Satisfacción profesional: Encuesta a profesionales con especialidad en clínica médica / Professional satisfaction: Survey of professionals specialized in clinical medicine

La satisfacción laboral es un tema de interés en los servicios de salud ya que existe relación entre el grado de calidad de los servicios ofrecidos y el nivel de satisfacción de lxs profesionales que trabajan en él. Es importante para nuestra especialidad y nuestro desempeño laboral conocer el grado de satisfacción que tienen lxs médicxs clínicxs con la especialidad, con la retribución económica que perciben y qué factores personales y laborales pueden afectar estas variables. Diseñamos este trabajo para conocer en mayor profundidad quienes somos lxs que ejercemos la atención clínica de lxs pacientes y cómo vemos distintos aspectos de nuestra especialidad, entre ellos la satisfacción profesional y la retribución económica. Los objetivos del trabajo son: o Conocer el grado de satisfacción que tienen lxs médicxs clínicxs con la especialidad. o Identificar si existen diferencias entre el grado de satisfacción que tienen lxs médicxs clínicos con la especialidad. o Conocer el grado de satisfacción que tienen lxs médicxs clínicxs con la retribución económica que perciben. o Identificar si existen diferencias entre el grado de satisfacción que tienen lxs médicxs clínicxs con la retribución económica. o Conocer la percepción de lxs médicxs clínicos sobre las causas del panorama retributivo actual. o Identificar la relación entre la satisfacción con la especialidad y la satisfacción económica. MATERIAL Y MÉTODOS: Estudio de corte transversal, observacional, descriptivo, a través de un cuestionario online difundido a médicxs clínicxs a través de redes sociales y otros medios de difusión entre el 26/05/22 y el 12/07/22. Población: Médicxs que trabajan en Argentina que ejercen como médicxs clínicxs. Análisis Estadístico: análisis descriptivo de los datos mediante medidas de tendencia central para las variables numéricas y frecuencias relativas para las variables categóricas. Asociaciones entre las variables independientes con las variables principales utilizando chi cuadrado y grado de probabilidad con test de Fisher. RESULTADOS: 524 médicos, 318 mujeres (61,4%) y 200 hombres (38,6%), de 25 a 75 años, edad promedio: 41 años Satisfacción con la especialidad: 75,5% (395) muy/bastantes satisfechos, 24,5% (127) algo/nada satisfechos. Sin diferencias significativas entre edad, género, años de ejercicio profesional, carga laboral, número de instituciones en las que trabajan, médicxs en formación con médicxs con especialidad finalizada. Mayor satisfacción con la especialidad en médicxs que volverían a elegir la especialidad (89% muy/bastante vs 46%, (OR 9, IC 5-14, p <0,00001), en médicxs que no se irían a otro país (85% vs 69%, OR 2.38, IC 1.52-3,7; p<0.0001) y en médicxs que realizaron recertificación (82% vs 72%, OR 1.73, IC 1.09-2.76, p<0,01). Retribución económica: 87% (454) poco/nada satisfechxs, 13% (69) muy/bastante satisfechxs. Mayor satisfacción en retribución económica con diferencias estadísticamente significativas en mayores a 40 años (16% de mayores a 40 años muy/bastante satisfechxs vs 9% de menores a 40 años, OR 1.8, IC 1.08-3.14, p<0.01), hombres (17% muy/bastante satisfechos vs 10% de las mujeres OR 1.7, IC 1.02-2.85, p 0.02), lxs que volverían a elegir la especialidad (17% muy/bastante satisfechos vs 3% en los que no volverían a elegir, OR 5.4, IC 2.3-12, p 0), lxs que no se irían a ejercer a otro país (21% muy/bastante satisfechxs vs 7% de lxs que no se irían, OR 3.6, IC 2.1-6.22, p 0), lxs que realizaron recertificación (18% muy/bastante satisfechxs vs 11% en lxs que no recertificaron, OR 1.73; IC 1.03-2.92; p <0,02). Al comparar las 2 variables principales: satisfacción con la especialidad y con la retribución económica vemos que de lxs médicxs que se encuentran muy o bastante satisfechxs con la especialidad, el 83% se encuentra poco o nada satisfecho con la retribución económica, 16,5% muy o bastante satisfecho con la misma. De lxs médicxs que se encuentran poco o nada satisfechxs con la especialidad, el 97% están poco o nada satisfechxs con la retribución económica, mientras que sólo el 3% se encuentran muy o bastante satisfechxs con la misma, siendo esta diferencia estadísticamente significativa (OR 6, IC 2.1-16.9, p 0). CONCLUSIÓN: Como resultado de esta encuesta y los datos analizados, podemos observar que el 75% de lxs médicxs clínicxs encuestadxs se encuentran satisfechxs con la especialidad. Sin embargo, el 87% de lxs encuestadxs no se encuentran satisfechxs con la retribución económica percibida, especialmente esto último en los médicxs más jóvenes y las mujeres. El 69% volvería a elegir la especialidad, estando este grupo más satisfechxs con la especialidad (89%) y con la retribución económica (17%).

Introduction: In recent years, we have observed an increasingly fragmented medicine, with doctors graduating from universities and desisting from training in fundamental "core" medical specialties, preferring subspecialties instead. This article arises from questions that stem from this observation. Objectives and methods: The general objective of this work is to assess the motivation of clinicians in the Argentine Republic and identify key determinants. This involves understanding their satisfaction with the specialization and financial remuneration, gauging whether they would choose internal medicine again, or if they would practice their profession abroad. This is a mixed qualitative-quantitative, descriptive, analytical, cross-sectional study, conducted in Argentina. It was based on an online survey administered to medical specialists in clinical medicine or those currently undergoing training, conducted between May and July 2022. Results: Data suggestive of positive motivation were taken to include satisfaction with the specialty and the potential desire to choose it again. On the other hand, negative motivation was identified by dissatisfaction with the specialty, a preference not to choose it again, the desire to leave the country, and dissatisfaction with remuneration. Discussion: It was observed that 3 out of 10 clinicians, even though satisfied with the specialty, would not choose it again, and 6 out of 10 would choose to leave the country. Within this latter group, dissatisfaction with remuneration emerged as a significantly stronger determinant compared to the other groups. In conclusion, while assessing the motivational level of clinicians in Argentina proves to be a very complex task, this study underscores a high level of positive motivation towards the specialization. However, material conditions such as dissatisfaction with remuneration, multiple employments, and work overload lead to an important level of disillusionment, contributing to negative motivation.

Odds of COVID-19-associated asthma exacerbations in children higher during Omicron wave.

BACKGROUND: We aimed to determine the association of COVID-19 variant wave with asthma exacerbations in children with asthma. METHODS: We conducted a retrospective cross-sectional study of children in the Western Pennsylvania COVID-19 Registry (WPACR). We extracted data for all children in the WPACR with asthma and compared their acute clinical presentation and outcomes during the Pre-Delta (7/1/20-6/30/21), Delta (8/1/21-12/14/21), and Omicron (12/15/21-8/30/22) waves. We conducted multivariable logistic regression analyses of SARS-CoV-2-associated asthma exacerbations, adjusting for characteristics that have been associated with COVID-19 outcomes in prior studies. RESULTS: Among 573 children with asthma in the WPACR during the study period, the proportion of children with COVID-19 who had an asthma exacerbation was higher during the Omicron wave than during the prior two variant waves (40.2% vs. 22.6% vs. 26.2%, p = 0.002; unadjusted OR = 2.12 [95% confidence interval (CI) = 1.39-3.22], p < 0.001). In our multivariable regression models, the odds of an asthma exacerbation were 2.8 times higher during the Omicron wave than during prior waves (adjusted OR = 2.80 [95% CI = 1.70-4.61]). Results were similar after additionally adjusting for asthma severity but were no longer significant after additionally adjusting for poor asthma control. CONCLUSION: The proportion of children with asthma experiencing an asthma exacerbation during SARS-CoV-2 infection was higher during Omicron than prior variant waves, adding to the body of evidence that COVID-19-associated respiratory symptoms vary by variant. These findings provide additional support for vaccination and prevention.

The Impact of SARS-CoV-2 Infection on Symptom Control and Lung Function in Children with Asthma.

Rationale: Little is known about the long-term impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on children with asthma. Objectives: To determine whether SARS-CoV-2 infection affects symptom control and lung function in children with asthma. Methods: Using data from clinical registries and the electronic health record, we conducted a prospective case-control study of children with asthma aged 6-21 years who had (cases) or did not have (control subjects) SARS-CoV-2 infection, comparing baseline and follow-up asthma symptom control and spirometry within an ∼18-month time frame and, for cases, within 18 months of acute coronavirus disease (COVID-19). Results: A total of 171 cases had baseline and follow-up asthma symptom data, and 114 cases had baseline and follow-up spirometry measurements. There were no significant differences in asthma symptom control (P = 0.50), forced expiratory volume in 1 second (P = 0.47), forced vital capacity (P = 0.43), forced expiratory volume in 1 second/forced vital capacity (P = 0.43), or forced expiratory flow, midexpiratory phase (P = 0.62), after SARS-CoV-2 infection. Compared with control subjects (113 with symptom data and 237 with spirometry data), there were no significant differences in follow-up asthma symptom control or lung function. A similar proportion of cases and control subjects had poorer asthma symptom control (17.5% vs. 9.7%; P = 0.07) or worse lung function (29.0% vs. 32.5%; P = 0.50) at follow-up. Patients whose asthma control worsened after COVID-19 had a shorter time to follow-up (3.5 [1.5-7.5] vs. 6.1 [3.1-9.8] mo; P = 0.007) and were more likely to have presented with an asthma exacerbation during COVID-19 (46% vs. 26%; P = 0.04) than those without worse control. Conclusions: We found no significant differences in asthma symptom control or lung function in youth with asthma up to 18 months after acute COVID-19, suggesting that COVID-19 does not affect long-term asthma severity or control in the pediatric population.

Synergistic combination of aztreonam and ceftazidime/avibactam against resistant Stenotrophomonas maltophilia on pancreatitis.

INTRODUCTION: Stenotrophomonas maltophilia is a Gram-negative, opportunistic pathogen associated with a high morbidity and mortality rate. We report our clinical experience in treating a patient with infected pancreatic necrosis caused by multidrug-resistant (MDR) S. maltophilia with a novel drug combination. CASE REPORT: A 65-year-old male with history of type II diabetes was admitted with acute pancreatitis, voluminous ascites, and signs of sepsis after undergoing an echo-endoscopy procedure with pancreas biopsy to investigate a Wirsung duct dilatation. Retroperitoneal fluid culture revealed S. maltophilia resistant to colistin and with intermediate susceptibility to trimethoprim-sulfamethoxazole and levofloxacin. The synergy between aztreonam (ATM) and ceftazidime/avibactam (CZA) was demonstrated using the combined disk pre-diffusion test. CONCLUSIONS: There are sparse data providing guidance on the optimal regimen against MDR S. maltophilia infections. Although in this case a surgical excision was essential, combination of ATM and CZA provided effective synergistic antimicrobial treatment with clinical cure of severe acute pancreatitis infected with S. maltophilia. The combined disk pre-diffusion test with ATM and CZA requires no special equipment and can be routinely performed in clinical microbiology labs. Combination of ATM with CZA should be considered for cases of MDR S. maltophilia infections with limited treatment options.

Influence of SARS-CoV-2 Status and Aging on the Nasal and Fecal Immunological Profiles of Elderly Individuals Living in Nursing Homes.

In the frame of SARS-CoV-2 infection, studies regarding cytokine profiling of mucosal-related samples are scarce despite being the primary infection sites. The objective of this study was to compare the nasal and fecal inflammatory profiles of elderly individuals living in a nursing home highly affected by COVID-19 (ELD1) with those of elderly individuals living in a nursing home with no cases of SARS-CoV-2 infection (ELD2) and, also, with those of healthy SARS-CoV-2-negative younger adults (YHA). BAFF/TNFSF13B, IL6, IL10 and TNF-α (immunological hallmarks of SARS-CoV-2 infection) were the only immune factors whose concentrations were different in the three groups. Their highest concentrations were achieved in the ELD1 group. Nasal and fecal concentrations of a wide number of pro-inflammatory cytokines were similar in the ELD1 and ELD2 groups but higher than those found in the YHA samples. These results reinforce the hypothesis that immunosenescence and inflammaging rendered the elderly as a highly vulnerable population to a neo-infection, such as COVID-19, which was evidenced during the first pandemic waves.

CRISPR-Directed Gene Editing as a Method to Reduce Chemoresistance in Lung Cancer Cells.

We are advancing a novel strategy for the treatment of solid tumors by employing CRISPR-directed gene editing to reduce levels of standard of care required to halt or reverse the progression of tumor growth. We intend to do this by utilizing a combinatorial approach in which CRISPR-directed gene editing is used to eliminate or significantly reduce the acquired resistance emerging from chemotherapy, radiation therapy, or immunotherapy. We will utilize CRISPR/Cas as a biomolecular tool to disable specific genes involved in the sustainability of resistance to cancer therapy. We have also developed a CRISPR/Cas molecule that can distinguish between the genome of a tumor cell in the genome of a normal cell, thereby conferring target selectivity onto this therapeutic approach. We envision delivering these molecules by direct injection into solid tumors for the treatment of squamous cell carcinomas of the lung, esophageal cancer, and head and neck cancer. We provide experimental details and methodology for utilizing CRISPR/Cas as a supplement to chemotherapy to destroy lung cancer cells.

Actualización en anomalías vasculares de la órbita en pediatría: diagnóstico por imágenes y tratamiento / Update on orbital vascular anomalies in pediatrics: imaging studies and management

Las anomalías vasculares de la órbita (AVO) son un grupo heterogéneo de patologías que pueden presentarse con frecuencia en el cono orbitario, la región periorbitaria o dentro de la órbita misma. Las AVO se dividen en tumores y malformaciones. Su presentación clínica más frecuente es el exoftalmos, asociado o no a alteración del eje visual. Además, pueden presentar complicaciones agudas, como hemorragia intralesional o celulitis entre las más frecuentes, y complicaciones crónicas, como ambliopía y afectación de la agudeza visual a largo plazo. La evolución de las técnicas de imágenes, el uso de nuevos fármacos y la utilización de innovadores procedimientos en radiología intervencionista han posibilitado obtener una mejora significativa en los procesos diagnósticos y terapéuticos de estos pacientes, permitiendo un diagnóstico y tratamiento preciso.

Orbital vascular anomalies (OVAs) are a heterogeneous group of disorders frequently found in the orbital cone, the periorbital region, or within the orbit itself. OVAs are divided into tumors and malformations. The most frequent clinical presentation is exophthalmos, associated or not with an alteration of the visual axis. They may also cause acute complications, being intralesional bleeding or cellulitis the most frequent, and chronic complications, such as amblyopia and long-term visual acuity impairment. The development of imaging techniques, the use of new drugs, and the implementation of innovative procedures in interventional radiology have resulted in a significant improvement in the diagnostic and therapeutic approaches to these patients, essential to an accurate diagnosis and management.

The Effect of Different Combinations of Practice Schedules on Motor Response Stability during Practice.

Many results in motor learning have indicated that relative and absolute timing dimensions are modulated by factors that modify response stability among trials. One of these factors is the combination of constant and variable practices. Although many researchers have investigated the combination of practice schedules, these researchers have used measurements that do not assess performance and motor response separately. This study aimed to investigate the effect of different combinations of practice schedules on motor response stability during practice. Participants performed a sequential key-pressing task with two goals: (1) to learn the relative timing dimension and (2) the absolute timing dimension. Participants were assigned to one of two groups: constant-variable or variable-constant. Our findings indicate an influence of the increase in variability over the practice in the constant-variable group. Precisely, the increase in variability of total time in the second half (constant-variable group) of practice was followed by the maintenance of the same level of cross-correlate between absolute timing error and variability of total time. Finally, our findings support the hypothesis that practicing in a constant schedule favors the relative timing dimension of learning regardless of the order in which the constant practice is provided.

Update on orbital vascular anomalies in pediatrics: imaging studies and management. / Actualización en anomalías vasculares de la órbita en pediatría: diagnóstico por imágenes y tratamiento.

Orbital vascular anomalies (OVAs) are a heterogeneous group of disorders frequently found in the orbital cone, the periorbital region, or within the orbit itself. OVAs are divided into tumors and malformations. The most frequent clinical presentation is exophthalmos, associated or not with an alteration of the visual axis. They may also cause acute complications, being intralesional bleeding or cellulitis the most frequent, and chronic complications, such as amblyopia and long-term visual acuity impairment. The development of imaging techniques, the use of new drugs, and the implementation of innovative procedures in interventional radiology have resulted in a significant improvement in the diagnostic and therapeutic approaches to these patients, essential to an accurate diagnosis and management.

Las anomalías vasculares de la órbita (AVO) son un grupo heterogéneo de patologías que pueden presentarse con frecuencia en el cono orbitario, la región periorbitaria o dentro de la órbita misma. Las AVO se dividen en tumores y malformaciones. Su presentación clínica más frecuente es el exoftalmos, asociado o no a alteración del eje visual. Además, pueden presentar complicaciones agudas, como hemorragia intralesional o celulitis entre las más frecuentes, y complicaciones crónicas, como ambliopía y afectación de la agudeza visual a largo plazo. La evolución de las técnicas de imágenes, el uso de nuevos fármacos y la utilización de innovadores procedimientos en radiología intervencionista han posibilitado obtener una mejora significativa en los procesos diagnósticos y terapéuticos de estos pacientes, permitiendo un diagnóstico y tratamiento preciso.

Multi-Omics-Based Autophagy-Related Untypical Subtypes in Patients with Cerebral Amyloid Pathology.

Recent multi-omics analyses paved the way for a comprehensive understanding of pathological processes. However, only few studies have explored Alzheimer's disease (AD) despite the possibility of biological subtypes within these patients. For this study, unsupervised classification of four datasets (genetics, miRNA transcriptomics, proteomics, and blood-based biomarkers) using Multi-Omics Factor Analysis+ (MOFA+), along with systems-biological approaches following various downstream analyses are performed. New subgroups within 170 patients with cerebral amyloid pathology (Aß+) are revealed and the features of them are identified based on the top-rated targets constructing multi-omics factors of both whole (M-TPAD) and immune-focused models (M-IPAD). The authors explored the characteristics of subtypes and possible key-drivers for AD pathogenesis. Further in-depth studies showed that these subtypes are associated with longitudinal brain changes and autophagy pathways are main contributors. The significance of autophagy or clustering tendency is validated in peripheral blood mononuclear cells (PBMCs; n = 120 including 30 Aß- and 90 Aß+), induced pluripotent stem cell-derived human brain organoids/microglia (n = 12 including 5 Aß-, 5 Aß+, and CRISPR-Cas9 apolipoprotein isogenic lines), and human brain transcriptome (n = 78). Collectively, this study provides a strategy for precision medicine therapy and drug development for AD using integrative multi-omics analysis and network modelling.

Metataxonomic Analysis of Milk Samples From SARS-CoV-2-Positive and SARS-CoV-2-Negative Women.

Objective: To assess the impact of SARS-CoV-2 viral infection on the metataxonomic profile and its evolution during the first month of lactation. Methods: Milk samples from 37 women with full-term pregnancies and mild SARS-CoV-2 infection and from 63 controls, collected in the first and fifth postpartum weeks, have been analyzed. SARS-CoV-2 RNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) both in cases and controls. After DNA extraction, the V3-V4 hypervariable region of the gene 16S rRNA was amplified and sequenced using the MiSeq system of Illumina. Data were submitted for statistical and bioinformatics analyses after quality control. Results: All the 1st week and 5th week postpartum milk samples were negative for SARS-CoV-2 RNA. Alpha diversity showed no differences between milk samples from the study and control group, and this condition was maintained along the observation time. Analysis of the beta-diversity also indicated that the study and control groups did not show distinct bacterial profiles. Staphyloccus and Streptococcus were the most abundant genera and the only ones that were detected in all the milk samples provided. Disease state (symptomatic or asymptomatic infection) did not affect the metataxonomic profile in breast milk. Conclusion: These results support that in the non-severe SARS-CoV-2 pregnant woman infection the structure of the bacterial population is preserved and does not negatively impact on the human milk microbiota.

Exon skipping induced by CRISPR-directed gene editing regulates the response to chemotherapy in non-small cell lung carcinoma cells.

We have been developing CRISPR-directed gene editing as an augmentative therapy for the treatment of non-small cell lung carcinoma (NSCLC) by genetic disruption of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2). NRF2 promotes tumor cell survival in response to therapeutic intervention and thus its disablement should restore or enhance effective drug action. Here, we report how NRF2 disruption leads to collateral damage in the form of CRISPR-mediated exon skipping. Heterogeneous populations of transcripts and truncated proteins produce a variable response to chemotherapy, dependent on which functional domain is missing. We identify and characterize predicted and unpredicted transcript populations and discover that several types of transcripts arise through exon skipping; wherein one or two NRF2 exons are missing. In one specific case, the presence or absence of a single nucleotide determines whether an exon is skipped or not by reorganizing Exonic Splicing Enhancers (ESEs). We isolate and characterize the diversity of clones induced by CRISPR activity in a NSCLC tumor cell population, a critical and often overlooked genetic byproduct of this exciting technology. Finally, gRNAs must be designed with care to avoid altering gene expression patterns that can account for variable responses to solid tumor therapy.

Complicaciones tromboembólicas de los pacientes internados por COVID-19 / Thromboembolic complications in patients with COVID-19

Resumen La enfermedad producida por el COVID-19 ha generado un problema sanitario mundial sin precedentes. La infección se considera como un potencial factor de riesgo para desarrollar complica ciones tromboembólicas, principalmente, embolia pulmonar, infarto de miocardio y accidente cerebrovascular. El objetivo de este trabajo fue describirlas en los pacientes internados por COVID-19 y su evolución. Se realizó un estudio observacional unicéntrico prospectivo que comparó las características basales, factores de riesgo, tasa de eventos tromboembólicos, estadía y mortalidad hospitalaria entre los pacientes que se internaron en cuidados intensivos o sala general. Se incluyeron 1125 pacientes, 124 internados en unidad cuidados intensivos y 1001 internados en sala general de internación. La edad promedio fue de 46 ± 18 años, con 585 (52%) de sexo femenino. La tasa global de eventos tromboembólicos fue de 4.4%, siendo significativamente mayor en los pacientes de UCI (29% vs. 1.4%; p < 0.001) a pesar del elevado uso de heparina profiláctica (91.1% vs. 84.9%; p < 0.1), comparados con los internados en SGI. Los factores predictores independientes de desarrollo de eventos tromboembólicos fueron: la edad, el dímero D y la creatinina. La mortalidad global fue 4.3%, siendo significativamente mayor en los pacientes de cuidados intensivos sobre los de sala general de internación (29% vs. 1.3%; p < 0.001). Los pacientes que requieren internación por COVID-19 presentan elevada tasa de eventos tromboembólicos a pesar del uso de tromboprofilaxis con heparina, generando un impacto pronóstico negativo sobre la supervivencia de aquellos internados en cuidados intensivos.

Abstract Coronavirus disease-19 has emerged as a devastating global public health crisis. An increased frequency of arterial and venous thrombosis was observed in COVID-19 infection. The objective of this study was to describe the thromboembolic complications of patients hospitalized for COVID-19 and their evolution. A prospective single-center study was conducted that compared the characteristics, risk factors, thromboembolic event rate, hospital stay and mortal ity among patients admitted to intensive care or general ward. The mean age of population was 46 ± 18 years, and 52% were female. The global rate of thromboembolic events was 4.4%, significantly higher in intensive unit patients (29% vs 1.4%; p < 0.001) despite the high use of prophylactic heparin (91.1% vs. 84.9%; p < 0.1). The independent predictive factors for the development of thromboembolic events were: age, D-dimer and creatinine. Of the patients admitted to intensive care, 45.1% required mechanical ventilation. Overall mortality was 4.3%, significantly higher in intensive care patients than in the general hospital ward (29% vs. 1.3%; p < 0.0001). Pa tients requiring hospitalization due to infection secondary to COVID-19 have a high rate of thromboembolic events despite the use of thromboprophylaxis with heparin, generating a negative prognostic impact on the survival of patients admitted to intensive care.

[Thromboembolic complications in patients with COVID-19]. / Complicaciones tromboembólicas de los pacientes internados por COVID-19.

Coronavirus disease-19 has emerged as a devastating global public health crisis. An increased frequency of arterial and venous thrombosis was observed in COVID-19 infection. The objective of this study was to describe the thromboembolic complications of patients hospitalized for COVID-19 and their evolution. A prospective single-center study was conducted that compared the characteristics, risk factors, thromboembolic event rate, hospital stay and mortality among patients admitted to intensive care or general ward. The mean age of population was 46 ± 18 years, and 52% were female. The global rate of thromboembolic events was 4.4%, significantly higher in intensive unit patients (29% vs 1.4%; p < 0.001) despite the high use of prophylactic heparin (91.1% vs. 84.9%; p < 0.1). The independent predictive factors for the development of thromboembolic events were: age, D-dimer and creatinine. Of the patients admitted to intensive care, 45.1% required mechanical ventilation. Overall mortality was 4.3%, significantly higher in intensive care patients than in the general hospital ward (29% vs. 1.3%; p < 0.0001). Patients requiring hospitalization due to infection secondary to COVID-19 have a high rate of thromboembolic events despite the use of thromboprophylaxis with heparin, generating a negative prognostic impact on the survival of patients admitted to intensive care.

La enfermedad producida por el COVID-19 ha generado un problema sanitario mundial sin precedentes. La infección se considera como un potencial factor de riesgo para desarrollar complicaciones tromboembólicas, principalmente, embolia pulmonar, infarto de miocardio y accidente cerebrovascular. El objetivo de este trabajo fue describirlas en los pacientes internados por COVID-19 y su evolución. Se realizó un estudio observacional unicéntrico prospectivo que comparó las características basales, factores de riesgo, tasa de eventos tromboembólicos, estadía y mortalidad hospitalaria entre los pacientes que se internaron en cuidados intensivos o sala general. Se incluyeron 1125 pacientes, 124 internados en unidad cuidados intensivos y 1001 internados en sala general de internación. La edad promedio fue de 46 ± 18 años, con 585 (52%) de sexo femenino. La tasa global de eventos tromboembólicos fue de 4.4%, siendo significativamente mayor en los pacientes de UCI (29% vs. 1.4%; p < 0.001) a pesar del elevado uso de heparina profiláctica (91.1% vs. 84.9%; p < 0.1), comparados con los internados en SGI. Los factores predictores independientes de desarrollo de eventos tromboembólicos fueron: la edad, el dímero D y la creatinina. La mortalidad global fue 4.3%, siendo significativamente mayor en los pacientes de cuidados intensivos sobre los de sala general de internación (29% vs. 1.3%; p < 0.001). Los pacientes que requieren internación por COVID-19 presentan elevada tasa de eventos tromboembólicos a pesar del uso de tromboprofilaxis con heparina, generando un impacto pronóstico negativo sobre la supervivencia de aquellos internados en cuidados intensivos.

Administration of Ligilactobacillus salivarius CECT 30632 to elderly during the COVID-19 pandemic: Nasal and fecal metataxonomic analysis and fatty acid profiling.

Elderly was the most affected population during the first COVID-19 and those living in nursing homes represented the most vulnerable group, with high mortality rates, until vaccines became available. In a previous article, we presented an open-label trial showing the beneficial effect of the strain Ligilactobacillus salivarius CECT 30632 (previously known as L. salivarius MP101) on the functional and nutritional status, and on the nasal and fecal inflammatory profiles of elderly residing in a nursing home highly affected by the pandemic. The objective of this post-hoc analysis was to elucidate if there were changes in the nasal and fecal bacteriomes of a subset of these patients as a result of the administration of the strain for 4 months and, also, its impact on their fecal fatty acids profiles. Culture-based methods showed that, while L. salivarius (species level) could not be detected in any of the fecal samples at day 0, L. salivarius CECT 30632 (strain level) was present in all the recruited people at day 120. Paradoxically, the increase in the L. salivarius counts was not reflected in changes in the metataxonomic analysis of the nasal and fecal samples or in changes in the fatty acid profiles in the fecal samples of the recruited people. Overall, our results indicate that L. salivarius CECT 30632 colonized, at least temporarily, the intestinal tract of the recruited elderly and may have contributed to improvements in their functional, nutritional, and immunological status, without changing the general structure of their nasal and fecal bacteriomes when assessed at the genus level. They also suggest the ability of low abundance bacteria to train immunity.

The history and geographic distribution of a KCNQ1 atrial fibrillation risk allele.

The genetic architecture of atrial fibrillation (AF) encompasses low impact, common genetic variants and high impact, rare variants. Here, we characterize a high impact AF-susceptibility allele, KCNQ1 R231H, and describe its transcontinental geographic distribution and history. Induced pluripotent stem cell-derived cardiomyocytes procured from risk allele carriers exhibit abbreviated action potential duration, consistent with a gain-of-function effect. Using identity-by-descent (IBD) networks, we estimate the broad- and fine-scale population ancestry of risk allele carriers and their relatives. Analysis of ancestral migration routes reveals ancestors who inhabited Denmark in the 1700s, migrated to the Northeastern United States in the early 1800s, and traveled across the Midwest to arrive in Utah in the late 1800s. IBD/coalescent-based allele dating analysis reveals a relatively recent origin of the AF risk allele (~5000 years). Thus, our approach broadens the scope of study for disease susceptibility alleles to the context of human migration and ancestral origins.

Administration of Ligilactobacillus salivarius MP101 in an Elderly Nursing Home during the COVID-19 Pandemic: Immunological and Nutritional Impact.

The elderly population living in nursing homes is particularly vulnerable to COVID-19 although individual susceptibility to SARS-CoV-2 infection may be related to the host microbiota. The objective of this work was to investigate the effect of Ligilactobacillus salivarius MP101 on the functional (Barthel index), cognitive (GDS/FAST), and nutritional (MNA) status as well as on the nasal and fecal inflammatory profiles of elderly residents living in a nursing home that is highly affected by COVID-19. A total of 25 residents participated in the trial, which involved the daily ingestion of a dairy product (L. salivarius MP101: 9.3 log10 CFU per unit) for 4 months. Nasal and fecal samples were analyzed for 37 immune factors at recruitment and at the end of the study. After the trial, no change in the GDS/FAST scores were found but, in contrast, the values for the Barthel index and the MNA score improved significantly. The concentrations of some immune factors changed significantly after the trial, including a decrease in the concentrations of BAFF/TNFSF13B, APRIL/TNFSF13, IL8, IL31, osteopontin, sTNF-R1, and sTNF-R2, and an increase in chitinase 3-like 1, IL19, IL35, and pentraxin 3 was also observed. In conclusion, L. salivarius MP101 seems to be a promising strain for improving or maintaining health in this highly vulnerable population.

Immediate Pre-Partum SARS-CoV-2 Status and Immune Profiling of Breastmilk: A Case-Control Study.

Objetive: To address the prevalence of SARS-CoV-2 and the evolutionary profile of immune compounds in breastmilk of positive mothers according to time and disease state. Methods: Forty-five women with term pregnancies with confirmed non-severe SARS-CoV-2 infection (case group), and 96 SARS-CoV-2 negative women in identical conditions (control group) were approached, using consecutive sample. Weekly (1st to 5th week postpartum) reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal swabs (cases) and breastmilk (cases and controls) were obtained. Concentration of cytokines, chemokines, and growth factors in breastmilk (cases and controls) were determined at 1st and 5th week post-partum. Results: Thirty-seven (study group) and 45 (control group) women were enrolled. Symptomatic infection occurred in 56.8% of women in the study group (48% fever, 48% anosmia, 43% cough). SARS-CoV-2 RNA was not found in breastmilk samples. Concentrations of cytokines (IFN-γ, IL-1ra, IL-4, IL-6, IL-9, IL-13, and TNF-α) chemokines (eotaxin, IP-10, MIP-1α, and RANTES) and growth factors (FGF, GM-CSF, IL7, and PDGF-BB) were higher in breastmilk of the study compared with the control group at 1st week postpartum. Immune compounds concentrations decreased on time, particularly in the control group milk samples. Time of nasopharyngeal swab to become negative influenced the immune compound concentration pattern. Severity of disease (symptomatic or asymptomatic infection) did not affect the immunological profile in breast milk. Conclusions: This study confirms no viral RNA and a distinct immunological profile in breastmilk according to mother's SARS-CoV-2 status. Additional studies should address whether these findings indicate efficient reaction against SARS-CoV-2 infection, which might be suitable to protect the recipient child.

MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site3. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules. Hyperphosphorylated, aggregation-prone tau forms the hallmark inclusions of tauopathies4. Mutations in MAPT cause familial frontotemporal dementia, and common variations forming the MAPT H1 haplotype are a significant risk factor in many tauopathies5 and Parkinson's disease. Notably, expression of MAPT-AS1 or minimal essential sequences from MAPT-AS1 (including MIR) reduces-whereas silencing MAPT-AS1 expression increases-neuronal tau levels, and correlate with tau pathology in human brain. Moreover, we identified many additional NATs with embedded MIRs (MIR-NATs), which are overrepresented at coding genes linked to neurodegeneration and/or encoding IDPs, and confirmed MIR-NAT-mediated translational control of one such gene, PLCG1. These results demonstrate a key role for MAPT-AS1 in tauopathies and reveal a potentially broad contribution of MIR-NATs to the tightly controlled translation of IDPs6, with particular relevance for proteostasis in neurodegeneration.