Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

Compilation of Evidence Supporting the Role of a T Helper 2 Reaction in the Pathogenesis of Acute Appendicitis.

Despite being the most common abdominal surgical emergency, the cause of acute appendicitis (AA) remains unclear, since in recent decades little progress has been made regarding its etiology. Obstruction of the appendicular lumen has been traditionally presented as the initial event of AA; however, this is often the exception rather than the rule, as experimental data suggest that obstruction is not an important causal factor in AA, despite possibly occurring as a consequence of the inflammatory process. Type I hypersensitivity reaction has been extensively studied, involving Th2 lymphocytes, and cytokines such as IL-4, IL-5, IL-9 and IL-13, which have well-defined functions, such as a positive-feedback effect on Th0 for differentiating into Th2 cells, recruitment of eosinophils and the release of eosinophilic proteins and the production of IgE with the activation of mast cells, with the release of proteins from their granules. Cytotoxic activity and tissue damage will be responsible for the clinical manifestation of the allergy. AA histological features are similar to those found in allergic reactions like asthma. The intestine has all the components for an allergic immune response. It has contact with hundreds of antigens daily, most of them harmless, but some can potentially induce an allergic response. In recent years, researchers have been trying to assess if allergy is a component of AA, with their latest advances in the understanding of AA as a Th2 reaction shown by the authors of this article.

Tryptase in Acute Appendicitis: Unveiling Allergic Connections through Compelling Evidence.

The aetiology of acute appendicitis (AA), the most frequent abdominal surgical emergency, is still unclarified. Recent epidemiologic, clinical and laboratorial data point to an allergic component in the pathophysiology of AA. Mastocytes participate in the Th2 immune response, releasing inflammatory mediators from their granules upon stimulation by IgE-specific antigens. Among the well-known mediators are histamine, serotonin and tryptase, which are responsible for the clinical manifestations of allergies. We conducted a prospective single-centre study to measure histamine and serotonin (commercial ELISA kit) and tryptase (ImmunoCAP System) concentrations in appendicular lavage fluid (ALF) and serum. Consecutive patients presenting to the emergency department with a clinical diagnosis of AA were enrolled: 22 patients with phlegmonous AA and 24 with gangrenous AA The control group was composed of 14 patients referred for colectomy for colon malignancy. Appendectomy was performed during colectomy. Tryptase levels were strikingly different between histological groups, both in ALF and serum (p < 0.001); ALF levels were higher than serum levels. Tryptase concentrations in ALF were 109 times higher in phlegmonous AA (APA) (796.8 (194.1-980.5) pg/mL) and 114 times higher in gangrenous AA (AGA) (837.4 (272.6-1075.1) pg/mL) than in the control group (7.3 (4.5-10.3) pg/mL. For the diagnosis of AA, the discriminative power of serum tryptase concentration was good (AUC = 0.825), but discriminative power was weak (AUC = 0.559) for the differential diagnosis between APA and AGA. Mastocytes are involved in AA during clinical presentations of both phlegmonous and gangrenous appendicitis, and no significant differences in concentration were found. No differences were found in serum and ALF concentrations of histamine and serotonin between histological groups. Due to their short half-lives, these might have elapsed by the time the samples were collected. In future research, these determinations should be made immediately after appendectomy. Our findings confirm the hypersensitivity type I reaction as an event occurring in the pathogenesis of AA: tryptase levels in ALF and serum were higher among patients with AA when compared to the control group, which is in line with a Th2 immune response and supports the concept of the presence of an allergic reaction in the pathogenesis of acute appendicitis. Our results, if confirmed, may have clinical implications for the treatment of AA.

Eosinophil Granule Proteins Involvement in Acute Appendicitis-An Allergic Disease?

Several pieces of evidence point to an allergic component as a trigger of acute appendicitis. As the Th2 immune response is characterized by eosinophil mobilization to the target organ and release of their cationic granule proteins, it is reasonable to investigate if the degranulation of eosinophils could be associated with the local injury. The primary aim of this study is to evaluate the participation of eosinophils granules proteins in acute appendicitis, both at local and systemic levels and the secondary aim is to evaluate the diagnostic accuracy of eosinophils granules proteins for the detection of acute appendicitis, as well as for distinguishing between complicated and uncomplicated acute appendicitis. Eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and eosinophil peroxidase (EP) are the most well-known eosinophil granule proteins. From August 2021 to April 2022, we present a prospective single-center study to evaluate the EDN, ECP, and EP concentrations simultaneously in appendicular lavage fluid (ALF) and the serum of 22 patients with acute phlegmonous appendicitis (APA), 24 with acute gangrenous appendicitis (AGA), and 14 normal controls. Concerning EDN, no differences were found between groups. ECP concentrations in ALF and serum were significantly higher in the histologically confirmed acute appendicitis compared to the control groups (p < 0.0001 and p < 0.0001, respectively). In ALF, no differences were found between ECP levels in APA: 38.85 ng/mL (IQR 26.50-51.77) and AGA 51.55 ng/mL (IQR 39.55-70.09) groups (p = 0.176). In the serum, no difference was found between ECP levels at APA: 39 ng/mL (IQR 21.30-56.90) and AGA: 51.30 ng/mL (IQR 20.25-62.59) (p = 0.100). For EP, the concentrations in ALF (p < 0.001) and serum (p < 0.001) were both higher in acute appendicitis compared to the control. In ALF, no difference was found between APA: 240.28 ng/mL (IQR 191.2-341.3) and AGA: 302.5 (IQR 227.7-535.85) (p = 0.236). In the serum, no differences were found between APA: 158.4 ng/mL (IQR 111.09-222.1) and AGA: 235.27 (IQR 192.33-262.51) (p = 0.179). Globally, the ALF concentrations were higher than serum concentrations, reflecting an intense inflammatory local reaction in AA. The optimal ECP cut-off for discriminating between acute appendicitis and the controls was >11.41 ng/mL, with a sensitivity of 93.5%, but with a specificity for identifying appendicitis of 21.4%, good discriminative power (AUC = 0.880). For EP, the optimal cut-off was >93.20 ng/mL, with a sensitivity of 87%, but with a specificity of 14.3% (AUC = 0.901), excellent discriminative power. For the diagnosis of perforated AA, the discriminative power of ECP and EP serum concentrations are weak (AUC = 0.562 and AUC = 0.664, respectively). Concerning the presence of peritonitis, the discriminative power of ECP and EP serum concentrations is acceptable, respectively: AUC = 0.724 and AUC = 0.735. Serum levels of EDN (p = 0.119), ECP (p = 0.586) and EP (p = 0.08) in complicated appendicitis were similar to uncomplicated appendicitis. Serum concentrations of ECP and EP can be added to decision-making AA diagnosis. A Th2-type immune response is present in AA. These data bring forward the role of an allergic reaction in the pathogenesis of acute appendicitis.

Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding.

BACKGROUND & AIMS: Failure to control oesophago-gastric variceal bleeding (OGVB) and acute-on-chronic liver failure (ACLF) are both important prognostic factors in cirrhosis. The aims of this study were to determine whether ACLF and its severity define the risk of death in OGVB and whether insertion of rescue transjugular intrahepatic shunt (TIPS) improves survival in patients with failure to control OGVB and ACLF. METHODS: Data on 174 consecutive eligible patients, with failure to control OGVB between 2005 and 2015, were collected from a prospectively maintained intensive care unit registry. Rescue TIPS was defined as technically successful TIPS within 72 hours of presentation with failure to control OGVB. Cox-proportional hazards regression analyses were applied to explore the impact of ACLF and TIPS on survival in patients with failure to control OGVB. RESULTS: Patients with ACLF (n = 119) were significantly older, had organ failures and higher white cell count than patients with acute decompensation (AD, n = 55). Mortality at 42-days and 1-year was significantly higher in patients with ACLF (47.9% and 61.3%) than in those with AD (9.1% and 12.7%, p <0.001), whereas there was no difference in the number of endoscopies and transfusion requirements between these groups. TIPS was inserted in 78 patients (AD 21 [38.2%]; ACLF 57 [47.8%]; p = 0.41). In ACLF, rescue TIPS insertion was an independent favourable prognostic factor for 42-day mortality. In contrast, rescue TIPS did not impact on the outcome of patients with AD. CONCLUSIONS: This study shows that in patients with failure to control OGVB, the presence and severity of ACLF determines the risk of 42-day and 1-year mortality. Rescue TIPS is associated with improved survival in patients with ACLF. LAY SUMMARY: Variceal bleeding that is not controlled by initial endoscopy is associated with high risk of death. The results of this study showed that in the occurrence of failure of the liver and other organs defines the risk of death. In these patients, insertion of a shunt inside the liver to drain the portal vein improves survival.

Mechanisms involved in the production of differently colored feathers in the structurally colored swallow tanager (Tersina viridis; Aves: Thraupidae).

Non-iridescent, structural coloration in birds originates from the feather's internal nanostructure (the spongy matrix) but melanin pigments and the barb's cortex can affect the resulting color. Here, we explore how this nanostructure is combined with other elements in differently colored plumage patches within a bird. We investigated the association between light reflectance and the morphology of feathers from the back and belly plumage patches of male swallow tanagers (Tersina viridis), which look greenish-blue and white, respectively. Both plumage patches have a reflectance peak around 550 nm but the reflectance spectrum is much less saturated in the belly. The barbs of both types of feathers have similar spongy matrices at their tips, rendering their reflectance spectra alike. However, the color of the belly feather barbs changes from light green at their tips to white closer to the rachis. These barbs lack pigments and their morphology changes considerably throughout. Toward the rachis, the barb is almost hollow, with a reduced area occupied by spongy matrix, and has a flattened shape. By contrast, the blue back feathers' barbs have melanin underneath the spongy matrix resulting in a much more saturated coloration. The color of these barbs is also even along the barbs' length. Our results suggest that the color differences between the white and greenish-blue plumage are mostly due to the differential deposition of melanin and a reduction of the spongy matrix near the rachis of the belly feather barbs and not a result of changes in the characteristics of the spongy matrix.

Stakeholders' perceptions of appropriate nature-based solutions in the urban context.

The concept of nature-based solutions (NBSs) has become increasingly popular among urban policymakers and planners to help them tackle the urban challenges arising from urban expansion and climate change. Stakeholders' involvement is a fundamental step, and stakeholders' perceptions and preferences can affect the development of NBS projects. This study aims to identify stakeholders' perceptions of the most critical urban challenges, the priority interventions, the preferred NBSs and the benefits of the NBSs, and to identify the determinants of these perceptions. A survey was administered to assess stakeholders' perceptions and views on implementing NBSs in two Portuguese cities with distinct urban, geographical, and socio-economic contexts. A binary logistic regression model was used to understand the determinants of the likelihood of the stakeholders' answers. According to the stakeholders, climate change is one of the main concerns in the urban context. It is usually associated with the incidence of heatwaves and water scarcity. Additionally, stakeholders are concerned about the low quantity and poor management of green spaces (GSs). They believe that it will be necessary to increase the GS, to recover some degraded areas, and to increase mobility. The preferred NBSs were planting more urban trees, making green shaded areas, and rehabilitating riverbanks. The main expected benefits were benefits for leisure and relaxation, reductions in air temperature, purer air, and improvements in public health. The results showed mostly coherent connections between the main concerns/priorities of the stakeholders and the perceived NBS benefits; however, some stakeholders did not present coherent connections, indicating low awareness of the current policy for implementing NBSs to overcome existing and future urban challenges.

Evolution between forest macrorefugia is linked to discordance between genetic and morphological variation in Neotropical passerines.

The central Andean rainforests and the Atlantic Forest are two similar biomes that are fully isolated by xerophytic and open-vegetation regions (the Chaco and Cerrado, respectively). Even though there is evidence suggesting that these rainforests have been connected in the past, their dynamics of connection, the geographic areas that bridged these regions, and the biological processes that have promoted diversification between them remain to be studied. In this research, we used three passerine species (Poecilotriccus plumbeiceps, Phylloscartes ventralis and Cacicus chrysopterus) as models to address whether the Andean and the Atlantic forests have acted as a refugia system (macrorefugia), and to evaluate biogeographic hypotheses of diversification and connection between them. In order to achieve these goals, we performed traditional phylogeographic analyses and compared alternative biogeographic scenarios by using Approximate Bayesian Computation. Additionally, we performed morphological analyses to evaluate phenotypic divergence between these regions. Our findings support that both rainforest regions acted as refugia, but that the impact of their isolation was stronger on the genetic than on the morphologic characters. Our results provided evidence that both geographic isolation as well as ecological factors have modeled the external traits of forest organisms in the region. Regarding the connection routes between the Andes and the Atlantic Forest, the genetic data rejected the hypothesis of a Chaco connection in the tested species, providing evidence for a connection through the Cerrado or through the transition between the Cerrado and Chaco, in a process that could have started as early as the Late Miocene.

Theoretical approaches to study the optical response of the red-legged honeycreeper's plumage (Cyanerpes cyaneus).

In this paper, we investigate the unusual color effect exhibited by the plumage of the heads of Cyanerpes cyaneus males, whose color turns from green to turquoise as the angle between the illumination and observation directions is increased. This singular color effect is characteristic of species that have quasi-ordered nanostructures of short-range order within the feather barbs. However, among species of the same family and even within feather patches of the same individual, one can find barbs with different characteristics, both macroscopic (curvature, shape, cross-sectional area) and in their internal microstructure. We apply the Korringa-Kohn-Rostoker method with the averaging technique to model the reflectance spectra for different angles of incidence and explain the dependence of the observed color with the incidence-collection angle. To investigate the influence of the disorder in the optical response of the spongy matrix, we apply the integral method for a two-dimensional cylinder system that simulates the distribution of air cavities within the $ \beta $ß-keratin medium. The experimental reflectance was interpreted as the result of multiple reflections in the internal interfaces generated by large air voids present within the spongy matrix. The application of rigorous methods to the study of natural photonic structures is of fundamental relevance for the design of efficient bioinspired artificial materials.

Contrasting evolutionary histories in Neotropical birds: Divergence across an environmental barrier in South America.

Avian diversity in the Neotropics has been traditionally attributed to the effect of vicariant forces promoting speciation in allopatry. Recent studies have shown that phylogeographical patterns shared among codistributed species cannot be explained by a single vicariant event, as species responses to a common barrier depend on the biological attributes of each taxon. The open vegetation corridor (OVC) isolates Amazonia and the Andean forests from the Atlantic Forest, creating a notorious pattern of avian taxa that are disjunctly codistributed in these forests. Here, we studied and compared the evolutionary histories of Ramphotrigon megacephalum and Pipraeidea melanonota, two passerines with allopatric populations east and west of the OVC that represent different subspecies. These species differ in their biological attributes: R. megacephalum is a sedentary, forest specialist mostly confined to bamboo understorey, whereas P. melanonota is a seasonal migrant and generalist species that ranges in a variety of closed and semi-open environments. We performed genetic and genomic analyses, complemented with the study of coloration and behavioural differentiation, to assess population divergence across the OVC. We found that the evolutionary histories of both R. megacephalum and P. melanonota have been shaped by this environmental barrier. However, these species responded in different and asynchronous manners to the establishment of the OVC and to past connections between the currently isolated South American forests, which can be mostly explained by their distinct ecologies and dispersal abilities. Our results support the fact that the biological attributes of species can make their evolutionary histories idiosyncratic.

The multiple applications of DNA barcodes in avian evolutionary studies.

DNA barcodes of birds are currently available for 41% of known species and for many different geographic areas; therefore, they are a rich data source to answer evolutionary questions. We review studies that have used DNA barcodes to investigate evolutionary processes in birds using diverse approaches. We also review studies that have investigated species in depth where taxonomy and DNA barcodes present inconsistencies. Species that showed low genetic interspecific divergence and lack of reciprocal monophyly either are the result of recent radiation and (or) hybridize, while species with large genetic splits in their COI sequences were determined to be more than one independent evolutionary unit. In addition, we review studies that employed large DNA barcode datasets to study the molecular evolution of mitochondrial genes and the biogeography of islands, continents, and even at a multi-continental scale. These studies showed that DNA barcodes offer high-quality data well beyond their main purpose of serving as a molecular tool for species identification.

Continental-scale analysis reveals deep diversification within the polytypic Red-crowned Ant Tanager (Habia rubica, Cardinalidae).

We explored the phylogeographic patterns of intraspecific diversity in the Red-crowned Ant Tanager (Habia rubica) throughout its continent-wide distribution, in order to understand its evolutionary history and the role of evolutionary drivers that are considered to promote avian diversification in the Neotropics. We sampled 100 individuals of H. rubica from Mexico to Argentina covering the main areas of its disjunct distribution. We inferred phylogenetic relationships through Bayesian and maximum parsimony methodologies based on mitochondrial and nuclear markers, and complemented genetic analyses with the assessment of coloration and behavioral differentiation. We found four deeply divergent phylogroups within H. rubica: two South American lineages and two Mexican and Middle American lineages. The divergence event between the northern and southern phylogroups was dated to c. 5.0 Ma, seemingly related to the final uplift of the Northern Andes. Subsequently, the two South American phylogroups split c. 3.5 Ma possibly due to the development of the open vegetation corridor that currently isolates the Amazonian and Atlantic forests. Diversification throughout Mexico and Middle America, following dispersion across the Isthmus of Panama, was presumably more recent and coincident with Pleistocene climatic fluctuations and habitat fragmentations. The analyses of vocalizations and plumage coloration showed significant differences among main lineages that were consistent with the phylogenetic evidence. Our findings suggest that the evolutionary history of H. rubica has been shaped by an assortment of diversification drivers at different temporal and spatial scales resulting in deeply divergent lineages that we recommend should be treated as different species.

Microscale patches of nonmotile phytoplankton.

Phytoplankton cells have evolved sophisticated strategies for actively responding to environmental signals, most notably to mechanical stresses of hydrodynamic origin. A largely unanswered question, however, is the significance of these cellular responses for the largely heterogeneous spatial distribution of cells found in the oceans. Motivated by the physiological regulation of buoyancy prevalent in nonmotile phytoplankton species, we solve here a minimal model for "active" sinking that incorporates these cellular responses. Within this model, we show how buoyancy regulation leads to intense patchiness for nonmotile species as compared to passive tracers, resulting in important variations in settling speeds and, as a consequence, determining escape rates to the deep ocean.

Cardiac Rehabilitation after an Acute Coronary Syndrome: The Impact in Elderly Patients.

INTRODUCTION: Cardiac rehabilitation (CR) has been shown to decrease mortality and morbidity, improve the control of risk factors and the quality of life of patients with coronary artery disease. However, the elderly are underrepresented in most studies and in real-life CR programs. Our goal was to evaluate the impact of CR after an acute coronary syndrome in the elderly population. METHODS: A cutoff of 65 years was used to dichotomize age. Our main focus was on the effects of ambulatory supervised exercise training on several surrogate markers, namely total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, body mass index, fasting glucose, glycated hemoglobin, probrain natriuretic peptide, International Physical Activity Questionnaire score, maximal exercise capacity, chronotropic response index and heart rate recovery. We evaluated those variables at the beginning and at the end of phase II of the CR program (after 3 months) and repeated the treadmill test at 12 months. RESULTS: A total of 548 patients with a recent acute coronary syndrome were enrolled; 37% were 65 years old or older. Both age groups had a statistically significant improvement in all the evaluated parameters. Interestingly, at 12 months both groups maintained the improvement in functional capacity seen immediately after 3 months. CONCLUSIONS: The benefits of CR in terms of functional capacity, metabolic profile and other prognostic parameters were significant in both younger and older patients. Therefore, all eligible patients should be referred to CR programs, irrespective of age.

The influence of carvedilol posology timing on clinically significant portal hypertension: insights from elastography measurements.

BACKGROUND AND AIMS: Carvedilol has emerged as the preferred ß-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. METHODS: In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. RESULTS: Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. CONCLUSION: The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.

Emergency department contribution to HCV elimination in the Iberian Peninsula.

BACKGROUND: Undiagnosed cases of hepatitis C virus (HCV) infection result in significant morbidity and mortality, further transmission, and increased public health costs. Testing in emergency departments (EDs) is an opportunity to expand HCV screening. The goal of this project was to increase the proportion of eligible patients screened for HCV in urban areas. METHODS: An opportunistic automated HCV screening program was implemented in the EDs of 4 public hospitals in Spain and Portugal at different periods between 2018 and 2023. HCV prevalence was prospectively evaluated, and single-step or reflex testing was used for confirmation in the same sample. RESULTS: More than 90% of the population eligible for testing were screened in the participating centers. We found HCV antibody seroprevalence rates ranging from 0.6 to 3.9%, with between 19 and 53% of viremic individuals. CONCLUSIONS: Opportunistic HCV screening in EDs is feasible, does not disrupt ED activities, is highly effective in increasing diagnosis, and contributes to WHO's HCV elimination goals.

[Long-term effects of a cardiac rehabilitation program in the control of cardiovascular risk factors]. / Efeitos a longo prazo de um programa de reabilitação cardíaca no controlo dos fatores de risco cardiovasculares.

INTRODUCTION: Cardiac rehabilitation programs are designed to improve patients' functional capacity, as well as to educate them and to monitor their cardiovascular risk factors. AIM: The study aims to evaluate the effects of cardiac rehabilitation programs in patients with coronary disease over a 12-month follow-up period with regard to control of cardiovascular risk factors. METHODS: This was a prospective study of patients diagnosed with coronary disease who completed an exercise-based cardiac rehabilitation program between January 2008 and December 2009 and who were not lost to follow-up. Patients were evaluated at an early stage (first medical consultation in phase II of the program) and 3, 6 and 12 months later, the following parameters being assessed: weight and body mass index, waist circumference, lipid profile, HbA1c in diabetic patients, blood pressure, smoking status and physical activity (using the International Physical Activity Questionnaire). RESULTS: In the sample of 256 patients (76.2% male, mean age 67 years), dyslipidemia proved to be the most prevalent risk factor (74.2%), followed by overweight (71.5%). There was a statistically significant improvement (p<0,05) in all risk factors studied at the end of phase II of the program, which was maintained at 6 and 12 months of follow-up, with the exception of body mass index (loss of statistical significance at 6-month assessment, p=0,92). CONCLUSION: This study highlights the need for cardiac rehabilitation programs in the context of secondary prevention of cardiovascular disease and the importance of implementing strategies that promote long-term maintenance of their benefits.

Treating Advanced Hepatocellular Carcinoma with Sorafenib: A 10-Year Single Center Experience.

Introduction: Sorafenib was the first therapy used for systemic treatment of unresectable hepatocellular carcinoma (HCC). Multiple prognosis factors associated with sorafenib therapy have been described. Objectives: The aim of this work was to evaluate survival and time to progression (TTP) on HCC patients treated with sorafenib, and check for predictive factors of sorafenib benefit. Materials and Methods: Retrospectively, data from all HCC patients treated with sorafenib in a Liver Unit from 2008 to 2018 were collected and analyzed. Results: Sixty-eight patients were included; 80.9% were male, the median age was 64.5 years, 57.4% had Child-Pugh A cirrhosis and 77.9% were BCLC stage C. Macrovascular invasion (MVI) was present in 25% of the patients and 25% of the subjects had other extrahepatic metastasis. The median survival was 10 months (IQR 6.0-14.8) and median TTP was 5 months (IQR 2.0-7.0). Survival and TTP were similar between Child-Pugh A and B patients: 11.0 months (IQR 6.0-18.0) for Child-Pugh A and 9.0 months (IQR 5.0-14.0) for Child-Pugh B (p = 0.336). In univariate analysis, larger lesion size (LS >5 cm), higher alpha-fetoprotein (AFP >50 ng/mL), and no history of locoregional therapy were statistically associated with mortality (HR 2.17, 95% CI 1.24-3.81; HR 3.49, 95% CI 1.90-6.42; HR 0.54, 95% CI 0.32-0.93, respectively), but only LS and AFP were independent predictive factors, as shown in multivariate analysis (LS: HR 2.08, 95% CI 1.10-3.96; AFP: HR 3.13, 95% CI 1.59-6.16). MVI and LS >5 cm were associated with TTP shorter than 5 months in univariate analysis (MVI: HR 2.80, 95% CI 1.47-5.35; LS: HR 2.1, 95% CI 1.08-4.11), but only MVI was an independent predictive factor of TTP shorter than 5 months (HR 3.42, 95% CI 1.72-6.81). Regarding safety data, 76.5% of patients reported at least one side effect (any grade), and 19.1% presented grade III-IV adverse effects leading to treatment discontinuation. Conclusions: We observed no significant difference in survival or TTP in Child-Pugh A or Child-Pugh B patients treated with sorafenib, as compared to more recent real-life studies. Lower primary LS and AFP were associated with a better outcome, and lower AFP was the main predictor of survival. The reality of systemic treatment for advanced HCC has recently changed and continues to evolve, but sorafenib remains a viable therapeutic option.

Introdução: O sorafenib foi o primeiro fármaco usado em primeira linha na terapêutica sistémica do carcinoma hepatocelular (CHC) em estadio avançado. Têm sido descritos múltiplos factores modificadores de prognóstico associados à sua utilização. Objectivos: Caracterizar um grupo de doentes com CHC que realizaram terapêutica com sorafenib, estudar a sobrevivência e o tempo até progressão (TAP), e avaliar os factores preditores de benefício. Material e Métodos: Estudo retrospectivo com recolha e análise dos dados relativos a todos os doentes com CHC tratados com sorafenib numa Unidade de Hepatologia, entre 2008 e 2018. Resultados: Foram incluídos no estudo sessenta e oito doentes; 80.9% do sexo masculino, com mediana de idades de 64.5 anos, 57.4% tinham cirrose em estadio A de Child-Pugh e 77.9% apresentavam CHC em estadio C do Barcelona Clínic Liver Cancer (BCLC). A invasão macrovascular (IMV) estava presente em 25% dos doentes, e também 25% dos doentes tinha metastização extra-hepática (que não a IMV). A mediana de sobrevivência foi de 10 meses (IQR 6.0-14.8) e a mediana de TAP foi de 5 meses (IQR 2.0­7.0). A sobrevivência e o TAP foram similares nos doentes Child-Pugh A e B: 11.0 meses (IQR 6.0­18.0) para Child-Pugh A e 9.0 meses (IQR 5.0­14.0) para Child-Pugh B (p = 0.336). Na análise univariada, o tamanho da lesão >5 cm (TL), alfa-fetoproteína > 50 ng/mL (AFP) e a ausência de terapêuticas locorregionais prévias (TLP) tiveram relação estatisticamente significativa com a mortalidade (TL: HR 2.17, 95% CI 1.24­3.81; AFP: HR 3.49, 95% CI 1.90­6.42; TLP: HR 0.54, 95% CI 0.32­0.93), mas apenas o TL e AFP foram fatores preditores independentes, como mostrou a análise multivariada (TL: HR 2.08, 95% CI 1.10­3.96; AFP: HR 3.13, 95% CI 1.59­6.16). A IMV e o TL >5 cm estiveram associados com o TAP <5 meses na análise univariada (IMV: HR 2.80, 95% CI 1.47­5.35; TL: HR 2.1, 95% CI 1.08­4.11), mas apenas a IMV foi um fator preditor independente de TAP <5 meses (HR 3.42, 95% CI 1.72­6.81). Relativamente aos dados de segurança, 76.5% dos doentes relataram pelo menos um efeito lateral (qualquer grau), e 19.1% apresentaram efeitos adversos de grau III-IV, que levaram à suspensão do fármaco. Conclusões: Não foi observada diferença significativa na sobrevivência ou no tempo até progressão nos doentes Child-Pugh A ou Child-Pugh B tratados com sorafenib, quando comparado com estudos real-life recentes. Menor TL e AFP estiveram associados a melhor outcome e um valor de AFP baixo mostrou-se o principal preditor de sobrevivência. A realidade da terapêutica sistémica para o CHC avançado alterou-se recentemente e continua em mudança, mas o sorafenib permanece uma alternativa terapêutica viável.