A combination of conserved and diverged responses underlies Theobroma cacao's defense response to Phytophthora palmivora.

BACKGROUND: Plants have complex and dynamic immune systems that have evolved to resist pathogens. Humans have worked to enhance these defenses in crops through breeding. However, many crops harbor only a fraction of the genetic diversity present in wild relatives. Increased utilization of diverse germplasm to search for desirable traits, such as disease resistance, is therefore a valuable step towards breeding crops that are adapted to both current and emerging threats. Here, we examine diversity of defense responses across four populations of the long-generation tree crop Theobroma cacao L., as well as four non-cacao Theobroma species, with the goal of identifying genetic elements essential for protection against the oomycete pathogen Phytophthora palmivora. RESULTS: We began by creating a new, highly contiguous genome assembly for the P. palmivora-resistant genotype SCA 6 (Additional file 1: Tables S1-S5), deposited in GenBank under accessions CP139290-CP139299. We then used this high-quality assembly to combine RNA and whole-genome sequencing data to discover several genes and pathways associated with resistance. Many of these are unique, i.e., differentially regulated in only one of the four populations (diverged 40 k-900 k generations). Among the pathways shared across all populations is phenylpropanoid biosynthesis, a metabolic pathway with well-documented roles in plant defense. One gene in this pathway, caffeoyl shikimate esterase (CSE), was upregulated across all four populations following pathogen treatment, indicating its broad importance for cacao's defense response. Further experimental evidence suggests this gene hydrolyzes caffeoyl shikimate to create caffeic acid, an antimicrobial compound and known inhibitor of Phytophthora spp. CONCLUSIONS: Our results indicate most expression variation associated with resistance is unique to populations. Moreover, our findings demonstrate the value of using a broad sample of evolutionarily diverged populations for revealing the genetic bases of cacao resistance to P. palmivora. This approach has promise for further revealing and harnessing valuable genetic resources in this and other long-generation plants.

Using in feed xylanase or stimbiotic to reduce the variability in corn nutritive value for broiler chickens.

This study investigated the effects of xylanase and stimbiotic (fiber fermentation enhancer) on the response of broiler chickens fed different corn varieties and determine correlations between variables of interest. Four corn genetic varieties were selected based on their range in nutrient composition. Diets containing 600 g/kg of each corn were supplemented with 0 or 100 g/ton of xylanase or stimbiotic. A total of 1,152 one-day-old male broiler chicks (Ross 308) were divided into 12 treatments, each with 8 pens and 12 birds per pen, for a 21-day study. On d 21, performance parameters were measured, and the ileal energy and organic matter (OM) digestibility and cecal xylanase activity determined. Stimbiotic supplementation improved mFCR compared with all other treatments. There was a treatment by corn variety interaction for body weight (BW), BW gain and coefficient of variation (CV) of BW (P ≤ 0.05). Birds fed corn Variety 1 (highest neutral dietary fiber, protein and soluble arabinoxylan content) supplemented with stimbiotic had the highest BW, while Variety 2 control diet had the lowest. The BW CV in corn Variety 2 was the highest, which improved with stimbiotic supplementation. The BW CV in corn Variety 1 responded better to stimbiotic than xylanase. There were no treatment differences on BW CV in corn Varieties 3 and 4. The lowest OM digestibility was observed in birds fed corn Variety 1 with xylanase, and the highest value was associated with corn Variety 3 with xylanase (highest total arabinoxylan). Xylanase and stimbiotic supplementation increased the endogenous xylanase activity regardless of the corn variety (P ≤ 0.05). Positive correlations between corn fiber contents and phytic acid and the arabinose:xylose ratio were seen, while nonstarch polysaccharide content was negatively correlated with apparent metabolizable energy. In conclusion, corn variety influenced nutrient digestibility and broiler chicken growth. The response to supplementation with xylanase or stimbiotic varied based on the nutritional profile of corn with regards to improvements in digestibility and performance in broiler chickens.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.

National Early Warning Score-2 for Identification of Patients with Intermediate-High-Risk Pulmonary Embolism.

Consensus statements have proposed the use of the National Early Warning Score 2 (NEWS2) to identify stable patients with acute pulmonary embolism (PE) and an intermediate-high risk of adverse outcomes. We aimed to externally validate NEWS2 and compare it to another predictive score (Bova). Using NEWS2 (cutoff ≥5 and ≥7) and the Bova score (cutoff >4), we classified patients as intermediate-high risk (vs. non-intermediate-high risk), and we compared the test characteristics of these risk classification tools for a complicated course within 30 days after PE diagnosis. We also assessed the validity of NEWS2 for predicting a complicated course by adding the results of echocardiography and troponin testing to the model. Of the 848 enrolled patients, the NEWS2 score ≥5 classified 471 (55.5%) and the Bova score classified 37 (4.4%) as intermediate-high risk. NEWS2 had a significantly lower specificity for a 30-day complicated course than Bova (45.4 vs. 96.3%, respectively; p < 0.001). Using the higher score threshold (≥7), the NEWS2 classified 99 (11.7%) as intermediate-high risk, and the specificity was 88.9% (difference with Bova, 7.4%; p < 0.001). The proportion of patients with intermediate-high risk PE was 2.4% for the combination of a positive troponin testing and echocardiographic right ventricle dysfunction and a positive NEWS2 (score ≥7), while the specificity was 97.8% (difference with Bova, 1.5%; p = 0.07). Bova outperforms NEWS2 for predicting a complicated course among stable patients with PE. Addition of troponin testing and echocardiography improved the specificity of NEWS2, although it was not superior to Bova. CLINICALTRIALS.GOV NUMBER: : NCT02238639.

Atypical Unilateral Birdshot Chorioretinitis in a Hispanic Female.

A 62-year-old female patient was evaluated for gradual vision loss, floaters, and photopsia in her left eye. A left fundus examination revealed vitreous cells, hypopigmented lesions, and retinal vasculitis, and a workup revealed a positive HLA-A29 serology, all of which findings were consistent with birdshot chorioretinopathy. The patient was treated with oral prednisone and mycophenolate mofetil, which resulted in the adequate control of her uveitis. Even though unilateral cases are exceedingly rare and do not meet the established research criteria, this case highlights the importance of not minimizing the significance of birdshot lesions in the differential of patients with unilateral multifocal chorioretinitis.

Usefulness of the National Early Warning Score for Risk Stratification of Stable Patients With Acute Symptomatic Pulmonary Embolism

Objectives: The aim of this study was to assess the performance of the National Early Warning Score 2 (NEWS2) in predicting a short-term complicated outcome in stable patients with acute symptomatic pulmonary embolism (PE). We also studied the ability of the NEWS2 score compared with the simplified Pulmonary Embolism Severity Index (sPESI) for identifying low-risk patients with acute PE. Methods: We performed a retrospective analysis of a prospective cohort composed of 848 patients with acute PE. The NEWS2 and the sPESI were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for a 30-day complicated outcome using the C statistic, which was obtained by logistic regression models and ROC curves. We also assessed the test and performance characteristics of the low-risk versus high-risk categories of each prediction rule. Results: Overall, 63 out of 848 patients died (7.4%; 95% confidence interval, 5.7%-9.2%) during the first month of follow-up. Both scores showed a similarly poor predictive value for 30-day complicated outcome (C statistic, 0.68 and 0.62). The sPESI classified fewer patients as low-risk (36.9% versus 44.5%; P<0.01). Compared with the NEWS2 score, the sPESI showed significantly higher sensitivity (92.1% versus 66.7%) and a better negative predictive value (98.4% versus 94.4%). Conclusion: Both scores provide similar information for stratifying the risk of a complicated outcome in stable patients with PE. The sPESI identified low-risk patients with PE better than the NEWS2 score. (AU)

Usefulness of the National Early Warning Score for Risk Stratification of Stable Patients With Acute Symptomatic Pulmonary Embolism.

OBJECTIVES: The aim of this study was to assess the performance of the National Early Warning Score 2 (NEWS2) in predicting a short-term complicated outcome in stable patients with acute symptomatic pulmonary embolism (PE). We also studied the ability of the NEWS2 score compared with the simplified Pulmonary Embolism Severity Index (sPESI) for identifying low-risk patients with acute PE. METHODS: We performed a retrospective analysis of a prospective cohort composed of 848 patients with acute PE. The NEWS2 and the sPESI were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for a 30-day complicated outcome using the C statistic, which was obtained by logistic regression models and ROC curves. We also assessed the test and performance characteristics of the low-risk versus high-risk categories of each prediction rule. RESULTS: Overall, 63 out of 848 patients died (7.4%; 95% confidence interval, 5.7%-9.2%) during the first month of follow-up. Both scores showed a similarly poor predictive value for 30-day complicated outcome (C statistic, 0.68 and 0.62). The sPESI classified fewer patients as low-risk (36.9% versus 44.5%; P<0.01). Compared with the NEWS2 score, the sPESI showed significantly higher sensitivity (92.1% versus 66.7%) and a better negative predictive value (98.4% versus 94.4%). CONCLUSION: Both scores provide similar information for stratifying the risk of a complicated outcome in stable patients with PE. The sPESI identified low-risk patients with PE better than the NEWS2 score.

Comparison of various prognostic scores for identification of patients with intermediate-high risk pulmonary embolism.

BACKGROUND: Various risk assessment tools have been proposed to identify stable patients with acute pulmonary embolism (PE) who are at high risk of early adverse outcome (i.e., intermediate-high risk). METHODS: We evaluated the ability of the 2019 ESC, Bova, modified FAST and PEITHO-3 models for predicting a 30-day complicated course (death, haemodynamic collapse, and/or recurrent PE) in a cohort of 848 stable patients with acute PE. We also tested whether replacement of echocardiographic right ventricle (RV) dysfunction by computed tomographic (CT) RV enlargement provides comparable prognostic information for identifying these patients. RESULTS: A complicated course occurred in 63 (7.4 %) of the 848 patients with PE during the first month of follow-up. The proportion of patients designated as having intermediate-high risk PE was 6.7 % with the ESC model, 4.4 % with the Bova score, 15.7 % with the FAST score, and 5.2 % with the PEITHO-3 model. However, among patients identified as intermediate-high risk, the 30-day complicated course rate was higher with the Bova score (21.6 %) than with the ESC model (17.5 %), the PEITHO-3 model (15.9 %), or the modified FAST score (14.3 %). When echocardiographic RV dysfunction was replaced by CT RV enlargement in the models, the proportion of patients classified as having intermediate-high risk PE and the rate of an adverse outcome among them slightly increased. CONCLUSIONS: The Bova score might identify patients with intermediate-high risk PE slightly better than the ESC, PEITHO-3, and modified FAST score. When echocardiography is not readily available, CT-assessed RV enlargement might be used for identifying intermediate-high risk PE. CLINICALTRIALS: gov number: NCT02238639.

Expression of oxysterols in human lenses: Implications of the sterol pathway in age-related cataracts.

Lanosterol, an oxysterol molecule, has been proposed to help maintain lens transparency by inhibiting the formation of protein aggregates. This sterol is produced by the enzyme lanosterol synthase and is part of a metabolic pathway that forms cholesterol as a final step. Abnormalities in lanosterol synthase are responsible for congenital cataracts. The αA-crystallin protein, which acts as a molecular chaperone to lanosterol synthase, has been reported to have anti-protein aggregation, anti-inflammatory and anti-apoptotic properties. In this work, we evaluated the correlation of lanosterol synthase and αA-crystallin in human cataractous lenses with the grade of opacity, as well as the expression of lanosterol synthase, farnesyl DPP, geranyl synthase and squalene epoxidase genes. Lanosterol synthase and αA-crystallin were overexpressed in cataractous lenses as well as farnesyl-DP synthase, squalene epoxidase, lanosterol synthase and geranyl synthase genes in cataratous lenses in comparison with normal lenses. Our data confirm that lanosterol synthase and the sterol pathway are upregulated in cataractous lenses. This argues for a functional role of the oxysterol pathway and its products as an important mediator in the pathogenesis of human cataracts.

Mitochondria and Endoplasmic Reticulum Stress in Retinal Organoids from Patients with Vision Loss.

Activating transcription factor 6 (ATF6), a key regulator of the unfolded protein response, plays a key role in endoplasmic reticulum function and protein homeostasis. Variants of ATF6 that abrogate transcriptional activity cause morphologic and molecular defects in cones, clinically manifesting as the human vision loss disease achromatopsia (ACHM). ATF6 is expressed in all retinal cells. However, the effect of disease-associated ATF6 variants on other retinal cell types remains unclear. Herein, this was investigated by analyzing bulk RNA-sequencing transcriptomes from retinal organoids generated from patients with ACHM, carrying homozygous loss-of-function ATF6 variants. Marked dysregulation in mitochondrial respiratory complex gene expression and disrupted mitochondrial morphology in ACHM retinal organoids were identified. This indicated that loss of ATF6 leads to previously unappreciated mitochondrial defects in the retina. Next, gene expression from control and ACHM retinal organoids were compared with transcriptome profiles of seven major retinal cell types generated from recent single-cell transcriptomic maps of nondiseased human retina. This indicated pronounced down-regulation of cone genes and up-regulation in Müller glia genes, with no significant effects on other retinal cells. Overall, the current analysis of ACHM patient retinal organoids identified new cellular and molecular phenotypes in addition to cone dysfunction: activation of Müller cells, increased endoplasmic reticulum stress, disrupted mitochondrial structure, and elevated respiratory chain activity gene expression.

The rationale, design, and methods of a trial to evaluate the efficacy and safety of oxygen therapy in patients with intermediate-risk acute pulmonary embolism.

BACKGROUND: In patients with intermediate-risk pulmonary embolism (PE), reversal of hypoxic vasoconstriction could constitute a target for treatment that protects the right ventricular (RV) function until endogenous fibrinolysis occurs. The Air vs oxygen for Intermediate-Risk pulmonary embolism (AIR) trial aims to assess the effect of oxygen therapy in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. METHODS AND ANALYSES: AIR is a prospective, multicenter, randomized, open-label, parallel-group, proof-of-concept trial. A total of 90 patients hospitalized with intermediate-risk PE and an oxygen saturation of 90% or higher at baseline will be randomized in a 1:1 fashion to receive supplemental oxygen or ambient air. The primary outcome is a RV/LV diameter ratio equal or less than 1.0 on echocardiography measured 48 hours after the start of treatment. Secondary efficacy outcomes are the numerical change in the ratio of the RV to the LV diameter measured 48 hours and 7 days after the start of treatment, with respect to the baseline ratio measured at randomization. Clinical adverse events will be also collected. RESULTS: Enrollment started in July 2019 and is expected to proceed until 2022. Median age of the first 50 patients was 74 years (interquartile range, 61-81), and 50% were female. CONCLUSIONS: This multicenter trial will provide information about the value of supplemental oxygen in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. The results will contribute to research that may assist patients with intermediate-risk PE in the future.

Fecal Microbiota and Hair Glucocorticoid Concentration Show Associations with Growth during Early Life in a Pig Model.

Identifying characteristics associated with fast or slow growth during early life in a pig model will help in the design of nutritional strategies or recommendations during infancy. The aim of this study was to identify if a differential growth during lactation and/or the nursery period may be associated with fecal microbiota composition and fermentation capacity, as well as to leave a print of glucocorticoid biomarkers in the hair. Seventy-five commercial male and female pigs showing extreme growth in the lactation and nursery periods were selected, creating four groups (First, lactation growth, d0−d21; second, nursery growth, d21−d62): Slow_Slow, Slow_Fast, Fast_Slow, and Fast_Fast. At d63 of life, hair and fecal samples were collected. Fast-growing pigs during nursery had higher cortisone concentrations in the hair (p < 0.05) and a tendency to have a lower cortisol-to-cortisone ratio (p = 0.061). Both lactation and nursery growth conditioned the fecal microbiota structure (p < 0.05). Additionally, fast-growing pigs during nursery had higher evenness (p < 0.05). Lactation growth influenced the relative abundance of eight bacterial genera, while nursery growth affected only two bacterial genera (p < 0.05). The fecal butyrate concentration was higher with fast growth in lactation and/or nursery (p < 0.05), suggesting it has an important role in growth, while total SCFA and acetate were related to lactation growth (p < 0.05). In conclusion, piglets' growth during nursery and, especially, the lactation period was associated with changes in their microbiota composition and fermentation capacity, evidencing the critical role of early colonization on the establishment of the adult microbiota. Additionally, cortisol conversion to cortisone was increased in animals with fast growth, but further research is necessary to determine its implications.

Body weight of newborn and suckling piglets affects their intestinal gene expression.

Modern hyperprolific sows must deal with large litters (16-20 piglets) which reduce piglet birthweight with a concomitant increase in the proportion of small and intrauterine growth retarded piglets. However, larger litters do not only have a greater variation of piglet weights, but also a greater variation in colostrum and milk consumption within the litter. To further understand the impact that body weight has on piglets, the present study aimed to evaluate the degree of physiological weakness of the smallest piglets at birth and during the suckling period (20 d) compared to their middle-weight littermates through their jejunal gene expression. At birth, light piglets showed a downregulation of genes related to immune response (FAXDC2, HSPB1, PPARGC1α), antioxidant enzymes (SOD2m), digestive enzymes (ANPEP, IDO1, SI), and nutrient transporter (SLC39A4) (P < 0.05) but also a tendency for a higher mRNA expression of GBP1 (inflammatory regulator) and HSD11ß1 (stress hormone) genes compared to their heavier littermates (P < 0.10). Excluding HSD11ß1 gene, all these intestinal gene expression differences initially observed at birth between light and middle-weight piglets were stabilized at the end of the suckling period, when others appeared. Genes involved in barrier function (CLDN1), pro-inflammatory response (CXCL2, IL6, IDO1), and stress hormone signaling (HSD11ß1) over-expressed compared to their middle-weight littermates (P < 0.05). In conclusion, at birth and at the end of suckling period, light body weight piglets seem to have a compromised gene expression and therefore impaired nutrient absorption, immune and stress responses compared to their heavier littermates.

Under hyperprolific situations, piglets must deal with a reduced birthweight and a severe sibling competition for nutrients. Therefore, light body weight newborn and suckling piglets may also have physiological disadvantages compared to their middle-weight littermates. To further understand the impact that body weight has on piglets, the present study aimed to evaluate the degree of physiological weakness of the smallest piglets at birth and during the suckling period (20 d) compared to their middle-weight littermates through their jejunal gene expression. Newborn light piglets downregulated genes related to immunity, antioxidant, and digestive activities, but also a tendency to upregulate other genes related to inflammation and stress responses. At the end of the suckling period, those genes expression differences vanished while others appear. Light weight piglets showed lower expression of genes involved in barrier function, inflammation, and stress responses compared to their middle-weight littermates. At birth and at the end of lactation, light piglets seem to have a compromised intestinal gene expression for nutrient absorption, immune and stress responses compared to their heavier littermates.

Untreated obstructive sleep apnea and cardiovascular outcomes in patients with acute symptomatic pulmonary embolism.

There is a paucity of data examining the prognostic significance of untreated obstructive sleep apnea (OSA) in hemodynamically stable patients with acute pulmonary embolism (PE). This prospective cohort study enrolled consecutive non-hypotensive patients with acute PE who underwent an overnight sleep study within 48 h after diagnosis. The patients were divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The study used a composite of fatal or nonfatal cardiovascular events, including PE-related death, other cardiovascular deaths, clinical deterioration requiring an escalation of treatment, recurrent venous thromboembolism, acute myocardial infarction, or stroke within 30-days after the diagnosis of PE as the primary outcome. Between January 1, 2018, and December 31, 2020, 283 eligible patients were prospectively enrolled in 2 academic hospitals, of whom 268 patients completed a sleep study within 7 days of PE diagnosis. OSA was found in 47% (95% confidence interval [CI], 41 to 54%) of patients. The primary outcome occurred in 13 (4.9%) patients within 30-days after the diagnosis of PE. The crude incidence of the composite was not significantly different in the OSA than the non-OSA group (30-day estimate, 6.3% versus 3.5%; P = 0.30). OSA did not significantly predict the incidence of the primary outcome after adjustment for age, sex, body mass index, systolic blood pressure, heart rate, and oxygen saturation (adjusted hazard ratio, 2.15; 95% confidence interval, 0.67-6.87). In this study, untreated OSA was not a significant multivariable predictor of adverse cardiovascular events in patients with acute PE.

Prognostic Significance of Findings on CTPA Supporting an Alternative Diagnosis to PE Among Patients Hospitalized for an Exacerbation of COPD: Predefined Subanalysis of the SLICE Trial. / Significado pronóstico de los diagnósticos alternativos a la TEP hallados en la tomografía computarizada de tórax de pacientes ingresados por agudización de EPOC: subanálisis predefinido del ensayo SLICE.

BACKGROUND: Among patients hospitalized for an exacerbation of chronic obstructive pulmonary disease (COPD), the SLICE trial showed that the addition of an active diagnostic strategy for pulmonary embolism (PE) to usual care compared with usual care alone did not improve a composite set of health outcomes. The objective of this subanalysis was to determine the frequency and prognostic significance of findings on computed tomography pulmonary angiogram (CTPA) supporting an alternative diagnosis to PE. METHODS: We analyzed all patients randomized to the intervention in the SLICE trial who received a CTPA that did not show PE. We used multivariable logistic regression to assess the independent association between findings supporting an alternative diagnosis to PE and a composite of readmission for COPD or death within 90 days after randomization. RESULTS: Among the 746 patients who were randomized, this subanalysis included 175 patients in the intervention group who received a CTPA that did not show PE. Eighty-four (48.0%) patients had acute bronchial infection, 13 (7.4%) had lung cancer, 10 (5.7%) had congestive heart failure, 8 (4.6%), 18 (10.3%) had other diagnoses, and 42 (24.0%) had a normal CTPA. In multivariable analysis, findings supporting an alternative diagnosis to PE were not significantly associated with the primary outcome (odds ratio: 0.64; 95% confidence interval: 0.30-1.38; P=0.26). CONCLUSIONS: Among patients hospitalized for an exacerbation of COPD, CTPA identified an alternative diagnosis in 76% of the patients. However, specific management of these patients was not associated with improved outcomes within 90 days after randomization.

Significado pronóstico de los diagnósticos alternativos a la TEP hallados en la tomografía computarizada de tórax de pacientes ingresados por agudización de EPOC: subanálisis predefinido del ensayo SLICE / Prognostic Significance of Findings on CTPA Supporting an Alternative Diagnosis to PE Among Patients Hospitalized for an Exacerbation of COPD: Predefined Subanalysis of the SLICE Trial

Antecedentes: El ensayo clínico SLICE no demostró un beneficio clínico de la búsqueda activa de la tromboembolia de pulmón (TEP) en pacientes que requirieron ingreso por agudización de su EPOC. El objetivo de este subanálisis fue determinar la frecuencia y el significado pronóstico del hallazgo de un diagnóstico alternativo a la TEP en la tomografía computarizada de tórax (TC) realizada a pacientes hospitalizados por EPOC agudizada. Métodos: Analizamos los pacientes del grupo intervención de SLICE que recibieron una TC con resultado negativo para TEP. Evaluamos mediante el uso de regresión logística multivariable la asociación entre un diagnóstico alternativo y el evento primario compuesto de reingreso por EPOC y la mortalidad por cualquier causa en los primeros 90 días después de la aleatorización. Resultados: Este análisis incluyó a 175 pacientes del grupo intervención que recibieron una TC con un resultado negativo para TEP. De ellos, 84 (48,0%) fueron diagnosticados de infección bronquial aguda, 13 (7,4%) de cáncer de pulmón, 10 (5,7%) de insuficiencia cardiaca, 8 (4,6%) de neumonía, 18 (10,3%) de otros diagnósticos, y en 42 (24,0%) pacientes la TC fue normal. En el análisis multivariable, un diagnóstico alternativo no se asoció de manera significativa con el evento primario (odds ratio: 0,64; IC 95%: 0,30-1,38; P=0,26). Conclusiones: Entre los pacientes que requieren ingreso por agudización de EPOC, la TC ofrece un diagnóstico alternativo a la TEP en el 76% de las ocasiones. El tratamiento específico de estas patologías no se asocia a un mejor pronóstico durante el seguimiento. (AU)

Background: Among patients hospitalized for an exacerbation of chronic obstructive pulmonary disease (COPD), the SLICE trial showed that the addition of an active diagnostic strategy for pulmonary embolism (PE) to usual care compared with usual care alone did not improve a composite set of health outcomes. The objective of this subanalysis was to determine the frequency and prognostic significance of findings on computed tomography pulmonary angiogram (CTPA) supporting an alternative diagnosis to PE. Methods: We analyzed all patients randomized to the intervention in the SLICE trial who received a CTPA that did not show PE. We used multivariable logistic regression to assess the independent association between findings supporting an alternative diagnosis to PE and a composite of readmission for COPD or death within 90 days after randomization. Results: Among the 746 patients who were randomized, this subanalysis included 175 patients in the intervention group who received a CTPA that did not show PE. Eighty-four (48.0%) patients had acute bronchial infection, 13 (7.4%) had lung cancer, 10 (5.7%) had congestive heart failure, 8 (4.6%), 18 (10.3%) had other diagnoses, and 42 (24.0%) had a normal CTPA. In multivariable analysis, findings supporting an alternative diagnosis to PE were not significantly associated with the primary outcome (odds ratio: 0.64; 95% confidence interval: 0.30-1.38; P=0.26). Conclusions: Among patients hospitalized for an exacerbation of COPD, CTPA identified an alternative diagnosis in 76% of the patients. However, specific management of these patients was not associated with improved outcomes within 90 days after randomization. (AU)

[Translated article] Prognostic Significance of Findings on CTPA Supporting an Alternative Diagnosis to PE Among Patients Hospitalized for an Exacerbation of COPD: Predefined Subanalysis of the SLICE Trial / Significado pronóstico de los diagnósticos alternativos a la TEP hallados en la tomografía computarizada de tórax de pacientes ingresados por agudización de EPOC: subanálisis predefinido del ensayo SLICE

Background: Among patients hospitalized for an exacerbation of chronic obstructive pulmonary disease (COPD), the SLICE trial showed that the addition of an active diagnostic strategy for pulmonary embolism (PE) to usual care compared with usual care alone did not improve a composite set of health outcomes. The objective of this subanalysis was to determine the frequency and prognostic significance of findings on computed tomography pulmonary angiogram (CTPA) supporting an alternative diagnosis to PE. Methods: We analyzed all patients randomized to the intervention in the SLICE trial who received a CTPA that did not show PE. We used multivariable logistic regression to assess the independent association between findings supporting an alternative diagnosis to PE and a composite of readmission for COPD or death within 90 days after randomization. Results: Among the 746 patients who were randomized, this subanalysis included 175 patients in the intervention group who received a CTPA that did not show PE. Eighty-four (48.0%) patients had acute bronchial infection, 13 (7.4%) had lung cancer, 10 (5.7%) had congestive heart failure, 8 (4.6%), 18 (10.3%) had other diagnoses, and 42 (24.0%) had a normal CTPA. In multivariable analysis, findings supporting an alternative diagnosis to PE were not significantly associated with the primary outcome (odds ratio: 0.64; 95% confidence interval: 0.30-1.38; P=0.26). Conclusions: Among patients hospitalized for an exacerbation of COPD, CTPA identified an alternative diagnosis in 76% of the patients. However, specific management of these patients was not associated with improved outcomes within 90 days after randomization. (AU)

Antecedentes: El ensayo clínico SLICE no demostró un beneficio clínico de la búsqueda activa de la tromboembolia de pulmón (TEP) en pacientes que requirieron ingreso por agudización de su EPOC. El objetivo de este subanálisis fue determinar la frecuencia y el significado pronóstico del hallazgo de un diagnóstico alternativo a la TEP en la tomografía computarizada de tórax (TC) realizada a pacientes hospitalizados por EPOC agudizada. Métodos: Analizamos los pacientes del grupo intervención de SLICE que recibieron una TC con resultado negativo para TEP. Evaluamos mediante el uso de regresión logística multivariable la asociación entre un diagnóstico alternativo y el evento primario compuesto de reingreso por EPOC y la mortalidad por cualquier causa en los primeros 90 días después de la aleatorización. Resultados: Este análisis incluyó a 175 pacientes del grupo intervención que recibieron una TC con un resultado negativo para TEP. De ellos, 84 (48,0%) fueron diagnosticados de infección bronquial aguda, 13 (7,4%) de cáncer de pulmón, 10 (5,7%) de insuficiencia cardiaca, 8 (4,6%) de neumonía, 18 (10,3%) de otros diagnósticos, y en 42 (24,0%) pacientes la TC fue normal. En el análisis multivariable, un diagnóstico alternativo no se asoció de manera significativa con el evento primario (odds ratio: 0,64; IC 95%: 0,30-1,38; P=0,26). Conclusiones: Entre los pacientes que requieren ingreso por agudización de EPOC, la TC ofrece un diagnóstico alternativo a la TEP en el 76% de las ocasiones. El tratamiento específico de estas patologías no se asocia a un mejor pronóstico durante el seguimiento. (AU)

Lateral tarsal strip through osteotomies for recurrent ectropion and eyelid laxity correction.

OBJECTIVE: to present a surgical technique for treating patients with recurrent ectropion and severe lower eyelid laxity. METHODS: Lateral tarsal strip and canthal fixation by osteotomy was performed in 6 patients with recurrent ectropion and 1 patient with extreme lower eyelid laxity secondary to an anophthalmic socket. Preoperative and postoperative photographs were evaluated in order to assess the outcomes of the procedure. Patients were followed up 4 weeks, 6 months, 12 months and 24 months of the postoperative period. The initial symptoms of the patients were eye redness, epiphora, foreign body sensation, aesthetic complaints, and facial asymmetry. Symptoms and aesthetic results were assessed by questioning, photographs, and fluorescein and lissamine green stains taken in each visit. RESULTS: No postoperative complications were observed. No recurrence episodes were reported during the follow-up period and physical appearance improvement and symptom severity reduction were maintained during the observation. CONCLUSION: Lateral tarsal strip through osteotomies is an effective surgical procedure for treating severe recurrent ectropion cases or lower eyelid laxity and could be considered as an alternative treatment option or even a primary surgical technique in selected difficult cases.

Microencapsulation Improved Fumaric Acid and Thymol Effects on Broiler Chickens Challenged With a Short-Term Fasting Period.

The first objective of this study was to demonstrate the usefulness of the microencapsulation technique to protect fumaric acid and thymol, avoiding their early absorption and ensuring their slow release throughout the gastrointestinal tract (GIT). For this purpose, the release of a lipid matrix microencapsulated brilliant blue (BB) was assessed in vitro, using a simulated broiler intestinal fluid, and in vivo. In vitro results showed that more than 60% of BB color reached the lower intestine, including 26.6 and 29.7% in the jejunum and ileum, respectively. The second objective was to determine the effects of microencapsulated fumaric acid, thymol, and their mixture on the performance and gut health of broilers challenged with a short-term fasting period (FP). One-day-old male ROSS 308 chickens (n = 280) were randomly distributed into seven treatments, with 10 replicates of four birds each. Dietary treatments consisted of a basal diet as negative control (NC), which was then supplemented by either non-microencapsulated fumaric acid (0.9 g/kg), thymol (0.6 g/kg), or a mixture of them. The same additive doses were also administered in a microencapsulated form (1.5 and 3 g/kg for the fumaric acid and thymol, respectively). At day 21, chickens were subjected to a 16.5-h short-term FP to induce an increase in intestinal permeability. Growth performance was assessed weekly. At day 35, ileal tissue and cecal content were collected from one bird per replicate to analyze intestinal histomorphology and microbiota, respectively. No treatment effect was observed on growth performance from day 1 to 21 (p > 0.05). Microencapsulated fumaric acid, thymol, or their mixture improved the overall FCR (feed conversion ratio) and increased ileal villi height-to-crypt depth ratio (VH:CD) (p < 0.001) on day 35 of the experiment. The microencapsulated mixture of fumaric acid and thymol increased cecal abundance of Bacteroidetes, Bacillaceae, and Rikenellaceae, while decreasing that of Pseudomonadaceae. These results indicate that the microencapsulation technique used in the current study can be useful to protect fumaric acid and thymol, avoiding early absorption, ensure their slow release throughout the GIT, and improve their effects on fasted broiler chickens.

Strategies of inorganic and organic trace mineral supplementation in gestating hyperprolific sow diets: effects on the offspring performance and fetal programming.

The aim of the present study was to evaluate the effect of trace mineral nutrition on sow performance, mineral content, and intestinal gene expression of neonate piglets when inorganic mineral sources (ITM) were partially replaced by their organic mineral (OTM) counterparts. At 35 d postmating, under commercial conditions, a total of 240 hyperprolific multiparous sows were allocated into three experimental diets: 1) ITM: with Zn, Cu, and Mn at 80, 15, and 60 mg/kg, respectively; 2) partial replacement trace mineral source (Replace): with a 30 % replacement of ITM by OTM, resulting in ITM + OTM supplementation of Zn (56 + 24 mg/kg), Cu (10.5 + 4.5 mg/kg), and Mn (42 + 18 mg/kg); and 3) Reduce and replace mineral source (R&R): reducing a 50% of the ITM source of Zn (40 + 24 mg/kg), Cu (7.5 + 4.5 mg/kg), and Mn (30 + 18 mg/kg). At farrowing, 40 piglets were selected, based on birth weight (light: <800 g, and average: >1,200 g), for sampling. Since the present study aimed to reflect results under commercial conditions, it was difficult to get an equal parity number between the experimental diets. Overall, no differences between experimental diets on sow reproductive performance were observed. Light piglets had a lower mineral content (P < 0.05) and a downregulation of several genes (P < 0.10) involved in physiological functions compared with their average littermates. Neonate piglets born from Replace sows had an upregulation of genes involved in functions like immunity and gut barrier, compared with those born from ITM sows (P < 0.10), particularly in light piglets. In conclusion, the partial replacement of ITM by their OTM counterparts represents an alternative to the totally inorganic supplementation with improvements on neonate piglet gene expression, particularly in the smallest piglets of the litter. The lower trace mineral storage together with the greater downregulation of gut health genes exposed the immaturity and vulnerability of small piglets.