[Mild SARS-CoV-2 infection in vulnerable patients: implementation of a clinical pathway for early treatment]. / Infección leve por SARS-CoV-2 en pacientes vulnerables: implantación de una vía clínica de tratamiento precoz.

INTRODUCTION: The objective of this report is to describe the clinical pathway for early treatment of patients with acute SARS-CoV-2 infection and to evaluate the first results of its implementation. METHODS: This is a descriptive and retrospective study of the implementation of a clinical pathway of treatment in outpatients (January 1 to June 30 2022). Clinical pathway: detection and referral systems from Primary Care, Emergency services, hospital specialities and an automated detection system; clinical evaluation and treatment administration in the COVID-19 day-hospital and subsequent clinical follow-up. Explanatory variables: demographics, comorbidity, vaccination status, referral pathways and treatment administration. OUTCOME VARIABLES: hospitalization and death with 30 days, grade 2-3 toxicity related to treatment. RESULTS: Treatment was administered to 262 patients (53,4% women, median age 60 years). The treatment indication criteria were immunosupression (68,3%), and the combination of age, vaccination status and comorbidity in the rest47,3% of the patients s received remdesivir, 35,9% nirmatrelvir/ritonavir, 13,4% sotrovimab and 2,4% combined treatment with a median of 4 days after symptom onset. Hospital admission was required for 6,1% of the patients, 3,8% related to progression COVID-19. No patient died. Toxicity grade 2-3 toxicity was reported in 18,7%, 89,8% dysgeusia and metallic tasted related nirmatrelvir/ritonavir. Seven patients discontinued treatment due to toxicity. CONCLUSION: The creation and implementation of a clinical pathway for non-hospitalized patients with SARS-CoV-2 infection is effective and it allows early accessibility and equity of currently available treatments.

Employment status, gender and health in Spanish women.

The present study analyzed relationships between employment status, gender role conformity, and health among adult Spanish women from a biopsychosocial approach. We first examined the potential relationship between employment status and conformity to feminine norms (CFNI), second, the relationship between employment status and general and psychological health, and finally, the relationship between CFNI and general and psychological health. Unemployed women (n = 103), employed women (n = 144), and full-time homemakers (n = 100) aged 18-70 yr completed a survey, including measures of psychological health (GHQ-12), general health (self-rated health), and CFNI. Data collection was conducted during 2014. Multiple logistic regression analyses produced odds ratios (OR) and 95 petrcent confidence intervals (CI) that showed that full-time homemakers were more likely to show higher levels of feminine norms conformity (OR = 2.04; 95 percent CI = 1.13-3.69; p = .017), although these differences were no longer significant when controlled for educational level. Unemployed women (OR = 3.27; 95 percent CI = 1.87-5.73; p < .001) and women who presented greater CFNI (OR = 1.56; 95 percent CI = 1.01-2.40; p = .044) were more likely to show psychological morbidity. Public health institutions should pay attention to the relevance of employment status and gender roles, given the relation of these factors to women's health.

Mild SARS-CoV-2 infection in vulnerable patients: implementation of a clinical pathway for early treatment.

INTRODUCTION: The objective of this report is to describe the clinical pathway for early treatment of patients with acute SARS-CoV-2 infection and to evaluate the first results of its implementation. METHODS: This is a descriptive and retrospective study of the implementation of a clinical pathway of treatment in outpatients (January 1 to June 30 2022). Clinical pathway: detection and referral systems from Primary Care, Emergency services, hospital specialities and an automated detection system; clinical evaluation and treatment administration in the COVID-19 day-hospital and subsequent clinical follow-up. Explanatory variables: demographics, comorbidity, vaccination status, referral pathways and treatment administration. OUTCOME VARIABLES: hospitalization and death with 30 days, grade 2-3 toxicity related to treatment. RESULTS: Treatment was administered to 262 patients (53,4% women, median age 60 years). The treatment indication criteria were immunosupression (68,3%), and the combination of age, vaccination status and comorbidity in the rest 47,3% of the patients s received remdesivir, 35,9% nirmatrelvir/ritonavir, 13,4% sotrovimab and 2,4% combined treatment with a median of 4 days after symptom onset. Hospital admission was required for 6,1% of the patients, 3,8% related to progression COVID-19. No patient died. Toxicity grade 2-3 toxicity was reported in 18,7%, 89,8% dysgeusia and metallic tasted related nirmatrelvir/ritonavir. Seven patients discontinued treatment due to toxicity. CONCLUSION: The creation and implementation of a clinical pathway for non-hospitalized patients with SARS-CoV-2 infection is effective and it allows early accessibility and equity of currently available treatments.

Thyroid abscess, an uncommon diagnosis: A case report and mini­review of the literature.

Thyroid abscess is a rare entity, commonly experienced by immunocompromised patients, or those who have anatomical abnormalities or a pre-existing thyroid disease. An early diagnosis continued by treatment with antibiotics and drainage of the abscess is the recommended therapeutic strategy for such cases. The present study describes a clinical case of this rare event, and also provides a brief literature review. The present study describes the case of a 48-year-old healthy male with no medical antecedents, apart from acute prostatitis treated with antibiotics for 6 days prior, who visited the Emergency Department of the authors' hospital with neck pain and progressive swelling of the mass. Diagnostic imaging confirmed the authors' suspicion of an abscess and revealed the lesion displacing the airway to the contralateral side. This restricted the mobility of the neck of the patient. As an emergency measure, the patient was then taken to the operating room for a neck examination. A hemithyroidectomy was finally performed. Following a prolonged hospital duration, he was discharged from the hospital and his recovery was uneventful without any voice alterations, hypocalcemia or recurrence.

Uterine carcinosarcoma with intestinal involvement: A case report and literature review.

Uterine carcinosarcoma (UCS) is a high-grade endometrial cancer characterized by two components: Carcinomatous (epithelial) and sarcomatous (stromal tissue) elements. The present study describes a clinical case of this type of UCS and also provides a brief literature review of this type of tumor. A 72-year-old female visited the emergency department of the authors' hospital with pain in the hypogastric region, intestinal dysrhythmia since 3 months prior, fever and a palpable abdominal mass. Laboratory test results revealed sepsis and mild anemia and an imaging test revealed a large uterine tumor with wide areas of necrosis and adenopathies. As determined by the multidisciplinary committee, surgery was considered the main treatment option and this was performed with no incidences. Carcinosarcoma is a rare tumor, which most frequently occurs in older women. The diagnosis is based on symptoms and imaging tests, such as ecography and scans. The gold standard of treatment is surgery, although it is possible that other types of therapies, such as chemotherapy and radiotherapy may also be effective, depending on the tumor stage. On the whole, the prognosis of patients with this type of tumor is poor, with a low survival rate, even in earlier stages due to its malignant component and the possibility for metastasis. Surgery is the optimal treatment for this type of tumor, if this is possible, always individualizing patients.

Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through interaction with cell surface proteoglycans.

Pregnancy-specific ß1 glycoproteins (PSGs) are the most abundant fetal proteins in the maternal bloodstream in late pregnancy. They are secreted by the syncytiotrophoblast and are detected around day 14 postfertilization. There are 11 human PSG genes, which encode a family of proteins exhibiting significant conservation at the amino acid level. We and others have proposed that PSGs have an immune modulatory function. In addition, we recently postulated that they are proangiogenic due to their ability to induce the secretion of VEGF-A and the formation of tubes by endothelial cells. The cellular receptor(s) for human PSGs remain unknown. Therefore, we conducted these studies to identify the receptor for PSG1, the highest expressed member of the family. We show that removal of cell surface glycosaminoglycans (GAGs) by enzymatic or chemical treatment of cells or competition with heparin completely inhibited binding of PSG1. In addition, PSG1 did not bind to cells lacking heparan or chondroitin sulfate on their surface, and binding was restored upon transfection with all four syndecans and glypican-1. Importantly, the presence of GAGs on the surface of endothelial cells was required for the ability of PSG1 to induce tube formation. This finding indicates that the PSG1-GAG interaction mediates at least some of the PSG1 proposed functions.

Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis is poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis is part of lung remodeling and sought to characterize pathways leading to lymphangiogenesis in IPF. We found that the diameter of lymphatic vessels in alveolar spaces in IPF lung tissue correlated with disease severity, suggesting that the alveolar microenvironment plays a role in the lymphangiogenic process. In bronchoalveolar lavage fluid (BALF) from subjects with IPF, we found short-fragment hyaluronic acid, which induced migration and proliferation of lymphatic endothelial cells (LECs), processes required for lymphatic vessel formation. To determine the origin of LECs in IPF, we isolated macrophages from the alveolar spaces; CD11b(+) macrophages from subjects with IPF, but not those from healthy volunteers, formed lymphatic-like vessels in vitro. Our findings demonstrate that in the alveolar microenvironment of IPF, soluble factors such as short-fragment hyaluronic acid and cells such as CD11b(+) macrophages contribute to lymphangiogenesis. These results improve our understanding of lymphangiogenesis and tissue remodeling in IPF and perhaps other fibrotic diseases as well.

[COVID-19 associated mucormycosis. A case in Argentina]. / Mucormicosis asociada a COVID-19. Un caso en Argentina.

SARS-CoV-2 virus disease presents variable severity. Recently, an increasing report of cases of COVID-19 associated mucormycosis (CAM) has been observed, mainly in patients with diabetes mellitus, diabetic ketoacidosis or under steroids treatment. The highest number of cases have been reported in India, with a prevalence of 0.27 % in hospitalized patients with COVID-19 during year 2020, which implies a 2.1-fold increase in the prevalence of mucormycosis compared to year 2019. Although corticosteroids treatment reduces mortality in patients with severe COVID-19, its prolonged use, in combination with other clinical and immunological factors, could increase the risk of invasive fungal infection. We report a case of CAM in Argentina. This report represents a warning for considering the diagnosis of invasive fungal infection in patients with severe COVID-19.

La enfermedad COVID-19 provocada por el virus SARS-CoV-2 presenta una gravedad variable. Recientemente se ha observado un aumento en el número de casos informados de mucormicosis asociada a COVID-19 (CAM), principalmente en personas con diabetes mellitus, cetoacidosis diabética o en tratamiento con esteroides. El mayor número de casos ha sido notificado en India, en donde la prevalencia de CAM en pacientes hospitalizados en el año 2020 fue de 0.27%, lo que implica un aumento en la prevalencia de mucormicosis de 2.1 veces respecto del año 2019. Si bien el tratamiento con corticoides reduce la mortalidad en pacientes con COVID-19 grave, su uso prolongado, en combinación con otros factores clínicos e inmunológicos, puede aumentar el riesgo de infección fúngica invasiva. Comunicamos un caso de CAM en Argentina. El presente informe representa una alerta para fundar sospecha de infección fúngica invasiva en pacientes con COVID-19.

Mucormicosis asociada a COVID-19. Un caso en Argentina / COVID-19 associated mucormycosis. A case in Argentina

Resumen La enfermedad COVID-19 provocada por el virus SARS-CoV-2 presenta una gravedad variable. Recientemente se ha observado un aumento en el número de casos informados de mucormicosis asociada a COVID-19 (CAM), principalmente en personas con diabetes mellitus, cetoacidosis diabética o en tratamiento con esteroides. El mayor número de casos ha sido notificado en India, en donde la prevalencia de CAM en pacientes hospitalizados en el año 2020 fue de 0.27%, lo que implica un aumento en la prevalencia de mucormicosis de 2.1 veces respecto del año 2019. Si bien el tratamiento con corticoides reduce la mortalidad en pacientes con COVID-19 grave, su uso prolongado, en combinación con otros factores clínicos e inmunológicos, puede aumentar el riesgo de infección fúngica invasiva. Comunicamos un caso de CAM en Argentina. El presente informe representa una alerta para fundar sospecha de infección fúngica invasiva en pacientes con COVID-19.

Abstract SARS-CoV-2 virus disease presents variable severity. Recently, an increasing report of cases of COVID-19 associated mucormycosis (CAM) has been observed, mainly in patients with diabetes mellitus, diabetic ketoacidosis or under steroids treatment. The highest number of cases have been reported in India, with a prevalence of 0.27 % in hospitalized patients with COVID-19 during year 2020, which implies a 2.1-fold increase in the prevalence of mucormycosis compared to year 2019. Although corticosteroids treatment reduces mortality in patients with severe COVID-19, its prolonged use, in combination with other clinical and immunological factors, could increase the risk of invasive fungal infection. We report a case of CAM in Argentina. This report represents a warning for considering the diagnosis of invasive fungal infection in patients with severe COVID-19.

TGF-beta3 is required for the adhesion and intercalation of medial edge epithelial cells during palate fusion.

Transforming growth factor-beta3 (TGF-beta3) plays a critical role during palate development, since mutations of the TGF-beta3 gene give rise to cleft palate in both humans and mice. Striking alterations have been reported in the behaviour and differentiation of medial edge epithelial (MEE) cells in TGF-beta3 knockout mouse palates. In the present paper, we provide evidence of alterations in MEE intercellular adhesion in TGF-beta3 -/- mouse palates using immunohistochemistry with monoclonal antibodies to a panel of cell adhesion and cytoskeletal molecules including E-cadherin, alpha and beta catenin, beta actin, vinculin and beta2 integrin. In vitro labeling of opposing MEE with two different lipophilic markers and subsequent analysis by confocal microscopy revealed that wild type MEE cells intercalate as soon as the midline epithelial seam forms. This finding indicates that the palate may elongate in a dorso-ventral direction by means of convergent extension, as occurs in other embryonic developmental processes. In contrast, this intercalation does not occur in the TGF-beta3 -/- MEE but it can be rescued by the exogenous addition of TGF-beta3. Thus, the substantial alteration of MEE intercellular adhesion observed in TGF-beta3 -/- palates may account for the defect in palatal shelf adhesion and the formation of cleft palate.

[A review of diseases related to the intake of gluten]. / REVISIÓN DE LAS PATOLOGÍAS RELACIONADAS CON LA INGESTA DE GLUTEN.

Cereals are considered a basic food. Through the development of cooking, the human being has produced high- gluten-content food, so that it could make the most of its nutritional properties. Wheat is becoming one of the key elements of the Mediterranean diet. Amongst gluten- intake-related pathologies- gluten is present mainly in wheat, barley and rye- celiac disease (CD) is the most well-known. CD is a chronic inflammatory condition which affects gastrointestinal tract which develops in genetically predisposed individuals. The most common manifestation of CD is nutrients malabsorption. This protein trigger other pathology, wheat allergy (WA), which is an adverse immunological effect to gluten due to E immunoglobulin. A recent increased in non celiac gluten sensitivity (NCGS) has also been noticed, defined as the emergence of a range of gluten-intake related symptoms in patients for which celiac disease and wheat allergy have been ruled out. This article discusses these three conditions with their phatogenic mecanisms and the different clinic manifestations.

Los cereales han sido considerados un alimento fundamental de la dieta. A través del desarrollo de la cocina, el ser humano ha producido alimentos ricos en gluten, con el fin de aprovechar al máximo las propiedades nutricionales de este alimento. De tal manera que el trigo se ha convertido en uno de los elementos centrales de la dieta mediterránea. Entre las patologías relacionadas con la ingesta de gluten, contenido principalmente en el trigo, la cebada y el centeno, la enfermedad celíaca (EC) es la más conocida. La EC es una condición inflamatoria crónica que afecta al tracto gastrointestinal y que se desarrolla en sujetos genéticamente predispuestos. La manifestación más común es la malabsorción de nutrientes. Otra patología condicionada por esta proteína es la alergia al trigo (AT), que constituye una reacción inmunológica adversa al gluten mediada por la inmunoglobulina E. Recientemente está aumentando la sensibilidad al gluten no celíaca (SGNC), definida como la aparición de una variedad de manifestaciones relacionadas con la ingestión de gluten, en pacientes en los que la enfermedad celíaca y la alergia al trigo han sido excluidas. En este artículo se describen estas tres entidades con sus mecanismos patogénicos y las diferentes manifestaciones clínicas.

Aryl hydrocarbon receptor-induced adrenomedullin mediates cigarette smoke carcinogenicity in humans and mice.

Cigarette smoking (CS) is a leading cause of death worldwide. The aryl hydrocarbon receptor (AHR) is partially responsible for tobacco-induced carcinogenesis although the underlying mechanisms involving early effector genes have yet to be determined. Here, we report that adrenomedullin (ADM) significantly contributes to the carcinogenicity of tobacco-activated AHR. CS and AHR activating ligands induced ADM in vitro and in vivo but not in AHR-deficient fibroblasts and mice. Ectopic transfection of AHR rescued ADM expression in AHR(-/-) fibroblasts whereas AHR blockage with siRNA in wild type cells significantly decreased ADM expression. AHR regulates ADM expression through two intronic xenobiotic response elements located close to the start codon in the ADM gene. Using tissue microarrays we showed that ADM and AHR were coupregulated in lung tumor biopsies from smoker patients. Microarray meta-analysis of 304 independent microarray experiments showed that ADM is elevated in smokers and smokers with cancer. In addition, ADM coassociated with a subset of AHR responsive genes and efficiently differentiated patients with lung cancer from nonsmokers. In a novel preclinical model of CS-induced tumor progression, host exposure to CS extracts significantly elevated tumor ADM although systemic treatment with the ADM antagonist NSC16311 efficiently blocked tobacco-induced tumor growth. In conclusion, ADM significantly contributes the carcinogenic effect of AHR and tobacco combustion products. We suggest that therapeutics targeting the AHR/ADM axis may be of clinical relevance in the treatment of tobacco-induced pulmonary malignancies.

Update on primary HIV-1 resistance in Argentina: emergence of mutations conferring high-level resistance to nonnucleoside reverse transcriptase inhibitors in drug-naive patients.

Here we present a survey including 52 drug-naive recently HIV-1-infected subjects from Buenos Aires City and province (79%) and 3 other regions in Argentina (21%). Recent infections were established from previous negative serology (32/52), indeterminate Western blot (12/52), or acute retroviral syndrome after high-risk HIV exposure (8/52) within 9 months before genotyping (median time, 4.2 months). Genotyping was performed from plasma by sequencing both protease and reverse transcriptase. Phylogenetic analysis combined with bootscanning resulted in 21 subtype B sequences and 31 B/F recombinants (RecBF). On protease, minor resistance-related mutations were found in both subtype B and RecBF with low frequencies. The substitution L89M, recently suggested as a resistance-related mutation in some subtype F viruses, was observed in 1 RecBF. On reverse transcriptase, major resistance-related mutations were found in 4 of 52 (7.7%) patients from different health centers: M41L (subtype B) and K103N+/-P225H (1 RecBF and 2 subtype B). The greater than 5% resistance threshold found indicates a need for sentinel resistance surveillances calling for an update in the current resistance testing guidelines in Argentina.

Snail family members and cell survival in physiological and pathological cleft palates.

Palate fusion is a complex process that involves the coordination of a series of cellular changes including cell death and epithelial to mesenchymal transition (EMT). Since members of the Snail family of zinc-finger regulators are involved in both triggering of the EMT and cell survival, we decided to study their putative role in palatal fusion. Furthermore, Snail genes are induced by transforming growth factor beta gene (TGF-beta) superfamily members, and TGF-beta(3) null mutant mice (TGF-beta(3)-/-) show a cleft palate phenotype. Here we show that in the wild-type mouse at the time of fusion, Snail is expressed in a few cells of the midline epithelial seam (MES), compatible with a role in triggering of the EMT in a small subpopulation of the MES. We also find an intriguing relationship between the expression of Snail family members and cell survival associated to the cleft palate condition. Indeed, Snail is expressed in the medial edge epithelial (MEE) cells in TGF-beta(3)-/-mouse embryo palates, where it is activated by the aberrant expression of its inducer, TGF-beta(1), in the underlying mesenchyme. In contrast to Snail-deficient wild-type pre-adhesion MEE cells, Snail-expressing TGF-beta(3) mutant MEE cells survive as they do their counterparts in the chick embryo. Interestingly, Slug is the Snail family member expressed in the chick MEE, providing another example of interchange of Snail and Slug expression between avian and mammalian embryos. We propose that in the absence of TGF-beta(3), TGF-beta(1) is upregulated in the mesenchyme, and that in both physiological (avian) and pathological (TGF-beta(3)-/-mammalian) cleft palates, it induces the expression of Snail genes promoting the survival of the MEE cells and permitting their subsequent differentiation into keratinized stratified epithelium.