A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study.

BACKGROUND: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. METHODS: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. RESULTS: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. CONCLUSIONS: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.

Temperature variability and metabolic adaptation in terrestrial and aquatic ectotherms.

Thermodynamics is a major factor determining rates of energy expenditure, rates of biochemical dynamics, and ultimately the biological and ecological processes linked with resilience to global warming in ectothermic organisms. Nonetheless, whether ectothermic organisms exhibit general adaptive metabolic responses to cope with worldwide variation in thermal conditions has remained as an open question. Here we combine a model comparison approach with a global dataset of standard metabolic rates (SMR), including 1,160 measurements across 788 species of aquatic invertebrates, insects, fishes, amphibians and reptiles, to investigate the association between metabolic rates and environmental temperatures in their respective habitats. Our analyses suggest that variation in SMR after removing allometric and thermodynamic effects is best explained by the temperature range encountered across seasons, which always provided a better fit than the average temperature for the hottest and coldest month and mean annual temperatures. This pattern was consistent across taxonomic groups and robust to sensitivity analyses. Nonetheless, aquatic and terrestrial lineages responded differently to seasonality, with SMR declining - 6.8% °C-1 of thermal range across seasons in aquatic organisms and increasing 2.8% °C-1 in terrestrial organisms. These responses may reflect alternative strategies to mitigate the impact of increments in warmer temperatures on energy expenditure, either by means of metabolic reduction in thermally homogeneous water bodies or effective behavioral thermoregulation to exploit temperature heterogeneity on land.

Molecular Docking and In Vitro Studies of Ochratoxin A (OTA) Biodetoxification Testing Three Endopeptidases.

Ochratoxin A (OTA) is considered one of the main mycotoxins responsible for health problems and considerable economic losses in the feed industry. The aim was to study OTA's detoxifying potential of commercial protease enzymes: (i) Ananas comosus bromelain cysteine-protease, (ii) bovine trypsin serine-protease and (iii) Bacillus subtilis neutral metalloendopeptidase. In silico studies were performed with reference ligands and T-2 toxin as control, and in vitro experiments. In silico study results showed that tested toxins interacted near the catalytic triad, similar to how the reference ligands behave in all tested proteases. Likewise, based on the proximity of the amino acids in the most stable poses, the chemical reaction mechanisms for the transformation of OTA were proposed. In vitro experiments showed that while bromelain reduced OTA's concentration in 7.64% at pH 4.6; trypsin at 10.69% and the neutral metalloendopeptidase in 8.2%, 14.44%, 45.26% at pH 4.6, 5 and 7, respectively (p < 0.05). The less harmful α-ochratoxin was confirmed with trypsin and the metalloendopeptidase. This study is the first attempt to demonstrate that: (i) bromelain and trypsin can hydrolyse OTA in acidic pH conditions with low efficiency and (ii) the metalloendopeptidase was an effective OTA bio-detoxifier. This study confirmed α-ochratoxin as a final product of the enzymatic reactions in real-time practical information on OTA degradation rate, since in vitro experiments simulated the time that food spends in poultry intestines, as well as their natural pH and temperature conditions.

Evaluation of trefoil factor 3 as a non-invasive biomarker of gastric intestinal metaplasia and gastric cancer in a high-risk population.

BACKGROUND: Adenocarcinoma is preceded by chronic atrophic gastritis, gastric intestinal metaplasia and dysplasia. Trefoil factor 3 (TFF3) is a peptide secreted by goblet cells, which is abundantly present in intestinal metaplasia. AIM: To evaluate the utility of serum TFF3 as a non-invasive biomarker for the diagnosis of intestinal metaplasia and gastric cancer. METHODS: Single-center, cross-sectional study of 274 patients who consecutively underwent upper gastrointestinal endoscopy with gastric biopsies (updated Sydney system). TFF3 levels were measured in serum by a commercial ELISA kit. Patients with normal histology or chronic atrophic gastritis without intestinal metaplasia comprised the control group. In addition, 14 patients with invasive gastric cancer were included as a reference group. The association between TFF3 levels and intestinal metaplasia was assessed by logistic regression. RESULTS: Patients with intestinal metaplasia (n=110) had a higher median TFF3 level as compared to controls (n=164), 13.1 vs. 11.9ng/mL, respectively (p=0.024). Multivariable logistic regression showed a no significant association between TFF3 levels and intestinal metaplasia (OR=1.20; 95%CI: 0.87-1.65; p-trend=0.273). The gastric cancer group had a median TFF3 level of 20.5ng/mL, and a significant association was found (OR=3.26; 95%CI: 1.29-8.27; p-trend=0.013). CONCLUSION: Serum levels of TFF3 do not discriminate intestinal metaplasia in this high-risk Latin American population. Nevertheless, we confirmed an association between TFF3 levels and invasive gastric cancer.

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study.

BACKGROUND: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. OBJECTIVE: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. METHODS: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. RESULTS: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. CONCLUSIONS: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

Autoimmune hepatitis triggered by COVID-19.

We present the case of a 60-year-old female with no drug allergies or toxic habits, with hypothyroidism, and receiving treatment with levothyroxine. She was admitted in February 2021 and presented with choluria of 72 hours duration; there were no abdominal or respiratory clinical symptoms, and no related fever. Medical examination findings included mucocutaneous jaundice and a recorded oxygen saturation of 97 % in ambient air. There was a notable pattern of cytolysis compatible with acute hepatitis, and no history hepatotoxic drugs. Screening was performed for acute hepatitis in addition to serology testing, determination of autoantibodies and immunoglobulins, a PCR test for COVID, and a radiologic study.

Thiopurine adherence: a high prevalence with low impact on UC outcomes.

INTRODUCTION: thiopurines are used as maintenance therapy in patients with ulcerative colitis (UC). There are contradictory results regarding the relationship between adherence to treatment and risk of relapse. OBJECTIVES: to quantify and evaluate the trends in thiopurine prescription rates, and to determine the impact and risk factors of non-adherence. METHODS: analytical, observational, retrospective study of UC patients taking thiopurines included in the ENEIDA single-center registry from October 2017 to October 2019. Adult patients in clinical remission at the beginning of the study on thiopurines maintenance treatment for at least 6 months before recruitment were included. Adherence was evaluated with an electronic pharmaceutical prescription system. Adherence was considered when 80 % or more of the prescribed medication was dispensed at the pharmacy. Kaplan-Meier curves and a regression model were used to examine year-to-year treatment dispensation, and to identify factors associated with non-adherence. RESULTS: a total of 41 patients were included, of whom 71 % were males with a mean age of 44 (14), and 26.8 % were concomitantly managed with biological therapy. Overall, 22 % were non-adherent to thiopurines. No predictive factors of non-adherence were identified. Adherence rate did not correlate with disease activity during two years of follow-up (OR 1.6; 95 % CI = 0.3-9.1). Left-sided colitis and concomitant biological treatment were related with disease relapse (p ≤ 0.01). CONCLUSION: adherence to thiopurines in UC patients is high (78 %). Non-adherence is not related to clinical or pharmacological factors. Adherence rate was not associated with disease activity.

The wild plant Gnaphalium lavandulifolium as a sentinel for biomonitoring the effects of environmental heavy metals in the metropolitan area of México Valley.

Biomonitoring is a valuable tool for assessing the presence and effects of air pollutants such as heavy metals (HM); due to their toxicity and stability, these compounds can affect human health and the balance of ecosystems. To assess its potential as a sentinel organism of HM pollution, the wild plant Gnaphalium lavandulifolium was exposed to four sites in the metropolitan area of México Valley (MAMV): Altzomoni (ALT) Coyoacán (COY), Ecatepec (ECA), and Tlalnepantla (TLA) during 2, 4, and 8 weeks, between October and November 2019. Control plants remained under controlled conditions. The chemical analysis determined twelve HM (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn) in the leaves. Macroscopic damage to the leaves, later determined in semi-thin sections under light microscopy, lead to a finer analysis. Transmission electron microscope (TEM) showed major structural changes: chromatin condensation, protoplast shrinkage, cytoplasm vacuolization, cell wall thinning, decreased number and size of starch grains, and plastoglobules in chloroplasts. All these characteristics of stress-induced programed cell death (sPCD) were related to the significant increase of toxic HM in the leaves of the exposed plants compared to the control (p < 0.05). Immunohistochemistry revealed a significant amount of proteases with caspase 3-like activity in ECA and TLA samples during long exposure times. Ultrastructural changes and sPCD features detected confirmed the usefulness of G. lavandulifolium as a good biomonitor of HM contamination. They supported the possibility of considering subcellular changes as markers of abiotic stress conditions in plants.

Update of the treatment of nosocomial pneumonia in the ICU.

In accordance with the recommendations of, amongst others, the Surviving Sepsis Campaign and the recently published European treatment guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), in the event of a patient with such infections, empirical antibiotic treatment must be appropriate and administered as early as possible. The aim of this manuscript is to update treatment protocols by reviewing recently published studies on the treatment of nosocomial pneumonia in the critically ill patients that require invasive respiratory support and patients with HAP from hospital wards that require invasive mechanical ventilation. An interdisciplinary group of experts, comprising specialists in anaesthesia and resuscitation and in intensive care medicine, updated the epidemiology and antimicrobial resistance and established clinical management priorities based on patients' risk factors. Implementation of rapid diagnostic microbiological techniques available and the new antibiotics recently added to the therapeutic arsenal has been reviewed and updated. After analysis of the categories outlined, some recommendations were suggested, and an algorithm to update empirical and targeted treatment in critically ill patients has also been designed. These aspects are key to improve VAP outcomes because of the severity of patients and possible acquisition of multidrug-resistant organisms (MDROs).

Comparative Proteomics and Functional Analysis Reveal a Role of Plasmodium falciparum Osmiophilic Bodies in Malaria Parasite Transmission.

An essential step in the transmission of the malaria parasite to the Anopheles vector is the transformation of the mature gametocytes into gametes in the mosquito gut, where they egress from the erythrocytes and mate to produce a zygote, which matures into a motile ookinete. Osmiophilic bodies are electron dense secretory organelles of the female gametocytes which discharge their contents during gamete formation, suggestive of a role in gamete egress. Only one protein with no functional annotation, Pfg377, is described to specifically reside in osmiophilic bodies in Plasmodium falciparum Importantly, Pfg377 defective gametocytes lack osmiophilic bodies and fail to infect mosquitoes, as confirmed here with newly produced pfg377 disrupted parasites. The unique feature of Pfg377 defective gametocytes of lacking osmiophilic bodies was here exploited to perform comparative, label free, global and affinity proteomics analyses of mutant and wild type gametocytes to identify components of these organelles. Subcellular localization studies with fluorescent reporter gene fusions and specific antibodies revealed an osmiophilic body localization for four out of five candidate gene products analyzed: the proteases PfSUB2 (subtilisin 2) and PfDPAP2 (Dipeptidyl aminopeptidase 2), the ortholog of the osmiophilic body component of the rodent malaria gametocytes PbGEST and a previously nonannotated 13 kDa protein. These results establish that osmiophilic bodies and their components are dispensable or marginally contribute (PfDPAP2) to gamete egress. Instead, this work reveals a previously unsuspected role of these organelles in P. falciparum development in the mosquito vector.

Mitochondrial phenotype during torpor: Modulation of mitochondrial electron transport system in the Chilean mouse-opossum Thylamys elegans.

Mammalian torpor is a phenotype characterized by a controlled decline of metabolic rate, generally followed by a reduction in body temperature. During arousal from torpor, both metabolic rate and body temperature rapidly returns to resting levels. Metabolic rate reduction experienced by torpid animals is triggered by active suppression of mitochondrial respiration, which is rapidly reversed during rewarming process. In this study, we analyzed the changes in the maximal activity of key enzymes related to electron transport system (complexes I, III and IV) in six tissues of torpid, arousing and euthermic Chilean mouse-opossums (Thylamys elegans). We observed higher maximal activities of complexes I and IV during torpor in brain, heart and liver, the most metabolically active organs in mammals. On the contrary, higher enzymatic activities of complexes III were observed during torpor in kidneys and lungs. Moreover, skeletal muscle was the only tissue without significant differences among stages in all complexes evaluated, suggesting no modulation of oxidative capacities of electron transport system components in this thermogenic tissue. In overall, our data suggest that complexes I and IV activity plays a major role in initiation and maintenance of metabolic suppression during torpor in Chilean mouse-opossum, whereas improvement of oxidative capacities in complex III might be critical to sustain metabolic machinery in organs that remains metabolically active during torpor.

Vedolizumab, an option in patients with inflammatory bowel disease intolerant to thiopurines and refractory to biological agents. / Vedolizumab, una opción en pacientes con enfermedad inflamatoria intestinal intolerantes a tiopurinas y refractarios a biológicos.

Vedolizumab (VDZ), a human monoclonal antibody that binds specifically to α4ß7-integrin, and is approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC), has demonstrated its efficacy in controlled clinical trials. OBJECTIVE: To describe a population treated with VDZ and to evaluate its long-term efficacy and safety in clinical practice. METHODS: An observational and multicentre study was carried out on patients with inflammatory bowel disease treated with VDZ for at least one year. An evaluation was performed on the activity indices, faecal calprotectin and C-reactive protein levels, hospital admissions, surgeries, and adverse events. RESULTS: A total of 73 patients were analysed (43 UC and 30 CD). More than one anti-TNF and more than one immunosuppressive was previously used by 74 and 23%, respectively, of UC patients, and 90 and 37%, respectively of CD patients. VDZ was stopped in 17 (23%) patients, 10 UC and 7 CD, due to a lack or loss of response before the first year, or due to adverse events. An intensification of the dose was required in 26 (63%) UC, and 16 (53%) CD patients. At 6 months, 70 and 42% of UC patients, and 80 and 43% of CD patients achieved a clinical response and remission, respectively. At one year, 58 and 35% of UC patients and 47 and 43% of CD patients, maintained the clinical response and remission, respectively. The C-reactive protein decreased significantly in both CD and UC patients. However, the decrease in faecal calprotectin was only achieved during follow-up in UC, but not in CD patients. Eight patients with CD that had been treated previously with ustekinumab avoided surgery at one year. A colectomy was performed on 8 (18.6%) UC patients, and 4 (13.3%) CD patients needed surgery. Six patients (8%) (5 UC and 1 CD) had adverse events. The concomitant use of corticosteroids or immunomodulators did not increase the efficacy. Those with a higher number of previous anti-TNF treatments showed less remissions in UC and responses in CD. CONCLUSIONS: After one year of VDZ, a clinical response and remission was induced in a considerable percentage of patients refractory to different biological or immunosuppressive therapies. VDZ can be considered as an alternative in those intolerant to immunosuppressives, with few adverse events.

Ned-19 inhibition of parasite growth and multiplication suggests a role for NAADP mediated signalling in the asexual development of Plasmodium falciparum.

BACKGROUND: Although malaria is a preventable and curable human disease, millions of people risk to be infected by the Plasmodium parasites and to develop this illness. Therefore, there is an urgent need to identify new anti-malarial drugs. Ca2+ signalling regulates different processes in the life cycle of Plasmodium falciparum, representing a suitable target for the development of new drugs. RESULTS: This study investigated for the first time the effect of a highly specific inhibitor of nicotinic acid adenine dinucleotide phosphate (NAADP)-induced Ca2+ release (Ned-19) on P. falciparum, revealing the inhibitory effect of this compound on the blood stage development of this parasite. Ned-19 inhibits both the transition of the parasite from the early to the late trophozoite stage and the ability of the late trophozoite to develop to the multinucleated schizont stage. In addition, Ned-19 affects spontaneous intracellular Ca2+ oscillations in ring and trophozoite stage parasites, suggesting that the observed inhibitory effects may be associated to regulation of intracellular Ca2+ levels. CONCLUSIONS: This study highlights the inhibitory effect of Ned-19 on progression of the asexual life cycle of P. falciparum. The observation that Ned-19 inhibits spontaneous Ca2+ oscillations suggests a potential role of NAADP in regulating Ca2+ signalling of P. falciparum.

Discontinuation of Infliximab in Patients With Ulcerative Colitis Is Associated With Increased Risk of Relapse: A Multinational Retrospective Cohort Study.

BACKGROUND & AIMS: Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission. METHODS: We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n = 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n = 111) with that of patients who continued scheduled treatment (controls, n = 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods. RESULTS: In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P < .001; hazard ratio, 3.41; 95% confidence interval, 1.88-6.20) and multivariable analysis (hazard ratio, 3.70; 95% confidence interval, 2.02-6.77). Rates of hospitalization and colectomy did not differ between groups. Thiopurines appeared to be the best treatment option after infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P = .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events. CONCLUSIONS: In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe.

A fast, non-invasive, quantitative staining protocol provides insights in Plasmodium falciparum gamete egress and in the role of osmiophilic bodies.

BACKGROUND: Ability of Plasmodium falciparum gametocytes to become extracellular during gametogenesis in the mosquito midgut is a key step of the parasite life cycle. Reliable and quantitative measurement of the efficiency of gamete egress is currently constrained by the fact that this phenomenon is usually observed and quantified in vitro either by live microscopy, by statistically limited ultrastructural analysis or by surface antibody-based protocols which can interfere with this fast and complex cellular process. METHODS: A protocol was developed based on fluorescent wheat germ agglutinin (WGA) surface staining of erythrocytes containing mature P. falciparum gametocytes. After a single centrifugation step and within minutes from the induction of gametogenesis, the activated gametes can be inspected for presence or absence of the fluorescent WGA staining of the host erythrocyte membrane and scored respectively as intracellular or emerged from the erythrocyte. RESULTS: Gametogenesis and gamete egress from WGA surface stained, infected erythrocytes occur with normal kinetics and efficiencies. Quantitative measurements of gamete egress can be obtained in live and in paraformaldehyde-fixed cells, which validates this protocol as a suitable tool both for live imaging studies and for higher throughput applications. The protocol was used here to provide functional information on the ability of gametes to egress through a single exit point induced in the host red blood cell membrane, and to re-analyse the phenotype of Pfg377- and osmiophilic body-defective gametes, suggesting that such parasite components are not directly involved in disruption and shedding of the erythrocyte membrane in female gamete egress. CONCLUSIONS: The development of a reliable, fast, non-invasive and quantitative protocol to finely describe and to measure efficiency of P. falciparum gamete egress is a significant improvement in the tools for functional studies on this key process of the parasite life cycle. This protocol can be used to investigate the molecular mechanisms underlying gamete egress and its adaptation to high throughput applications will enable identification of transmission blocking inhibitors.

Thermoregulatory capacities and torpor in the South American marsupial, Dromiciops gliroides.

During periods of adverse conditions small endotherms depend on a continuous supply of food and energy to maintain body temperature. Thus, rapid and reversible phenotypic modifications at different organizational levels are key for an efficient use of resources and survival. In this study, we provide a quantitative description of thermoregulatory capacities and energy-saving strategies in the Chilean marsupial Dromiciops gliroides. In particular, we evaluated the effect of thermal acclimation on basal metabolic rate (BMR), thermal conductance (C) and torpor patterns, as well as the presence of non-shivering thermogenesis (NST) as a rewarming mechanism in this marsupial. Non-significant effects of thermal acclimation were observed in BMR, C and body mass, but cold-acclimated individuals exhibited significantly longer torpor bouts. Also, minimum body temperature during torpor, inter-bout body temperature and arousal rewarming rate were lower in cold-acclimated animals. Furthermore, we found that D. gliroides did not display NST in response to Norepinephrine. Hence, despite the high regulation of torpor of other species, D. gliroides shows low flexibility in the ability to adjust energy expenditure and insulation properties, and (as in other marsupials) NST do not seems to be important as thermoregulatory mechanism.

[Recommendations of the Chilean Association for Digestive Endoscopy for the management of gastric pre-malignant lesions]. / Diagnóstico precoz de cáncer gástrico: Propuesta de detección y seguimiento de lesiones premalignas gástricas: protocolo ACHED.

An expert panel analyzed the available evidence and reached a consensus to release 24 recommendations for primary and secondary prevention of gastric cancer (CG) in symptomatic patients, with indication for upper GI endoscopy. The main recommendations include (1) Search for and eradicate H. pylori infection in all cases. (2) Systematic gastric biopsies (Sydney protocol) in all patients over 40 years of age or first grade relatives of patient with CG, to detect gastric atrophy, intestinal metaplasia or dysplasia. (3) Incorporate the OLGA system (Operative Link on Gastritis Assessment) to the pathological report, to categorize the individual risk of CG. (4) Schedule endoscopic follow-up according to the estimated risk of CG, namely annual for OLGA III- IV, every 3 years for OLGA I- II or persistent H. pylori infection, every 5 years for CG relatives without other risk factors and no follow-up for OLGA 0, H. pylori (-). (4) Establish basic human and material resources for endoscopic follow-up programs, including some essential administrative processes, and (5) Suggest the early CG/total CG diagnosis ratio of each institution and the proportion of systematic recording of endoscopic images, as quality indicators. These measures are applicable using currently available resources, they can complement any future screening programs for asymptomatic population and may contribute to improve the prognosis of CG in high-risk populations.

Enhanced Catalytic Hydrogenation of Olefins in Sulfur-Rich Naphtha Using Molybdenum Carbide Supported on γ-Al2O3 Spheres under Steam Conditions: Simulating the Hot Separator Stream Process.

Spheres comprising 10 wt.% Mo2C/γ-Al2O3, synthesized through the sucrose route, exhibited unprecedented catalytic activity for olefin hydrogenation within an industrial naphtha feedstock that contained 23 wt.% olefins, as determined by supercritical fluid chromatography (SFC). The catalyst demonstrated resilience to sulfur, exhibiting no discernible deactivation signs over a tested 96 h operational period. The resultant hydrogenated naphtha from the catalytic process contained only 2.5 wt.% olefins when the reaction was conducted at 280 °C and 3.44 × 106 Pa H2, subsequently blended with Athabasca bitumen to meet pipeline specifications for oil transportation. Additionally, the carbide catalyst spheres effectively hydrogenated olefins under steam conditions without experiencing any notable hydrogenation in the aromatics. We propose the supported carbide catalyst as a viable alternative to noble metals, serving as a selective agent for olefin elimination from light petroleum distillates in the presence of steam and sulfur, mitigating the formation of gums and deposits during the transportation of diluted bitumen (dilbit) through pipelines.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.