A biofloc system avoids the adverse effects of diets with suboptimal protein levels on zootechnical performance, intestinal histomorphometry, and protein metabolism of Nile tilapia juvenile fed Spirulina biomass (Arthrospira platensis) as an alternative protein source.

This study aimed to evaluate the effect of the biofloc technology (BFT) system and the replacement of fish meal with Spirulina biomass on productive performance, intestinal histomorphometry, plasma biochemistry, and oxidative stress of Nile tilapia juveniles (Oreochromis niloticus) fed suboptimal levels of protein. Two factors were evaluated: production systems (clear water × BFT) and replacement of fish meal with Spirulina (0, 33, 66 e 100%). The design was in a 2 × 4 randomized factorial scheme with four replications, and the fish were evaluated for 48 days. Four isoproteic (28% crude protein) diets were formulated with gross energy values close to 4300 kcal kg-1. Nile tilapia juveniles (0.23 ± 0.01 g) were distributed in 16 circular tanks (70 L) at seven fish/tank. The diets were formulated with protein levels approximately 20% below that required for the species and life stage. No interaction was observed between the factors evaluated (production systems × Spirulina inclusion). Rearing the fish in the BFT system avoided the adverse effects of diets with suboptimal protein levels on performance, intestinal histomorphometry, and protein metabolism. Lower values lower lipid peroxidation and higher antioxidant capacity were observed in fish reared in the BFT system, showing evidence of improvements in antioxidant responses and lower levels of physiological oxidative stress. Spirulina completely replaced fish meal in the diets of Nile tilapia juveniles without adverse effects on intestinal morphometry, protein metabolism, and antioxidant response. Replacing 66% of fish meal with Spirulina improved the productive performance, regardless of the rearing system.

Phase Behavior of Drug-Lipid-Surfactant Ternary Systems toward Understanding the Annealing-Induced Change.

The present study systematically investigates the effect of annealing conditions and the Kolliphor P 407 content on the physicochemical and structural properties of Compritol (glyceryl behenate) and ternary systems prepared via melt cooling (Kolliphor P 407, Compritol, and a hydrophilic API) representing solid-lipid formulations. The physical properties of Compritol and the ternary systems with varying ratios of Compritol and Kolliphor P 407 were characterized using differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS) and infrared (IR) spectroscopy, and hot-stage microscopy (HSM), before and after annealing. The change in the chemical profiles of different Compritol components as a function of annealing was evaluated using 1H NMR spectroscopy. While no change in the polymorphic form of API and Kolliphor P 407 occurred during annealing, a systematic conversion of the α- to ß-form was observed in the case of Compritol. Furthermore, the polymorphic transformation of Compritol was found to be dependent on the Kolliphor P 407 content. As per the Flory-Huggins mixing theory, higher miscibility was observed in the case of monobehenin-Kolliphor P 407, monobehenin-dibehenin, and dibehenin-tribehenin binary mixtures. The miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin was confirmed by 1H NMR analysis. The observed higher miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin is proposed as the trigger for the physical separation from the 1,3-diglyceride and triglycerides during melt solidification of the formulations. The phase separation is postulated as the mechanism underlying the formation of a stable ß-polymorphic form (a native form of 1,3-diglyceride) of Compritol upon annealing. This finding is expected to have an important implication for developing stable solid-lipid-surfactant-based drug formulations.

PM10 exposure interacts with abdominal obesity to increase blood triglycerides: a cross-sectional linkage study.

BACKGROUND: Blood lipids and glucose levels dysregulation represent potential mechanisms intermediating the adverse cardiovascular effects of ambient particulate matter (PM) exposure. This study aims to estimate the effect of long-term PM10 exposure on blood lipids and glucose levels and to assess the potential mediation and/or modification action of abdominal obesity (AO) (waist-to-height ratio). METHODS: Our study was based on 2,390 participants of the first Portuguese Health Examination Survey (INSEF, 2015) with available data on blood lipids and glucose parameters and living within a 30-km radius of an air quality monitoring station with available PM10 measurements. PM10 concentrations were acquired from the air quality monitoring network of the Portuguese Environment Agency. Generalized linear models were used to assess the effect of 1-year PM10 exposure on blood lipids and glucose levels. An interaction term was introduced in the models to test the modification action of AO. RESULTS: We found an association between PM10 and non-fasting blood triglycerides (TG) after adjustment for age, sex, education, occupation, lifestyles-related variables and temperature but only in participants with AO. Per each 1 µg/m3 PM10 increment, there was a 1.84% (95% confidence interval: 0.02-3.69) increase in TG. For the remaining blood lipid and glucose parameters, no associations were found. CONCLUSIONS: Our study demonstrates that even at low levels of exposure, long-term PM10 exposure interacts with AO to increase blood TG. Our findings suggest that reducing both AO prevalence and PM10 below current standards would result in additional health benefits for the population.

How can the built environment affect the impact of autonomous vehicles' operational behaviour on air quality?

Autonomous vehicles (AVs) are pointed out as the technology that will reshape the concept of mobility, with significant implications for the economy, the environment, and society. This fact will bring new challenge to cities urban planning. Research to anticipate the AVs impacts, maximizing their benefits and reduce trade-offs are currently crucial. This work investigates the potential challenges and benefits of gradually replace internal combustion engine human driven vehicles with different penetration rates of AVs - 10%, 30%, 50%, 70%, 90%, and 100% - in urban roads of different characteristics, either in terms of traffic singularities or volumes, and its related implications on air quality. For that purpose, two urban areas with distinct features, Porto and Aveiro, were selected as case studies, and a modelling setup composed of a traffic model, an emission model, and a local air quality model was applied. The results revealed that the AVs benefits are directly linked with the urban design and the road characteristics. In the Aveiro case study, the AVs promoted positive changes with average reductions in daily NOx emissions (compared with the baseline scenario, without AVs) ranging between -2.1% (for C10%) and -7.7% (for C100%). In line with the emissions impacts, positive effects were found on air quality, with average reductions of NO2 concentrations up to -4% (for C100%). In Porto urban area, slight differences in NOx emissions were obtained (<2%), which implied no changes in the air quality levels. The distinct impact of AVs in the study areas is mostly explained by the traffic light coordination system and directional split distributions in the main roads. These results provide valuable insights to support decision-makers in the definition of strategies that allow the integration of these new emerging technologies in the road infrastructure, considering the features of the urban design, traffic profile and road characteristics.

Non-Paralytic Pontine Exotropia as a Predominant Sign of Brainstem Infarction - A Case Report.

The association of internuclear ophthalmoplegia (INO) with exotropia in the contralateral eye is a rare finding, known as non-paralytic pontine exotropia (NPPE). We report a case of an 80-year-old woman with acute onset of diplopia on admission who presented with left eye exotropia with left-beating nystagmus whilst fixating with the right eye and inability to adduct the right eye on left gaze. Brain magnetic resonance imaging showed two small areas of vertebrobasilar territory ischaemic stroke, one beneath the inferior portion of the aqueduct and another in the right occipital lobe. Our case highlights an interesting clinical manifestation of brainstem infarction that, along with ocular motility examination, allowed us to review its pathophysiology, including the influence of the contralateral paramedian pontine reticular formation stimulation in the mechanism of contralateral exotropia in NPPE. The fast clinical resolution of these cases can explain the scarcity of NPPE reports.

Effects of thymol supplementation on performance, mortality and branchial energetic metabolism in grass carp experimentally infected by Aeromonas hydrophila.

We determined whether thymol supplementation of would minimize the negative effects of Aeromonas hydrophila infection on branchial energy metabolism, weight loss and mortality in grass carp (Ctenopharyngodon idella). We found that the infected fish all died, while 62.5% of those supplemented with 100 mg/kg thymol survived. Cytosolic and mitochondrial creatine kinase (CK) activities, as well as adenylate kinase (AK) and pyruvate kinase (PK) activities were significant lower in gills of A. hydrophila-infected fish than those of the control group, and adenosine triphosphate (ATP) levels were significant lower in the infected group. Finally, branchial reactive oxygen species (ROS) were significant higher in A. hydrophila-infected fish than in the control group. Supplementation with 100 and 300 mg thymol/kg diet prevented inhibition of branchial cytosolic and mitochondrial CK activities caused by infection, and also inhibited the reduction of branchial ATP levels. Supplementation with 100, 200 and 300 mg thymol/kg prevented the inhibition of branchial AK and PK activities induced by aeromonosis. Supplementation of 100 mg thymol/kg prevented weight loss after A. hydrophila infection. These data suggest that supplementation with 100 mg thymol/kg exerts potent bactericidal properties and augments longevity. Supplementation at all concentrations of thymol prevented A. hydrophila-induced branchial bioenergetics; nevertheless, higher concentrations were associated with side-effects.

Unravelling the anticancer potential of functionalized chromeno[2,3-b]pyridines for breast cancer treatment.

A selection of new chromeno[2,3-b]pyridines was prepared from chromenylacrylonitriles and N-substituted piperazines, using a novel and efficient synthetic procedure. The compounds were tested for their anticancer activity using breast cancer cell lines MCF-7, Hs578t and MDA-MB-231 and the non-neoplastic cell line MCF-10A for toxicity evaluation. In general, compounds showed higher activity towards the luminal breast cancer subtype (MCF-7), competitive with the reference compound Doxorubicin. The in vivo toxicity assay using C. elegans demonstrated a safe profile for the most active compounds. Chromene 3f revealed a promising drug profile, inhibiting cell growth and proliferation, inducing cell cycle arrest in G2/M phase, apoptosis and microtubule destabilization. The new compounds presented exciting bioactive features and may be used as lead compounds in cancer related drug discovery.

Benefits of thymol supplementation on performance, the hepatic antioxidant system, and energetic metabolism in grass carp.

Thymol is an herbal food additive used to improve animal performance. Thymol acts via its potential to enhance productive and reproductive performance, and by improving bioavailability of nutrients in fish. Nevertheless, the exact mechanisms associated with these phenomena remain poorly understood, although recent evidence has suggested the involvement of the phosphotransfer network and antioxidant status. Therefore, the aim of this study was to determine whether the improvement of the antioxidant/oxidant status and the phosphoryl transfer network may be involved in enhanced growth performance in grass carp (Ctenopharyngodon idella) fed with various levels of thymol (100, 200, and 300 mg/kg feed). Thymol-supplementation (100 mg/kg feed) produced higher body weight and weight gain for 60-day post-feeding compared to the control group. Specific growth rate was higher; while feed conversion ratio was lower in fish that consumed 100 mg of thymol/kg compared to other groups. Hepatic lactate dehydrogenase activity and lipid peroxidation levels were lower in the thymol-supplemented group (100 mg/kg feed) than in the control group, while reactive oxygen species were lower in all supplemented groups than in the control group. Hepatic superoxide dismutase (300 mg/kg feed) and glutathione peroxidase (100, 200, and 300 mg/kg feed) activities, as well as antioxidant capacity against peroxyl radicals (100 mg/kg feed) were higher in these groups than in the control group. Based on these data, we conclude that 100 mg thymol/kg dietary supplementation increased growth performance of fingerling grass carp. Finally, hepatic adenylate kinase activity was lower in the thymol supplemented group (100 mg/kg feed) than in the control group. Thymol supplementation (100 mg/kg feed) improved hepatic energy metabolism, while practically all tested concentrations of thymol enhanced hepatic antioxidant status, all of which may be pathways involved in increased growth performance in fingerling grass carp.

Generation of deep ultraviolet sub-2-fs pulses.

We demonstrate the generation of few-cycle deep ultraviolet pulses via frequency upconversion of 5-fs near-infrared pulses in argon using a laser-fabricated gas cell. The measured spectrum extends from 210 to 340 nm, corresponding to a transform-limited pulse duration of 1.45 fs. We extract from a dispersion-free second-order cross-correlation measurement a pulse duration of 1.9 fs, defining a new record in the deep ultraviolet spectral range.

[How to properly use beta-blockers ?] / Comment utiliser correctement les ß-bloquants ?

Known since the 1950s, competitive ß-adrenergic receptor antagonists, namely ß-blockers (BB), constitute today a large and heterogeneous class of drugs with multiple clinical indications. Despite their daily use, can we choose the most appropriate BB for each of these indications? A better knowledge of the individual properties of BB (bioavailability, cardioselectivity, vasodilator and metabolic effects) could help to optimize their clinical benefits especially in polymorbid patients, frequently suffering from metabolic syndrome, peripheral arteriopathy or asthma/chronic obstructive pulmonary disease (COPD) supposed to be potential contraindications to their use.

Connus depuis les années 50, les antagonistes compétitifs des récepteurs ß-adrénergiques, ou ß-bloquants (BB), constituent aujourd'hui une classe ample et hétérogène de médicaments avec de multiples indications cliniques. Malgré leur utilisation quotidienne, savons-nous choisir le BB le plus approprié pour chacune de ces indications ? Une meilleure connaissance des propriétés individuelles des BB (biodisponibilité, cardiosélectivité, effets vasodilatateur et métabolique) devrait permettre d'optimaliser leurs bénéfices surtout chez des patients polymorbides, fréquemment atteints d'un syndrome métabolique, d'une artériopathie périphérique ou d'un asthme/bronchopneumopathie chronique obstructive (BPCO) supposés être des contre-indications potentielles à leur emploi.

Integrating health on air quality assessment--review report on health risks of two major European outdoor air pollutants: PM and NO2.

Quantifying the impact of air pollution on the public's health has become an increasingly critical component in policy discussion. Recent data indicate that more than 70% of the world population lives in cities. Several studies reported that current levels of air pollutants in urban areas are associated with adverse health risks, namely, cardiovascular diseases and lung cancer. IARC recently classified outdoor air pollution and related particulate matter (PM) as carcinogenic to humans. Despite the air quality improvements observed over the last few years, there is still continued widespread exceedance within Europe, particularly regarding PM and nitrogen oxides (NOx). The European Air Quality Directive 2008/50/EC requires Member States to design appropriate air quality plans for zones where air quality does not comply with established limit values. However, in most cases, air quality is only quantified using a combination of monitored and modeled data and no health impact assessment is carried out. An integrated approach combining the effects of several emission abatement measures on air quality, impacts on human health, and associated implementation costs enables an effective cost-benefit analysis and an added value to the decision-making process. Hence, this review describes the basic steps and tools for integrating health into air quality assessment (health indicators, exposure-response functions). In addition, consideration is given to two major outdoor pollutants: PM and NO2. A summary of the health metrics used to assess the health impact of PM and NO2 and recent epidemiologic data are also described.

[Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients]. / Abordagem à Infeção pelo Vírus Citomegálico em Doentes Submetidos a Transplante Alogénico de Progenitores Hematopoiéticos.

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

O vírus citomegálico (CMV) é um tipo de vírus de ácido desoxirribonucleico de dupla cadeia que pertence à família herpesviridae. Após uma infeção primária, o vírus torna-se latente em vários tipos de glóbulos brancos. A infeção por CMV pode permanecer latente ou tornar-se ativa, especialmente em indivíduos imunodeprimidos, como aqueles submetidos a transplantes de células progenitoras hematopoiéticas (TPH), onde a reativação do CMV pode ocorrer. Neste contexto, a infeção por CMV é comum e associada a elevadas taxas de morbilidade e mortalidade. A pneumonite é uma das complicações mais graves, com taxas de mortalidade superiores a 50%. Além disso, mesmo na ausência de doença específica do órgão, a infeção por CMV está relacionada com um aumento da mortalidade não relacionada com a recidiva da neoplasia hematológica. Dada a frequência e gravidade desta infeção em doentes submetidos a TPH, é crucial implementar estratégias eficazes de monitorização, prevenção e tratamento. Este protocolo foi desenvolvido para identificar os grupos de doentes que se beneficiam de uma abordagem sistematizada para a infeção por CMV e definir a estratégia mais adequada para cada grupo. A monitorização da carga viral de CMV no sangue periférico é fundamental, especialmente em doentes com risco moderado a elevado de infeção ativa. A profilaxia primária com letermovir (fármaco antiviral) é recomendada para reduzir a incidência de infeção ativa, especialmente em doentes com alto risco. A profilaxia secundária com valganciclovir (fármaco antiviral) é recomendada após um episódio de infeção ativa, enquanto o tratamento de antecipação e de doença é baseado na monitorização da carga viral e na resposta clínica. Este protocolo visa melhorar a abordagem da infeção por CMV em doentes submetidos a TPH, garantindo uma abordagem preventiva e terapêutica eficaz e segura.

Using low-cost sensors to assess real-time comfort and air quality patterns in indoor households.

People spend most of their time in indoor environments without knowing about the air quality in these spaces. In this study, indoor low-cost sensors were used (for 5 months) to assess the comfort and air quality patterns in two indoor households. To strengthen the robustness of the considered approach and build confidence in the obtained comfort and indoor air quality (IAQ) levels, the sensor measurements were also compared against information from reference monitoring equipment; in which, high correlation coefficients were obtained (> 0.85) and also low errors (on average 22%). The IAQ results were strongly influenced by the residents' activity and behaviour, the outdoor weather conditions, and indoor/outdoor air pollution sources. Overall, the recommended values of temperature and relative humidity for the occupant's comfort in indoor environments were not fulfilled. The highest particulate matter (PM) levels were recorded at the weekend (on average +14% higher), while maximum CO2 and CO levels were obtained on the weekdays (on average +9% higher). PM daily profiles followed the outdoor concentrations with the maximum levels at the end of the night and the lowest values in the early morning/mid-afternoon. The highest and lowest CO2 concentrations were registered in the early morning (< 1536 ppm) and mid-afternoon (< 627 ppm), respectively, while the CO daily profiles showed a high impact of outdoor emissions, with the minimum concentrations up to 0.81 mg m-3 (at 10 a.m. or 6 p.m.), and a maximum concentration of 1.87 mg m-3 (at 10 p.m.). Real-time comfort conditions and IAQ levels are a powerful approach to providing fast decisions to minimise human exposure and prevent negative health impacts.

Optimizing Contraceptive Prescription in Smoking Women: A Quality Improvement Study.

Introduction Family planning is fundamental in primary care (PC), and informed counseling helps to guide contraceptive choices. Combined hormonal contraceptives (CHC) pose cardiovascular risks, particularly when combined with smoking. According to the World Health Organization, the recommended global clinical decision is to refrain from employing CHC in female smokers aged 35 or older. This study aimed to improve contraception prescription for female smokers aged 35-54 in PC. Methods This study was conducted in a Portuguese Family Health Unit (FHU) from October 2021 to August 2022, and it followed the Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines and the Plan-Do-Study-Act approach. Female smokers aged 35-54 were included and evaluated in three moments: baseline evaluation (October 2021), intermediate evaluation (February 2022), and post-intervention evaluation (August 2022). Interventions involved educating medical staff, creating patient awareness campaigns, and evaluating contraceptive methods. The established quality-defining goal was to decrease the prevalence of female smokers aged 35 or above using CHC to ≤5%. Results CHC prevalence among smoking women aged 35-54 decreased from 16.4% to 8.5% after nine months of the initial intervention. There was an increase in progestogen-only methods usage over time, from 25.7% to 34.0%. Discussion Despite not fully achieving the predefined goal, interventions led to a substantial reduction of CHC use among smoking women aged 35-54. Collaborative efforts between healthcare professionals and patients played a pivotal role in optimizing care and reducing cardiovascular risk. This study underscores the importance of continuous quality improvement, collaborative interventions, and knowledge updates in Family Medicine practice. While conducted in a single FHU, the intervention's multidimensional approach holds the potential for broader applicability. Conclusion In the future, healthcare teams should continue to reflect on achieved results, maintain knowledge, and empower patients in contraceptive method choices. The study contributes to improved care quality and highlights the positive impact on medical practice and patient outcomes.

Classification of Continuous ECG Segments - Performance Analysis of a Deep Learning Model.

Classification of electrocardiogram (ECG) signals plays an important role in the diagnosis of heart diseases. It is a complex and non-linear signal, which is the first option to preliminary identify specific pathologies/conditions (e.g., arrhythmias). Currently, the scientific community has proposed a multitude of intelligent systems to automatically process the ECG signal, through deep learning techniques, as well as machine learning, where this present high performance, showing state-of-the-art results. However, most of these models are designed to analyze the ECG signal individually, i.e., segment by segment. The scientific community states that to diagnose a pathology in the ECG signal, it is not enough to analyze a signal segment corresponding to the cardiac cycle, but rather an analysis of successive segments of cardiac cycles, to identify a pathological pattern.In this paper, an intelligent method based on a Convolutional Neural Network 1D paired with a Multilayer Perceptron (CNN 1D+MLP) was evaluated to automatically diagnose a set of pathological conditions, from the analysis of the individual segment of the cardiac cycle. In particular, we intend to study the robustness of the referred method in the analysis of several simultaneous ECG signal segments. Two ECG signal databases were selected, namely: MIT-BIH Arrhythmia Database (D1) and European ST-T Database (D2). The data was processed to create datasets with two, three and five segments in a row, to train and test the performance of the method. The method was evaluated in terms of classification metrics, such as: precision, recall, f1-score, and accuracy, as well as through the calculation of confusion matrices.Overall, the method demonstrated high robustness in the analysis of successive ECG signal segments, which we can conclude that it has the potential to detect anomalous patterns in the ECG signal. In the future, we will use this method to analyze the ECG signal coming in real-time, acquired by a wearable device, through a cloud system.Clinical Relevance-This study evaluates the potential of a deep learning method to classify one or several segments of the cardiac cycle and diagnose pathologies in ECG signals.

Comparative evaluation of visual outcomes after bilateral implantation of an advanced or conventional monofocal intraocular lens.

PURPOSE: To assess the clinical outcomes and patient satisfaction of the Tecnis Eyhance, an advanced monofocal intraocular lens (IOL), compared to a conventional monofocal IOL. DESIGN: Retrospective case-control study. METHODS: This study included 120 eyes of 60 patients (30 patients in each group) who underwent bilateral cataract surgery either with the implantation of conventional monofocal IOLs (Tecnis PCB00), as a control group, or advanced monofocal IOLs (Tecnis Eyhance ICB00). Ophthalmological evaluation included the measurement of binocular corrected distance visual acuity (CDVA), monocular and binocular uncorrected distance visual acuity (UDVA), and uncorrected intermediate VA (UIVA). In addition the binocular defocus curve was analyzed. Furthermore a subjective questionnaire (Catquest-9SF) was used to assess vision and life quality. RESULTS: The average binocular UDVA was 20/22 in the ICB00 group and 20/20 in the PCB00 model (p = 0.62). The average monocular UIVA was 20/32 in the ICB00 group and 20/40 in the control group (p < 0.001). We found the binocular UIVA, had a mean value of 20/30 in the ICB00, compared to 20/40 in the control group (p < 0.001). The reported dysphotopsia was not significantly different between both groups (p = 0.56). Regarding the life quality questionnaire, the ICB00 group showed less difficulty in activities requiring intermediate vision. CONCLUSION: Our results demonstrated a significant improvement in visual acuity for intermediate distance in the ICB00 group compared to the control group, without compromising distance visual acuity. We also found a greater capability for intermediate distance activities (namely for computer use and reading price tags) when comparing ICB00 patients with the control group.

What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care. / O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos.

OBJECTIVE: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. METHODS: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. RESULTS: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. CONCLUSION: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

OBJETIVO: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. MÉTODOS: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. RESULTADOS: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). CONCLUSÃO: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

Severe Colchicine Intoxication: A Case Report and Review of Literature in Adults.

Colchicine is used in the treatment of multiple diseases such as gout and auto-immune diseases. Although cases of multiorgan failure have been described in adults with doses usually higher than 0.8 mg/kg, the epidemiology data are scarce and the intoxication mechanisms are not well-known. The authors present the case of a 66-year-old male patient, with a medical history of depression, admitted to the emergency room (ER) due to intentional colchicine ingestion after taking 90 mg (approximately 1.125 mg/kg) 12 hours prior to medical evaluation. Besides some dizziness and sleepiness, he showed no other alteration in the physical examination. After the administration of activated charcoal, he was transferred to the intensive care unit (ICU). The laboratory findings showed mild hepatic dysfunction, acute kidney injury, and metabolic lactic acidosis. Despite treatment, severe clinical worsening with multiorgan failure, including respiratory failure complicated with multiple episodes of cardiac dysrhythmias and finally with persistent cardiac arrest, lead to the patient's death after 13 hours of admission in the ER. Among drug intoxications, high doses of colchicine ingestion can lead to rapid multiorgan dysfunction, and patients with a severe overdose can experience irreversible multiorgan failure without presenting the typical initial gastrointestinal symptoms. Thus, it is necessary for the physicians to be alert to these situations and to be aware of the epidemiological data and clinical profile of this specific poisoning that should be managed in ICU. The authors perform a review of the cases of colchicine poisoning reported in adults between 2017 and 2019 and the differences in clinical management and outcomes.

Long-term macular vascular density measured by OCT-A in children with retinopathy of prematurity with and without need of laser treatment.

PURPOSE: To assess long-term vascular density measured by optical coherence tomography angiography (OCT-A) in former preterm children with history of retinopathy of prematurity (ROP) with and without need of laser treatment. METHODS: This observational study included former preterm children that developed ROP stage 2 or 3. Infants were divided in two groups according to previous need of laser treatment, and underwent a complete ophthalmologic evaluation, including assessment of macular morphologic and vascular parameters by OCT-A. RESULTS: Fifteen eyes were included in group 1 (laser-requiring ROP) and 19 in group 2 (non-treated ROP). Group 1 had lower mean gestational age and birth weight values than group 2 (p < 0.001 and p < 0.001, respectively). Best corrected visual acuity (BCVA) was lower in group 1 (0.08 ± 0.04 logMAR vs 0.04 ± 0.07 logMAR, p = 0.03). Laser-requiring ROP had lower vascular parameters, especially of central and internal vascular density (9.15 ± 2.75 vs 10.52 ± 0.86 mm-1, p = 0.05; 13.74 ± 1.00 vs 15.86 ± 0.64 mm-1, p = 0.05; respectively), and lower avascular zone circularity (0.58 ± 0.06 vs 0.76 ± 0.02, p < 0.001). Mean macular thickness was higher in group 1 (300.50 ± 10.50 vs 281.11 ± 2.50 µm, p = 0.05). Best corrected visual acuity (BCVA) was correlated with superficial vascular density (p < 0.05). CONCLUSION: Laser-requiring ROP seems to result in a decrease of long-term BCVA, which is at least partially attributed to a decrease in superficial macular vascular density. However, prematurity degree was more pronounced in children that required treatment, which might have influenced our results.