[Sulfhemoglobinemia secondary to the use of zopiclone. Report of two cases]. / Sulfohemoglobinemia secundaria a zopiclona. Casos clínicos.

Sulfhemoglobin (SulfHb) is formed by hemoglobin (Hb) oxidation by sulfur compounds. Sulfhemoglobinemia is mainly associated with drugs or intestinal bacterial overgrowth. Patients present with central cyanosis, an abnormal pulse oximetry and normal arterial oxygen partial pressure. These features are shared with methemoglobinemia (MetHb) whose diagnosis requires an arterial co-oximetry. Depending on the device used, SulfHb may produce interference with this technique. We report two females aged 31 and 43 years, consulting at the emergency room with cyanosis. Both had a history of acute and chronic, high dose zopiclone ingestion. Pulse oximetry showed desaturation but with normal arterial oxygen partial pressure. Cardiac and pulmonary diseases were ruled out. Co-oximetry in two different analyzers showed interference or normal MetHb percentages. No other complications ensued, and cyanosis decreased over days. Since MetHb was discarded among other causes of cyanosis in a compatible clinical context, the diagnosis of sulfhemoglobinemia was made. The confirmatory method is not available in Chile. The presence of SulfHb is difficult to diagnose, confirmatory tests are not readily available, and it frequently interferes with arterial co-oximetry. This is attributed to a similar absorbance peak of both pigments in arterial blood. Venous co-oximetry can be useful in this context. SulfHb is a self-limited condition in most cases, however it must be differentiated from methemoglobinemia to avoid inappropriate treatments like methylene blue.

Adipose tissue inflammation and metabolic syndrome. The proactive role of probiotics.

PURPOSE: The first part of this review focuses on the role of cells and molecules of adipose tissue involved in metabolic syndrome-induced inflammation and in the maintenance of this pathology. In the second part of the review, the potential role of probiotics-modulating metabolic syndrome-related inflammatory components is summarized and discussed. METHODS: The search for the current scientific literature was carried out using ScienceDirect, PubMed, and Google Scholar search engines. The keywords used were: metabolic syndrome, obesity, insulin resistant, adipose tissue, adipose tissue inflammation, chronic low-grade inflammation, immune cells, adipokines, cytokines, probiotics, and gut microbiota. RESULTS AND CONCLUSIONS: Chronic low-grade inflammation that characterized metabolic syndrome can contribute to the development of the metabolic dysfunctions involved in the pathogenesis of its comorbidities. Adipose tissue is a complex organ that performs metabolic and immune functions. During metabolic syndrome, an imbalance in the inflammatory components of adipose tissue (immune cells, cytokines, and adipocytokines), which shift from an anti-inflammatory to a pro-inflammatory profile, can provoke metabolic syndrome linked complications. Further knowledge concerning the immune function of adipose tissue may contribute to finding better alternatives for the treatment or prevention of such disorders. The control of inflammation could result in the management of many of the pathologies related to metabolic syndrome. Due to the strong evidence that gut microbiota composition plays a role modulating the body weight, adipose tissue, and the prevalence of a low-grade inflammatory status, probiotics emerge as valuable tools for the prevention of metabolic syndrome and health recovery.

Promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions are associated with tumor differentiation, nodal involvement and survival.

Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision medicine workflows. DNA from 21 HNSCC and 10 healthy oral tissue samples was hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. A total of 738 DMRs were unique to laryngeal cancer (n=7), 889 DMRs were unique to oral cavity cancer (n=10) and 363 DMRs were unique to pharyngeal cancer (n=6). Based on the genome-wide analysis and a Gene Ontology analysis, 10 candidate genes were selected to test for prognostic value and association with clinicopathological features. TIMP3 was associated with tumor differentiation in oral cavity cancer (P=0.039), DAPK1 was associated with nodal involvement in pharyngeal cancer (P=0.017) and PAX1 was associated with tumor differentiation in laryngeal cancer (P=0.040). A total of five candidate genes were selected, DAPK1, CDH1, PAX1, CALCA and TIMP3, for a prevalence study in a larger validation cohort: Oral cavity cancer samples (n=42), pharyngeal cancer tissues (n=25) and laryngeal cancer samples (n=52). PAX1 hypermethylation differed across HNSCC anatomic subsites (P=0.029), and was predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (P=0.043) and Cox regression analysis of overall survival (P=0.001) showed that DAPK1 methylation is associated with better prognosis in HNSCC. The findings of the present study showed that the HNSCC subsites oral cavity, pharynx and larynx display substantial differences in aberrant DNA methylation patterns, which may serve as prognostic biomarkers and therapeutic targets.

Four new species of mygalomorph spiders (Araneae, Halonoproctidae and Theraphosidae) from the Colombian Pacific region (Bahía Solano, Chocó).

The Colombian Pacific coast is an amazing natural region, immersed in one of the most unknown biodiversity hotspots in the world. An expedition carried out in the north of this area, at the Jardín Botánico del Pacífico (JBP) in Bahía Solano, Chocó, focused on studying the diversity of the mygalomorph spider fauna, allowed us to discover four new species included in the families Halonoproctidae and Theraphosidae. The trapdoor species Ummidiasolanasp. nov., and the theraphosids species Euthycaeluscunampiasp. nov. (Schismatothelinae), Melloinapacificasp. nov. (Glabropelmatinae), and Neischnocolusmecanasp. nov. (Theraphosinae) are illustrated, diagnosed, and described in detail. Photographs of somatic features and copulatory organs and a distribution map are provided. Morphological, taxonomical, and biogeographical aspects are discussed for each species. All these taxonomic novelties represent the first records of these genera for the region, expanding the range of geographic distribution of each of them. This work constitutes the first effort focused on characterizing the community of Mygalomorphae species in the Chocó Biogeographic Region.

A Case of Multidrug-Resistant (MDR) Tuberculosis and HIV Co-Infection.

Pulmonary tuberculosis (TB) infection is a public health concern in the United States. Mycobacterium tuberculosisantimicrobial resistance is a global public health concern. We present a case of a young man from Venezuela who presented to a hospital in New York and was newly diagnosed with pulmonary tuberculosis, human immunodeficiency virus (HIV), and syphilis. His TB isolate was found to be resistant to multiple anti-TB drugs, presenting unusual challenges in treating multidrug-resistant TB with HIV co-infection.

Functional Characterization and Toxicity of Pectin from Red Chilto Fruit Waste (Peels).

BACKGROUND: Food and agricultural wastes constitute a rich source of functional ingredients for the food, pharmaceutical, and cosmetic industries. In this context, by-products from the red variety of Solanum betaceum fruits (chilto) from Northwestern Argentina are suitable sources for pectin extraction. METHODS: In this study, pectin from the peels of red chilto fruits was extracted and characterized. RESULTS: The recovery yield of red chilto peel pectin was about 24%, and it was co-extracted with 40.0 mg phenolic compounds, 6.5 mg anthocyanins, and 4.7 g proteins per 100 g of pectin. The pectin obtained from red chilto showed proper technological functionality displaying water and oil holding capacities of 4.2 and 2.0%, respectively, an emulsifying capacity of 83%, emulsion stability of 87.5%, foaming capacity of 21.1%, and foaming stability of 79.1%. The pectin displayed antioxidant activity with the ability to scavenge ABTS radical, superoxide anion, and H2O2. The polysaccharide exhibited in vitro hypoglycemic potential and inhibited the α-amylase enzyme, retarded glucose diffusion, and improved the cellular uptake of glucose in a Saccharomyces cerevisiae model. The extract was non-toxic on acute toxicity tests. CONCLUSIONS: Red chilto pectin showed potential as a new and safe functional ingredient for the design of foods, health products, and cosmetics.

Ventilatory Parameters in Obstetric Patients With COVID-19 and Impact of Delivery: A Multicenter Prospective Cohort Study.

BACKGROUND: Current evidence on obstetric patients requiring advanced ventilatory support and impact of delivery on ventilatory parameters is retrospective, scarce, and controversial. RESEARCH QUESTION: What are the ventilatory parameters for obstetric patients with COVID-19 and how does delivery impact them? What are the risk factors for invasive mechanical ventilation (IMV) and for maternal, fetal, and neonatal mortality? STUDY DESIGN AND METHODS: Prospective, multicenter, cohort study including pregnant and postpartum patients with COVID-19 requiring advanced ventilatory support in the ICU. RESULTS: Ninety-one patients were admitted to 21 ICUs at 29.2 ± 4.9 weeks; 63 patients (69%) delivered in ICU. Maximal ventilatory support was as follows: IMV, 69 patients (76%); high-flow nasal cannula, 20 patients (22%); and noninvasive mechanical ventilation, 2 patients (2%). Sequential Organ Failure Assessment during the first 24 h (SOFA24) score was the only risk factor for IMV (OR, 1.97; 95% CI, 1.29-2.99; P = .001). Respiratory parameters at IMV onset for pregnant patients were: mean ± SD plateau pressure (PP), 24.3 ± 4.5 cm H2O; mean ± SD driving pressure (DP), 12.5 ± 3.3 cm H2O; median static compliance (SC), 31 mL/cm H2O (interquartile range [IQR], 26-40 mL/cm H2O); and median Pao2 to Fio2 ratio, 142 (IQR, 110-176). Respiratory parameters before (< 2 h) and after (≤ 2 h and 24 h) delivery were, respectively: mean ± SD PP, 25.6 ± 6.6 cm H2O, 24 ± 6.7 cm H2O, and 24.6 ± 5.2 cm H2O (P = .59); mean ± SD DP, 13.6 ± 4.2 cm H2O, 12.9 ± 3.9 cm H2O, and 13 ± 4.4 cm H2O (P = .69); median SC, 28 mL/cm H2O (IQR, 22.5-39 mL/cm H2O), 30 mL/cm H2O (IQR, 24.5-44 mL/cm H2O), and 30 mL/cm H2O (IQR, 24.5-44 mL/cm H2O; P = .058); and Pao2 to Fio2 ratio, 134 (IQR, 100-230), 168 (IQR, 136-185), and 192 (IQR, 132-232.5; P = .022). Reasons for induced delivery were as follows: maternal, 43 of 71 patients (60.5%); maternal and fetal, 21 of 71 patients (29.5%); and fetal, 7 of 71 patients (9.9%). Fourteen patients (22.2%) continued pregnancy after ICU discharge. Risk factors for maternal mortality were BMI (OR, 1.10; 95% CI, 1.006-1.204; P = .037) and comorbidities (OR, 4.15; 95% CI, 1.212-14.20; P = .023). Risk factors for fetal or neonatal mortality were gestational age at delivery (OR, 0.67; 95% CI, 0.52-0.86; P = .002) and SOFA24 score (OR, 1.53; 95% CI, 1.13-2.08; P = .006). INTERPRETATION: Contrary to expectations, pregnant patient lung mechanics were similar to those of the general population with COVID-19 in the ICU. Delivery was induced mainly for maternal reasons, but did not change ventilatory parameters other than Pao2 to Fio2 ratio. SOFA24 score was the only risk factor for IMV. Maternal mortality was associated independently with BMI and comorbidities. Risk factors for fetal and neonatal mortality were SOFA24 score and gestational age at delivery.

Roadmapping technique in the hybrid operating room for the microsurgical treatment of complex intracranial aneurysms.

OBJECTIVE: To describe the roadmapping technique and our three-year experience in the management of intracranial aneurysms in the hybrid operating room. METHODS: We analyzed all patients who underwent surgical clipping for cerebral aneurysms with the roadmapping technique from January 2017 to September 2019. We report demographic, clinical, and morphological variables, as well as clinical and radiological outcomes. We further describe three illustrative cases of the technique. RESULTS: A total of 13 patients were included, 9 of which (69.2%) presented with subarachnoid hemorrhage, with a total of 23 treated aneurysms. All patients were female, with a mean age of 47.7 years (range 31-63). All cases were anterior circulation aneurysms, the most frequent location being the ophthalmic segment of the internal carotid artery (ICA) in 11 cases (48%), followed by posterior communicating in 8 (36%), and ICA bifurcation in 2 (8%). Intraoperative clip repositioning was required in 9 aneurysms (36%) as a result of the roadmapping technique in the hybrid operating room. There were no residual aneurysms in our series, nor reported mortality. CONCLUSIONS: The roadmapping technique in the hybrid operating room offers a complementary tool for the adequate occlusion of complex intracranial aneurysms, as it provides a real time fluoroscopic-guided clipping technique, and clip repositioning is possible in a single surgical stage, whenever a residual portion of the aneurysm is identified. This technique also provides some advantages, such as immediate vasospasm identification and treatment with intra-arterial vasodilators, balloon proximal control for certain paraclinoid aneurysms, and simultaneous endovascular treatment in selected cases during a single stage.

In Vitro Hypoglycemic and Anti-Inflammatory Potential and Toxicity of Powders from Pulp and by-Products of Ziziphus mistol from Argentina.

BACKGROUND: The Ziziphus mistol fruit (vulgar name mistol) is used in northwestern Argentina in traditional food and beverage preparations and popular medicines for liver and respiratory disorders. AIMS: The aim of this research was to evaluate the hypoglycemic and anti-inflammatory activity in pulp powders and sub-products (skin and seeds) of mistol fruit, along with their toxicity. METHODS: Powders from mistol seeds, pulp, and skin were obtained. Antioxidant capacity and inhibitory activity against key enzymes involved in metabolic syndrome were determined by in vitro assays. RESULTS: The mistol powders obtained from the different fruit parts reduced glucose bioaccessibility. Before and after simulated gastroduodenal digestion, the polyphenol-enriched extracts (PEE) obtained from mistol powders increased glucose uptake by yeast cells and inhibited the pivotal enzymes of the inflammatory pathway (cyclooxygenase-2, lipooxygenase-1, and phospholipase A2). The analyzed mistol powders did not show acute toxicity or genotoxicity in model organisms and cell cultures. CONCLUSIONS: These results evince the potentiality of both the pulp from Z. mistol fruits and residual biomass (seeds and skin) to obtain biofunctional powders to use as supplements for metabolic disorders associated with chronic diseases.

Expression of Brown and Southern Black Widow Spider (Araneae: Theridiidae) Latrotoxins Is Tissue- and Life Stage-Specific for α-Latroinsectotoxins and δ-Latroinsectotoxins and Is Ubiquitous for α-Latrotoxins.

Widow spiders are widely known for their potent venom toxins that make them among the few spiders of medical concern. The latrotoxins are the most well-studied widow toxins and include both the vertebrate-specific latrotoxins and the insect-specific latroinsectotoxins (LITs). Previous studies have shown that toxins are not limited to expression in the venom glands of adult spiders; however, gaps exist in latrotoxin screening across all life stages for brown widows, Latrodectus geometricus and southern black widows, Latrodectus mactans. In this study, we screened male and female venom gland, cephalothorax, and abdomen tissues, spiderling cephalothorax and abdomen tissues, and eggs of both L. geometricus and L. mactans, for the presence of three latrotoxins: α-latrotoxin (α-LTX), and α- and δ-latroinsectotoxins (α/δ-LITs). Widows were locally collected. Extracted RNA was used to prepare cDNA that was analyzed by PCR for the presence or absence of latrotoxin expression. Results show that expression profiles between the two species are very similar but not identical. Expression of α-LTX was found in all life stages in all tissues examined for both species. For both species, no LIT expression was detected in eggs and variable patterns of α-LIT expression were detected in spiderlings and adults. Notably, δ-LIT could only be detected in females for both species. Our results show that latrotoxin expression profiles differ within and between widow species. Data on their expression distribution provide further insight into the specific latrotoxins that contribute to toxicity profiles for each life stage in each species and their specific role in widow biology.

Impact of liberal versus conservative saturation targets on gas exchange indices in COVID-19 related acute respiratory distress syndrome: a physiological study. / Impacto de alvos de saturação liberais versus conservadores sobre os índices de troca gasosa na síndrome do desconforto respiratório agudo relacionada à COVID-19: um estudo fisiológico.

OBJECTIVE: To compare gas exchange indices behavior by using liberal versus conservative oxygenation targets in patients with moderate to severe acute respiratory distress syndrome secondary to COVID-19 under invasive mechanical ventilation. We also assessed the influence of high FiO2 on respiratory system mechanics. METHODS: We prospectively included consecutive patients aged over 18 years old with a diagnosis of COVID-19 and moderate-severe acute respiratory distress syndrome. For each patient, we randomly applied two FiO2 protocols to achieve SpO2 88% - 92% or 96%. We assessed oxygenation indices and respiratory system mechanics. RESULTS: We enrolled 15 patients. All the oxygenation indices were significantly affected by the FiO2 strategy (p < 0.05) selected. The PaO2/FiO2 deteriorated, PA-aO2 increased and Pa/AO2 decreased significantly when using FiO2 to achieve SpO2 96%. Conversely, the functional shunt fraction was reduced. Respiratory mechanics were not affected by the FiO2 strategy. CONCLUSION: A strategy aimed at liberal oxygenation targets significantly deteriorated gas exchange indices, except for functional shunt, in COVID-19-related acute respiratory distress syndrome. The respiratory system mechanics were not altered by the FiO2 strategy.Clinical Trials Register: NCT04486729.

OBJETIVO: Comparar o comportamento dos índices de troca gasosa conforme o uso de alvos de oxigenação liberais em comparação a conservadores em pacientes com síndrome do desconforto respiratório agudo moderada a grave secundária à COVID-19 e em uso de ventilação mecânica; avaliar a influência da FiO2 elevada na mecânica do sistema respiratório. MÉTODOS: Foram incluídos prospectivamente pacientes consecutivos com idades acima de 18 anos, diagnóstico de COVID-19 e síndrome do desconforto respiratório agudo moderada e grave. Para cada paciente, aplicou-se aleatoriamente dois protocolos de FiO2 para obter SpO2 de 88% a 92% ou 96%. Avaliaram-se os índices de oxigenação e a mecânica do sistema respiratório. RESULTADOS: Foram incluídos 15 pacientes. Todos seus índices foram significantemente afetados pela estratégia de FiO2 (p < 0,05). A proporção PaO2/FiO2 deteriorou, o PA-aO2 aumentou e o Pa/AO2 diminuiu significantemente com a utilização de FiO2 para obter SpO2 96%. Opostamente, a fração de shunt funcional foi reduzida. A mecânica respiratória não foi afetada pela estratégia de FiO2. CONCLUSÃO: Uma estratégia com alvos liberais de oxigenação deteriorou significantemente os índices de troca gasosa, com exceção do shunt funcional, em pacientes com síndrome do desconforto respiratório agudo relacionada à COVID-19. A mecânica do sistema respiratório não foi alterada pela estratégia de FiO2.Registro Clinical Trials: NCT04486729.

Solanum betaceum Fruits Waste: A Valuable Source of Bioactive Compounds to Be Used in Foods and Non-Foods Applications.

The fruit supply chain generates large amounts of waste that are often used as animal feed and in the production of both composts and fertilizers and biogas (anaerobic digestion). Since these types of procedures imply high economic costs related to drying, storage, and transport processes, more efficient and environmentally friendly utilization and recycling of this kind of waste are becoming significant for governments and industries. However, improper waste disposal increases the burden on the environment. Many of these fruit wastes, such as Solanum betaceum fruit waste, viz., peels, seeds, and pomace, could be considered potent bio-resource materials for several applications in the food and non-food industries due to their richness in valuable compounds. The basic composition of Solanum betaceum fruits seed has a high content of protein (20%), fiber (around 25%), sugar (11-20%) and low lipid content (0.4%), while S. betaceum peel has a low content of sugar (2-9%), protein (8-10%) and lipid (0.2-0.8%) and high fiber content (23%). Regarding the phytochemicals, the wastes have a high level of phenolics (0.2-0.6%) and pigments such as anthocyanins (0.06%). The inherent bioactive compounds of waste can be used as natural ingredients for foods, cosmetics, medicines, and the production of packaging materials production. Along this line, the present review covers all possible approaches for the valorization of S.betaceum waste in the food and non-food sectors.

[Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study]. / Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en Argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19.

During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough supplies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Buenos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.

Clinical characteristics, respiratory management, and determinants of oxygenation in COVID-19 ARDS: A prospective cohort study.

PURPOSE: To identify determinants of oxygenation over time in patients with COVID-19 acute respiratory distress syndrome (ARDS); and to analyze their characteristics according to Berlin definition categories. MATERIALS AND METHODS: Prospective cohort study including consecutive mechanically ventilated patients admitted between 3/20/2020-10/31/2020 with ARDS. Epidemiological and clinical data on admission; outcomes; ventilation, respiratory mechanics and oxygenation variables were registered on days 1, 3 and 7 for the entire population and for ARDS categories. RESULTS: 1525 patients aged 61 ± 13, 69% male, met ARDS criteria; most frequent comorbidities were obesity, hypertension, diabetes and respiratory disease. On admission, 331(21%), 849(56%) and 345(23%) patients had mild, moderate and severe ARDS; all received lung-protective ventilation (mean tidal volumes between 6.3 and 6.7 mL/kg PBW) and intermediate PEEP levels (10-11 cmH2O). PaO2/FiO2, plateau pressure, static compliance, driving pressure, ventilation ratio, pH and D-dimer >2 mg/L remained significantly different among the ARDS categories over time. In-hospital mortality was, respectively, 55%, 58% and 70% (p < 0.000). Independent predictors of changes of PaO2/FiO2 over time were BMI; preexistent respiratory disease; D-dimer >2 mg/L; day 1-PEEP, and day 1-ventilatory ratio. CONCLUSION: Hypoxemia in patients with COVID-19-related ARDS is associated with comorbidities, deadspace and activated coagulation markers, and disease severity-reflected by the PEEP level required.

Engineered red blood cells (activating antigen carriers) drive potent T cell responses and tumor regression in mice.

Activation of T cell responses is essential for effective tumor clearance; however, inducing targeted, potent antigen presentation to stimulate T cell responses remains challenging. We generated Activating Antigen Carriers (AACs) by engineering red blood cells (RBCs) to encapsulate relevant tumor antigens and the adjuvant polyinosinic-polycytidylic acid (poly I:C), for use as a tumor-specific cancer vaccine. The processing method and conditions used to create the AACs promote phosphatidylserine exposure on RBCs and thus harness the natural process of aged RBC clearance to enable targeting of the AACs to endogenous professional antigen presenting cells (APCs) without the use of chemicals or viral vectors. AAC uptake, antigen processing, and presentation by APCs drive antigen-specific activation of T cells, both in mouse in vivo and human in vitro systems, promoting polyfunctionality of CD8+ T cells and, in a tumor model, driving high levels of antigen-specific CD8+ T cell infiltration and tumor killing. The efficacy of AAC therapy was further enhanced by combination with the chemotherapeutic agent Cisplatin. In summary, these findings support AACs as a potential vector-free immunotherapy strategy to enable potent antigen presentation and T cell stimulation by endogenous APCs with broad therapeutic potential.

Superiority of craniotomy over supportive care for octogenarians and nonagenarians in operable acute traumatic subdural hematoma.

OBJECTIVE: Neurosurgical evacuation in elderly trauma patients is controversial. We analyzed impact of craniotomy for acute subdural hematoma on survival in octogenarians and nonagenarians. Methods The study population included all patients aged ≥ 80 years who presented with acute traumatic SDHs 09/01/15 - 01/01/20, with radiography indicating operative eligibility (i.e. MLS >5 mm and/or overall thickness >10 mm). Of 1054 TBIs aged ≥ 80 years, 104 (9.87%) were surgically indicated. Of these, 35 received craniotomy and 69 received supportive measures due to family/patient wishes or surgeon's professional decision. We analyzed these data using a Poisson regression adjusted for influence of covariates. RESULTS: Of 35 craniotomies, 21 (60.00%) were deceased at 2 years of follow-up, compared to 48 (69.57%) deceased of 69 non-surgical patients. No significant demographic differences existed between these groups, other than age (craniotomy patients were younger; median age 84 vs 86; p < 0.001). In outcomes, the craniotomy cohort survived longer and in higher proportions (p = 0.028; Gehan-Breslow-Wilcoxon). When adjusting for covariates, this effect became more pronounced: craniotomy patients died at 41.1% the rate of non-surgical ones. Of all the covariates, only initial GCS significantly impacted the protective effect of craniotomy. In a logarithmic relationship, each point on initial GCS was associated with less benefit from surgery. We also found that patients with GCS< 3 were overall less likely to benefit from surgery. Our conclusions are limited by the impact of patient/surgeon choice on whether or not to operate. It is possible healthier subjects elected for craniotomies. We have attempted to correct for this by including comorbidities as covariates in our regression analyses. CONCLUSIONS: Our results indicate a surgical benefit for this elderly cohort, consistent with prior findings of benefit in the setting of severe traumatic aSDH. Patients with worse neurologic impairment, i.e. low GCS, had the greatest survival benefit from surgical intervention.

Precision health diagnostic and surveillance network uses S gene target failure (SGTF) combined with sequencing technologies to track emerging SARS-CoV-2 variants.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic revealed a worldwide lack of effective molecular surveillance networks at local, state, and national levels, which are essential to identify, monitor, and limit viral community spread. SARS-CoV-2 variants of concern (VOCs) such as Alpha and Omicron, which show increased transmissibility and immune evasion, rapidly became dominant VOCs worldwide. Our objective was to develop an evidenced-based genomic surveillance algorithm, combining reverse transcription polymerase chain reaction (RT-PCR) and sequencing technologies to quickly identify highly contagious VOCs, before cases accumulate exponentially. METHODS: Deidentified data were obtained from 508,969 patients tested for coronavirus disease 2019 (COVID-19) with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA-certified clinical laboratories in Puerto Rico (n = 86,639) and in three CLIA-certified clinical laboratories in the United States (n = 422,330). RESULTS: TaqPath data revealed a frequency of S Gene Target Failure (SGTF) > 47% for the last week of March 2021 in both, Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021. The weekly SGTF rate in US samples was high (>8%) from late December to early January and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico was concurrent with a sharp increase in VOCs among all SARS-CoV-2 sequences from Puerto Rico uploaded to Global Influenza Surveillance and Response System (GISAID) (n = 461). Alpha variant frequency increased from <1% in the last week of January 2021 to 51.5% of viral sequences from Puerto Rico collected in the last week of March 2021. CONCLUSIONS: According to the proposed evidence-based algorithm, approximately 50% of all SGTF patients should be managed with VOCs self-quarantine and contact tracing protocols, while WGS confirms their lineage in genomic surveillance laboratories. Our results suggest this workflow is useful for tracking VOCs with SGTF.

Lactic Acid Bacteria Strains Differently Modulate Gut Microbiota and Metabolic and Immunological Parameters in High-Fat Diet-Fed Mice.

Background: Dietary strategies, including the use of probiotics as preventive agents that modulate the gut microbiota and regulate the function of adipose tissue, are suitable tools for the prevention or amelioration of obesity and its comorbidities. We aimed to evaluate the effect of lactic acid bacteria (LAB) with different adipo- and immuno-modulatory capacities on metabolic and immunological parameters and intestinal composition microbiota in high-fat-diet-induced in mice fed a high-fat diet Methods: Balb/c weaning male mice were fed a standard (SD) or high-fat diet (HFD) with or without supplementation with Limosilactobacillus fermentum CRL1446 (CRL1446), Lactococcus lactis CRL1434 (CRL1434), or Lacticaseibacillus casei CRL431 (CRL431) for 45 days. Biochemical and immunological parameters, white-adipose tissue histology, gut microbiota composition, and ex vivo cellular functionality (adipocytes and macrophages) were evaluated in SD and HFD mice. Results: CRL1446 and CRL1434 administration, unlike CRL431, induced significant changes in the body and adipose tissue weights and the size of adipocytes. Also, these strains caused a decrease in plasmatic glucose, cholesterol, triglycerides, leptin, TNF-α, IL-6 levels, and an increase of IL-10. The CRL1446 and CRL1434 obese adipocyte in ex vivo functionality assays showed, after LPS stimulus, a reduction in leptin secretion compared to obese control, while with CRL431, no change was observed. In macrophages from obese mice fed with CRL1446 and CRL1434, after LPS stimulus, lower levels of MCP-1, TNF-α, IL-6 compared to obese control were observed. In contrast, CRL431 did not induce modification of cytokine values. Regarding gut microbiota, all strain administration caused a decrease in Firmicutes/Bacteroidetes index and diversity. As well as, related to genus results, all strains increased, mainly the genera Alistipes, Dorea, Barnesiella, and Clostridium XIVa. CRL1446 induced a higher increase in the Lactobacillus genus during the study period. Conclusions: The tested probiotic strains differentially modulated the intestinal microbiota and metabolic/immunological parameters in high-fat-diet-induced obese mice. These results suggest that CRL1446 and CRL1434 strains could be used as adjuvant probiotics strains for nutritional treatment to obesity and overweight. At the same time, the CRL431 strain could be more beneficial in pathologies that require regulation of the immune system.

Clinical characteristics and outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study.

BACKGROUND: Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country. METHODS: In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete. FINDINGS: Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52-70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7-22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0-7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H2O (8-12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO2) to fractional inspired oxygen (FiO2) was 160 (IQR 111-218), respiratory system compliance 36 mL/cm H2O (29-44), driving pressure 12 cm H2O (10-14), and FiO2 0·60 (0·45-0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01-1·03]), Charlson score (1·16 [1·11-1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10-1·71]), vasopressor use on day 1 (1·29 [1·07-1·55]), D-dimer concentration (1·02 [1·01-1·03]), PaO2/FiO2 on day 1 (0·998 [0·997-0·999]), arterial pH on day 1 (1·01 [1·00-1·01]), driving pressure on day 1 (1·05 [1·03-1·08]), acute kidney injury (1·66 [1·36-2·03]), and month of admission (1·10 [1·03-1·18]) as independent predictors of mortality. INTERPRETATION: In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere. FUNDING: None. TRANSLATION: For the Spanish translation of the Summary see Supplementary Materials section.

Integral use of Argentinean Solanum betaceum red fruits as functional food ingredient to prevent metabolic syndrome: effect of in vitro simulated gastroduodenal digestion.

The "red chilto" (Solanum betaceum Cav) is a native fruit from the Yungas forest of Argentina. Red chilto is a neglected and underutilized native species (NUS). The objective of this work was to evaluate the potentiality of pulp, seed and skin from "red chilto" as a functional food ingredient to add value to a native resource of Argentine Yungas to promote sustainable integral use of it. The powders have low carbohydrate and sodium content and are a source of vitamin C, phenolic acids (rosmarinic acid and caffeoylquinic acid), anthocyanins, condensed tannins, carotenoids, potassium, and fiber. The phenolics of chilto powders showed, before and after simulated gastroduodenal digestion, antioxidant activity (ABTS•+; H2O2; O2 •; HO•) and were able to inhibit enzymes related to metabolic syndrome, such as α-glucosidase, α-amylase and lipase. Chilto powder showed hypoglycemic effect by increasing glucose adsorption, decreasing glucose diffusion rate and by promoting glucose transport across the cell membrane. These results suggest the potential of Argentinean "red chilto" fruits as functional food ingredients or dietary supplements to prevent metabolic syndrome principally by its antioxidant, hypoglycemic and hypolipemic effects.