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This study examined the effects of advanced lung cancer (stage IV non-small cell lung cancer [NSCLC]) on patients in Mexico, focusing on the health, financial, and caregiver burdens. Researchers studied adults over 18 years of age undergoing cancer treatment at four medical centers across Mexico, analyzing treatment costs and time lost due to illness. All costs were updated to 2022 Mexican pesos (MXN) values. Treating one patient for 1 year can cost up to MXN 1 million in public hospitals and more than MXN 2 million in private hospitals. Patients might lose about 84–335 days of work annually, with caregivers losing 13–30 days. These lost workdays significantly impact finances, costing approximately MXN50,000–178,000 per patient per year in public hospitals and MXN438,000 in private hospitals. The study concludes that understanding these costs can help create better treatment plans, improving patient care and reducing financial burdens. By aligning treatment strategies across public and private healthcare settings, patients could benefit from more consistent and effective care, potentially leading to better health outcomes and reducing the overall impact of the disease on their lives and the broader healthcare system.

Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock.

We present the total ionizing dose (TID) dependencies of output resistance of the 1.8- and 1.5-V stub series-terminated logic (SSTL18/15) transmitter drivers fabricated with commercial 65-nm technology. The analysis showed the radiation-induced resistance growth that was attributed to the interface-trap buildup in unsalicided polysilicon resistors. The growth accelerates at a low-dose rate (LDR). We also discuss the results for 24 h of annealing at room temperature (RTA) followed by high-temperature annealing (HTA) for 168 h, the layout dependencies, and the significance of the observed effects at higher absorbed doses.

Because one-third of patients deteriorate after their admission to the emergency department, assessing the prognosis of COVID-19 patients is of great importance. However, to date, only lymphopenia and the partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio have been reported as partly predictive of COVID-19–related further deterioration, and their association has not been evaluated. We asked whether other key biomarkers of SARS-CoV-2 immunologic defects—increase in circulating immature granulocytes, loss of monocyte HLA-DR (mHLA-DR) expression, and monocyte differentiation blockade—could also predict further COVID-19 deterioration. A series of 284 consecutive COVID-19 patients, with the sole inclusion criterion of being an adult, were prospectively enrolled at emergency department admission (day 0) of 2 different hospitals: 1 for the exploratory cohort (180 patients) and 1 for the confirmatory cohort (104 patients). Deterioration was assessed over the next 7 days. Neither increased immature granulocyte levels nor monocyte differentiation blockade predicted patient worsening. Among more than 30 clinical, biological, and radiological parameters, the value of decreased P/F ratio and lymphopenia for prediction of further COVID-19 deterioration was strongly confirmed, and the loss of mHLA-DR was the only additional independent marker. Combined together in a simple OxyLymphoMono score, the 3 variables perfectly predicted patients who did not worsen and correctly predicted worsening in 59% of cases. By highlighting lymphocyte and monocyte defects as preceding COVID-19 deterioration, these results point on early immunosuppression in COVID-19 deterioration. Combining P/F ratio, lymphopenia, and loss of mHLA-DR together in a simple and robust score could offer a pragmatic method for COVID-19 patient stratification.Preceding COVID-19 deterioration, increase in low HLA-DR monocytes points on early COVID-19 immunosuppression and, with lymphopenia, is the only independent biological parameter predicting COVID-19 worsening.

Stroke is a leading cause of death in the US and around the world but with limited treatment options. Survivors often present with long-term cognitive and neurological deficits. Stem cell-based therapy has emerged as a potential treatment for stroke. While stem cell transplantation in stroke has reached clinical trials, mostly safety outcomes have been reported with efficacy readouts warranting more studies. In an effort to optimize the stem cell regimen for stroke, here we conducted vis-a-vis comparison of different routes of transplantation, namely, intracerebral, intraarterial, and intranasal delivery of expanded human CD34 + stem cells, called ProtheraCytes, in the established stroke model of transient middle cerebral artery occlusion (MCAO) using adult Sprague-Dawley rats. After adjusting for the dose and subacute timing of cell delivery, animals were randomly assigned to receive either ProtheraCytes or vehicle. Motor and neurological assays from days 7 to 28 post-stroke revealed significant functional recovery across all 3 delivery routes of ProtheraCytes compared to vehicle-treated stroke rats. Additionally, ProtheraCytes-transplanted stroke rats displayed significantly reduced infarct size and cell loss in the peri-infarct area coupled with enhanced neurogenesis and angiogenesis compared to vehicle-treated stroke rats. These results highlight the safety and efficacy of transplanting ProtheraCytes, including via the minimally invasive intranasal route, in conferring robust and stable behavioral and histological positive outcomes in experimental stroke.Graphical AbstractStem cell-derived extracellular vesicles promote recovery of ischemic cells. The present study demonstrates a novel mechanism of action mediating stem cell-induced therapeutic effects in ischemic stroke. Whereas the long-standing view of stem cell repair of the stroke brain implicates cell replacement, our findings implicates a process of by-stander effects, whereby stem cells release extracellular vesicles (EVs), in particular CD-63-labeled EVs, which appear to target the vasculature and enhance vascular endothelial growth factor zlevels, while dampening inflammation (Iba-1 cells) and increasing neural cell proliferation (DCX). Altogether, these reparative processes rescue the neurovascular unit via a multi-pronged mechanism involving EV release, vasculogenesis, anti-inflammation, and neurogenesis.

Les hépatites virales B et C sont des maladies endémiques au Bénin. Mais il n’existe aucune donnée sur ce que les patients savent réellement de leur maladie. Le but de ce travail est d’évaluer les connaissances et croyances des patients infectés par rapport à leur pathologie. Il s’agit d’une étude prospective. Elle incluait tous les patients atteints d’hépatite virale chronique B ou C admis dans le Service de gastroentérologie pendant la période d’étude. 102 patients étaient inclus, dont 83 pour l’hépatite B et 19 pour l’hépatite C. Leurs connaissances sur l’agent causal et l’organe atteint étaient satisfaisantes. Quant aux modes de contamination, 92 patients (90,2%) évoquaient la voie sanguine, 89 (87,3%) la vie dans l’entourage d’une personne contaminée, 84 (82,4%) la voie sexuelle et 81 (79,4%) la transmission mère-enfant. De fausses croyances étaient relevées chez 42,2% des personnes interrogées pour l’étiologie et 88,2% pour les voies de transmission. Les méthodes de prévention étaient peu connues. Près de la moitié des patients ignoraient l’existence de traitements efficaces contre les hépatites B et C. Ces résultats mettent en évidence la sous — information des malades quant à leur maladie. La méconnaissance des possibilités thérapeutiques entretient l’idée fausse selon laquelle les hépatites virales n’ont pas de traitement en médecine conventionnelle. Il y a lieu de renforcer l’éducation des patients afin de les amener à vivre mieux avec leur maladie, et à être plus efficaces dans la prévention de la transmission de l’hépatite à leur entourage. Viral hepatitis B and C are endemic diseases in Benin. But there is no data on what the patients really know about their illness. The aim of this study is to evaluate the knowledge and beliefs of infected patients in relation to their disease. This is a prospective study. It included all patients with viral hepatitis B or C admitted in the department of gastroenterology during the period of survey. 102 patients were included, of which 83 for viral hepatitis B and 19 for viral hepatitis C. Patients’ knowledge about the causative agent and the affected organ were satisfying. The modes of transmission reported are: blood transmission: 92 patients (90.2%); exposure to chronically infected household members: 89 (87.3%); sexual contacts: 84 (82.3%) and transmission from mother to newborn baby: 81 (79.4%). Among peoples investigated, 88.2% had false beliefs about the causative agent and 42.2% about the modes of transmission. Methods of prevention were little known. Nearly half of surveyed patients were unaware of the existence of efficient treatments against viral hepatitis B and C. These results show that patients with chronic hepatitis B or C are lacking in information about their disease. Ignorance about therapeutic possibilities maintains the misconception that chronic viral hepatitis B and C have no treatments in conventional medicine. It is necessary to improve patients’ knowledge about these infections in order to get them to live better with their disease, and to be more efficient in preventing transmission of hepatitis to household members.

IMPORTANCE: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). MAIN OUTCOMES AND MEASURES: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS: At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,−0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,−0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS: In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02908308

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.

Patient-specific models have increasingly gained significance in medical and research domains. In the context of hemodynamic studies, computational fluid dynamics emerges as a highly innovative and promising approach. We propose to augment these computational studies with cell-based experiments in individualized artery geometries using personalized scaffolds and vascular cell experiments. Previous research has demonstrated that the development of Sickle Cell Disease (SCD)-Related Vasculopathy is dependent on personal geometries and flow characteristics of the carotid artery. This fact leaves conventional animal experiments unsuitable for gaining patient-specific insights into cellular signaling, as they cannot replicate the personalized geometry. These personalized dynamics of cellular signaling may further impact disease progression, yet remains unclear. This paper presents a six-step methodology for creating personalized large artery scaffolds, focusing on high-precision models that yield biologically interpretable patient-specific results. The methodology outlines the creation of personalized large artery models via Additive Manufacturing suitably for supporting cell culture and other cellular experiments. Additionally, it discusses how different Computer-Aided-Design (CAD) construction modes can be used to obtain high-precision personalized models, while simplifying model reconfigurations and facilitating adjustments to general designs such as system connections to bioreactors, fluidic systems and visualization tools. A proposal for quality control measures to ensure geometric congruence for biological relevance of the results is added. This innovative, interdisciplinary approach appears promising for gaining patient-specific insights into pathophysiology, highlighting the importance of personalized medicine for understanding complex diseases.

Temperature and water vapor are known to fluctuate on multiple scales. In this study 27 years of airborne measurements of temperature and relative humidity from In‐service Aircraft for a Global Observing System (IAGOS) are used to parameterize the distribution of water vapor in the upper troposphere and lower stratosphere. The parameterization is designed to simulate water vapor fluctuations within gridboxes of atmospheric general circulation models (AGCMs) with typical size of a few tens to a few hundred kilometers. The distributions currently used in such models are often not supported by observations at high altitude. More sophisticated distributions are key to represent ice supersaturation, a physical phenomenon that plays a major role in the formation of natural cirrus and contrail cirrus. Here the observed distributions are fitted with a beta law whose parameters are adjusted from the gridbox mean variables. More specifically the standard deviation and skewness of the distributions are expressed as empirical functions of the average temperature and specific humidity, two typical prognostic variables of AGCMs. Thus, the distribution of water vapor is fully parameterized for a use in these models. The new parameterization reproduces the observed distributions with a determination coefficient always greater than 0.917 and with a mean value of 0.997. The parameterization is robust to a selection of various geographical subsets of data and to gridbox sizes varying between 25 and 300 km. Temperature and water vapor fluctuate in the atmosphere on different scales, from micrometers to thousands of kilometers. In this study we use airborne measurements of temperature and water vapor to study the spatial variability of humidity in the upper troposphere and lower stratosphere. The observations are used to build a simple modeling of water vapor distribution on scales from tens of kilometers to hundreds of kilometers, which is designed to be used in atmospheric general circulation models (AGCMs), the atmospheric components of Earth system models. This new modeling of water vapor fluctuations aims to increase the physical representation of cirrus clouds and aviation‐induced cloudiness in AGCMs. The observed water vapor distributions are modeled with a beta distribution, whose parameters are completely determined as empirical functions of two major variables of AGCMs, the average temperature in a gridbox, and the average water vapor in a gridbox. Overall, the modeled distributions fit those observed very well. The fine‐scale distribution of water vapor in the upper troposphere is fully parameterized for use in atmospheric general circulation modelsThe parameterization is empirical and based on 257 million airborne observations made between 1995 and 2021This parameterization aims to improve the quality of the simulation of ice supersaturation, and the formation of cirrus and contrail clouds The fine‐scale distribution of water vapor in the upper troposphere is fully parameterized for use in atmospheric general circulation models The parameterization is empirical and based on 257 million airborne observations made between 1995 and 2021 This parameterization aims to improve the quality of the simulation of ice supersaturation, and the formation of cirrus and contrail clouds

Despite their essential role in the high‐latitude climate, the representation of mixed‐phase clouds is still a challenge for Global Climate Models (GCMs)'s cloud schemes. In this study we propose a methodology for robustly assessing Arctic mixed‐phase cloud properties in a climate model using airborne measurements. We leverage data collected during the RALI‐THINICE airborne campaign that took place near Svalbard in August 2022 to evaluate the simulation of mid‐level clouds associated with Arctic cyclones. Simulations are carried out with the new limited‐area configuration of the ICOLMDZ model which combines the recent icosahedral dynamical core DYNAMICO and the physics of LMDZ, the atmospheric component of the IPSL‐CM Earth System Model. Airborne radar and microphysical probes measurements are then used to evaluate the simulated clouds. A comparison method has been set‐up to guarantee as much as possible the spatiotemporal co‐location between observed and simulated cloud fields. We mostly focus on the representation of ice and liquid in‐cloud contents and on their vertical distribution. Results show that the model overestimates the amount of cloud condensates and exhibits a poor cloud phase spatial distribution, with too much liquid water far from cloud top and too much ice close to it. The downward gradual increase in snowfall flux is also not captured by the model. This in‐depth model evaluation thereby pinpoints priorities for further improvements in the ICOLMDZ cloud scheme. Mixed‐phase clouds, where ice crystals and supercooled liquid droplets coexist at sub‐zero temperatures, are ubiquitous in the polar regions. Albeit essential for the high‐latitude climate, they are still poorly represented by climate models. In this study, original measurements from the RALI‐THINICE airborne campaign, which took place in the Svalbard region in August 2022, are used to assess how the ICOLMDZ atmospheric model represents Arctic mixed phase clouds. A methodology is developed to make robust and co‐located model‐aircraft observation comparisons. In situ cloud probes and onboard radars are then used to evaluate the simulated amounts of liquid water and ice in clouds as well as the snowfall flux in deep clouds associated with the transit of Arctic cyclones. The results of the model evaluation show an overall overestimation of cloud condensates with too much liquid water far from cloud top and too much ice close to it. Airborne RALI‐THINICE observations are used to evaluate Arctic clouds in the new limited area version of the ICOLMDZ modelA methodology has been developed to make robust and co‐located model‐observation comparisonsICOLMDZ simulates overly high amounts of liquid and ice in clouds particularly near cloud top Airborne RALI‐THINICE observations are used to evaluate Arctic clouds in the new limited area version of the ICOLMDZ model A methodology has been developed to make robust and co‐located model‐observation comparisons ICOLMDZ simulates overly high amounts of liquid and ice in clouds particularly near cloud top

High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days −6, –3, +1, and +4 and melphalan (200 mg/m2 IV) on day –2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM–treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.

ABSTRACTThe work scheduling flexibility enjoyed by drivers of ride-sourcing platforms poses challenges for these platforms in effectively managing their workforce. A key to resolving these challenges is to understand how drivers set up their work schedule so as to inform management decisions. This letter summarizes our investigation of ride-sourcing drivers’ working hour decisions. Leveraging comprehensive data from Didi Chuxing, a ride-hailing company in China, we calibrate two classic models from previous studies on taxi labor markets to examine drivers’ reactions to earnings in deciding their working hours. Our results suggest that, when deciding whether to continue a shift, drivers pay more attention to future income opportunities and the time already spent working rather than their current earning level.

L’immunothérapie a bouleversé la prise en charge du mélanome et beaucoup d’autres cancers. Elle peut néanmoins induire la stimulation de lymphocytes T dirigées contre des antigènes autologues non tumoraux et être responsable de toxicités. De rares cas de panniculite granulomateuse ont été décrits, s’inscrivant dans le cadre des réactions sarcoïdosiques immunomédiées. Nous décrivons le premier cas, à notre connaissance de lymphome T sous-cutané de type panniculite(LTSCP) induit par l’immunothérapie.

BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients with the sepsis syndrome, but its mechanisms frequently remain undetermined. Hemophagocytosis has been reported as a cause of thrombocytopenia in various diseases. This prospective study was designed to assess: (1) the incidence of hemophagocytosis in patients suffering from both the sepsis syndrome and unexplained thrombocytopenia, and (2) the circulating level of the macrophage-colony-stimulating factor (M-CSF) according to the presence or absence of hemophagocytosis. METHODS: Fifty consecutive patients diagnosed with both the sepsis syndrome and thrombocytopenia of undetermined origin were studied. Hemophagocytosis was diagnosed based on microscopical examination of sternal bone marrow aspiration by two independent observers. Serum M-CSF concentrations were measured in each patient and compared with levels of a normal population (n = 59). Causes and severity of sepsis syndromes as well as serum M-CSF levels were compared beween patients with and without hemophagocytosis. RESULTS: Hemophagocytosis was diagnosed in 32 patients (64%). Mean serum M-CSF levels were increased in patients when compared with normal subjects (539 [+ or -] 141 versus 208 [+ or -] 82 IU/mL: P < 0.001), and higher in patients with than without hemophagocytosis (580 [+ or -] 145 versus 457 [+ or -] 89 IU/mL: P = 0.01). Multiorgan dysfunction and infection were independent risk factors of hemophagocytosis (odds ratio = 31.3 and 6.8, 95% confidence interval (CI) = 5.4 to 177.6 and 1.0 to 47.4, P < 0.0001 and P = 0.03, respectively). CONCLUSIONS: Hemophagocytosis is a frequent cause of unexplained thrombocytopenia in patients with severe sepsis syndrome. Our results suggest that M-CSF is overproduced in the sepsis syndrome, particularly when hemophagocytosis is present. The role of M-CSF in the initiation and development of hemophagocytosis remains to be determined. Am J Med. 1997;103:114-120. [C] 1997 by Excerpta Medica, Inc.

IMPORTANCE: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (UBA1) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described. OBJECTIVE: To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any UBA1 variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies. RESULTS: All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function UBA1 variation in both samples for all patients. CONCLUSIONS AND RELEVANCE: This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.

Near-hanging experiences are life-threatening events about which few data are available.

En métropole, près de 20 nouveaux cas de lèpre sont diagnostiqués chaque année. L’incidence de la tuberculose en France est de 8/100 000 habitants et l’association des 2 mycobactéries a été exceptionnellement rapportée. Nous rapportons un cas de co-infection lèpre Borderline Tuberculoïde (BT) et tuberculose disséminée, diagnostiqué en métropole.

Low reactive oxygen species (ROS) levels are well‐established characteristics of mouse hematopoietic stem cells (HSCs). However, little is known about these levels in human HSCs. This study aimed at quantifying ROS levels in human CD34+CD38lowand CD34+CD38highhuman progenitors from bone marrow, cord blood and cells mobilized for autologous HSC transplantation. A specifically devised multiparameter flow cytometry method was used to quantify ROS levels (H2DCFDA staining) in sub‐populations of primary cells. Results were confirmed by assessing gene expression level of the ROS scavenger GPX3,a key determinant of HSC self‐renewal, in sorted CD34+CD38lowand CD34+CD38highcells. CD34+CD38lowcells from bone marrow and cord blood displayed significantly lower levels of ROS than CD34+CD38highcells and other leukocytes. Moreover, the correlation between ROS and GPX3expression was verified in sorted CD34+CD38lowand CD34+CD38highcells. These results confirm, in human, data previously reported in mice. Moreover, the flow cytometry assay we developed could allow for a more precise enumeration of repopulating primitive progenitors in the course of HSC transplantation.

La plasmocytose cutanée est une dermatose rare décrite en 1976 et observée surtout chez des patients d’ascendance asiatique. Elle forme habituellement des macules et des plaques érythémateuses à brunâtres du tronc et du visage, avec en histologie des infiltrats dermiques composés de plasmocytes matures bien différenciés. La pathogenèse et la place nosographique de cette affection sont encore mal établies. Nous présentons un cas de plasmocytose cutanée chez une femme d’ascendance européenne, particulière par la présence d’un signe de Darier.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for transformation in secondary acute myeloid leukemia. This study focused on the redox metabolism of bone marrow (BM) cells from 97 patients compared with 25 healthy controls. The level of reactive oxygen species (ROS) was quantified by flow cytometry in BM cell subsets as well as the expression level of 28 transcripts encoding for major enzymes involved in the antioxidant cellular response. Our results highlight increased ROS levels in BM nonlymphoid cells and especially in primitive CD34posCD38low progenitor cells. Moreover, we identified a specific antioxidant signature, dubbed “antioxidogram,” for the different MDS subgroups or secondary acute myeloblastic leukemia (sAML). Our results suggest that progression from MDS toward sAML could be characterized by 3 successive molecular steps: (1) overexpression of enzymes reducing proteic disulfide bonds (MDS with <5% BM blasts [GLRX family]); (2) increased expression of enzymes detoxifying H2O2 (MDS with 5% to 19% BM blasts [PRDX and GPX families]); and finally (3) decreased expression of these enzymes in sAML. The antioxidant score (AO-Score) defined by logistic regression from the expression levels of transcripts made it possible to stage disease progression and, interestingly, this AO-Score was independent of the revised International Scoring System. Altogether, this study demonstrates that MDS and sAML present an important disturbance of redox metabolism, especially in BM stem and progenitor cells and that the specific molecular antioxidant response parameters (antioxidogram, AO-Score) could be considered as useful biomarkers for disease diagnosis and follow-up.

Les formes avancées de lymphomes T cutanés primitifs (LTCP) telles que le mycosis fongoïde (MF) tumoral (MFT) et le syndrome de Sézary (SS) ont un pronostic défavorable et l’allogreffe de cellules souches hématopoïétiques (aCSH) est la seule option curative potentielle. Cependant, l’aCSH est associée à des complications fréquentes, notamment la maladie du greffon contre l’hôte (GVH). Le ruxolitinib, un inhibiteur de JAK1/2, s’est avéré efficace dans le traitement de la GVH chronique (GVHc) réfractaire aux corticostéroïdes (CTC) sans augmenter l’incidence des rechutes dans un essai incluant essentiellement des patients atteints d’hémopathies myéloïdes.

La nécrolyse épidermique toxique (NET) est un effet indésirable médicamenteux cutanéomuqueux rare et potentiellement mortel. Le mogamulizumab est une immunoglobuline IgG1 qui se lie sélectivement au CC chemokine récepteur 4 (CCR4), un récepteur de chemokines impliqué dans le homingcellulaire cutané, exprimé sur les lymphocytes T régulateurs (Tregs) et les cellules tumorales dans le mycosis fongoïde (MF) et le syndrome de Sézary (SS). Le mogamulizumab a été initialement développé pour la leucémie et le lymphome à cellules T de l’adulte (ATLL) et est actuellement approuvé comme traitement systémique de deuxième ligne dans le MF et le SS.

La sarcoïdose hypodermique, dite de Darier-Roussy, est une forme rare de sarcoïdose caractérisée par une infiltration granulomateuse de l’hypoderme se manifestant par la présence de nodules sous cutanés. Les caractéristiques sémiologiques, le pronostic et les traitements de ces formes sont très peu décrits.

Le syndrome VEXAS (vacuoles, enzyme E1, lié à l’X, autoinflammatoire, somatique) est une maladie autoinflammatoire sévère de l’adulte récemment décrite, causée par des mutations somatiques acquises dans le gène codant pour l’enzyme activatrice de l’ubiquitine 1 (UBA1). Des atteintes cutanées à type de syndrome de Sweet, en particulier le syndrome de Sweet histiocytoïde (SSH), peuvent être associées au syndrome VEXAS. Nous avons comparé les caractéristiques cliniques et histologiques du SSH chez des patients atteints ou non du syndrome VEXAS et nous avons cherché à caractériser davantage les lésions cutanées chez les patients atteints.

The current assessment of the Antarctic surface mass balance mostly relies on reanalysis products or climate model simulations. However, little is known about the ability of models to reliably represent the microphysical processes governing the precipitation. This study makes use of recent ground‐based precipitation measurements at Dumont d'Urville station in Adélie Land to evaluate the representation of the precipitation microphysics in the Polar version of the Weather Research Forecast (Polar WRF) atmospheric model. During two summertime snowfall events, high‐resolution simulations are compared to measurements from an X‐band polarimetric radar and from a Multi‐Angle Snowflake Camera (MASC). A radar simulator and a “MASC” simulator in Polar WRF make it possible to compare similar observed and simulated variables. Radiosoundings and surface‐meteorological observations were used to assess the representation of the regional dynamics in the model. Five different microphysical parameterizations are tested. The simulated temperature, wind, and humidity fields are in good agreement with the observations. However, the amount of simulated surface precipitation shows large discrepancies with respect to observations, and it strongly differs between the simulations themselves, evidencing the critical role of the microphysics. The inspection of vertical profiles of reflectivity and mixing ratios revealed that the representation of the sublimation process by the low‐level dry katabatic winds strongly influences the actual amount of precipitation at the ground surface. By comparing the simulated radar signal as well as MASC and model particle size distributions, it is also possible to identify the microphysical processes involved and to pinpoint shortcomings within the tested parameterizations. The microphysics of Antarctic snowfall in Polar WRF is compared to radar and MASC measurements at Dumont d'Urville stationDespite the constrained circulation, large discrepancies between microphysical schemes appear in the amount of simulated precipitationShortcomings in state‐of‐the‐art microphysical schemes are identified, particularly regarding the sublimation and aggregation processes

Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation.

The hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound (TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI (PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events.

Shipborne observations from the CAPRICORN‐2018 field campaign were used to investigate the characteristics and variability of precipitation across different sectors of an extra‐tropical cyclone on 16 February 2018, over the Southern Ocean (SO). Three distinct time periods—frontal, post‐frontal, and cyclone—were identified during the day. The frontal passage recorded a total accumulation of 1.9 mm, where the precipitation phases were primarily composed of rain (96%), while the cyclone period recorded the largest precipitation (4.0 mm), where the precipitation phases varied with snow (10%), mixed‐phase (40%), and rain (50%). The BASTA radar suggests the freezing level was shallow (∼500 m) with snow present above. The cloud top heights, observed by a C‐band radar, were shallower in the cyclone period, although deeper cloud depths of ∼6 km were sporadically recorded. Increased surface fluxes and a southerly wind direction indicate that cold air advection, was likely the main cause of high precipitation during the cyclone period. A non‐precipitating multi‐layer cloud structure with a geometrically thin (200 m) homogeneous layer of supercooled liquid water (SLW) overlaying shallow boundary layer convection was seen during the post‐frontal period. The ship‐borne observations were used to evaluate Weather Research & Forecasting (WRF) simulations with different microphysics settings. We found the frontal precipitation intensity is well reproduced, but it is underestimated during the cyclone period. This study represents a unique set of observations and highlights the need for understanding how ice processes and potentially horizontal advection contribute to the development of precipitation and convection over the SO. There are still significant differences between current precipitation products over the Southern Ocean (SO). This makes it harder to understand the hydrological cycle and different meteorological processes in the region. In this study, we used the shipborne observations from the Clouds, Aerosols, Precipitation, Radiation, and atmospherIc Composition Over the southeRn oceaN(CAPRICORN) 2018 field campaign to investigate the characteristics and variability of precipitation across different sectors of an extra‐tropical cyclone on 16 February 2018, over the SO. Overall, the frontal passage recorded a total accumulation of 1.9 mm, with 96% of its phases being rain, while the cyclone period recorded the highest precipitation (4.0 mm), with 10% being snow and 40% being mixed. In addition, we made use of the observations to evaluate simulations run with the Weather Research and Forecasting Model (WRF) using a variety of cloud microphysics parameters. We observed that the intensity of the precipitation along the front is reproduced quite well, but that it is significantly underestimated throughout the cyclone period. This work highlights the importance of knowing the role that ice processes and potentially horizontal advection play in the formation of precipitation over the high latitudes of the SO. Distinctive characteristics of precipitation across different sectors of an extra‐tropical cyclone are observedLargest precipitation was recorded during the cyclone period where its phases were largely constituted of mixed‐phase and snowWRF reproduced the frontal precipitation intensity, while it is underestimated during the cyclone period Distinctive characteristics of precipitation across different sectors of an extra‐tropical cyclone are observed Largest precipitation was recorded during the cyclone period where its phases were largely constituted of mixed‐phase and snow WRF reproduced the frontal precipitation intensity, while it is underestimated during the cyclone period

Primary testicular lymphoma (PTL) and diffuse large B-cell lymphoma with secondary testicular involvement (DLBCL-T) are rare subtypes of lymphomas associated with poor prognosis and a high risk of central nervous system (CNS) relapse. The optimal CNS prophylaxis strategy for these subtypes remains uncertain. High-dose methotrexate (HD-MTX) is debated for CNS prophylaxis, but its efficacy in this setting is unknown. This study aimed to retrospectively analyze the use of HD-MTX in combination with chemotherapy (R HD-MTX CHOP) as frontline treatment for PTL and DLBCL-T and to compare the biological characteristics of these two forms of testicular involvement.

Background

Similarly, to sepsis, cardiac surgery with cardiopulmonary bypass (CPB) induces major changes in leukocyte subsets. Immature granulocytes (IGs) increase both in sepsis and after open‐heart surgery. Secondary infections are a major complication of cardiac surgery with CPB. We hypothesized that the assessment of leukocyte subsets with multicolor flow cytometry (FCM) could help the front‐line clinician to better identify patients at high risk of infectious complications in this clinical setting. In this single‐center observational pilot study, we identified 26 leukocyte subsets using three combinations of antibodies (from 5 to 10 colors per combinations): one devoted to granulocytes, one to lymphocyte subpopulations and one for rare cells (plasma cells and dendritic cells). Blood samples were obtained preoperatively and immediately after open‐heart surgery under CPB in 59 patients without immuno‐depression, chronic or neoplastic inflammatory disease, and immunosuppressive treatment. Secondary infections during hospital stay were recorded. Patients exhibited postoperative NK and T‐cell lymphopenia, increased levels of IGs and monocytes with low levels of surface HLA DR. Twelve patients developed secondary infectious complications. Only immediate postoperative IG levels were significantly higher in these patient (6.6 [6; 7.39] G/L vs. 3.8 [2.67; 5.72] G/L, P= 0.01). Patients with immediate postoperative increase of IGs developed more frequently infectious complication (10/22 [46%] vs. 2/37 [5%]: P< 0.001). This study suggests that postoperative increase of IGs is related to postoperative organ failure and promises to help in early identification of patients at risk of infectious complications after open‐heart surgery under CPB. © 2018 International Clinical Cytometry Society

Lateral heterostructures with planar integrity form the basis of two-dimensional (2D) electronics and optoelectronics. Here we report that, through a two-step chemical vapor deposition (CVD) process, high-quality lateral heterostructures can be constructed between metallic and semiconducting transition metal disulfide (TMD) layers. Instead of edge epitaxy, polycrystalline monolayer MoS2in such junctions was revealed to nucleate from the vertices of multilayered VS2crystals, creating one-dimensional junctions with ultralow contact resistance (0.5 kΩ·μm). This lateral contact contributes to 6-fold improved field-effect mobility for monolayer MoS2, compared to the conventional on-top nickel contacts. The all-CVD strategy presented here hence opens up a new avenue for all-2D-based synthetic electronics.

In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU.