Management of Patients with Suspected or Confirmed Antibiotic Allergy: Executive Summary of Guidelines from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC).

Suspected or confirmed antibiotic allergy is a frequent clinical circumstance that influences antimicrobial prescription and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs in several countries. These guidelines aim to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. An expert panel (11 members of various scientific societies) formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence, and formulated graded recommendations when possible. The answers to all the questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy was recommended to improve antibiotic selection and, consequently, clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated, as were recommendations on the implementation and monitoring of the impact of the guidelines. Antimicrobial stewardship programs and allergists should design and implement activities that facilitate the most appropriate use of antibiotics in these patients.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

[Pharmacological treatment of COVID-19: Narrative review of the Working Group in Infectious Diseases and Sepsis (GTEIS) and the Working Groups in Transfusions and Blood Products (GTTH)]. / Tratamiento farmacológico de la COVID-19: revisión narrativa de los Grupos de Trabajo de Enfermedades Infecciosas y Sepsis (GTEIS) y del Grupo de Trabajo de Transfusiones Hemoderivados (GTTH).

Infection by the SARS-CoV-2 virus, known as COVID-19 (COronaVIrus Disease-19) was initially detected in China in December 2019, and has subsequently spread rapidly throughout the world, to the point that on March 11 the World Health Organization (WHO) reported that the outbreak could be defined as a pandemic. COVID-19 disease ranges from mild flu-like episodes to other serious and even life-threatening conditions, mainly due to acute respiratory failure. These patients are frequently admitted to our Intensive Care Units in relation to acute respiratory distress syndrome. The lack of a treatment based on scientific evidence has led to the use of different management guidelines, in many cases with rapid changes in the applied protocols. Recent reviews in reputed journals have underscored the lack of proven therapies and the need for clinical trials to establish clear and objective treatment guidelines. The present study provides an update on the currently applied treatment, and intends to offer help in relation to daily care, without seeking to replace the protocols adopted in each individual center.

[Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU]. / Manejo de las complicaciones infecciosas asociadas con la infección por coronavirus en pacientes graves ingresados en UCI.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

Hypoxia modulates the transcriptional immunological response in Oncorhynchus kisutch.

Oncorhynchus kisutch is the third most cultivated salmonid species in the Chilean salmon industry and its farming conditions are characterised by high stocking density leading to the generation of high levels of organic matter (food - feces) and decomposition. In addition to the increasingly frequent hypoxic oceanographic events, these inappropriate farming conditions increase the demand for oxygen within the fish farm pen and lead to the appearance of hypoxic events that are harmful to fish.This study aimed to evaluate the stress response (cortisol) and transcription of genes involved in the immune response in head kidney and spleen of Oncorhynchus kisutch subjected to chronic hypoxic stress conditions. The fish were exposed to 100%, 60%, 50%, 35%, and 25% of DO for 28 days, then the blood (plasma), head kidney and spleen were removed. We observed mortality in the 25% DO group at days 15 and 20. Plasma cortisol increased significantly under 35% and 25% DO conditions compared to control. Transcription of Toll-like receptors (TLR1, TLR5M, TLR8, and TLR9) and cytokines (IL-1ß, IL6, IL10, TNF-α) increased in the head kidney only in the 50% DO group, while in spleen there was an increase of these markers in the conditions of 60%, 35%, and 25% DO. As for the markers involved in cell-mediated immunity, CD4-MHCII and CD8-MHCI do not have a clear expression pattern, although there was down-regulation in MHCII transcription in the head kidney, in all the hypoxia conditions evaluated. Finally, IgM transcription was increased in the spleen in all hypoxia conditions, although it wasn't always statistically significant compared to the control. These results indicate that chronic hypoxia induces the stress response, increasing plasma cortisol levels and modulating the transcription of genes involved in the innate and adaptive immune response. The expression patterns were tissue-specific, indicating that the degree of hypoxia differentially affects the transcription of genes involved in the immune response of Oncorhynchus kisutch.

Effect of forage type in the ovine diet on the nutritional profile of sheep milk cheese fat.

The high nutritional value of sheep milk can be advantageous in the manufacture of cheese, and fat plays an important role in sheep cheese properties. The aim of this study was to investigate the effect of feeding common hay or silage diets used in commercial farms on the nutritional value of sheep cheese fat. We also monitored the effect of cheese ripening period on the fatty acid profile. Cheeses were produced from milk of sheep fed hay and silage diets from 8 farms, on 4 separate occasions (February, May, August, and November) over a 1-yr period. Eighty-four individual fatty acids were determined and identified by gas chromatography. Ripening time (100 and 180 d) significantly reduced moisture, acidity, and water activity of cheeses but did not affect the fatty acid content. However, hay feeding, compared with silage feeding, led to cheeses with 1.5- and 1.3-fold higher contents of vaccenic acid and conjugated linoleic acid, without detrimental changes in saturated and n-3 (omega-3) fatty acid composition. Hay forages could be a low-cost alternative for producing cheese with a fatty acid profile suitable for human health, which is an aspect of great interest to the food industry.

Impact and risk factors of non-adherence to 5-aminosalicylates in quiescent ulcerative colitis evaluated by an electronic management system.

BACKGROUND AND OBJECTIVE: To determine the impact of non-adherence to 5-Aminosalicylates (5-ASA) on the risk of flares and to identify risk factors of non-adherence. METHODS: Observational, cohort study of ulcerative colitis (UC) patients in clinical remission at least 6 months on 5-ASA monotherapy maintenance prescribed by an electronic management program. Adherence was considered when 80% of the prescribed 5-ASA had been dispensed at the pharmacy. The study analyzed the existence and degree of 5-ASA adherence, disease course, UC phenotypic expression, and 5-ASA dose and regimen, and consumption of non-UC chronic drugs during 2-year follow-up. RESULTS: The study included 274 patients, 49% males with a median age of 38 (27-49) years old. Overall, 41% of patients were non-adherent to 5-ASA. Risk of flares was reduced in the adherent group (36% vs 54%; OR = 0,484; p = 0,004), mainly the mild ones (26% vs 38%; OR = 0,559; p = 0,031). Non-adherence was associated with younger age at diagnosis (32 (26-45) vs 41.5 (21-50), p = 0.000) and no-consumption of other chronic treatments (1.1 vs 2.1; OR = 1709; p = 0,048). CONCLUSION: Non-adherence to 5-ASA evaluated by the pharmaceutical management system was at 41% with a higher risk of relapse. Younger patients and patients who do not receive non-UC chronic treatments showed lower adherence rate.

Lectins from Eichornia crassipens and Lemna minor may be involved in Vibrio Cholerae El Tor adhesion.

Vibrio cholerae (Vc) has been isolated from roots of aquatic plants during epidemic or interepidemic periods. It has been suggested that the lectins from the roots of aquatic plants play a role as reservoirs of Vc. In this paper, we evaluated the activity of lectins from Lemna minor and Eichornia crassipens plants as potential mediators of the Vc strain El Tor (Vct). We found that Lemna minor extract showed high specificity towards blood groups O and B. Eichornia crassipens extract showed high specificity towards blood group A and O. Sugar competition experiments demonstrated that Lemna minor extract showed a high recognition to Neu5Ac (acid N acetyl neuraminic or sialic acid) and GlcNAc (N-acetyl D glucoseamine) in group B; and GlcNAc in group O. Eichornia crassipens, the recognition was that of GalNAc (N-acetyl-D-galactoseamine) and GlcNAc in group O; and Fuc (L-Fucose) and GlcNAc in group A. Lemna minor and Eichornia crassipens protein extracts (p-ext) increased Vct proliferation and protected to the red cells group O against the hemolytic activity of Vct. Both p-exts did not show any statistical significance on agglutination to Vct when compared to the results from phosphate buffer. According to the results, lectins present in roots may be involved in the proliferation and survival of Vct.

Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation.

As traditional antidepressants act only after weeks/months, the discovery that ketamine, an antagonist of glutamate/N-methyl-D-aspartate (NMDA) receptors, elicits antidepressant actions in hours has been transformative. Its mechanism of action has been elusive, though enhanced mammalian target of rapamycin (mTOR) signaling is a major feature. We report a novel signaling pathway wherein NMDA receptor activation stimulates generation of nitric oxide (NO), which S-nitrosylates glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Nitrosylated GAPDH complexes with the ubiquitin-E3-ligase Siah1 and Rheb, a small G protein that activates mTOR. Siah1 degrades Rheb leading to reduced mTOR signaling, while ketamine, conversely, stabilizes Rheb that enhances mTOR signaling. Drugs selectively targeting components of this pathway may offer novel approaches to the treatment of depression.

Ventilator-associated pneumonia by methicillin-susceptible Staphylococcus aureus: do minimum inhibitory concentrations to vancomycin and daptomycin matter?

The use of vancomycin minimum inhibitory concentration (MIC) as an outcome predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia has become an important topic for debate in the last few years. Given these previous results, we decided to investigate whether MICs to vancomycin or daptomycin had any effect on the evolution of patients with ventilator-associated pneumonia (VAP) due to MSSA. An observational, retrospective, multicenter study was conducted among patients with MSSA VAP. We analyzed the relationship between vancomycin and daptomycin MICs and early clinical response (72 h), 30-day mortality, intensive care unit (ICU) length of stay (LOS), and duration on mechanical ventilation. Univariate and multivariate analyses were performed. Sixty-six patients from 12 centers were included. Twenty-six patients (39%) had an infection due to MSSA strains with a vancomycin MIC ≥1.5 µg/mL. Daptomycin MIC was determined in 58 patients, of whom 17 (29%) had an MIC ≥1.0 µg/mL. Ten patients (15%) did not respond to first-line treatment. Only daptomycin MIC ≥1.0 µg/mL had a significant association [odds ratio (OR): 30.00; 95% confidence interval (CI): 2.91-60.41] with early treatment failure. The 30-day mortality was 12% (n = 8). Any variable was associated with mortality in the multivariate analysis. None of the variables studied were associated with ICU LOS or duration on mechanical ventilation. In patients with MSSA VAP, vancomycin MIC does not influence the response to antibiotic treatment or the 30-day mortality. Daptomycin MIC was directly related to early treatment failure.

Dietary linseed oil increases trans-10,cis-15 18:2 in caprine milk fat.

Trans-10,cis-15 18:2 has been recently detected and characterized in digestive contents and meat and adipose tissue of ruminants, but its presence in milk and dairy products is hardly known. The aim of this study was to quantify trans-10,cis-15 18:2 in milk fat, better understand its metabolic origin, and help to elucidate the mechanisms of rumen biohydrogenation when the diet composition might affect ruminal environment. To address these objectives, 16 dairy goats were allocated to 2 simultaneous experiments (2 groups of goats and 2 treatments in each experiment). Experimental treatments consisted of basal diets with the same forage-to-concentrate ratio (33/67) and 2 starch-to-nonforage neutral detergent fiber (NDF) ratios (0.8 and 3.1), which were supplemented or not with 30 g/d of linseed oil for 25 d in a crossover design. Trans-10,cis-15 18:2 contents in milk fat were determined by gas chromatography fitted with an extremely polar capillary column (SLB-IL111). Levels of trans-10,cis-15 18:2 in individual milk fat samples ranged from 0 to 0.2% of total fatty acids, and its content in milk fat increased 8 fold due to linseed oil supplementation, substantiating the predominant role of α-linolenic acid in its formation. The trans-10,cis-15 18:2 levels in milk fat were similar in both experiments, despite the fact starch-to-nonforage NDF ratio of their respective basal diets greatly differed. In conclusion, trans-10,cis-15 18:2 was clearly related to linseed oil supplementation, and its increase in milk fat was comparable when the basal diets were rich in either nonforage NDF or starch.

Lipopolysaccharide-Induced Ionized Hypocalcemia and Acute Kidney Injury in Carotid Chemo/Baro-Denervated Rats.

The acute kidney injury (AKI) observed during sepsis is due to an uncontrolled release of inflammatory mediators. Septic patients develop electrolytic disturbances and one of the most important is ionized hypocalcemia. AKI adversely affects the function of other organs and hypocalcemia is associated with cardiovascular and respiratory dysfunctions. Since carotid body chemoreceptors modulate the systemic inflammatory response during sepsis syndromes, we used pentobarbitone-anesthetized male Sprague-Dawley rats in control condition (SHAM surgery) and after bilateral carotid neurotomy (carotid chemo/baro-denervated, BCN). We evaluate serum creatinine (CRE), serum neutrophil gelatinase-associated lipocaline (NGAL), ionized calcium (iCa) and cardiac Troponin I (cTnI) 90 min after the IP administration of 15 mg/kg lipopolysaccharide (LPS) or saline. In the SHAM group, LPS failed to induce significant changes CRE, NGAL, or iCa, and increased cTnI. Conversely, in the BCN group LPS increased CRE and NGAL, decreased iCa, and enhanced the increase of cTnI. Our results suggest that carotid chemo/baro-receptors might contribute to the regulation of both renal function and calcemia during sepsis. In addition, results imply that the carotid chemo-baroreceptors serve as an immunosensory organ.

Marginal bone loss around implants placed in maxillary native bone or grafted sinuses: a retrospective cohort study.

OBJECTIVES: To assess differences in marginal bone loss around implants placed in maxillary pristine bone and implants placed following maxillary sinus augmentation over a period of 3 years after functional loading. MATERIAL AND METHODS: Two cohorts of subjects (Group 1: Subjects who received sinus augmentation with simultaneous implant placement; Group 2: Subjects who underwent conventional implant placement in posterior maxillary pristine bone) were included in this retrospective study. Radiographic marginal bone loss was measured around one implant per patient on digitized panoramic radiographs that were obtained at the time of prosthesis delivery (baseline) and 12, 24, and 36 months later. The influence of age, gender, smoking habits, history of periodontal disease, and type of prosthetic connection (internal or external) on marginal bone loss was analyzed in function of the type of osseous support (previously grafted or pristine). RESULTS: A total of 105 subjects were included in this study. Cumulative radiographic marginal bone loss ranged from 0 mm to 3.9 mm after 36 months of functional loading. There were statistically significant differences in marginal bone loss between implants placed in grafted and pristine bone at the 12-month assessment, but not in the subsequent progression rate. External prosthetic connection, smoking, and history of periodontitis negatively influenced peri-implant bone maintenance, regardless of the type of osseous substrate. CONCLUSIONS: Implants placed in sites that received maxillary sinus augmentation exhibited more marginal bone loss than implants placed in pristine bone, although marginal bone loss mainly occurred during the first 12 months after functional loading. Implants with external implant connection were strongly associated with increased marginal bone loss overtime.

Time-dependent variations in milk fatty acid content of goats fed 3 different plant oils.

The effect of sampling time on milk fatty acid (FA) composition after separately adding 3 plant oils to an oil-free control diet (67% cereal-soybean-based concentrate and 33% alfalfa hay) was studied in 12 Malagueña goats. Individual animals were randomly allocated to 1 of the 4 treatments: control, 48 g/d of added high oleic (OSO) or regular (RSO) sunflower oil, or linseed oil (LO). Individual milk samples were taken at 0 (covariate), 1, 12, 24, 72, 120, 192, 312, and 504 h after the beginning of the experiment. Milk FA contents (g/100g of total FA methyl esters) were analyzed in a completely randomized design with repeated measures using PROC MIXED of SAS (SAS Institute Inc., Cary, NC). Comparing results of 15 chosen FA (for example, medium-chain saturated FA trans-11 C18:1, cis-9,trans-11 C18:2, trans-10 C18:1, and C18:3n-3) indicated that throughout the duration of the experiment, feeding the control diet had little influence on the concentrations of most FA in milk. Most changes in milk FA composition due to oil supplementation had occurred within 192 h since the beginning of the experiment. However, the concentrations of 2 FA (trans-10 C18:1 in RSO and C18:3n-3 in LO treatments) continued to change until 504 h. By comparing FA values in milk fat from oil treatments with those of the control at the same sampling times, typical value differences for the 3 supplementary oils found at 504 h (21 d) were also observed at 312 h from the beginning of the experiment (13 d) and even earlier in some FA, such as medium-chain saturated FA at 120 h in RSO and LO and at 72 h in OSO, cis-9,trans-11 C18:2 and trans-10 C18:1 at 24h in RSO, trans-11 C18:1 at 12h in RSO and LO, and C18:3n-3 at 1h in LO. In the conditions assayed in these experiments, reliable results of milk FA changes were obtained at sampling times shorter than 21 d. Monitoring early changes in milk FA after the addition of plant oils to diets could help in the study of rumen and mammary metabolism of dietary FA.

Short communication: Feeding linseed oil to dairy goats with competent reticular groove reflex greatly increases n-3 fatty acids in milk fat.

A crossover experiment was designed to compare the effects of 2 ways of feeding linseed oil on milk fat fatty acid (FA) composition. Ten lactating goats, trained to keep competent their inborn reticular groove reflex, received a daily dose of linseed oil (38 g/d) either with their solid (concentrate) feed (CON) or emulsified in skim milk and bottle-fed (BOT). Two groups of 5 goats received alternative and successively each of the treatments in two 15-d periods. α-Linolenic acid in milk fat rose up to 13.7% in the BOT versus 1.34% in the CON treatment. The n-6 to n-3 FA ratio was significantly reduced in goats receiving bottle-fed linseed oil (1.49 vs. 0.49). Contents of rumen biohydrogenation intermediates of dietary unsaturated FA were high in milk fat of goats under the CON treatment but low in those in the BOT treatment. These results point to a clear rumen bypass of the bottle-fed linseed oil. This strategy allows obtaining milk fat naturally very rich in n-3 FA and very low in trans FA. Translating this approach into practical farm conditions could enable farmers to produce milk enriched in specific FA.

[Bacterial coinfection in the critically-ill COVID-19 patient: incidence, impact and need for antimicrobial therapy]. / Coinfección bacteriana en el paciente COVID-19 crítico: incidencia, impacto y necesidad de tratamiento antibiótico.

OBJECTIVE: To assess the frequency of bacterial coinfection upon ICU admission in SARS-CoV-2 pneumonia patients, its microbiology, and impact on prognosis.The secondary objective was to identify risk factors for coinfection on admission. METHODS: Retrospective study, including patients with SARS-CoV-2 pneumonia admitted to the ICU.We defined bacterial coinfection by respiratory symptoms, radiological data, positive and clinically significant microbiological results in samples obtained in the first 48 h of admission and/or a determination of procalcitonin ≥ 0.5 ng/mL in the first 48 h.We evaluated demographic variables, comorbidities, SARS-CoV-2 infection data, severity scores, treatments received, need for respiratory support and outcomes (ICU and hospital mortality). RESULTS: A total of 182 patients were analyzed, 62 (34.1%) with bacterial coinfection.The most frequent microbiology was S. pneumoniae and M. pneumoniae. 96.1% of the patients received antibiotic therapy on admission, 98.9% corticosteroids, 27.5% tocilizumab, and 7.7% remdesivir.85.7% required invasive mechanical ventilation.The SOFA score (OR: 1.315, 95% CI1.116-1.548) and the delay in ICU admission (OR: 0.899, 95% CI 0.831-0.972) were related to the risk of coinfection. Bacterial coinfection increases the risk of death in hospital (OR 2.283; 95% CI 1.011.5.151; p=0.047). CONCLUSIONS: Bacterial coinfection is common in COVID patients admitted to the ICU and increases the risk of death. It is not possible to identify with certainty, at the time of admission, which patients do not benefit from antibiotic treatment.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Inhibition of ∆9-desaturase activity with sterculic acid: effect on the endogenous synthesis of cis-9 18:1 and cis-9, trans-11 18:2 in dairy sheep.

This study was conducted in lactating ewes to examine the involvement of ∆(9)-desaturase in mammary lipogenesis, especially in the endogenous synthesis of cis-9, trans-11 18:2 and cis-9 18:1, because no information on this matter was available for dairy sheep. With this aim, 6 Assaf ewes were monitored in a 15-d experiment, which included a 5-d pretreatment period, a 5-d treatment period, and a 5-d posttreatment period. During the treatment period, ewes received 0.5 g/d of sterculic acid (a cyclopropene fatty acid that inhibits ∆(9)-desaturase), delivered intravenously in 4 equal doses at 6-h intervals. Animals were fed pasture to supply mainly α-linolenic acid and minimize the amount of milk cis-9, trans-11 18:2 of ruminal origin. Sterculic acid administration was calculated to inhibit ∆(9)-desaturase by 70% based on the milk content of cis-9 14:1. This inhibition resulted in decreases in the milk content of the enzyme products (e.g., cis-9 10:1, cis-9 14:1, cis-9 16:1, cis-9 18:1, and cis-9, trans-11 18:2) and increases in its substrates (e.g., 14:0, 18:0, and trans-11 18:1), as well as in reductions in the desaturase indexes. Some other milk fatty acids, further to previously reported products or substrates of ∆(9)-desaturase (e.g., cis-15 18:1 and cis-9, cis-15 18:2, or trans-11, trans-15 18:2, and cis-9, trans-11, trans-15 18:3), were also affected by sterculic acid administration. Endogenous synthesis was the major source of cis-9 18:1 and cis-9, trans-11 18:2, accounting for 63 and 74% of its content in milk fat, respectively. To our knowledge, the present study provides the first estimates of endogenous synthesis of these 2 bioactive fatty acids in ovine milk fat.

Effects of feeding increasing dietary levels of high oleic or regular sunflower or linseed oil on fatty acid profile of goat milk.

In this work, the effects of increasing amounts of 3 plant oils in diets on the fatty acid (FA) profile of goat milk were studied. The study consisted of 3 experiments, one per oil tested (linseed oil, LO; high oleic sunflower oil, HOSFO; and regular sunflower oil, RSFO). The 3 experiments were conducted successively on 12 Malagueña goats, which were assigned at random to 1 of 4 treatments: 0, 30, 48, and 66 (H) g of added oil/d. A basal diet made of alfalfa hay and pelleted concentrate (33:67) was used in all of the experiments. For each animal, milk samples collected after 15 d on treatments were analyzed for fat, protein, lactose, and FA composition, whereas individual milk yield was measured the last 3 d of each experiment. Oil supplementation affected neither dry matter intake nor milk production traits. Increasing the oil supplementation decreased the content of saturated FA (especially 16:0) in milk fat and increased mono- and polyunsaturated FA in a linear manner. Vaccenic acid content linearly increased with the oil supplementation by 370, 217, and 634% to 5.32, 2.66, and 5.09 g/100 g of total FA methyl esters with the H diet in LO, HOSFO, and RSFO experiments, respectively. Rumenic acid content linearly increased with LO and RSFO supplementation by 298 and 354% from 0.53 and 0.41 g/100 g of total FA methyl esters with the 0 g of added oil/d diet. The content of trans-10-18:1 was not affected by LO supplementation but showed an increasing linear trend with HOSFO supplementation and linearly increased with RSFO supplementation. The ratio of n-6 to n-3 polyunsaturated FA in milk fat was decreased by about 70% with the H diet in the LO experiment and it was increased by 54 and 82% with the H diet in the HOSFO and RSFO experiments. In conclusion, LO supplementation in this work seemed to be the most favorable alternative compared with HOSFO or RSFO supplementation.