Evaluation of Toll-like Receptor 4 (TLR4) Involvement in Human Atrial Fibrillation: A Computational Study.

In the present study, we have explored the involvement of Toll-like Receptor 4 (TLR4) in atrial fibrillation (AF), by using a meta-analysis of publicly available human transcriptomic data. The meta-analysis revealed 565 upregulated and 267 downregulated differentially expressed genes associated with AF. Pathway enrichment analysis highlighted a significant overrepresentation in immune-related pathways for the upregulated genes. A significant overlap between AF differentially expressed genes and TLR4-modulated genes was also identified, suggesting the potential role of TLR4 in AF-related transcriptional changes. Additionally, the analysis of other Toll-like receptors (TLRs) revealed a significant association with TLR2 and TLR3 in AF-related gene expression patterns. The examination of MYD88 and TICAM1, genes associated with TLR4 signalling pathways, indicated a significant yet nonspecific enrichment of AF differentially expressed genes. In summary, this study offers novel insights into the molecular aspects of AF, suggesting a pathophysiological role of TLR4 and other TLRs. By targeting these specific receptors, new treatments might be designed to better manage AF, offering hope for improved outcomes in affected patients.

Stearate-Coated Biogenic Calcium Carbonate from Waste Seashells: A Sustainable Plastic Filler.

Waste seashells from aquaculture are a massive source of biogenic calcium carbonate (bCC) that can be a potential substitute for ground calcium carbonate and precipitated calcium carbonate. These last materials find several applications in industry after a surface coating with hydrophobic molecules, with stearate as the most used. Here, we investigate for the first time the capability of aqueous stearate dispersions to coat bCC powders from seashells of market-relevant mollusc aquaculture species, namely the oyster Crassostrea gigas, the scallop Pecten jacobaeus, and the clam Chamelea gallina. The chemical-physical features of bCC were extensively characterized by different analytical techniques. The results of stearate adsorption experiments showed that the oyster shell powder, which is the bCC with a higher content of the organic matrix, showed the highest adsorption capability (about 23 wt % compared to 10 wt % of geogenic calcite). These results agree with the mechanism proposed in the literature in which stearate adsorption mainly involves the formation of calcium stearate micelles in the dispersion before the physical adsorption. The coated bCC from oyster shells was also tested as fillers in an ethylene vinyl acetate compound used for the preparation of shoe soles. The obtained compound showed better mechanical performance than the one prepared using ground calcium. In conclusion, we can state that bCC can replace ground and precipitated calcium carbonate and has a higher stearate adsorbing capability. Moreover, they represent an environmentally friendly and sustainable source of calcium carbonate that organisms produce by high biological control over composition, polymorphism, and crystal texture. These features can be exploited for applications in fields where calcium carbonate with selected features is required.

A New Approach for Bioremediation of Olive Mill Wastewaters: Combination of Straw Filtration and Nanofiltration.

A combination of straw filtration and nanofiltration was investigated for the first time as a sustainable approach aimed at valorizing olive mill wastewaters (OMWs) within a circular economy strategy. Ground straw filters with different granulometry (120, 250 and 500 µm) were tested in the first step to clarify the raw wastewater. The 500 µm filter offered the best performance due to a lower exposed surface of the filtering fibers and a shorter filtering time, allowing us to reduce about 70% of the chemical oxygen demand (COD) of the raw wastewater. Three different commercial membranes in a flat-sheet configuration with a molecular weight cut-off (MWCO) in the range 150-500 Da were tested to fractionate the clarified wastewater according to a dead-end configuration. Among the investigated membranes, a polymeric membrane of 500 Da (NFA-12A) exhibited the highest productivity in selected operating conditions (steady-state values of 11.4 L/m2 h at 20 bar and 24 ± 2 °C). In addition, flux decays for this membrane were lower than the other two tested membranes, indicating a lower propensity to fouling phenomena. Higher rejections towards total polyphenols and total antioxidant activity (TAA) (76.6% and 73.2%, respectively) were also observed for this membrane. Flavanols and hydroxycinnamic acids were retained by more than 99%. The combination of straw filtration and NF with the NFA-12A membrane allowed us to reduce the COD of raw OMWs up to 97.6%. The retentate fraction of this membrane exhibited a TAA of 18.9 ± 0.7 mM Trolox, supporting its propensity for the development of innovative formulations of interest in food and nutraceutical applications.

Out of Touch.

This Viewpoint discusses the role of touch in medical tradition and its importance in medicine today.

Pathophysiological Hypothesis of COVID-19 Psychosis.

ABSTRACT: In December 2019, a new coronavirus called SARS-CoV-2 was discovered in patients with pneumonia of unknown cause. Although respiratory symptoms mainly characterize infection by this virus, neuropsychiatric manifestations of the disease are becoming more and more frequent. Among them, the appearance of psychotic outbreaks in patients experiencing the infection or after a short time after it has resolved is remarkable. This narrative review aims to describe the possible relationship between SARS-CoV-2 and the onset of psychosis by developing the neurotropic capacities of the virus and analyzing the neurobiology of psychoses.

In Silico Analysis Reveals the Modulation of Ion Transmembrane Transporters in the Cerebellum of Alzheimer's Disease Patients.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. AD hallmarks are extracellular amyloid ß (Aß) plaques and intracellular neurofibrillary tangles in the brain. It is interesting to notice that Aß plaques appear in the cerebellum only in late stages of the disease, and then it was hypothesized that it can be resistant to specific neurodegenerative mechanisms. However, the role of cerebellum in AD pathogenesis is not clear yet. In this study, we performed an in silico analysis to evaluate the transcriptional profile of cerebellum in AD patients and non-AD subjects in order to deepen the knowledge on its role in AD. The analysis evidenced that only the molecular function (MF) "active ion transmembrane transporter activity" was overrepresented. Regarding the 21 differentially expressed genes included in this MF, some of them may be involved in the ion dyshomeostasis reported in AD, while others assumed, in the cerebellum, an opposite regulation compared to those reported in other brain regions in AD patients. They might be associated to a protective phenotype, that may explain the initial resistance of cerebellum to neurodegeneration in AD. Of note, this MF was not overrepresented in prefrontal cortex and visual cortex indicating that it is a peculiarity of the cerebellum.

Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective.

According to the Geroscience concept that organismal aging and age-associated diseases share the same basic molecular mechanisms, the identification of biomarkers of age that can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) age is becoming of paramount importance. These people will be in fact at higher (or lower) risk for many different age-associated diseases, including cardiovascular diseases, neurodegeneration, cancer, etc. In turn, patients suffering from these diseases are biologically older than healthy age-matched individuals. Many biomarkers that correlate with age have been described so far. The aim of the present review is to discuss the usefulness of some of these biomarkers (especially soluble, circulating ones) in order to identify frail patients, possibly before the appearance of clinical symptoms, as well as patients at risk for age-associated diseases. An overview of selected biomarkers will be discussed in this regard, in particular we will focus on biomarkers related to metabolic stress response, inflammation, and cell death (in particular in neurodegeneration), all phenomena connected to inflammaging (chronic, low-grade, age-associated inflammation). In the second part of the review, next-generation markers such as extracellular vesicles and their cargos, epigenetic markers and gut microbiota composition, will be discussed. Since recent progresses in omics techniques have allowed an exponential increase in the production of laboratory data also in the field of biomarkers of age, making it difficult to extract biological meaning from the huge mass of available data, Artificial Intelligence (AI) approaches will be discussed as an increasingly important strategy for extracting knowledge from raw data and providing practitioners with actionable information to treat patients.

Growth and Primary Metabolism of Lettuce Seedlings (Lactuca sativa L.) Are Promoted by an Innovative Iron-Based Fenton-Composted Amendment.

Information regarding the physiological and molecular plant responses to the treatment with new biofertilizers is limited. In this study, a fast-composting soil amendment obtained from solid waste by means of a Fenton reaction was assessed to evaluate the effects on the growth of Lactuca sativa L. var. longifolia seedlings. Growth rate, root biomass, chlorophyll concentration, and total soluble proteins of seedlings treated with the 2% fast-composting soil amendment showed significant increases in comparison with the control seedlings. Proteomic analysis revealed that the soil amendment induced the up-regulation of proteins belonging to photosynthesis machinery, carbohydrate metabolism, and promoted energy metabolism. Root proteomics indicated that the fast-composting soil amendment strongly induced the organs morphogenesis and development; root cap development, lateral root formation, and post-embryonic root morphogenesis were the main biological processes enriched by the treatment. Overall, our data suggest that the addition of the fast-composting soil amendment formulation to the base soils might ameliorate plant growth by inducing carbohydrate primary metabolism and the differentiation of a robust root system.

The Role of Cannabinoid Type 2 Receptors in Parkinson's Disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disease and currently represents a clear unmet medical need. Therefore, novel preventive and therapeutic strategies are needed. Cannabinoid type 2 (CB2) receptors, one of the components of the endocannabinoid system, can regulate neuroinflammation in PD. Here, we review the current preclinical and clinical studies investigating the CB2 receptors in PD with the aim to clarify if these receptors could have a role in PD. Preclinical data show that CB2 receptors could have a neuroprotective action in PD and that the therapeutic targeting of CB2 receptors could be promising. Indeed, it has been shown that different CB2 receptor-selective agonists exert protective effects in different PD models. Moreover, the alterations in the expression of CB2 receptors observed in brain tissues from PD animal models and PD patients suggest the potential value of CB2 receptors as possible novel biomarkers for PD. However, to date, there is no direct evidence of the role of CB2 receptors in PD. Further studies are strongly needed in order to fully clarify the role of CB2 receptors in PD and thus pave the way to novel possible diagnostic and therapeutic opportunities for PD.

Inosine in Neurodegenerative Diseases: From the Bench to the Bedside.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), currently represent major unmet medical needs. Therefore, novel therapeutic strategies are needed in order to improve patients' quality of life and prognosis. Since oxidative stress can be strongly involved in neurodegenerative diseases, the potential use of inosine, known for its antioxidant properties, in this context deserves particular attention. The protective action of inosine treatment could be mediated by its metabolite urate. Here, we review the current preclinical and clinical studies investigating the use of inosine in AD, PD, ALS, and MS. The most important properties of inosine seem to be its antioxidant action and its ability to raise urate levels and to increase energetic resources by improving ATP availability. Inosine appears to be generally safe and well tolerated; however, the possible formation of kidney stones should be monitored, and data on its effectiveness should be further explored since, so far, they have been controversial. Overall, inosine could be a promising potential strategy in the management of neurodegenerative diseases, and additional studies are needed in order to further investigate its safety and efficacy and its use as a complementary therapy along with other approved drugs.

The Role of Cytotoxic T-Lymphocyte Antigen 4 in the Pathogenesis of Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system that presents heterogeneous clinical manifestations and course. It has been shown that different immune checkpoints, including Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), can be involved in the pathogenesis of MS. CTLA-4 is a critical regulator of T-cell homeostasis and self-tolerance and represents a key inhibitor of autoimmunity. In this scopingreview, we resume the current preclinical and clinical studies investigating the role of CTLA-4 in MS with different approaches. While some of these studies assessed the expression levels of CTLA-4 on T cells by comparing MS patients with healthy controls, others focused on the evaluation of the effects of common MS therapies on CTLA-4 modulation or on the study of the CTLA-4 blockade or deficiency in experimental autoimmune encephalomyelitis models. Moreover, other studies in this field aimed to discover if the CTLA-4 gene might be involved in the predisposition to MS, whereas others evaluated the effects of treatment with CTLA4-Ig in MS. Although these results are of great interest, they are often conflicting. Therefore, further studies are needed to reveal the exact mechanisms underlying the action of a crucial immune checkpoint such as CTLA-4 in MS to identify novel immunotherapeutic strategies for MS patients.

Effects of Prone Position on Lung Recruitment and Ventilation-Perfusion Matching in Patients With COVID-19 Acute Respiratory Distress Syndrome: A Combined CT Scan/Electrical Impedance Tomography Study.

OBJECTIVES: Prone positioning allows to improve oxygenation and decrease mortality rate in COVID-19-associated acute respiratory distress syndrome (C-ARDS). However, the mechanisms leading to these effects are not fully understood. The aim of this study is to assess the physiologic effects of pronation by the means of CT scan and electrical impedance tomography (EIT). DESIGN: Experimental, physiologic study. SETTING: Patients were enrolled from October 2020 to March 2021 in an Italian dedicated COVID-19 ICU. PATIENTS: Twenty-one intubated patients with moderate or severe C-ARDS. INTERVENTIONS: First, patients were transported to the CT scan facility, and image acquisition was performed in prone, then supine position. Back to the ICU, gas exchange, respiratory mechanics, and ventilation and perfusion EIT-based analysis were provided toward the end of two 30 minutes steps (e.g., in supine, then prone position). MEASUREMENTS AND MAIN RESULTS: Prone position induced recruitment in the dorsal part of the lungs (12.5% ± 8.0%; p < 0.001 from baseline) and derecruitment in the ventral regions (-6.9% ± 5.2%; p < 0.001). These changes led to a global increase in recruitment (6.0% ± 6.7%; p < 0.001). Respiratory system compliance did not change with prone position (45 ± 15 vs 45 ± 18 mL/cm H2O in supine and prone position, respectively; p = 0.957) suggesting a decrease in atelectrauma. This hypothesis was supported by the decrease of a time-impedance curve concavity index designed as a surrogate for atelectrauma (1.41 ± 0.16 vs 1.30 ± 0.16; p = 0.001). Dead space measured by EIT was reduced in the ventral regions of the lungs, and the dead-space/shunt ratio decreased significantly (5.1 [2.3-23.4] vs 4.3 [0.7-6.8]; p = 0.035), showing an improvement in ventilation-perfusion matching. CONCLUSIONS: Several changes are associated with prone position in C-ARDS: increased lung recruitment, decreased atelectrauma, and improved ventilation-perfusion matching. These physiologic effects may be associated with more protective ventilation.

The PI3K/Akt/mTOR pathway: A potential pharmacological target in COVID-19.

Coronavirus disease 2019 (COVID-19) has emerged as a serious threat to global health. The disregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) cell signaling pathway observed in patients with COVID-19 has attracted attention for the possible use of specific inhibitors of this pathway for the treatment of the disease. Here, we review emerging data on the involvement of the PI3K/Akt/mTOR pathway in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the clinical studies investigating its tailored inhibition in COVID-19. Current in silico, in vitro, and in vivo data convergently support a role for the PI3K/Akt/mTOR pathway in COVID-19 and suggest the use of specific inhibitors of this pathway that, by a combined mechanism entailing downregulation of excessive inflammatory reactions, cell protection, and antiviral effects, could ameliorate the course of COVID-19.

Respiratory Drive in Patients with Sepsis and Septic Shock: Modulation by High-flow Nasal Cannula.

BACKGROUND: Experimental and pilot clinical data suggest that spontaneously breathing patients with sepsis and septic shock may present increased respiratory drive and effort, even in the absence of pulmonary infection. The study hypothesis was that respiratory drive and effort may be increased in septic patients and correlated with extrapulmonary determinant and that high-flow nasal cannula may modulate drive and effort. METHODS: Twenty-five nonintubated patients with extrapulmonary sepsis or septic shock were enrolled. Each patient underwent three consecutive steps: low-flow oxygen at baseline, high-flow nasal cannula, and then low-flow oxygen again. Arterial blood gases, esophageal pressure, and electrical impedance tomography data were recorded toward the end of each step. Respiratory effort was measured as the negative swing of esophageal pressure (ΔPes); drive was quantified as the change in esophageal pressure during the first 500 ms from start of inspiration (P0.5). Dynamic lung compliance was calculated as the tidal volume measured by electrical impedance tomography, divided by ΔPes. The results are presented as medians [25th to 75th percentile]. RESULTS: Thirteen patients (52%) were in septic shock. The Sequential Organ Failure Assessment score was 5 [4 to 9]. During low-flow oxygen at baseline, respiratory drive and effort were elevated and significantly correlated with arterial lactate (r = 0.46, P = 0.034) and inversely with dynamic lung compliance (r = -0.735, P < 0.001). Noninvasive support by high-flow nasal cannula induced a significant decrease of respiratory drive (P0.5: 6.0 [4.4 to 9.0] vs. 4.3 [3.5 to 6.6] vs. 6.6 [4.9 to 10.7] cm H2O, P < 0.001) and effort (ΔPes: 8.0 [6.0 to 11.5] vs. 5.5 [4.5 to 8.0] vs. 7.5 [6.0 to 12.6] cm H2O, P < 0.001). Oxygenation and arterial carbon dioxide levels remained stable during all study phases. CONCLUSIONS: Patients with sepsis and septic shock of extrapulmonary origin present elevated respiratory drive and effort, which can be effectively reduced by high-flow nasal cannula.

Prevalence of stress, burnout syndrome, anxiety and depression among physicians of a teaching hospital during the COVID-19 pandemic. / Prevalencia de estrés, síndrome de desgaste profesional, ansiedad y depresión en médicos de un hospital universitario durante la pandemia de COVID-19.

INTRODUCTION: Health care workers experience a tremendous strain while performing their activities, very frequently leading to stress, burnout syndrome, and psychopathological impact. The COVID-19 pandemic may cause physicians to suffer these effects even to a greater extent. Our objective was to describe the frequency of stress, burnout syndrome, anxiety, and depression during the pandemic, and analyze the associations with different independent outcome measures. METHODS: Observational, cross-sectional study conducted 2 months after the lockdown was established in Argentina. Clinical specialists, surgeons, emergency physicians, and those with no direct contact with patients were surveyed using a sociodemographic questionnaire and 3 self-administered inventories: Health Professions Stress Inventory, Maslach Burnout Inventory, and Hospital Anxiety and Depression Scale. RESULTS: The prevalence of stress was 93.7 % (95 % confidence interval [CI]: 90.33-96.2), burnout syndrome 73.5 % (95 % CI: 68.2-78.4), anxiety 44 % (95 % CI: 38.4-49.8), and depression 21.9 % (95 % CI: 17.3-26.9). No association was observed between the frequency and medical specialty. The frequency of burnout syndrome, anxiety, and depression was significantly higher among residents and physicians working in the emergency department. CONCLUSIONS: Residents and emergency physicians working 24-hour shifts showed significantly higher percentages of burnout syndrome, anxiety, and depression compared to staff and head physicians. These findings may be associated with a higher workload and less experience. It is compulsory to take preventive and therapeutic measures to protect those in the pandemic front line.

Introducción. Los trabajadores de la salud se encuentran sometidos a una gran tensión en el desarrollo de sus actividades, lo que genera alta frecuencia de estrés, desgaste laboral e impacto psicopatológico. La pandemia de COVID-19 podría provocar un incremento de estas entidades en los médicos. El objetivo fue describir la frecuencia de estrés, síndrome de desgaste profesional (burnout), ansiedad y depresión durante la pandemia, y analizar las asociaciones con distintas variables independientes. Métodos. Estudio observacional, transversal, realizado dos meses después del inicio de la cuarentena en Argentina. Se encuestó a médicos de especialidades clínicas, quirúrgicas, solo de emergencias, y a aquellos sin contacto directo con pacientes, mediante un cuestionario sociodemográfico y tres inventarios autoadministrados: Health Professions Stress Inventory, Maslach Burnout Inventory y la Escala de ansiedad y depresión hospitalaria. Resultados. La prevalencia de estrés fue del 93,7 % (IC95 %: 90,33-96,2), burnout 73,5 % (IC95 %: 68,2-78,4), ansiedad 44 % (IC95 %: 38,4- 49,8) y depresión 21,9 % (IC95 %: 17,3-26,9). No se observó asociación entre la frecuencia y el tipo de especialidad realizada. La frecuencia de burnout, ansiedad y depresión fue significativamente mayor en los médicos residentes y en aquellos que trabajan en emergencias. Conclusiones. Los médicos residentes y quienes trabajan en emergencias en turnos de 24 horas mostraron porcentajes significativamente más altos de burnout, ansiedad y depresión, en comparación con médicos de planta y con aquellos en posiciones de liderazgo. Estos hallazgos pueden estar asociados con una mayor carga de trabajo y una menor experiencia. Es mandatorio tomar medidas preventivas y terapéuticas para preservar a quienes hacen frente a esta pandemia. Palabras clave: COVID-19.

Water-Based Aerosol for Book Deacidification: Experimental Apparatus and Theoretical Interpretation of Results.

One of the major problems in book conservation is the long-term deconstructive effect of acidity introduced into the paper by several additives, which, in the presence of humidity, generates a hydrogen cation with a strong catalytic role in cellulose depolymerization. Many types of treatment have been used in the past, but up to now, research for less-invasive, fast and cheap methods is still vividly ongoing. In this study, an approach to book deacidification is presented, where alkaline water solutions are administered to bound books in the form of micrometer-sized aerosol droplets, without using vacuum apparatus accessories. Alkaline clouds treatments were alternated with gentle air fluxes of drying steps. Few cycles are required to achieve uniform deacidification of books. The treatment could be conducted with proper apparatus on large volumes, resulting in rapid treatment time and low cost. The titration curve reporting the variation of book pH, with respect to the amount of absorbed alkaline aerosol, was built and interpreted in terms of a chemical model for the neutralization process. FTIR, PXRD and XRF spectroscopies were used to characterize the book chemistry. The effects of the treatment on the book were evaluated by measuring the degree of polymerization (DP) of the paper and the colorimetric coordinates of the paper and ink. Artificial aging tests revealed a general increase in the aging stability of the deacidified paper samples with respect to the untreated samples. Finally, the alkaline reserve data are discussed.

Modified Technique for Wirsung-Pancreatogastric Anastomosis after Pancreatoduodenectomy: A Single Center Experience and Systematic Review of the Literature.

BACKGROUND: The mortality rate following pancreaticoduodenectomy (PD) has been decreasing over the past few years; nonetheless, the morbidity rate remains elevated. The most common complications after PD are post-operative pancreatic fistula (POPF) and delayed gastric emptying (DGE) syndrome. The issue as to which is the best reconstruction method for the treatment of the pancreatic remnant after PD is still a matter of debate. The aim of this study was to retrospectively analyze the morbidity rate in 100 consecutive PD reconstructed with Wirsung-Pancreato-Gastro-Anastomosis (WPGA), performed by a single surgeon applying a personal modification of the pancreatic reconstruction technique. METHODS: During an 8-year period (May 2012 to March 2020), 100 consecutive patients underwent PD reconstructed with WPGA. The series included 57 males and 43 females (M/F 1.32), with a mean age of 68 (range 41-86) years. The 90-day morbidity and mortality were retrospectively analyzed. Additionally, a systematic review was conducted, comparing our technique with the existing literature on the topic. RESULTS: We observed eight cases of clinically relevant POPF (8%), three cases of "primary" DGE (3%) and four patients suffering "secondary" DGE. The surgical morbidity and mortality rate were 26% and 6%, respectively. The median hospital stay was 13.6 days. The systematic review of the literature confirmed the originality of our modified technique for Wirsung-Pancreato-Gastro-Anastomosis. CONCLUSIONS: Our modified double-layer WPGA is associated with a very low incidence of POPF and DGE. Also, the technique avoids the risk of acute hemorrhage of the pancreatic parenchyma.

Cardiac Imaging in Athlete's Heart: The Role of the Radiologist.

Athlete's heart (AH) is the result of morphological and functional cardiac modifications due to long-lasting athletic training. Athletes can develop very marked structural myocardial changes, which may simulate or cover unknown cardiomyopathies. The differential diagnosis between AH and cardiomyopathy is necessary to prevent the risk of catastrophic events, such as sudden cardiac death, but it can be a challenging task. The improvement of the imaging modalities and the introduction of the new technologies in cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) can allow overcoming this challenge. Therefore, the radiologist, specialized in cardiac imaging, could have a pivotal role in the differential diagnosis between structural adaptative changes observed in the AH and pathological anomalies of cardiomyopathies. In this review, we summarize the main CMR and CCT techniques to evaluate the cardiac morphology, function, and tissue characterization, and we analyze the imaging features of the AH and the key differences with the main cardiomyopathies.

Unmatched ventilation and perfusion measured by electrical impedance tomography predicts the outcome of ARDS.

BACKGROUND: In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO2/FiO2 and compliance. METHODS: Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units. RESULTS: Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27-47]% vs. 21[17-27]%, p < 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07-1.39, p = 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79-0.97, p < 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 [27-38]% vs. 18 [13-21]%, p < 0.001), while the opposite was true for perfusion (28 [22-38]% vs. 36 [32-44]%, p < 0.001). Higher percentage of only perfused units was correlated with lower dorsal ventilation (r = - 0.486, p < 0.001) and with lower PaO2/FiO2 ratio (r = - 0.293, p = 0.039). CONCLUSIONS: EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.

Prevalencia de estrés, síndrome de desgaste profesional, ansiedad y depresión en médicos de un hospital universitario durante la pandemia de COVID-19 / Prevalence of stress, burnout syndrome, anxiety and depression among physicians of a teaching hospital during the COVID-19 pandemic

Introducción. Los trabajadores de la salud se encuentran sometidos a una gran tensión en el desarrollo de sus actividades, lo que genera alta frecuencia de estrés, desgaste laboral e impacto psicopatológico. La pandemia de COVID-19 podría provocar un incremento de estas entidades en los médicos. El objetivo fue describir la frecuencia de estrés, síndrome de desgaste profesional (burnout), ansiedad y depresión durante la pandemia, y analizar las asociaciones con distintas variables independientes. Métodos. Estudio observacional, transversal, realizado dos meses después del inicio de la cuarentena en Argentina. Se encuestó a médicos de especialidades clínicas, quirúrgicas, solo de emergencias, y a aquellos sin contacto directo con pacientes, mediante un cuestionario sociodemográfico y tres inventarios autoadministrados: Health Professions Stress Inventory, Maslach Burnout Inventory y la Escala de ansiedad y depresión hospitalaria. Resultados. La prevalencia de estrés fue del 93,7 % (IC95 %: 90,33-96,2), burnout 73,5 % (IC95 %: 68,2-78,4), ansiedad 44 % (IC95 %: 38,4-49,8) y depresión 21,9 % (IC95 %: 17,3-26,9). No se observó asociación entre la frecuencia y el tipo de especialidad realizada. La frecuencia de burnout, ansiedad y depresión fue significativamente mayor en los médicos residentes y en aquellos que trabajan en emergencias. Conclusiones. Los médicos residentes y quienes trabajan en emergencias en turnos de 24 horas mostraron porcentajes significativamente más altos de burnout, ansiedad y depresión, en comparación con médicos de planta y con aquellos en posiciones de liderazgo. Estos hallazgos pueden estar asociados con una mayor carga de trabajo y una menor experiencia. Es mandatorio tomar medidas preventivas y terapéuticas para preservar a quienes hacen frente a esta pandemia.

Introduction. Health care workers experience a tremendous strain while performing their activities, very frequently leading to stress, burnout syndrome, and psychopathological impact. The COVID-19 pandemic may cause physicians to suffer these effects even to a greater extent. Our objective was to describe the frequency of stress, burnout syndrome, anxiety, and depression during the pandemic, and analyze the associations with different independent outcome measures. Methods. Observational, cross-sectional study conducted 2 months after the lockdown was established in Argentina. Clinical specialists, surgeons, emergency physicians, and those with no direct contact with patients were surveyed using a sociodemographic questionnaire and 3 self-administered inventories: Health Professions Stress Inventory, Maslach Burnout Inventory, and Hospital Anxiety and Depression Scale. Results. The prevalence of stress was 93.7 % (95 % confidence interval [CI]: 90.33-96.2), burnout syndrome 73.5 % (95 % CI: 68.2-78.4), anxiety 44 % (95 % CI: 38.4-49.8), and depression 21.9 % (95 % CI: 17.3-26.9). No association was observed between the frequency and medical specialty. The frequency of burnout syndrome, anxiety, and depression was significantly higher among residents and physicians working in the emergency department. Conclusions. Residents and emergency physicians working 24-hour shifts showed significantly higher percentages of burnout syndrome, anxiety, and depression compared to staff and head physicians. These findings may be associated with a higher workload and less experience. It is compulsory to take preventive and therapeutic measures to protect those in the pandemic front line.