Glycine by enteral route does not improve major clinical outcomes in severe COVID-19: a randomized clinical pilot trial.

There is a worrying scarcity of drug options for patients with severe COVID-19. Glycine possesses anti-inflammatory, cytoprotective, endothelium-protective, and platelet-antiaggregant properties, so its use in these patients seems promising. In this open label, controlled clinical trial, inpatients with severe COVID-19 requiring mechanical ventilation randomly received usual care (control group) or usual care plus 0.5 g/kg/day glycine by the enteral route (experimental group). Major outcomes included mortality, time to weaning from mechanical ventilation, total time on mechanical ventilation, and time from study recruitment to death. Secondary outcomes included laboratory tests and serum cytokines. Patients from experimental (n = 33) and control groups (n = 23) did not differ in basal characteristics. There were no differences in mortality (glycine group, 63.6% vs control group, 52.2%, p = 0.60) nor in any other major outcome. Glycine intake was associated with lower fibrinogen levels, either evaluated per week of follow-up (p < 0.05 at weeks 1, 2, and 4) or as weighted mean during the whole hospitalization (608.7 ± 17.7 mg/dl vs control 712.2 ± 25.0 mg/dl, p = 0.001), but did not modify any other laboratory test or cytokine concentration. In summary, in severe COVID-19 glycine was unable to modify major clinical outcomes, serum cytokines or most laboratory tests, but was associated with lower serum fibrinogen concentration.Registration: ClinicalTrials.gov NCT04443673, 23/06/2020.

Cytomegalovirus infection and disease in systemic lupus erythematosus patients at a high-complexity hospital in southwestern Colombia.

Cytomegalovirus (CMV) infection and disease is a condition usually described in immunocompromised patients, but among them, those with connective tissue diseases are poorly represented. Here we present the clinical, laboratory characteristics, management and outcomes of systemic lupus erythematosus (SLE) patients who presented with a CMV infection/disease to a high complexity hospital in southwestern Colombia between 2011 and 2020. 16 SLE patients were found to have a CMV infection. SLE was predominantly characterized by renal involvement (10 patients; 62.50%), and 14 patients (87.5%) were receiving steroids previous to the CMV infection. The entire sample required hospital admission, mainly related to acute kidney injury, and nine patients were admitted to the intensive care unit (ICU). Gastrointestinal organ damage was the most common CMV disease manifestation. All patients received ganciclovir, five of them (31.25%) suffered from septic shock, and seven (43.75%) died. Age ≥38 years and the presence of septic shock at admission were correlated to the mortality outcome. To our knowledge, this is the first publication evaluating SLE patients with CMV infection/disease in a Colombian population.

Photobiomodulation on isolated mitochondria at 810 nm: first results on the efficiency of the energy conversion process.

In this paper the photobiomodulation on isolated mitochondria of bovine liver is studied as a thermodynamic process of conversion of energy. This analysis is conducted by considering a particular set-up for the photobiomodulation experiments of interest. It allows, in particular, the computation of the electromagnetic field and the related energetic quantities in the stimulated organelles. The measurements of the excess of biochemical power density produced by the illuminated mitochondria are performed at regular time intervals after the experiments. The calculations and the measurements finally allow us to obtain the first results on the efficiency of the process of conversion of electromagnetic energy into excess of biochemical energy released by the isolated organelles.

Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.

Two-stage targeted maximum likelihood estimation for mixed aggregate and individual participant data analysis with an application to multidrug resistant tuberculosis.

In this study, we develop a new method for the meta-analysis of mixed aggregate data (AD) and individual participant data (IPD). The method is an adaptation of inverse probability weighted targeted maximum likelihood estimation (IPW-TMLE), which was initially proposed for two-stage sampled data. Our methods are motivated by a systematic review investigating treatment effectiveness for multidrug resistant tuberculosis (MDR-TB) where the available data include IPD from some studies but only AD from others. One complication in this application is that participants with MDR-TB are typically treated with multiple antimicrobial agents where many such medications were not observed in all studies considered in the meta-analysis. We focus here on the estimation of the expected potential outcome while intervening on a specific medication but not intervening on any others. Our method involves the implementation of a TMLE that transports the estimation from studies where the treatment is observed to the full target population. A second weighting component adjusts for the studies with missing (inaccessible) IPD. We demonstrate the properties of the proposed method and contrast it with alternative approaches in a simulation study. We finally apply this method to estimate treatment effectiveness in the MDR-TB case study.

Lung function is related to salivary cytokines and hormones in healthy children. An exploratory cross-sectional study.

Pulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z-score or percent predicted. Ninety-six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in boys were associated with zR5-R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM-CSF. This endogenous influence is a novel concept that warrants in-depth characterization.

Reference equations using segmented regressions for impulse oscillometry in healthy subjects aged 2.7-90 years.

Background: Published reference equations for impulse oscillometry (IOS) usually encompass a specific age group but not the entire lifespan. This may lead to discordant predicted values when two or more non-coincident equations can be applied to the same person, or when a person moves from one equation to the next non-convergent equation as he or she gets older. Thus, our aim was to provide a single reference equation for each IOS variable that could be applied from infancy to old age. Methods: This was an ambispective cross-sectional study in healthy nonsmokers, most of whom lived in Mexico City, who underwent IOS according to international standards. A multivariate piecewise linear regression, also known as segmented regression, was used to obtain reference equations for each IOS variable. Results: In a population of 830 subjects (54.0% female) aged 2.7 to 90 years (54.8% children ≤12 years), segmented regression estimated two breakpoints for age in almost all IOS variables, except for R5-R20 in which only one breakpoint was detected. With this approach, multivariate regressions including sex, age, height and body mass index as independent variables were constructed, and coefficients for calculating predicted value, lower and upper limits of normal, percentage of predicted and z-score were obtained. Conclusions: Our study provides IOS reference equations that include the major determinants of lung function, i.e. sex, age, height and body mass index, that can be easily implemented for subjects of almost any age.

Enfermedad pulmonar intersticial difusa secundaria a neumonitis por hipersensibilidad de patrón mixto: reporte de caso y revisión de literatura / Diffuse interstitial lung disease secondary to mixed pattern hypersensitivity pneumonitis: Case report and literature review

La enfermedad pulmonar intersticial difusa (EPID) supone un amplio grupo heterogéneo de enfermedades caracterizadas por hallazgos en su intersticio pulmonar, específicamente relacionados con su engrosamiento, lo cual impacta significativamente en el intercambio gaseoso y la mecánica ventilatoria del paciente. El diagnóstico se genera acorde a la clínica del paciente, el uso de imágenes y la histopatología. El tratamiento guarda relación directa con el patrón pulmonar estructural que presente la EPID. Se presenta el caso clínico de una paciente femenina de 32 años, indígena, quien ingresa por exacerbación de disnea, con antecedente de neumonitis por hipersensibilidad, adicional a otros antecedentes clínicos que guardan relación estrecha con la EPID.

Diffuse interstitial lung disease (ILD) is a large heterogeneous group of diseases characterized by findings in the pulmonary interstitium, specifically changes related to thickening of the interstitium, which significantly impacts the patient's gas exchange and ventilatory mechanics. The diagnosis is generated according to the patient's clinical presentation, imaging and histopathology. The treatment is directly related to the structural pulmonary pattern of ILD. We present the clinical case of a 33-year-old female patient of indigenous ethnicity who is admitted for exacerbation of dyspnea, with a history of hypersensitivity pneumonitis in addition to other clinical antecedents that are closely related to ILD.

Diagnostic Performance of Anti-dsDNA Tests by Indirect Immunofluorescence and Enzyme-linked Immunosorbent Assay in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Several laboratory techniques for anti double-stranded (ds) DNA detection in systemic lupus erythematosus (SLE) are available, with variable diagnostic performance. We aimed to evaluate anti-dsDNA's diagnostic performance by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (EIA). METHODS: We conducted a single-center retrospective (2015 to 2020) study. Patients with anti-dsDNA tests by IIF and EIA were included. We evaluated the indications, applications, concordance, positive predictive value (PPV) of anti-dsDNA to confirm SLE diagnosis or flares, and associations of disease manifestations with positivity with each technique. RESULTS: A total of 1368 reports of anti-dsDNA tests by IIF and EIA and the corresponding medical records of the patients were analyzed. The main indication for anti-dsDNA testing was to help in the diagnosis of SLE in 890 (65%) of the samples, and the main application after obtaining the results was SLE exclusion in 782 (57.2%) cases. The combination with the highest frequency was the negativity result by both techniques in 801 (58.5%) cases (Cohen kappa 0.57). Both methods were positive in 300 patients with SLE (Cohen kappa 0.42). The PPVs of anti-dsDNA tests to confirm diagnosis/flare was 79.64% (95% CI, 75.35-83.35) by EIA, 78.75% (95% CI, 74.27-82.62) by IIF, and 82% (95% CI, 77.26-85.93) when both were positive. CONCLUSIONS: Anti-dsDNA detection by IIF and EIA are complementary and may indicate different clinical patterns in patients with SLE. The detection of anti-dsDNA antibodies by both techniques has a higher PPV than either separately for confirming SLE diagnosis or flares. These results highlight the need for evaluating both methods in clinical practice.

Trends (2007-2019) of major atopic diseases throughout the life span in a large Mexican population.

Background: Major atopic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma share the same atopic background, but they often show differences in their epidemiological behavior. Objective: We aimed to report the profile of these atopic diseases in a large Mexican population, including their age-related incidences, male:female (M:F) ratios, recent time trends, and association with altitude. Methods: Registries from the largest, nationwide health institution in Mexico (more than 34 million insured subjects), were reviewed. New cases of AD, AR, and asthma diagnosed each year by family physicians from 2007 to 2019 were adjusted by the corresponding insured population to estimate incidence rates. Results: Incidences of the 3 atopic diseases were highest in the 0-4 years age-group and progressively decreased thereafter until adolescence. Asthma and AR, but not AD, were more frequent in males during childhood (M:F ratios of 1.5, 1.3, and 0.95, respectively), but predominated in females during adulthood (M:F ratios of 0.52, 0.68, and 0.73, respectively). Time trends showed an initial increasing trend of annual incidences, with a peak around 2009-2011, and a downward trend afterward. This decreasing trend was seen in all age-groups and was more evident for AD (∼50% drop) and asthma (∼40% drop) than for AR (∼20% drop). Geographical distribution suggested that incidences of asthma and AR, but not of AD, had an inverse association with altitude. Conclusion: Annual incidences of the 3 major atopic diseases have declined in recent years in almost all age groups, and their epidemiological profile during the life span showed contrasting differences according to age, sex, and ecological association with altitude, mainly regarding AD.

Mesenchymal stem cells attenuate the proinflammatory cytokine pattern in a guinea pig model of chronic cigarette smoke exposure.

AIMS: Cigarette smoke often induces pulmonary and systemic inflammation. In animal models, mesenchymal stem cells (MSC) tend to ameliorate these effects. We aimed to explore the local and systemic expression of cytokines in guinea pigs chronically exposed to cigarette smoke, and their modifications by MSC. MAIN METHODS: Concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α, INF-É£, TSG-6, MMP-9, TIMP-1, and/or TIMP-2 in serum and bronchoalveolar lavage (BALF) from animals exposed to tobacco smoke (20 cigarettes/day, 5 days/week for 10 weeks) were determined, and mRNA expression of some of them was measured in lung tissue. Intratracheal instillation of allogeneic bone marrow MSC (5x106 cells in 1 ml) was done at week 2. KEY FINDINGS: After cigarette smoke, IL-6 and IFN-γ increased in serum and BALF, while IL-1ß and IL-12 decreased in serum, and TSG-6 and TIMP-2 increased in BALF. IL-1ß had a paradoxical increase in BALF. MSC had an almost null effect in unexposed animals. The intratracheal administration of MSC in guinea pigs exposed to cigarette smoke was associated with a statistically significant decrease of IL-12 and TSG-6 in serum, as well as a decrease of IL-1ß and IFN-γ and an increase in TIMP-1 in BALF. Concerning mRNA expression in lung tissue, cigarette smoke did not modify the relative amount of the studied transcripts, but even so, MSC decreased the IL-12 mRNA and increased the TIMP-1 mRNA. SIGNIFICANCE: A single intratracheal instillation of MSC reduces the pulmonary and systemic proinflammatory pattern induced by chronic exposure to cigarette smoke in guinea pigs. TRIAL REGISTRATION: Not applicable.

Epidemiological characterization of patients with sarcoidosis in a high complexity hospital in southwestern Colombia

Introduction: Epidemiological studies on sarcoidosis in Colombia are scarce, and although recent reports from the north of the country have been published, clinical-epidemiological associations are not clear. Our aim was to characterize patients with sarcoidosis diagnosed at Fundación Valle del Lili in Cali, Colombia. Methods: A retrospective study of a series of sarcoidosis cases was conducted between 2011 and 2019. Demographic, clinical, laboratory, imaging, histopathological, and treatment variables were analyzed. Results: A total of 34 patients with a diagnosis of sarcoidosis were found. The majority were women (n = 25; 73%), and the mean age was 50 years. The main symptoms of onset were erythema nodosum (n = 11; 33%), arthritis (n = 10; 30%), and cough (n = 9; 27%). In 64% of the cases, there was pulmonary involvement, with pulmonary nodules, mediastinal adenopathy, and interstitial lung disease found in 54%, 50%, and 36% of cases, respectively. In 85% of cases, there were extrapulmonary manifestations, mainly cutaneous (50%). Angiotensin-converting enzyme (ACE) was elevated in 62% of the cases in which it was measured (n = 16; 47%). During the diagnostic process, 23 biopsies were performed, of which 95% showed granulomas with noncaseating necrosis. Most of the patients (76%) were controlled with prednisolone, at an average dose of 20 mg (7.5-50 mg) per day. Conclusions: Sarcoidosis was more frequent in women and mestizos, and it presented earlier in men. Elevated ACE was not associated with extrapulmonary involvement. Calcium-phosphorus profile and antinuclear antibodies were not useful to establish the diagnosis.

Introducción: En Colombia son escasos los estudios epidemiológicos sobre la sarcoidosis; aunque recientemente se han publicado reportes del norte del país, son grupos muestrales pequeños, por lo que no quedan claras las asociaciones clínico-epidemiológicas. Nuestro objetivo fue caracterizar pacientes con sarcoidosis en la Fundación Valle del Lili, en Cali, Colombia. Métodos: Se realizó un estudio retrospectivo de una serie de casos de sarcoidosis entre el 2011 y el 2019. Se analizaron variables demográficas, clínicas, de laboratorio, imagenológicas, histopatológicas y de tratamiento. Resultados: Se encontraron 34 pacientes con diagnóstico de sarcoidosis, la mayoría fueron mujeres (n = 25; 73%), y la edad promedio fue 50 anos. Los principales síntomas de inicio fueron eritema nudoso (n = 11; 33%), artritis (n = 10; 30%) y tos (n = 9; 27%). En el 64% de los casos hubo compromiso pulmonar, y se encontraron nódulos pulmonares, adenopatías mediastinales y enfermedad pulmonar intersticial en un 54, 50 y 36% de los casos, respectivamente. En el 85% de los casos hubo manifestaciones extrapulmonares, principalmente cutáneas (50%). Los niveles de enzima conversora de angiotensina estuvieron elevados en el 62% de los casos en los que fue medida (n = 16; 47%). Durante el proceso diagnóstico se realizaron 23 biopsias, de las cuales el 95% evidenció granulomas con necrosis no caseificante. La mayoría de los pacientes (76%) fueron controlados con prednisolona, a una dosis promedio de 20 mg (7,5-50 mg) por día. Conclusiones: La sarcoidosis fue más frecuente en mujeres y mestizos. La presentación fue más temprana en hombres. La enzima conversora de angiotensina no se relacionó con compromiso extrapulmonar. Ni el perfil fósforo-calcio ni los anticuerpos antinucleares fueron útiles para establecer el diagnóstico.

Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen.

Infections and disease caused by the obligate human pathogen Bordetella pertussis (Bp) are increasing, despite widespread vaccinations. The current acellular pertussis vaccines remain ineffective against nasopharyngeal colonization, carriage, and transmission. In this work, we tested the hypothesis that Bordetella polysaccharide (Bps), a member of the poly-ß-1,6-N-acetyl-D-glucosamine (PNAG/PGA) family of polysaccharides promotes respiratory tract colonization of Bp by resisting killing by antimicrobial peptides (AMPs). Genetic deletion of the bpsA-D locus, as well as treatment with the specific glycoside hydrolase Dispersin B, increased susceptibility to AMP-mediated killing. Bps was found to be both cell surface-associated and released during laboratory growth and mouse infections. Addition of bacterial supernatants containing Bps and purified Bps increased B. pertussis resistance to AMPs. By utilizing ELISA, immunoblot and flow cytometry assays, we show that Bps functions as a dual surface shield and decoy. Co-inoculation of C57BL/6J mice with a Bps-proficient strain enhanced respiratory tract survival of the Bps-deficient strain. In combination, the presented results highlight the critical role of Bps as a central driver of B. pertussis pathogenesis. Heterologous production of Bps in a non-pathogenic E. coli K12 strain increased AMP resistance in vitro, and augmented bacterial survival and pathology in the mouse respiratory tract. These studies can serve as a foundation for other PNAG/PGA polysaccharides and for the development of an effective Bp vaccine that includes Bps.

Modeling treatment effect modification in multidrug-resistant tuberculosis in an individual patientdata meta-analysis.

Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. However, this task is statistically challenging and typically requires large amounts of data. Investigators may be interested in using the individual patient data from multiple studies to estimate these treatment effect models. Our data arise from a systematic review of observational studies contrasting different treatments for multidrug-resistant tuberculosis, where multiple antimicrobial agents are taken concurrently to cure the infection. We propose a marginal structural model for effect modification by different patient characteristics and co-medications in a meta-analysis of observational individual patient data. We develop, evaluate, and apply a targeted maximum likelihood estimator for the doubly robust estimation of the parameters of the proposed marginal structural model in this context. In particular, we allow for differential availability of treatments across studies, measured confounding within and across studies, and random effects by study.

Lesión miocárdica en una paciente con lupus eritematoso sistémico: Un reto diagnóstico / Myocardial lesion in a patient with systemic lupus erythematosus: A diagnostic challenge

Resumen Mujer de 37 años con antecedentes de lupus eritematoso sistémico (LES), tromboembolia pulmonar y trombosis venosa profunda, quien consultó por dolor torácico, con hallazgos de elevación de la troponina, disfunción sistólica del ventrículo izquierdo y alteraciones de la contractilidad segmentaria, además de anti-DNA elevado y complemento consumido. La angiografía coronaria mostró estenosis grave en el tercio medio de la arteria descendente anterior, que fue intervenida con angioplastia más stent medicado. La resonancia magnética cardiaca reveló infarto agudo de miocardio extenso en el territorio de la arteria descendente anterior, sin miocarditis. Se descartó compromiso cardiaco por LES, se continuó igual terapia inmunosupresora, se añadió manejo para enfermedad coronaria y egresó por buena evolución. El enfoque de las causas de lesión miocárdica en un paciente con LES supone un reto, dadas las múltiples posibilidades en el espectro de compromiso cardiaco, ya que varias estructuras se pueden ver afectadas. La miocarditis y la pericarditis se consideran las más frecuentes, pero el compromiso coronario no puede descartarse, independientemente de la edad y de la presencia de factores de riesgo tradicionales, puesto que el componente inflamatorio de la patología autoinmunitaria confiere un desarrollo acelerado de ateroesclerosis. La multimodalidad diagnóstica y el enfoque interdisciplinario son necesarios para aclarar el mecanismo de la lesión y así brindar un tratamiento dirigido.

Abstract A 37-year-old woman with a history of systemic lupus erythematosus (SLE), pulmonary thromboembolism and deep vein thrombosis consulted for chest pain, with findings of elevated troponin, left ventricular systolic dysfunction, and segmental contractility abnormalities, as well as elevated anti-DNA and complement consumption. Coronary angiography showed severe stenosis of the middle third of the anterior descending artery, which was treated with angioplasty plus a medicated stent. Cardiac magnetic resonance imaging revealed an extensive acute myocardial infarction in the area supplied by the anterior descending artery, without myocarditis. Cardiac involvement in SLE was ruled out, immunosuppressive treatment was maintained, coronary disease treatment was added, and she was discharged due to improvement. Identifying the causes of myocardial insult in a patient with SLE is challenging, given the multiple possibilities across the cardiac involvement spectrum, in which several structures may be affected. Myocarditis and pericarditis are considered to be the most frequent, but coronary involvement cannot be ruled out, regardless of age or the presence of traditional risk factors, since the inflammatory component of the autoimmune disease accelerates the development of atherosclerosis. Multimodal diagnostics and an interdisciplinary approach are necessary to clarify the mechanism of injury and provide targeted treatment.

Sustained volume decreases in simple renal cysts after sclerotherapy using NBCA with or without hydrodissection.

The present study aimed to determine the effectiveness of sclerotherapy using NBCA (Histoacryl Blue®; B. Braun, Melgungen, Germany), with or without hydrodissection, for the treatment of simple renal cysts. Materials and Methods: Patients who presented to an interventional radiology clinic for the diagnosis of symptomatic renal cysts which had previously been identified at an outpatient clinic were selected for inclusion in this study. A total of 28 patients were randomly divided into 2 groups, based on whether or not they underwent hydrodissection along with ultrasound-guided NBCA-based sclerotherapy. Sonographs were performed at 0, 7, and 180 days post-procedure to record the residual volume of the renal cysts and to determine the efficacy of the procedure. Results: A total of 32 cysts in 28 patients were treated with sclerotherapy, 18 (64%) females and 10 (36%) males. The average age of the patients was 61.8 years (range: 33-89 years). All patients reported an improvement in symptoms associated with the existing renal cysts at 7 and 180 days post-procedure, and at 7 days post-procedure a statistically significant reduction in cyst volume was observed (all patients: 96.8%; group A: 96%; group B: 97.6%). The reduced cyst volume was still observed 180 days post-procedure (all patients: 98.6%; group A: 98.2%; group B: 98.9%). There was no significant difference between the two treatment groups. Conclusion: There is a significant and persistent reduction in the volume of renal cysts, in addition to an improvement of the associated symptoms, after treatment with NBCA-based sclerotherapy, with or without hydrodissection.

Granuloma no caseificante como primera manifestación de artritis reumatoide. A propósito de un caso / Noncaseating granuloma as first manifestation of rheumatoid arthritis: a case report

RESUMEN Los nódulos reumatoides se han descrito en cerca del 30% de los pacientes con artritis reumatoide, se localizan generalmente a nivel subcutáneo, pero son poco frecuentes en órganos viscerales; generalmente aparecen en estados tardíos de la enfermedad. Su apariencia puede ser confundida con otras condiciones clínicas en las localizaciones atípicas. Presentamos el caso de una paciente que comenzó con nódulos reumatoides en el hígado como primera manifestación de artritis reumatoide.

ABSTRACT The rheumatoid nodules have been described in 30% of patients with rheumatoid arthritis. There are localized generally at subcutaneous planes, are rare in visceral organs, and appear tipically in advance stages of the disease. Its appearance in atyipical localizations can be confused with other conditions. We are going to discuss a patient who debuted with rheumatoid nodules in the liver as first manifestation of rheumatoid arthritis.

Electromagnetic Dosimetry for Isolated Mitochondria Exposed to Near-Infrared Continuous-Wave Illumination in Photobiomodulation Experiments.

This paper presents results on the electromagnetic field computed inside isolated mitochondria when they are exposed to near-infrared illuminations with reference to photobiomodulation experiments. The accurate calculation of the electromagnetic dose is considered to be important for a better understanding of the mechanism of interaction of light with these organelles and to improve the reliability and repeatability of the experiments. To get such results, we introduce several models. Even though they refer to a well-defined experimental setup, different models are necessary to take into account the possible different dispositions of the mitochondria, and of the differences in their dimensions and in their constitutive parameters. Different wavelengths and polarizations are considered as well. The effects of all parameters on the electromagnetic field inside mitochondria are discussed. © 2021 Bioelectromagnetics Society.

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It.

COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.

Reproducibility of minor salivary gland biopsy reports in Sjögren's syndrome and its correlation with disease biomarkers.

INTRODUCTION/OBJECTIVE: Sjögren's syndrome (SS) is a systemic autoimmune disease that is challenging to diagnose. Although minor salivary gland biopsy (MSGB) is a useful ancillary study, different factors make its interpretation difficult. Also, the significance of distinct histopathological findings is unknown. We aimed to determine the concordance between pathologists and rheumatologists in interpreting the MSGB results, as well as the correlation between MSGB findings, paraclinical features, and SS diagnosis. METHODS: This descriptive retrospective study reviewed medical charts from 998 individuals from a single center where MSGBs had been performed. Rheumatologists interpreted biopsy reports from pathologists, and interobserver variability was calculated. Logistic regression using immunological parameters and histological findings was performed. RESULTS: We included 998 patients with a median age of 55 years (45-64 years); the majority of patients were females (n = 934, 93.6%). Chisholm and Mason's scoring system was the most frequently used scale (55.1%). There was a good correlation between pathologists and rheumatologists for diagnosing SS using MSGB findings (Cohen's kappa 0.91). We observed a strong association between interstitial plasmocytes and SS (OR 24, 95% CI 9.09-64.94, p = 0). CONCLUSION: The MSGB is an essential tool for the diagnosis of SS. Although different factors may negatively affect its reproducibility, histological findings, such as interstitial plasmocytes, may predict the risk of developing SS. Key Points • We provide information based on 998 patients with suspected SS diagnosis. • Chisholm and Mason's scale is the most frequently used compared to Greenspan's and Tarpley's scales. • There is good correlation between pathologists and rheumatologists for the diagnosis of SS using MSGB.