Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Fisiología respiratoria: difusión de gases / Gas diffusion

El principal objetivo del sistema respiratorio es permitir un adecuado aporte de oxígeno y remoción del dióxido de carbono. Para esto, debe ocurrir una adecuada difusión de gases en la membrana alvéolo-capilar, proceso pasivo en el que el oxígeno se mueve hacia el capilar y el dióxido de carbono hacia el alvéolo. La ley de Fick establece los determinantes de la difusión, los que están dados por propiedades de la membrana alvéolo-capilar y de los gases. Las características únicas de la membrana alvéolo-capilar favorecen la difusión de gases, pero es el gradiente de presión parcial de los gases el principal determinante. El oxígeno pasa fácilmente por la membrana alvéolo-capilar y se une rápidamente a la hemoglobina, saturándola, cuando se iguala la presión parcial de oxígeno alveolar y la capilar se detiene la difusión de este gas; por lo que la difusión de oxígeno en reposo está limitada por perfusión. El dióxido de carbono difunde 20 veces más rápido que el oxígeno en la membrana alvéolo-capilar, y aunque su gradiente de presión sea menor, el equilibrio se logra aproximadamente en el mismo tiempo. La difusión del oxígeno es más lenta que la del dióxido de carbono debido a su menor solubilidad. En condiciones patológicas tanto el oxígeno como el dióxido de carbono pueden ser limitados por difusión. Para medir la capacidad de difusión la técnica más utilizada es la capacidad de difusión de monóxido de carbono, ya que este gas solo está limitado por difusión.

The main objective of the respiratory system is allowing an adequate supply of oxygen and the removal of carbon dioxide from the tissues. To achieve this, an adequate diffusion of gases must occur in the alveolus-capillary membrane, which is a passive process in which oxygen moves towards the capillary and carbon dioxide towards the alveolus. Fick's law establishes the determinants of diffusion, which are given by properties of the alveolar-capillary membrane and properties of gases. The unique characteristics of the capillary-alveolar membrane favor the diffusion of gases, but it is the partial pressure gradient of the gases the main determinant. Oxygen passes easily through the alveolar-capillary membrane and rapidly binds to hemoglobin, saturating it. When the partial pressure of alveolar oxygen is matched, the diffusion of this gas stops; therefore, the diffusion of oxygen is limited by perfusion. Carbon dioxide diffuses 20 times faster than oxygen in the capillary-alveolar membrane, and although its pressure gradient is less than oxygen, equilibrium is achieved in approximately the same time. The diffusion of oxygen is slower than that of carbon dioxide due to its lower solubility. Under pathological conditions both oxygen and carbon dioxide can be diffusion-limited. To measure the diffusion capacity, the most used technique is the carbon monoxide diffusion capacity, since this gas is only limited by diffusion.

Electrostatic wipes as simple and reliable methods for influenza virus airborne detection.

The performance of an in-house protocol for virus detection on commercialized electrostatic wipes (EWs) was assessed experimentally by impregnating them with suspensions of cytomegalovirus, adenovirus, and influenza virus, and by determining the recovery efficiency, repeatability, and detection limit of the protocol. The protocol was sensitive enough to detect 4 log10 gene copies of virus. At room temperature, influenza RNA was stable on EWs for at least four days. When EWs were placed high in 32 influenza-infected patients' rooms, influenza RNA was detectable in 75% (N = 24) of EWs, suggesting that EWs are simple and reliable methods for influenza virus airborne detection.

La auscultación pulmonar en el siglo 21 / Lung auscultation in the 21th century

La auscultación pulmonar es parte fundamental del examen físico para el diagnóstico de las enfermedades respiratorias. La estandarización que ha alcanzado la nomenclatura de los ruidos respiratorios, sumado a los avances en el análisis computacional de los mismos, han permitido mejorar la utilidad de esta técnica. Sin embargo, el rendimiento de la auscultación pulmonar ha sido cuestionado por tener una concordancia variable entre profesionales de la salud. Aun cuando la incorporación de nuevas herramientas diagnósticas de imágenes y función pulmonar han revolucionado la precisión diagnóstica en enfermedades respiratorias, no existe tecnología que permita reemplazar la técnica de auscultación pulmonar para guiar el proceso diagnóstico. Por una parte, la auscultación pulmonar permite seleccionar a aquellos pacientes que se beneficiarán de una determinada técnica diagnóstica, se puede repetir cuantas veces sea necesario para tomar decisiones clínicas, y frecuentemente permite prescindir de exámenes adicionales que no siempre son fáciles de realizar o no se encuentran disponibles. En esta revisión se presenta el estado actual de la técnica de auscultación pulmonar y su rendimiento objetivo basado en la nomenclatura actual aceptada para los ruidos respiratorios, además de resumir la evidencia principal de estudios de concordancia de auscultación pediátrica y su análisis objetivo a través de nueva tecnología computacional.

Lung auscultation is an essential part of the physical examination for diagnosing respiratory diseases. The terminology standardization for lung sounds, in addition to advances in their analysis through new technologies, have improved the use of this technique. However, traditional auscultation has been questioned due to the limited concordance among health professionals. Despite the revolu tionary use of new diagnostic tools of imaging and lung function tests allowing diagnostic accuracy in respiratory diseases, no technology can replace lung auscultation to guide the diagnostic process. Lung auscultation allows identifying those patients who may benefit from a specific test. Moreover, this technique can be performed many times to make clinical decisions, and often with no need for- complicated and sometimes unavailable tests. This review describes the current state-of-the-art of lung auscultation and its efficacy based on the current respiratory sound terminology. In addition, it describes the main evidence on respiratory sound concordance studies among health professionals and its objective analysis through new technology.

[Lung auscultation in the 21th century]. / La auscultación pulmonar en el siglo 21.

Lung auscultation is an essential part of the physical examination for diagnosing respiratory diseases. The terminology standardization for lung sounds, in addition to advances in their analysis through new technologies, have improved the use of this technique. However, traditional auscultation has been questioned due to the limited concordance among health professionals. Despite the revolu tionary use of new diagnostic tools of imaging and lung function tests allowing diagnostic accuracy in respiratory diseases, no technology can replace lung auscultation to guide the diagnostic process. Lung auscultation allows identifying those patients who may benefit from a specific test. Moreover, this technique can be performed many times to make clinical decisions, and often with no need for- complicated and sometimes unavailable tests. This review describes the current state-of-the-art of lung auscultation and its efficacy based on the current respiratory sound terminology. In addition, it describes the main evidence on respiratory sound concordance studies among health professionals and its objective analysis through new technology.

Effects of Initial Soil Moisture, Clod Size, and Clay Content on Ammonia Volatilization after Subsurface Band Application of Urea.

Ammonia losses from broadcast urea vary based on soil physical and chemical properties; however, less is known about how soil properties affect NH losses after subsurface banding of urea. Therefore, three field trials were established to determine how initial soil moisture, clod size, and clay content affect NH volatilization from subsurface-banded (0.025-m depth) urea using wind tunnels. The first study measured volatilization after banding in a loamy mixed frigid Typic Humaquept at 50, 100, 150, 200, or 250 g kg gravimetric water content (WC). Study 2 measured volatilization from the same soil after covering the bands with soil clods that ranged from <2 to >24 mm in diameter, whereas Study 3 measured volatilization from transplanted, acidic soils with clay contents ranging from 5 to 57%. Cumulative 17-d NH losses for study one ranged from 8.3 to 20.8% of applied N, with the soil wetted to 200 g kg WC experiencing the greatest losses. For Study 2, cumulative NH volatilization losses ranged from 10.8 to 20.8% of applied N, with the greatest losses from the largest clod sizes. For Study 3, NH losses ranged from 2.5 to 51.7% of applied N, with the NH losses correlated to the maximum pH measured in the band ( < 0.001), and to the soil cation exchange capacity ( = 0.054), titratable acidity ( = 0.072), and clay content ( = 0.100). However, the soil with high silt, not sand, content had the highest volatilization losses, suggesting that high silt soils may have the greatest potential for NH volatilization.

[Eosinopenia in 2018]. / L'éosinopénie en 2018.

Since 1893, eosinopenia is a biological test to help a diagnosis of bacterial infection. Several publications have confirmed this hypothesis, particularly in the intensive care, pneumology and pediatric units. The value of this marker has been identified in vascular cerebral diseases and coronary bypass. Its contribution seems as relevant as procalcitonin, without extra cost. The diagnostic performance of this test was reinforced by a composite score (CIBLE score) that may improve its value in daily routine. Finally, monitoring eosinopenia appears to be a reliable mortality marker.

Mecanismos fisiopatológicos de taquipnea / Physiopathological mechanisms of tachypnea

Tachypnea is a common symptom in respiratory diseases, generally triggered for metabolic compensation purposes. Its presence results from integrated complex mechanisms, both physiological and pathological; for a good clinical approach, it is indispensable to know these mechanisms.

La taquipnea es la manifestación más común de las enfermedades respiratorias y obedece generalmente a una respuesta de compensación metabólica. Su presencia resulta de mecanismos de integración complejos tanto fisiológicos como patológicos que es necesario conocer para el mejor abordaje clínico de un paciente.

[A predictive bacterial infection score according to eosinophil level: An observational study]. / Proposition d'un score prédictif d'infection bactérienne selon le taux d'éosinophiles : étude observationnelle.

INTRODUCTION: Several studies have shown that eosinopenia less than 0.04g/L is a marker of bacterial infection in the presence of unexplained inflammatory syndrome. The aim of our study was to test this hypothesis and to propose a predictive score for bacterial infection (score CIBLE, C reactive protein, bacterial infections, levels of leucocytes and eosinophils). PATIENTS AND METHODS: This was a single-center observational study of patients admitted to an internal medicine department in the year 2015 and presenting with an inflammatory biological syndrome. Patients were divided into 2 groups: bacterial infections (group 1) and nonbacterial inflammatory diseases (group 2). RESULTS: One hundred and ninety patients were included: 92 men (48.4 %) and 98 women (51.6 %). Mean age was 73.5±18.2 years [19-104]. Group 1 consisted of 124 patients (65.2 %) and group 2 of 66 patients (34.8 %). ROC analysis confirmed a cut-off level for eosinophils count at 0.04g/L as discriminant to predict bacterial infection. In a multivariate analysis, the eosinophil/neutrophil ratio, a history of COPD, the C reactive protein concentration, patient age and initial temperature were the most significant variables. They were used to build the CIBLE score. For a score higher than or equal to 87, the probability of a bacterial infection is at least 70 %. CONCLUSION: The CIBLE score appears to be a relevant and inexpensive tool to establish a probability for bacterial infection.

Incommensurately modulated twin structure of nyerereite Na1.64K0.36Ca(CO3)2.

The incommensurately modulated twin structure of nyerereite Na1.64K0.36Ca(CO3)2 has been first determined in the (3 + 1)-dimensional symmetry group Cmcm(α00)00s with modulation vector q = 0.383a*. Unit-cell values are a = 5.062 (1), b = 8.790 (1), c = 12.744 (1) Å. Three orthorhombic components are related by threefold rotation about [001]. Discontinuous crenel functions are used to describe the occupation modulation of Ca and some CO3 groups. The strong displacive modulation of the O atoms in vertexes of such CO3 groups is described using x-harmonics in crenel intervals. The Na, K atoms occupy mixed sites whose occupation modulation is described in two ways using either complementary harmonic functions or crenels. The nyerereite structure has been compared both with the commensurately modulated structure of K-free Na2Ca(CO3)2 and with the widely known incommensurately modulated structure of γ-Na2CO3.

Brain-derived neurotrophic factor of the cerebral microvasculature: a forgotten and nitric oxide-dependent contributor of brain-derived neurotrophic factor in the brain.

AIM: Evidence that brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition, is expressed by cerebral endothelial cells led us to explore in rats the contribution of the cerebral microvasculature to BDNF found in brain tissue and the link between cerebrovascular nitric oxide (NO) and BDNF production. METHODS: Brain BDNF protein levels were measured before and after in situ removal of the cerebral endothelium that was achieved by brain perfusion with a 0.2% CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulphonate) solution. BDNF protein and mRNA levels as well as levels of endothelial NO synthase phosphorylated at serine 1177 (P-eNOSser1177 ) were measured in cerebral microvessel-enriched fractions. These fractions were also exposed to glycerol trinitrate. Hypertension (spontaneously hypertensive rats) and physical exercise training were used as experimental approaches to modulate cerebrovascular endothelial NO production. RESULTS: CHAPS perfusion resulted in a marked decrease in brain BDNF levels. Hypertension decreased and exercise increased P-eNOSser1177 and BDNF protein levels. However, BDNF mRNA levels that were increased by exercise did not change after hypertension. Finally, in vitro exposure of cerebral microvessel-enriched fractions to glycerol trinitrate enhanced BDNF production. CONCLUSION: These data reveal that BDNF levels measured in brain homogenates correspond for a large part to BDNF present in cerebral endothelial cells and that cerebrovascular BDNF production is dependent on cerebrovascular endothelial eNOS activity. They provide a paradigm shift in the cellular source of brain BDNF and suggest a new approach to improve our understanding of the link between endothelial function and cognition.

Multivessel Revascularization Does Not Increase Contrast-Induced Acute Kidney Injury Incidence in Acute Myocardial Infarction: A Meta-Analysis.

BACKGROUND: Recent studies and meta-analysis have shown that complete revascularization (CR) compared with infarct-related artery revascularization (IRA) during percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) is associated with decreased mortality. However, it is unclear if CR versus IRA in STEMI during indexed hospitalization is associated with risk of contrast-induced acute kidney injury (CI-AKI). METHODS: A database search was conducted for all randomized controlled trials that enrolled STEMI patients and compared CR versus IRA and reported CI-AKI. Comprehensive Meta-Analysis Version 2.0 (Wiley, Chichester) was used to determine summary effect size with a fixed-effect model and expressed as a risk ratio with 95 % confidence intervals. RESULTS: A total of four trials were identified and had a mean follow-up of 24.5 ± 9.9 months, a total sample size of 1537, a mean age of 63.8 ± 1.2 versus 64.2 ± 2.1 years, 31.2 ± 5.3 versus 30.1 ± 4.7 % three-vessel disease, and 33.7 ± 4.1 versus 37.2 ± 4.5 % anterior STEMI in the CR versus IRA groups, respectively. A total of 276.7 ± 25.2 versus 186.7 ± 15.3 mL contrast was used in the CR versus IRA respectively (p = 0.006). There were no statistical significant differences between the two groups in the reported incidence of CI-AKI (1.3 % CR vs. 1.9 % IRA; p = 0.4), major bleeding (1.7 % CR vs. 2.5 % IRA; p = 0.4) and stroke (1.1 % CR vs. 0.4 % IRA; p = 0.24). However, there was a significantly increased incidence of cardiovascular death (2.0 % CR vs. 4.7 % IRA; p = 0.01) and ischemia-driven revascularization (6.2 % CR vs. 18.3 % IRA; p < 0.01). CONCLUSION: In the index hospitalization, CR in STEMI patients is associated with significant risk reduction in cardiac death and revascularization and a non-significant reduced trend of CI-AKI, despite increased use of contrast when compared with IRA.

Safety and efficacy of everolimus-eluting bioresorbable vascular scaffolds versus durable polymer everolimus-eluting metallic stents assessed at 1-year follow-up: A systematic review and meta-analysis of studies.

BACKGROUND: The Absorb bioresorbable vascular scaffold (BVS) was developed to address long-term safety issues of metallic drug-eluting stents. However, it may be associated with an increased event risk during the first year. METHODS: A systematic literature search was performed (in MEDLINE/PubMed, Cochrane CENTRAL, EMBASE, and scientific meeting abstracts) to identify studies that compared BVS and cobalt-chromium durable polymer everolimus-eluting stents (EES). For randomized clinical trials and non-randomized propensity score matched studies that reported 1-year outcome data, fixed/random-effects models were used to generate pooled estimates of outcomes, presented as odds ratios (OR) with 95%-confidence intervals (CI). RESULTS: The 1-year follow-up data of 6 trials with 5588 patients were analyzed. A device-oriented composite endpoint (DOCE - cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR)) was reached by 308 BVS or EES patients (195/3253 vs. 113/2315). Meta-analysis showed that patients who received BVS had an increased risk of MI (4.3% vs. 2.3%; OR:1.63, 95%-CI: 1.18-2.25, p<0.01) and definite-or-probable scaffold thrombosis (1.3% vs. 0.6%; OR:2.10, 95%-CI: 1.13-3.87, p=0.02). However, there was no significant between-group difference in risk of DOCE (6.0% vs. 4.9%; OR:1.19, 95%-CI: 0.94-1.52, p=0.16), cardiac death (0.8% vs. 0.7%; OR:1.14, 95%-CI: 0.54-2.39, p=0.73), or TLR (2.5% vs. 2.5%; OR: 0.98, 95%-CI:0.69-1.40, p=0.92). CONCLUSIONS: During the first year of follow-up, patients treated with BVS had a higher incidence of MI and scaffold thrombosis. The risk of DOCE was not significantly different. As BVS may pay off later, future robust data on long-term clinical outcome will be of paramount importance.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[Amyloidosis: Up-to-date]. / Actualités sur les amyloses.

Amyloidosis is mainly a systemic disease belonging to protein-folding diseases. The past 10 years have shown significant progress in typing and the clinical management of amyloidosis, in the identification of novel prognostic markers for risk-stratification, and also in the development of new therapeutic agents. Biological molecular techniques are now able to type amyloidosis which were unidentified. Cardiac MRI and biomarkers allow a precise risk-stratification, especially in AL amyloidosis. If necessary, this prognostic evaluation may lead to rapid changes in the chemotherapy treatment. Emerging treatments rely on biotherapies, gene therapy, immunotherapy and blocking analogous agents. They give hope about an increase of survival of patients with systemic amyloidosis.

Polypharmacy in Older Adults With Hypertension: A Comprehensive Review.

Older adults are more likely to take more than two medications for medical conditions, and polypharmacy is associated with increased risk of adverse events (fall injury, hyperkalemia and hypokalemia, heart failure, and blood pressure exacerbation), polypharmacy mismanagement, drug-drug interaction, and increased costs. Knowledge of drugs that interact with known antihypertensive agents is paramount to avoiding or reducing adverse events, hospitalizations, and health care dollars. Innovative approaches such as use of a fixed-dose combination pill, ingestible sensor system, electronic reminder system, medical audits, and the integration of a pharmacist in the care of patients should be implemented to avoid polypharmacy mismanagement.