Kappa: 0.65; 95% CI 0.50–0.80), since residents proposed diuretics in 23 patients (9.5%) while their counterparts had the same suggestion in 35 patients (14.4%). Overall agreement of responses to simple clinical questions was also good-to-excellent. Intraclass correlation coefficient exceeded 0.75 for measurement of ventricular and inferior vena cava size. Conclusions A limited training program aiming at acquiring the basic level in critical care echocardiography enables ICU residents novice in ultrasonography to propose therapeutic interventions with a good-to-excellent agreement with experienced operators.

Introduction: Cancers of unknown primary are aggressive and rare malignancies with a complex diagnosis and management. Here we present a case in which imaging, pathology, and molecular biology did not match for a specific tumor site and the importance of a multidisciplinary team for these complicated cases. Case Presentation: A man in his 70s with strong smoking history under workup for suspicion of metastatic lung cancer underwent lung mass biopsy. Immunohistochemical stains corresponded to hepatocellular/cholangiocarcinoma or germ cell tumor; however, dedicated liver and testicular studies including imaging and iscochrome 12p FISH were negative. Additionally, somatic variant profiling was not specific for any malignancy nor targetable variants. Given the pattern of disease, risk factors, and patient history, the patient received treatment for lung adenocarcinoma (carboplatin, pemetrexed, and pembrolizumab). The patient had a drastic improvement in dyspnea, weight gain, and was able to return to work. Conclusion: This report describes a case in which immunohistochemistry and molecular profiling did not identify the tissue of origin and highlights the importance of a multidisciplinary team to reach a diagnosis and guide treatment without delaying patient care in patients with these diagnoses.

Abstract A second autologous stem‐cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti‐CD38 and immunotherapy, its role remains debated. We conducted a real‐life study in 10 French centers (1996–2017) involving 267 RMM patients receiving ASCT2. The median age was 61 years, with 49% females. Most patients received melphalan 200 mg/m² before ASCT2, with low early mortality (1%). Very good partial response or better (VGPR+) rate post ASCT2 was 78%. Post ASCT2, 48% received consolidation therapy and 40% maintenance therapy. Median event‐free survival (EFS) after ASCT2 was 2.6 years (95% confidence interval [CI]: 2.3–2.8), and 2‐year EFS estimate was 63% (95% CI: 57–70). Median overall survival (OS) was 8.1 years (95% CI: 5.9–NA), and 2‐year OS estimate was 92% (95% CI: 88–95). Multivariate analysis revealed that VGPR+ status and maintenance therapy post ASCT2 were associated with better EFS (hazard ratio [HR]: 0.6; 95% CI: 0.3–0.9, p = 0.012 and HR: 0.4; 95% CI: 0.3–0.6, p

IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.

Abstract Background Coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been proposed in this setting, but optimal criteria to select target patients remain unknown. Our hypothesis is that evaluation of right ventricular (RV) function could be helpful. The aims of our study were to report the incidence and outcomes of patients eligible for ECMO according to EOLIA criteria, and to identify a subgroup of patients with RV injury, which could be a target for ECMO. Methods Retrospective observational study involving 3 French intensive care units (ICUs) of teaching hospitals. Patients with confirmed SARS-CoV-2 infection between March 2020 and March 2021, presenting ARDS and with available echocardiography, were included. Patients were classified in three groups according to whether or not they met the EOLIA criteria and the presence of RV injury (RVI) (“EOLIA −”, “EOLIA + RVI −” and “EOLIA + RVI + ”). RVI was defined by the association of RV to left ventricular end-diastolic area ratio > 0.8 and paradoxical septal motion. Kaplan–Meier survival curves were used to analyze outcome as well as a Cox model for 90 day mortality. Results 915 patients were hospitalized for COVID-19, 418 of them with ARDS. A total of 283 patients with available echocardiography were included. Eighteen (6.3%) patients received ECMO. After exclusion of these patients, 107 (40.5%) were classified as EOLIA −, 126 (47.5%) as EOLIA + RVI −, and 32 (12%) as EOLIA + RVI + . Ninety-day mortality was 21% in the EOLIA-group, 44% in the EOLIA + RVI-group, and 66% in the EOLIA + RVI + group (p

Studying precipitation falling over Antarctica is crucial as snowfall represents the main water input term for the polar cap. However, precipitation observations still remain scarce – and, more particularly, in the atmospheric column – due to numerous experimental issues related to the white continent. This paper aims at helping to close this observation gap by presenting 7 years of Micro Rain Radar (Metek MRR-2) data at the Dumont d'Urville station in coastal Adélie Land, East Antarctica. Statistics are calculated on three radar variables (equivalent reflectivity, mean Doppler velocity and signal-to-noise ratio (SNR)) to outline the main characteristics of the radar dataset. Seasonal and interannual variabilities are also investigated, but no significant temporal trends are detected, except for the seasonal mean Doppler velocity, which is higher in summer and lower in winter. We then use the snowfall rate (S) data from a collocated snow gauge to estimate the MRR precipitation profile from the radar equivalent reflectivity (Ze) through a locally derived Ze–S relation. We find the relation Ze=43.3S0.88. The processing method used to obtain this relation, data quality and uncertainty considerations are discussed in the paper. In order to give an example of application of the dataset, a brief statistical comparison of the MRR precipitation rate along the vertical with model data from the ERA5 reanalysis and the LMDZ climate model is performed, which notably shows that models underestimate heavy precipitation events. All datasets are available on the PANGAEA database with the associated DOI: https://doi.org/10.1594/PANGAEA.962727 (Wiener et al., 2023).

Introduction The diagnosis of endometriomas in patients with endometriosis is of primary importance because it influences the management and prognosis of infertility and pain. Imaging techniques are evolving constantly. This study aimed to systematically assess the diagnostic accuracy of transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) in detecting endometrioma using the surgical visualisation of lesions with or without histopathological confirmation as reference standards in patients of reproductive age with suspected endometriosis.Methods PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov databases were searched from their inception to 12 October 2022, using a manual search for additional articles. Two authors independently performed title, abstract and full-text screening of the identified records, extracted study details and quantitative data and assessed the quality of the studies using the ‘Quality Assessment of Diagnostic Accuracy Study 2’ tool. Bivariate random-effects models were used to determine the pooled sensitivity and specificity, compare the two imaging modalities and evaluate the sources of heterogeneity.Results Sixteen prospective studies (10 assessing TVUS, 4 assessing MRI and 2 assessing both TVUS and MRI) were included, representing 1976 participants. Pooled TVUS and MRI sensitivities for endometrioma were 0.89 (95% confidence interval ‘CI’, 0.86–0.92) and 0.94 (95% CI, 0.74–0.99), respectively (indirect comparison p-value of 0.47). Pooled TVUS and MRI specificities for endometrioma were 0.95 (95% CI, 0.92–0.97) and 0.94 (95% CI, 0.89–0.97), respectively (indirect comparison p-value of 0.51). These studies had a high or unclear risk of bias. A direct comparison (all participants undergoing TVUS and MRI) of the modalities was available in only two studies.Conclusion TVUS and MRI have high accuracy for diagnosing endometriomas; however, high-quality studies comparing the two modalities are lacking.

Abstract Background Angioimmunoblastic T‐cell lymphoma (AITL) is one of the most frequent peripheral T‐cell lymphomas (PTCL) in western countries. Skin involvement is common and may reveal the malignancy. Despite its frequency, skin involvement in AITL has been poorly described. Objectives We aimed to analyze the cutaneous expression of PTCL of TFH origin and its prognostic impact. Methods We conducted a multicenter retrospective cohort study by retrieving histopathological reports including the mention ‘AITL’ or ‘PTCL with T‐follicular helper phenotype’ (PTCL‐TFH) from five French tertiary hospital centers. Results From 2000 to 2022, we reviewed 382 histopathological records and identified 52 AITL cases and 5 PTCL‐TFH cases with cutaneous involvement. Thirty‐two (56%) patients were males with a mean age of 63 years. Fifty‐six (98%) patients presented with lymphadenopathy, 32 (56%) splenomegaly and 17 (30%) hepatomegaly. B signs were present in 34 (60%) patients. Skin lesions were present on the lower limbs in 44 (77%) patients, trunk in 38 (67%) patients, upper limbs in 35 (61%) and head in 27 (47%). Macules and papules were the most frequent lesions found in 47 (82%) patients, followed by nodules in 10 (17%) patients, erythemato‐squamous plaques in 10 (17%) patients, purpura in 9 (16%), urticaria in 9 (16%) and blisters in 5 (9%) patients. Erythroderma affected seven patients (12%). A skin biopsy was taken in 50 patients and revealed a specific lymphomatous infiltrate in 36 cases. A dominant skin T‐cell clone was detected in 13 out of 17 (76%) patients. Among the 14 patients with a nonspecific dermatitis, various histopathological patterns were observed including interface dermatitis, psoriasiform dermatitis, vasculitis, bullous dermatitis, granulomatous dermatitis and thrombotic vasculopathy. After a median follow‐up of 24 months (range, 0–121 months), median overall survival was 121 months (95% CI, 25.2–NA). At last follow‐up, 33 patients (58%) were alive, 20 (35%) were in complete remission and 7 (12%) were in partial remission; 30 (53%) patients experienced at least one relapse, including nodal relapses in 24 (80%) cases and cutaneous relapses in 12 (40%). Conclusions This study revealed the deep heterogeneity of skin presentations in AITL. Atypical skin presentations were common and included blistering, purpuric and psoriasiform eruptions.

Abstract We have previously shown that intracardiac delivery of autologous CD34+ cells after acute myocardial infarction (AMI) is safe and leads to long term improvement. We are now conducting a multicenter, randomized, controlled Phase I/IIb study in post-AMI to investigate the safety and efficacy of intramyocardial injection of expanded autologous CD34+ cells (ProtheraCytes) (NCT02669810). Here, we conducted a series of in vitro studies characterizing the growth factor secretion, exosome secretion, gene expression, cell surface markers, differentiation potential, and angiogenic potential of ProtheraCytes clinical batches to develop a potency assay. We show that ProtheraCytes secrete vascular endothelial growth factor (VEGF) and its concentration is significantly correlated with the number of CD34+ cells obtained after expansion. ProtheraCytes also secrete exosomes containing proangiogenic miRNAs (126, 130a, 378, 26a), antiapoptotic miRNAs (21 and 146a), antifibrotic miRNAs (133a, 24, 29b, 132), and miRNAs promoting myocardial regeneration (199a and 590). We also show that ProtheraCytes have in vitro angiogenic activity, express surface markers of endothelial progenitor cells, and can differentiate in vitro into endothelial cells. After the in vitro characterization of multiple ProtheraCytes clinical batches, we established that measuring the concentration of VEGF provided the most practical, reliable, and consistent potency assay.

During the austral summer 2019/2020, three vertically pointing K-band Doppler profilers (Micro Rain Radar PRO, MRR-PRO) were deployed along a transect across the Sør Rondane Mountains, directly south of the scientific base Princess Elisabeth Antarctica. The MRR-PRO devices were placed at locations corresponding to different stages of the interaction between the complex terrain and the typical flow associated with precipitating systems. The radar measurements, alongside information from the ERA5 reanalysis and a set of high-resolution Weather Research and Forecasting (WRF) simulations, have been used to study the spatial variability in snowfall across the transect. Radar observations reveal differences in the frequency of occurrence of virga and surface precipitation above the transect. An analysis of the WRF outputs reveals the presence of a relatively dry layer above the radar locations, reaching a constant altitude of 3.5 km above mean sea level. Due to the complex terrain, the depth of the layer varies across the transect, affecting sublimation and the occurrence of virgae. Combined information from the ERA5 reanalysis, the WRF simulations, and ground-level measurements suggests that orographic lifting enhances precipitation above the highest mountain peaks. Finally, the analysis of the succession of virga and surface precipitation above the sites shows that, in most cases, they represent different stages of the same large-scale events. This study reveals the significant spatial variability in the occurrence of precipitation in a region of complex terrain, emphasizing the importance of collecting snowfall measurements in the mountainous regions of the Antarctic continent.

Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

Abstract Primary cutaneous follicle centre lymphomas (PCFCLs) are cutaneous proliferation of centrocytes and centroblasts, with a generally indolent evolution. Secondary systemic spread of disease is a rare event, which significantly impairs prognosis. Recently published study by Zhou and al. proposed criteria aiming to predict such evolution at initial stage: (i) rearrangement of Bcl2, (ii) Ki67% index 30% Ki67% indexes and no mutations among the four proposed genes. These findings run contrary to these previously proposed criteria, highlighting the molecular heterogeneity of this rare disease.

Abstract Background Except in a few retrospective studies mainly including patients under chemotherapy, information regarding the impact of immunosuppressive therapy on the prognosis of patients admitted to the intensive care unit (ICU) for septic shock is scarce. Accordingly, the PACIFIC study aimed to asses if immunosuppressive therapy is associated with an increased mortality in patients admitted to the ICU for septic shock. Methods This was a retrospective epidemiological multicentre study. Eight high enroller centres in septic shock randomised controlled trials (RCTs) participated in the study. Patients in the “exposed” group were selected from the screen failure logs of seven recent RCTs and excluded because of immunosuppressive treatment. The “non-exposed” patients were those included in the placebo arm of the same RCTs. A multivariate logistic regression model was used to estimate the risk of death. Results Among the 433 patients enrolled, 103 were included in the “exposed” group and 330 in the “non-exposed” group. Reason for immunosuppressive therapy included organ transplantation (n = 45 [44%]) or systemic disease (n = 58 [56%]). ICU mortality rate was 24% in the “exposed” group and 25% in the “non-exposed” group (p = 0.9). Neither in univariate nor in multivariate analysis immunosuppressive therapy was associated with a higher ICU mortality (OR: 0.95; [95% CI 0.56–1.58]: p = 0.86 and 1.13 [95% CI 0.61–2.05]: p = 0.69, respectively) or 3-month mortality (OR: 1.13; [95% CI 0.69–1.82]: p = 0.62 and OR: 1.36 [95% CI 0.78–2.37]: p = 0.28, respectively). Conclusions In this study, long-term immunosuppressive therapy excluding chemotherapy was not associated with significantly higher or lower ICU and 3-month mortality in patients admitted to the ICU for septic shock.

This article focuses on the environmental impact of nuclear energy and addresses the following major environmental issues associated with nuclear power generation: ① controlling the radioactive discharge from nuclear installations under normal operation and evaluating their non-radioactive environmental impact (water withdrawals and non-radioactive discharges); ② long-term management of spent fuel and radioactive waste (radwaste), notably that disposed off in geological repositories; ③ prevention and mitigation of severe nuclear accidents and their radioactive releases and; ④ improving nuclear safety to restrict its environmental impact and to contribute toward the public acceptance of nuclear energy. Nuclear energy, with its very low emissions of green house gases, has a unique capacity to generate massive and on-demand dispatchable amounts of electricity. The annual effective radiation dose delivered to the public surrounding nuclear power plants under normal operation is negligible. Considerable efforts have been made to define sustainable management of high-level long-lived radwaste that is disposed in geological formations. The return of experience from severe nuclear accidents in the past has informed and propelled major improvements in several aspects of nuclear energy production—including reactor design and operational management as well as in the development of accident-management guidelines—and has proved to be highly valuable. The environmental risks in the event of a severe accident have been substantially reduced and protocols have been established to minimize the release of radioactive materials and avoid the large-scale evacuation of people in the event of a severe nuclear accident. Efforts must be continued to improve reactor safety and enhance the transparency of the industry and the authorities that support and control nuclear power to further reduce the environmental impact.