Chronic Obstructive Pulmonary Disease in Heart Failure: Challenges in Diagnosis and Treatment for HFpEF and HFrEF.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is common in heart failure (HF), and it has a significant impact on the prognosis and quality of life of patients. Additionally, COPD is independently associated with lower adherence to first-line HF therapies. In this review, we outline the challenges of identifying and managing HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction with coexisting COPD. RECENT FINDINGS: Spirometry is necessary for COPD diagnosis and prognosis but is underused in HF. Therefore, misdiagnosis is a concern. Also, disease-modifying drugs for HF and COPD are usually safe but underprescribed when HF and COPD coexist. Patients with HF-COPD are poorly enrolled in clinical trials. Guidelines recommend that HF treatment should be offered regardless of COPD presence, but modern registries show that undertreatment persists. Treatment gaps could be attenuated by ensuring an accurate and earlier COPD diagnosis in patients with HF, clarifying the concerns related to pharmacotherapy safety, and increasing the use of non-pharmacologic treatments. Acknowledging the uncertainties, this review aims to provide key clinical resources to support better physician-patient co-decision-making and improve collaboration between health professionals.

Influence of Sex and a High-Fiber Diet on the Gut Microbiome of Alentejano Pigs Raised to Heavy Weights.

This study investigates the influence of sex and a dietary transition on the gut microbiota of a local Portuguese pig breed. Three groups of male Alentejano pigs (n = 10 each) were raised between ~40 and 160 kg LW. Group C included pigs that were surgically castrated, while the I group included intact ones; both were fed with commercial diets. The third group, IExp, included intact pigs that were fed commercial diets until ~130 kg, then replaced by an experimental diet based on legumes and agro-industrial by-products between ~130 and 160 kg. Fecal samples were collected two weeks before slaughter. The total DNA was extracted and used for 16S metabarcoding on a MiSeq® System. The dietary transition from a commercial diet to the experimental diet substantially increased and shifted the diversity observed. Complex carbohydrate fermenting bacteria, such as Ruminococcus spp. and Sphaerochaeta spp., were significantly more abundant in IExp (q < 0.05). On the other hand, castrated pigs presented a significantly lower abundance of the potential probiotic, Roseburia spp. and Lachnospiraceae NK4A136 group (q < 0.01), bacteria commonly associated with better gut health and lower body fat composition. Understanding the role of gut microbiota is paramount to ensure a low skatole deposition and consumers' acceptance of pork products from non-castrated male pigs.

Influence of Sex on Meat and Fat Quality from Heavy Alentejano Pigs Finished Outdoors on Commercial and High Fiber Diets.

This work aimed to examine the effects of sex on meat and fat quality traits from thirty Portuguese Alentejano (AL) pigs reared in outdoor conditions. These pigs were divided into three groups and fed ad libitum. From ~40 to 130 kg LW, castrated (C group) and intact animals (I and IExp) consumed commercial diets. Until slaughter (~160 kg), C and I pigs remained on commercial diets, and IExp changed to a more sustainable experimental diet with locally produced pulses and byproducts. Samples were collected from the Longissimus lumborum (LL), Psoas major (PM), and dorsal subcutaneous fat (DSF). At ~160 kg, the PM muscle of intact pigs presented lower intramuscular fat content than that of C pigs, while total collagen was higher. Additionally, PM myoglobin was lower and lightness (L*) was higher in intact pigs. Regarding DSF, moisture and total protein contents were higher and total lipids were lower in intact than in castrated pigs, while color parameters were not significantly different. Finally, antioxidant capacity measured in the LL muscle showed an overall lower value in intact pigs. However, lipid oxidation values were not significantly different between the experimental groups and only increased with storage time. Outdoor-reared intact AL pigs produced leaner and less saturated pork and fat compared to castrated ones. Despite the lower antioxidant activity observed in the LL muscles of intact pigs, the lipid oxidative stability of cooked meat was not different among the experimental groups.

Transcriptomic Profiling of Subcutaneous Backfat in Castrated and Intact Alentejano Pigs Finished Outdoors with Commercial and Fiber-Rich Diets.

In this work, we studied the backfat transcriptome of surgically castrated (C), intact (I) and intact fed an experimental diet (IE) outdoor-reared male Alentejano (AL) pigs. The experimental diet was a high-fiber diet with locally produced legumes and by-products associated with a boar taint reduction effect. At slaughter (~160 kg), backfat samples were collected for total RNA sequencing. Intact pigs presented leaner carcasses, more total collagen, and more unsaturated intramuscular fat content than C animals. A total of 2726 differentially expressed genes (DEGs, |log2 FC|> 0.58, q < 0.05) were identified between C and I with overexpressed genes related to muscular activity (MYH1, ACTA1) or collagen metabolism (COL1A1, COL1A2) in I pigs. Between C and IE, 1639 DEGs of genes involved in lipidic metabolism (LEP, ME1, FABP4, ELOVL6) were overexpressed in C. Finally, only 28 DEGs were determined between I and IE. Clustering results indicated a drastic influence of the testis in the transcriptome of subcutaneous fat of AL pigs, while the diet had a marginal effect. Diet can reduce stress by increasing satiety in animals, and could have induced an increase of skatole degradation due to the higher expression of the CYP2A19 gene in the IE group.

Outdoor Finishing of Intact Male Portuguese Alentejano Pigs on a Sustainable High-Fiber Diet: Impacts on Blood, Growth, Carcass, Meat Quality and Boar Taint Compounds.

This trial evaluated the effect of sex on the blood, growth, carcass, meat quality, and boar taint compounds in male Alentejano (AL) pigs (n = 30). From ~40 to 130 kg LW, castrated (C) and intact pigs (I and IExp groups) were fed commercial diets ad libitum. Between ~130 and 160 kg (slaughter), C and I pigs continued on commercial diets, while IExp were fed an experimental diet containing locally produced pulses and by-products aimed at reducing boar taint. At ~160 kg, blood urea levels were higher in IExp than C pigs, triacylglycerols were lower in both intact groups, and cortisol was lower in IExp. IExp pigs exhibited faster growth, improved feed conversion ratio, carcass higher commercial yield and leaner meat than C pigs. The loin intramuscular fat in intact pigs was lower, less saturated and more polyunsaturated, while total collagen was higher. Fat androstenone content was higher in intact pigs and skatole content was similar across treatments, although they were below threshold values for consumer detection. Finally, although boar taint compounds were low in intact AL pigs raised outdoors, adding pulses and by-products to the experimental diet did not result in a reduction in fat skatole content compared to pigs fed the commercial diet.

Exercise intolerance in post-coronavirus disease 2019 survivors after hospitalisation.

Rationale: Post-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation. Methods: This prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd 90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis. Measurements and main results: 87 patients were evaluated; mean±sd peak oxygen consumption was 19.5±5.0 mL·kg-1·min-1, and the tertiles were ≤17.0, 17.1-22.2 and ≥22.3 mL·kg-1·min-1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg-1·min-1 reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg-1·min-1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption. Conclusions: Exercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.

Diaphragm Ultrasound in Critically Ill Patients on Mechanical Ventilation-Evolving Concepts.

Mechanical ventilation (MV) is a life-saving respiratory support therapy, but MV can lead to diaphragm muscle injury (myotrauma) and induce diaphragmatic dysfunction (DD). DD is relevant because it is highly prevalent and associated with significant adverse outcomes, including prolonged ventilation, weaning failures, and mortality. The main mechanisms involved in the occurrence of myotrauma are associated with inadequate MV support in adapting to the patient's respiratory effort (over- and under-assistance) and as a result of patient-ventilator asynchrony (PVA). The recognition of these mechanisms associated with myotrauma forced the development of myotrauma prevention strategies (MV with diaphragm protection), mainly based on titration of appropriate levels of inspiratory effort (to avoid over- and under-assistance) and to avoid PVA. Protecting the diaphragm during MV therefore requires the use of tools to monitor diaphragmatic effort and detect PVA. Diaphragm ultrasound is a non-invasive technique that can be used to monitor diaphragm function, to assess PVA, and potentially help to define diaphragmatic effort with protective ventilation. This review aims to provide clinicians with an overview of the relevance of DD and the main mechanisms underlying myotrauma, as well as the most current strategies aimed at minimizing the occurrence of myotrauma with special emphasis on the role of ultrasound in monitoring diaphragm function.

A TaqMan® Assay Allows an Accurate Detection and Quantification of Fusarium spp., the Causal Agents of Tomato Wilt and Rot Diseases.

In tomato plants, Fusarium spp. have been increasingly associated with several wilt and rot diseases that are responsible for severe yield losses. Here, we present a real-time PCR TaqMan® MGB (Minor Groove Binder) assay to detect and discriminate Fusarium spp. from other fungal species that affect tomato plants. The methodology used is based on the selective amplification of the internal transcribed spacer (ITS) region of Fusarium spp. This assay revealed to be highly specific and sensitive for Fusarium species, targeting only the 29 Fusarium isolates from the 45 tested isolates associated to tomato diseases. Sensitivity was assessed with serial dilutions of Fusarium genomic DNA, with the limit of detection of 3.05 pg. An absolute DNA quantification method was also established, based on the determination of the absolute number of target copies. Finally, the effectiveness of the assay was successfully validated with the detection and quantification of Fusarium spp. in potentially infected tomato plants from an experimental field and in control plants grown under controlled conditions. The established methodology allows a reliable, sensitive, and reproducible estimation of Fusarium accumulation in infected tomato plants, gaining new insights for disease control and providing an additional tool in the screening of resistant plants.

Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: Prospective cohort study.

BACKGROUND: Coronavirus disease (COVID-19) survivors exhibit multisystemic alterations after hospitalization. Little is known about long-term imaging and pulmonary function of hospitalized patients intensive care unit (ICU) who survive COVID-19. We aimed to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and identify risk factors associated with chest computed tomography (CT) lesion severity. METHODS: A prospective cohort study of COVID-19 patients admitted to a tertiary hospital ICU in Brazil (March-August/2020), and followed-up six-twelve months after hospital admission. Initial assessment included: modified Medical Research Council dyspnea scale, SpO2 evaluation, forced vital capacity, and chest X-Ray. Patients with alterations in at least one of these examinations were eligible for CT and pulmonary function tests (PFTs) approximately 16 months after hospital admission. Primary outcome: CT lesion severity (fibrotic-like or non-fibrotic-like). Baseline clinical variables were used to build a machine learning model (ML) to predict the severity of CT lesion. RESULTS: In total, 326 patients (72%) were eligible for CT and PFTs. COVID-19 CT lesions were identified in 81.8% of patients, and half of them showed mild restrictive lung impairment and impaired lung diffusion capacity. Patients with COVID-19 CT findings were stratified into two categories of lesion severity: non-fibrotic-like (50.8%-ground-glass opacities/reticulations) and fibrotic-like (49.2%-traction bronchiectasis/architectural distortion). No association between CT feature severity and altered lung diffusion or functional restrictive/obstructive patterns was found. The ML detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity(sensitivity,0.78±0.02;specificity,0.79±0.01;F1-score,0.78±0.02;positive predictive rate,0.78±0.02; accuracy,0.78±0.02; and area under the curve,0.83±0.01). CONCLUSION: ICU hospitalization due to COVID-19 led to respiratory system alterations six-twelve months after hospital admission. Male sex and critical disease acute phase, characterized by a longer ICU and IMV period, and need for tracheostomy and vasoactive drugs, were risk factors for severe CT lesions six-twelve months after hospital admission.

Vocal Impact in Patients With Unilateral Diaphragmatic Paralysis.

OBJECTIVES: This study aimed to investigate the possible vocal impact confirmed by diagnostic tests, the degree of perception of possible vocal impairment by patients with Unilateral Diaphragmatic paralysis (UDP) and its correlation with ventilatory weakness. METHODS: The researchers conducted an analytical, observational and case-control study with 70 individuals, including 35 UDP patients and 35 healthy patients in a control group, who underwent the following assessments: 1) Self-assessment of voice handicap (VHI-10); 2) Self-Assessment of Quality of Life (SF-36); 3) Self-Assessment of Dyspnea (MRC); 4) Objective vocal measures (Maximum Phonation Time (MPT) in /a/, /s/, /z/ and glottal-to-noise excitation ratio); 5) Functional respiratory pressures (Spirometry and maximum ventilatory pressures); 6) General degree of dysphonia - G on the GRBAS Scale. The sex, age and body mass index (BMI) of the individuals were the variables used to match the sample of this study. RESULTS: When compared with controls, patients with UDP had a restrictive functional pattern and inspiratory weakness, with symptoms of dyspnea and worsening quality of life. When associated with a possible vocal impact, these patients had voice handicap and decreased MPT values for all phonemes, especially /a/. There was also a correlation between vocal performance and inspiratory weakness. However, it should be noted that, despite having vocal impairment, many patients did not report the perception of this fact, somehow neglecting such impairment. CONCLUSIONS: In addition to the expected weakness of the ventilatory muscles, patients with UDP had clinically verified vocal impact, and those who had greater inspiratory weakness also had greater voice impairment. Finally, it is relevant that not all patients perceived such vocal impact, which showed a very reduced perception of this impairment in patients with UDP.

Evaluation of quality of online shopping services in times of COVID-19 based on E-S-QUAL model and Fuzzy TOPSIS method.

This paper aims to propose an approach to evaluate the quality of online shopping services in times of pandemic COVID-19, from the ordering of quality attributes taking into account customers' perception. The proposed approach was developed from a structured questionnaire containing 25 quality attributes adapted from the E-S-QUAL model and applied to consumers of online shopping services. Fuzzy set theory was used in the approach to simplify the subjectivity of human judgment, along with the extension of Technique for Order Performance by Similarity to Ideal Solution (TOPSIS). Therefore, this research was classified as applied, exploratory, quantitative and survey. To achieve the research objective, 819 questionnaires were collected. Among the main findings, it is highlighted that the attributes "product availability", "products with excellent quality", "confidence in online shopping processes" and "ease of buying online" were the ones that presented the best perceptions of quality by the respondents. At the other end, the attributes "opinion sharing on social networks", "buying online is a good option when you have little time", "distraction in online shopping searches" and "shopping online is a pleasure" showed the highest level of dissatisfaction with the service. Thus, this article highlights the importance of online shopping services in times of the pandemic caused by COVID-19, and its main contribution and originality is the development of an approach that aims to support the decision-making process, establishing strategic actions for the continuous improvement of online shopping services with the reduction of subjectivity in customer perception and with successive refinements.

Persistence of symptoms and return to work after hospitalization for COVID-19.

Many patients hospitalized with COVID-19 were unable to return to work or their return was delayed due to their health condition. The aim of this observational study was to evaluate the impact of moderate-to-severe and critical COVID-19 infection on persistence of symptoms and return to work after hospital discharge. In this study, two thirds of hospitalized patients with pulmonary involvement reported persistence of symptoms six months after COVID-19 infection, such as memory loss (45.5%), myalgia (43.9%), fatigue (39.4%), and dyspnea (25.8%), and 50% slowly returned to work, with repercussions due to fatigue and/or loss of energy.

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series.

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).

Robotic Lung Volume Reduction Surgery With Extracorporeal Membrane Oxygenation.

Lobectomy for consolidation of failed endoscopic lung volume reduction for emphysema has been reported in selected patients with favorable results but with considerable morbidity. The challenging issues in such patients are frailty caused by severe emphysema itself, poor tolerance to single-lung ventilation, target lobe hyperinflation, and inability to use gas inflation for the minimally invasive resection. Careful planning, including use of a robotic platform and extracorporeal membrane oxygenation support, can circumvent such difficulties and ensure a safe, minimally invasive resection in the high-risk emphysematous patient.

Defense Strategies: The Role of Transcription Factors in Tomato-Pathogen Interaction.

Tomato, one of the most cultivated and economically important vegetable crops throughout the world, is affected by a panoply of different pathogens that reduce yield and affect product quality. The study of tomato-pathogen system arises as an ideal system for better understanding the molecular mechanisms underlying disease resistance, offering an opportunity of improving yield and quality of the products. Among several genes already identified in tomato response to pathogens, we highlight those encoding the transcription factors (TFs). TFs act as transcriptional activators or repressors of gene expression and are involved in large-scale biological phenomena. They are key regulators of central components of plant innate immune system and basal defense in diverse biological processes, including defense responses to pathogens. Here, we present an overview of recent studies of tomato TFs regarding defense responses to biotic stresses. Hence, we focus on different families of TFs, selected for their abundance, importance, and availability of functionally well-characterized members in response to pathogen attack. Tomato TFs' roles and possibilities related to their use for engineering pathogen resistance in tomato are presented. With this review, we intend to provide new insights into the regulation of tomato defense mechanisms against invading pathogens in view of plant breeding.

Quantitative CT Analysis in Chronic Hypersensitivity Pneumonitis: A Convolutional Neural Network Approach.

RATIONALE AND OBJECTIVES: Chronic hypersensitivity pneumonitis (cHP) is a heterogeneous condition, where both small airway involvement and fibrosis may simultaneously occur. Computer-aided analysis of CT lung imaging is increasingly used to improve tissue characterization in interstitial lung diseases (ILD), quantifying disease extension, and progression. We aimed to quantify via a convolutional neural network (CNN) method the extent of different pathological classes in cHP, and to determine their correlation to pulmonary function tests (PFTs) and mosaic attenuation pattern. MATERIALS AND METHODS: The extension of six textural features, including consolidation (C), ground glass opacity (GGO), fibrosis (F), low attenuation areas (LAA), reticulation (R) and healthy regions (H), was quantified in 27 cHP patients (age: 56 ± 11.5 years, forced vital capacity [FVC]% = 57 ± 17) acquired at full-inspiration via HRCT. Each class extent was correlated to PFTs and to mosaic attenuation pattern. RESULTS: H showed a positive correlation with FVC%, FEV1% (forced expiratory volume), total lung capacity%, and diffusion of carbon monoxide (DLCO)% (r = 0.74, r = 0.78, r = 0.73, and r = 0.60, respectively, p < 0.001). GGO, R and C negatively correlated with FVC% and FEV1% with the highest correlations found for R (r = -0.44, and r = -0.46 respectively, p < 0.05); F negatively correlated with DLCO% (r = -0.42, p < 0.05). Patients with mosaic attenuation pattern had significantly more H (p = 0.04) and lower R (p = 0.02) and C (p = 0.0009) areas, and more preserved lung function indices (higher FVC%; p = 0.04 and DLCO%; p = 0.05), but did not show more air trapping in lung function tests. CONCLUSION: CNN quantification of pathological tissue extent in cHP improves its characterization and shows correlation with PFTs. LAA can be overestimated by visual, qualitative CT assessment and mosaic attenuation pattern areas in cHP represents patchy ILD rather than small-airways disease.

A Convolutional Neural Network Approach to Quantify Lung Disease Progression in Patients with Fibrotic Hypersensitivity Pneumonitis (HP).

Rationale and Objectives To evaluate associations between longitudinal changes of quantitative CT parameters and spirometry in patients with fibrotic hypersensitivity pneumonitis (HP). Materials and Methods Serial CT images and spirometric data were retrospectively collected in a group of 25 fibrotic HP patients. Quantitative CT analysis included histogram parameters (median, interquartile range, skewness, and kurtosis) and a pretrained convolutional neural network (CNN)-based textural analysis, aimed at quantifying the extent of consolidation (C), fibrosis (F), ground-glass opacity (GGO), low attenuation areas (LAA) and healthy tissue (H). Results At baseline, FVC was 61(44-70) %pred. The median follow-up period was 1.4(0.8-3.2) years, with 3(2-4) visits per patient. Over the study, 8 patients (32%) showed a FVC decline of more than 5%, a significant worsening of all histogram parameters (p≤0.015) and an increased extent of fibrosis via CNN (p=0.038). On histogram analysis, decreased skewness and kurtosis were the parameters most strongly associated with worsened FVC (respectively, r2=0.63 and r2=0.54, p<0.001). On CNN classification, increased extent of fibrosis and consolidation were the measures most strongly correlated with FVC decline (r2=0.54 and r2=0.44, p<0.001). Conclusion CT histogram and CNN measurements provide sensitive measures of functional changes in fibrotic HP patients over time. Increased fibrosis was associated with FVC decline, providing index of disease progression. CNN may help improve fibrotic HP follow-up, providing a sensitive tool for progressive interstitial changes, which can potentially contribute to clinical decisions for individualizing disease management.