Dexamethasone phosphate and penetratin co-eluting contact lenses: a strategy to enhance ocular drug permeability.

Contact lenses (CLs) have been suggested as drug delivery platforms capable of increasing the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, the drug released from CLs still encounters the barrier effect of the ocular tissues, which considerably reduces the efficacy of administration. This work aims at the development of CLs able to simultaneously deliver an anti-inflammatory drug (dexamethasone sodium phosphate) and a cell-penetrating peptide (penetratin), the latter acting as a drug carrier across the tissues. Hydroxyethyl methacrylate (HEMA)-based hydrogels were functionalized with acrylic acid (AAc) and/or aminopropyl methacrylamide (APMA) to serve as CL materials with increased affinity for the drug and peptide. APMA-functionalized hydrogels sustained the dual release for 8 h, which is compatible with the wearing time of daily CLs. Hydrogels demonstrated suitable light transmittance, swelling capacity and in vitro biocompatibility. The anti-inflammatory activity of the drug was not compromised by the presence of the peptide nor by sterilization. The ocular distribution of the drug after 6 h of CL wearing was evaluated in vivo in rabbits and revealed that the amount of drug in the cornea and aqueous humor significantly increased when the drug was co-delivered with penetratin.

Consensus document of the management of type 2 diabetes and heart failure: Consejo Interamericano de Falla Cardíaca e Hipertensión Pulmonar (CIFACAH) and Inter-American Society of Cardiology (IASC).

Heart failure (HF) syndrome is a global public health issue. On the other hand, type 2 diabetes is a risk factor associated with overweight/obesity and a sedentary lifestyle. This consensus aims to compile information available on the relationship between HF and type 2 diabetes and present, in a summarized and practical way, the management recommendations based on scientific evidence. The document includes the description of the epidemiology of HF and type 2 diabetes; pathophysiology of HF and type 2 diabetes; cardiovascular complications of type 2 diabetes; stages of HF; management of type 2 diabetes in patients with HF; and management of HF in patients with type 2 diabetes. Lastly, in the conclusions section, the growing trend of both events and the need to start preventive activities is presented, as well as the favorable role of antidiabetic drugs in the treatment of patients with HF.

El síndrome de insuficiencia cardíaca (IC) es un problema de salud pública global. Por su parte, la diabetes tipo 2 es un factor de riesgo asociado a sobrepeso/obesidad y sedentarismo. El presente consenso busca recopilar la información disponible sobre la relación entre la IC y la diabetes tipo 2, y presentar, de manera práctica y resumida, las recomendaciones de manejo basadas en la evidencia científica. El documento se estructura en la descripción de la epidemiología de la IC y la diabetes tipo 2; la fisiopatología de la IC y la diabetes tipo 2; las complicaciones cardiovasculares de la diabetes tipo 2; los estadios de la IC; el manejo de la diabetes tipo 2 en pacientes con IC; y el manejo de la IC en pacientes con diabetes tipo 2. Por último, en el apartado de conclusiones se presenta una clara tendencia creciente de ambos eventos y se señala la necesidad del inicio de actividades preventivas, así como también el papel favorable de los fármacos antidiabéticos en el tratamiento de los pacientes con IC.

Consensus document on anemia and iron deficiency in heart failure: Consejo Interamericano de Falla Cardiaca e Hipertensión Pulmonar (CIFACAH) of the Interamerican Society of Cardiology (IASC).

Heart failure is a pathology that affects 1% of the population and is accompanied by iron deficiency as a comorbidity in 50% of cases. Anemia, meanwhile, is present between 22-37%. This is a consensus document that seeks to synthesize the information available on anemia and iron deficiency and its behavior in patients with HF, which is divided into pathophysiology, classification, clinical scenarios and algorithms (clinical pathways), treatment, and follow-up. This article integrates international recommendations based on evidence and presents a synthesis of management strategies.

La insuficiencia cardíaca (IC) es una patología que afecta al 1% de la población y se encuentra acompañada de deficiencia de hierro como comorbilidad en el 50% de los casos. La anemia, por su parte, está presente en el 22-37% de los casos de IC. Este es un documento de consenso que busca sintetizar la información disponible sobre la anemia y la deficiencia de hierro, y su comportamiento en pacientes con IC, que se divide en fisiopatología, clasificación, escenarios clínicos y algoritmos (rutas de manejo), tratamiento y seguimiento. Este artículo integra las recomendaciones internacionales basadas en la evidencia y se presenta una síntesis de las estrategias de manejo.

Cuestionario de conocimientos nutricionales aplicados en el deporte: Propuesta inicial de instrumento

El conocimiento nutricional es clave para la formación de hábitos alimentarios y en la modulación del comportamiento alimentario. La alimentación y nutrición son cruciales durante la adolescencia sobre todo en jóvenes deportistas. El objetivo de esta investigación fue analizar la validez teórica y los índices de discriminación y dificultad del cuestionario de conocimientos nutricionales aplicados en el deporte utilizando la teoría de respuesta al ítem en deportistas juveniles de 14 a 19 años. Este estudio instrumental se desarrolló en cinco fases: generación de ítems, revisión por panel de expertos, pilotaje, aplicación y depuración final. Participaron 261 adolescentes de 14 a 19 años e integrantes de disciplinas colectivas en selecciones Nacional y clubes profesionales. Se determinaron los índices de dificultad y de discriminación para cada uno de los ítems. Los ítems 1 (0,354) y 2 (0,285) del factor antes, 3 (0,315) y 6 (0,408) del factor durante, 7 (0,354) y 10 (0,408) del factor después, 3 (0,254) y 9 (0,231) del factor hidratación y, 2 (0,362) y 5 (0,323) del factor suplementación, fueron los que presentaron mayor grado de discriminación. El cuestionario de conocimientos nutricionales aplicados en el deporte está compuesto por 30 ítems divididos en cinco factores cada uno de ellos con seis ítems. La propuesta inicial del cuestionario es una herramienta valida teóricamente y con índices de dificultad y discriminación adecuados para evaluar el conocimiento nutricional en jóvenes deportistas. Su aplicación permite conocer potenciales brechas en conocimientos claves y diseñar estrategias educativas específicas para subsanarlas.

Nutritional knowledge plays a fundamental role in the formation of dietary habits and the modulation of eating behaviour. Nutrition and diet are crucial during adolescence, especially for young athletes. The purpose of this research was to analyse the theoretical validity and indices of discrimination and difficulty of the questionnaire on nutritional knowledge applied in sports using item response theory in youth athletes aged 14 to 19. This instrumental study was conducted in five phases: item generation, expert panel review, pilot testing, application, and final refinement. A total of 261 adolescents aged 14 to 19, who were members of national team and collective disciplines of professional clubs, participated. Difficulty and discrimination indices were determined for each item. Items 1 (0.354) and 2 (0.285) of the before factor, 3 (0.315) and 6 (0.408) of the during factor, 7 (0.354) and 10 (0.408) of the post factor, 3 (0.254) and 9 (0.231) of the hydration factor, and 2 (0.362) and 5 (0.323) of the supplementation factor showed the highest degree of discrimination. The questionnaire on nutritional knowledge applied in sports consists of 30 items divided into five factors, each with six items. The initial questionnaire proposal is a theoretically valid tool and with adequate difficulty and discrimination indices to evaluate nutritional knowledge in young athletes. Its application allows for identifying potential gaps in key knowledge and designing specific educational strategies to address them.

Family connections in the treatment of relatives of people with eating disorders and personality disorders: study protocol of a randomized control trial.

BACKGROUND: Eating disorders (EDs) are serious disorders that significantly affect not only the lives of patients, but also those of their family members who often experience high levels of burden, suffering and helplessness. If, in addition to ED, the patient has a personality disorder (PD), the psychological distress experienced by family members can be devastating. However, few treatments have been developed for family members of people with ED and PD. Family Connections (FC) is a programme that has been shown to be effective for family members of people with borderline personality disorder. The overall aims of this work are: (a) to adapt FC for application to family members of patients with BPD-PD (FC: ED-PD); (b) to analyse, in a randomised controlled clinical trial, the efficacy of this programme in a Spanish population, compared to a control condition consisting of treatment as usual optimised treatment (TAU-O); (c) to analyse the feasibility of the intervention protocol; (d) to analyse whether the changes that may occur in relatives are related to improvements in the family climate and/or improvements observed in patients; and (e) to analyse the perceptions and opinions of relatives and patients about the two intervention protocols. METHODS: The study uses a two-arm randomised controlled clinical trial with two experimental conditions: adaptation of FC programme (FC: ED-PD) or Treatment as usual optimised (TAU-O). Participants will be family members of patients who meet DSM-5 criteria for ED and PD or dysfunctional personality traits. Participants will be assessed before and after treatment and at one-year follow-up. The intention-to-treat principle will be used when analysing the data. DISCUSSION: The results obtained are expected to confirm the effectiveness of the programme and its good acceptance by family members. Trial registration ClinicalTrials.gov Identifier: NCT05404035. Accepted: May 2022.

Nanostructured Lipid Carriers for Enhanced Transscleral Delivery of Dexamethasone Acetate: Development, Ex Vivo Characterization and Multiphoton Microscopy Studies.

Corticosteroids, although highly effective for the treatment of both anterior and posterior ocular segment inflammation, still nowadays struggle for effective drug delivery due to their poor solubilization capabilities in water. This research work aims to develop nanostructured lipid carriers (NLC) intended for periocular administration of dexamethasone acetate to the posterior segment of the eye. Pre-formulation studies were initially performed to find solid and liquid lipid mixtures for dexamethasone acetate solubilization. Pseudoternary diagrams at 65 °C were constructed to select the best surfactant based on the macroscopic transparency and microscopic isotropy of the systems. The resulting NLC, obtained following an organic solvent-free methodology, was composed of triacetin, Imwitor® 491 (glycerol monostearate >90%) and tyloxapol with Z-average = 106.9 ± 1.2 nm, PDI = 0.104 ± 0.019 and zeta potential = -6.51 ± 0.575 mV. Ex vivo porcine sclera and choroid permeation studies revealed a considerable metabolism in the sclera of dexamethasone acetate into free dexamethasone, which demonstrated higher permeation capabilities across both tissues. In addition, the NLC behavior once applied onto the sclera was further studied by means of multiphoton microscopy by loading the NLC with the fluorescent probe Nile red.

Spanish adaptation of the Burden Assessment Scale in family caregivers of people diagnosed with borderline personality disorder.

BACKGROUND: Caregiving is a strong source of stress and leads the family caregiver to experience the burden of being responsible for the care of a severely mentally ill family member. The Burden Assessment Scale (BAS) assesses burden in family caregivers. This study aimed to analyze the psychometric properties of the BAS in a sample of family caregivers of people diagnosed with Borderline Personality Disorder (BPD). METHODS: Participants were 233 Spanish family caregivers (157 women and 76 men aged between 16-76 years old, M = 54.44, SD = 10.09) of people diagnosed with BPD. The BAS, the Multicultural Quality of Life Index, and the Depression Anxiety Stress Scale-21 were used. RESULTS: An exploratory analysis resulted in a three-factor 16-item model (Disrupted Activities; Personal and Social Dysfunction; Worry, Guilt, and Being Overwhelmed) with an excellent fit (χ2(101) = 56.873, p = 1.000, CFI = 1.000, TLI = 1.000, RMSEA = .000, SRMR = .060), good internal consistency (ω = .93), a negative correlation with quality of life, and a positive correlation with anxiety, depression, and stress. CONCLUSION: The model obtained for the BAS is a valid, reliable, and useful tool for assessing burden in family caregivers of relatives diagnosed with BPD.

Saturated and unsaturated triglyceride-enriched diets modify amino acid content in the mice hippocampus.

Elevated intake of fat modulates l-glutamate (l-Glu) turnover within the hippocampus (HIP). Our aim has been to investigate the effect of saturated vs unsaturated fat on the content of l-Glu and other amino acids involved in synaptic transmission within the HIP. The study was carried out in male mice fed (2 h or 8 weeks) with standard chow or with diets enriched either with saturated (SOLF) or unsaturated triglycerides (UOLF). An in vitro assay was performed in HIP slices incubated with palmitic (PA), oleic (OA), or lauric acid (LA). Amino acids were quantified by capillary electrophoresis. While both diets increased the amount of l-Glu and l-aspartate and decreased l-glutamine levels, only UOLF affected d-serine and taurine levels. γ-Aminobutyric acid was specifically decreased by SOLF. In vitro assays revealed that PA and OA modified l-Glu, glycine, l-serine and d-serine concentration. Our results suggest that fatty acids contained in SOLF and UOLF have an impact on HIP amino acid turnover that may account, at least partially, for the functional changes evoked by these diets.

Regional specific effect of saturated vs unsaturated fat on leptin receptor signalling in mice brain areas regulating feeding.

Leptin receptors (LepR) are expressed in brain areas controlling food intake homeostasis, such as the hypothalamus, the hippocampus and the prefrontal cortex. In a previous study we reported that long-term intake of saturated and monounsaturated fat alters hypothalamic LepR signalling. The current study aims at investigating the effect of foods high in either saturated (SOLF) or monounsaturated fat (UOLF) on LepR functionality in the hippocampus and the prefrontal cortex. Male mice were placed on SOLF/UOLF (eight weeks), then treated with recombinant murine leptin (1 mg/kg). After 60 min, brain regions were dissected and processed for western blot of phosphorylated STAT3 (pSTAT3), Akt (pAkt) and AMPK (pAMPK). Levels of SOCS3 were also quantified. SOLF itself increased basal levels of pSTAT3, while UOLF impaired leptin-induced phosphorylation of both Akt and AMPK. SOCS3 levels were specifically increased by UOLF within the prefrontal cortex. Our results show that SOLF and UOLF differently affect LepR signalling within the hippocampus and the prefrontal cortex, which points to the complex effect of saturated and unsaturated fat on brain function, particularly in areas regulating food intake.

Effects of saturated versus unsaturated fatty acids on metabolism, gliosis, and hypothalamic leptin sensitivity in male mice.

BACKGROUND: Development of obesity and its comorbidities is not only the result of excess energy intake, but also of dietary composition. Understanding how hypothalamic metabolic circuits interpret nutritional signals is fundamental to advance towards effective dietary interventions. OBJECTIVE: We aimed to determine the metabolic response to diets enriched in specific fatty acids. METHODS: Male mice received a diet enriched in unsaturated fatty acids (UOLF) or saturated fatty acids (SOLF) for 8 weeks. RESULTS: UOLF and SOLF mice gained more weight and adiposity, but with no difference between these two groups. Circulating leptin levels increased on both fatty acid-enriched diet, but were higher in UOLF mice, as were leptin mRNA levels in visceral adipose tissue. In contrast, serum non-esterified fatty acid levels only rose in SOLF mice. Hypothalamic mRNA levels of NPY decreased and of POMC increased in both UOLF and SOLF mice, but only SOLF mice showed signs of hypothalamic astrogliosis and affectation of central fatty acid metabolism. Exogenous leptin activated STAT3 in the hypothalamus of all groups, but the activation of AKT and mTOR and the decrease in AMPK activation in observed in controls and UOLF mice was not found in SOLF mice. CONCLUSIONS: Diets rich in fatty acids increase body weight and adiposity even if energy intake is not increased, while increased intake of saturated and unsaturated fatty acids differentially modify metabolic parameters that could underlie more long-term comorbidities. Thus, more understanding of how specific nutrients affect metabolism, weight gain, and obesity associated complications is necessary.

Effects of a Mealworm (Tenebrio molitor) Extract on Metabolic Syndrome-Related Pathologies: In Vitro Insulin Sensitivity, Inflammatory Response, Hypolipidemic Activity and Oxidative Stress.

The mealworm (Tenebrio molitor Linnaeus 1758) is gaining importance as one of the most popular edible insects. Studies focusing on its bioactivities are increasing, although alternative forms of consumption other than the whole insect or flour, such as bioactive non-protein extracts, remain underexplored. Furthermore, the incidence of metabolic syndrome-related pathologies keeps increasing, hence the importance of seeking novel natural sources for reducing the impact of certain risk factors. The aim was to study the potential of a non-protein mealworm extract on metabolic syndrome-related pathologies, obtained with ethanol:water (1:1, v/v) by ultrasound-assisted extraction. We characterized the extract by gas-chromatography mass-spectrometry and assessed its hypolipidemic potential, its ability to scavenger free radicals, to attenuate the inflammatory response in microglial cells, to affect mitochondrial respiration and to enhance insulin sensitivity in mouse hepatocytes. The extract contained fatty acids, monoglycerides, amino acids, certain acids and sugars. The mealworm extract caused a 30% pancreatic lipase inhibition, 80% DPPH· scavenging activity and 55.9% reduction in the bioaccessibility of cholesterol (p = 0.009). The extract was effective in decreasing iNOS levels, increasing basal, maximal and ATP coupled respiration as well as enhancing insulin-mediated AKT phosphorylation at low insulin concentrations (p < 0.05). The potential of a non-protein bioactive mealworm extract against metabolic syndrome-related pathologies is shown, although further studies are needed to elucidate the mechanisms and relationship with compounds.

Effect of Lauric vs. Oleic Acid-Enriched Diets on Leptin Autoparacrine Signalling in Male Mice.

High-fat diets enriched with lauric acid (SOLF) do not enhance leptin production despite expanding white adipose tissue (WAT). Our study aimed at identifying the influence of SOLF vs. oleic acid-enriched diets (UOLF) on the autoparacrine effect of leptin and was carried out on eight-week-old mice consuming control chow, UOLF or SOLF. Phosphorylation of kinases integral to leptin receptor (LepR) signalling pathways (705Tyr-STAT3, 473Ser-Akt, 172Thr-AMPK), adipocyte-size distribution, fatty acid content, and gene expression were analyzed in WAT. SOLF enhanced basal levels of phosphorylated proteins but reduced the ability of leptin to enhance kinase phosphorylation. In contrast, UOLF failed to increase basal levels of phosphorylated proteins and did not modify the effect of leptin. Both SOLF and UOLF similarly affected adipocyte-size distribution, and the expression of genes related with adipogenesis and inflammation. WAT composition was different between groups, with SOLF samples mostly containing palmitic, myristic and lauric acids (>48% w/w) and UOLF WAT containing more than 80% (w/w) of oleic acid. In conclusion, SOLF appears to be more detrimental than UOLF to the autoparacrine leptin actions, which may have an impact on WAT inflammation. The effect of SOLF and UOLF on WAT composition may affect WAT biophysical properties, which are able to condition LepR signaling.

Multicultural Quality of Life Index in Relatives of People With Borderline Personality Disorder.

Purpose: The aim of the present study was to confirm the original factor structure of the Multicultural Quality of Life Index (MQLI) and analyze its psychometric properties in a sample of caregivers of people with borderline personality disorder (BPD). Methods: The MQLI was administered to 233 relatives of people with BPD. Participants completed the MQLI, the Depression, Anxiety and Stress Scale (DASS-21), and the Connor-Davidson Resilience Scale (CD-RISC). Results: Factor analysis of the relatives indicated that the MQLI generated a one-factor solution. The MQLI showed good internal consistency, ϖ = 0.91 [95% CI (0.90, 0.93)] and correlated significantly and positively with the CD-RISC (r s = 0.576) and negatively with the DASS-21 (r s = -0.583). Conclusion: Consistent with other studies, the MQLI demonstrated feasibility, strong internal consistency, and good convergent and discriminant validity, which means it is a psychometrically robust measure for the assessment of quality of life in relatives of people with BPD. Along with other validation studies, this measure will be a useful tool for assessing quality of life in relatives of people with mental disorders.

Microwave-Assisted Acid Hydrolysis vs. Conventional Hydrolysis to Produce Sapogenin-Rich Products from Fenugreek Extracts.

The acid hydrolysis of saponins is commonly performed by conventional heating to produce sapogenin-rich products of bioactive interest, but alternative hydrolysis methods and their impact on bioactivity have been unexplored. We compared the conventional method with microwave-assisted acid hydrolysis (MAAH) of a commercial saponin-rich extract from a typical saponin source, fenugreek, focusing on the study of temperature (100, 120, 130, 140, 150 °C) and time (10, 20, 30, 40 min) of hydrolysis. The impact of these factors was assayed on both the sapogenin yield and the bioactivity of the hydrolyzed products, specifically their antioxidant and lipase inhibitory activities. The highest sapogenin content (34 g/100 g extract) was achieved by MAAH at 140 °C and 30 min, which was higher than conventional hydrolysis at both reference conditions (100 °C, 60 min, 24.6 g/100 g extract) and comparative conditions (140 °C, 30 min, 17 g/100 g extract) (p < 0.001). Typical steroid artifacts from sapogenins were observed in very small amounts, regardless of the method of hydrolysis. Antioxidant activity of MAAH hydrolyzed extracts (around 80% DPPH inhibition) was barely affected by time and temperature, but pancreatic lipase inhibitory activity was higher (>65%) at lower MAAH temperature (<130 °C) and time (<30 min) of hydrolysis. MAAH is shown as a valid alternative to produce selective sapogenin-rich extracts from fenugreek with minor impact on their bioactivities, and whose magnitude can be modulated by the hydrolysis conditions.

Effectiveness of family connections intervention for family members of persons with personality disorders in two different formats: Online vs face-to-face.

Introduction: Personality disorders (PD) have a serious impact on the lives of individuals who suffer from them and those around them. It is common for family members to experience high levels of burden, anxiety, and depression, and deterioration in their quality of life. It is curious that few interventions have been developed for family members of people with PD. However, Family Connections (FC) (Hoffman and Fruzzetti, 2005) is the most empirically supported intervention for family members of people with Borderline Personality Disorder (BPD). Aim: The aim of this study is to explore the effectiveness of online vs face-to-face FC. Given the current social constraints resulting from SARS-CoV-2, interventions have been delivered online and modified. Method: This was a non-randomized pilot study with a pre-post evaluation and two conditions: The sample consisted of 45 family members distributed in two conditions: FC face-to-face (20) performed by groups before the pandemic, and FC online (25), performed by groups during the pandemic. All participants completed the evaluation protocol before and after the intervention. Results: There is a statistically significant improvement in levels of burden (η 2 = 0.471), depression, anxiety, and stress (η 2 = 0.279), family empowerment (η 2 = 0.243), family functioning (η 2 = 0.345), and quality of life (µ2 η 2 = 0.237). There were no differences based on the application format burden (η 2 = 0.134); depression, anxiety, and stress (η 2 = 0.087); family empowerment (η 2 = 0,27), family functioning (η 2 = 0.219); and quality of life (η 2 = 0.006), respectively). Conclusions: This study provides relevant data about the possibility of implementing an intervention in a sample of family members of people with PD in an online format without losing its effectiveness. During the pandemic, and despite the initial reluctance of family members and the therapists to carry out the interventions online, this work shows the effectiveness of the results and the satisfaction of the family members. These results are particularly relevant in a pandemic context, where there was no possibility of providing help in other ways. All of this represents a great step forward in terms of providing psychological treatment.

Family connections vs treatment at usual optimized in the treatment of relatives of people with suicidal behavior disorder: study protocol of a randomized control trial.

BACKGROUND: Relatives of people diagnosed with suicidal behavior disorder (SBD) feel guilty, afraid, hopeless, depression and anxiety. It is necessary to help the relatives of people with SBD to reduce their discomfort and burden. Family Connections (FC) is a program that has been shown to be effective in reducing burden, depression, and anxiety, and increasing dominance and validating behaviors in relatives of people with borderline personality disorder. However, there are no RCTs that demonstrate the efficacy of the FC program in patients with SBD. Our research team adapted FC for relatives of people with SBD for delivery in the Spanish population (FC-SBD). The FC-SBD program contains 12 two-hour sessions held once a week. The first aim is to verify the efficacy of the FC-SBD intervention for relatives of people diagnosed with SBD in a randomized control trial with a Spanish sample. The second objective is to analyze the feasibility and acceptance of FC-SBD in relatives. The third aim is to analyze whether the changes produced in the psychological variables in the relatives after the intervention are related to changes in the psychological variables of the patients. This paper presents the study protocol. METHODS: The study design consists of a two-arm randomized controlled trial with two conditions: FC-SBD or Treatment as usual optimized (TAU-O). Participants will be relatives of patients who meet DSM-5 criteria for SBD. The caregivers` primary outcome measures will be the BAS. Secondary outcomes will be DASS-21, FES, DERS, QoL. The patient's primary outcome measures will be the frequency of critical incidents with the family member with SBD. Secondary measures will be the INQ, PHQ-9, OASIS. Participants will be assessed at pretreatment, post-treatment, and 6-month follow-up. The intention-to-treat principle will be used when analyzing the data. DISCUSSION: This study will provide results that confirm the efficacy of the FC-SBD in relatives of people with SBD. These results will also confirm its good acceptance by family members and help us to find out whether it is a good program to improve the prevention of suicidal behaviors in the family environment. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05157607 . Registered 15 December 2021.

National Registry of Acute Coronary Syndrome in Paraguay (RENASCA-PY).

OBJECTIVE: To determine the initial management and in-hospital mortality of patients with acute coronary syndrome who attended referral hospitals in Paraguay. METHOD: Observational, multicenter study, in patients over 18 years with a confirmed diagnosis of acute coronary syndrome. RESULTS: 780 patients were included from May 2015 to February 2016; the mean age was 64.1 ± 12.3 years, 64.1% male. The clinical presentation was acute coronary syndrome with ST elevation in 40.1% and without elevation in 59.9%. In patients with ST elevation there is a high percentage of late attendance, more than 12 h of evolution in 49.8%; those with less than 12 h of evolution underwent reperfusion in 52.2% of the cases, received fibrinolytics in 36.3% of the cases, and primary percutaneous coronary intervention 15.9%. In-hospital mortality for acute coronary syndrome was 10.3%, with ST-segment elevation was 12.8%, and without ST-segment elevation was 8.6%. CONCLUSIONS: The management of acute coronary syndrome in Paraguay needs a comprehensive approach, which promotes earlier care, and increases the implementation of reperfusion therapies in the health services network, in order to improve the therapeutic response rates and decrease hospital mortality.

OBJETIVO: Determinar el tratamiento inicial y la mortalidad intrahospitalaria de pacientes con síndrome coronario agudo que acudieron a centros hospitalarios de referencia de Paraguay. MÉTODO: Estudio observacional y multicéntrico en pacientes mayores de 18 años con diagnóstico confirmado de síndrome coronario agudo. RESULTADOS: Se incluyó a 780 pacientes desde mayo de 2015 hasta febrero de 2016; la edad media fue de 64.1 ± 12.3 años y el género masculino representó el 64.1%. La presentación clínica fue la de síndrome coronario agudo con elevación del ST en 40.1% y sin elevación del ST en 59.9%. En pacientes con elevación del ST se observó un alto porcentaje de consultas tardías, mayor de 12 h de evolución en 49.8%; en aquéllos con menos de 12 h de evolución se indicó la reperfusión en 52.2%, el 36.3% recibió fibrinolíticos y 15.9% intervención coronaria percutánea primaria. La mortalidad hospitalaria del síndrome coronario agudo fue de 10.3%, con elevación del segmento ST en 12.8% y sin elevación del segmento ST en 8.6%. CONCLUSIONES: El tratamiento del síndrome coronario agudo en el Paraguay requiere un abordaje integral, que promueva consultas más tempranas y aumente la institución de tratamientos de reperfusión en la red de servicios de salud; el objetivo es mejorar los índices de respuesta terapéutica y disminuir la mortalidad hospitalaria.

Predictors of pathologic complete response to neoadjuvant treatment in HER2-overexpressing breast cancer: a retrospective analysis using real-world data.

The human epidermal growth factor receptor 2 (ERBB2, HER2 or HER2/neu) is a transmembrane tyrosine kinase receptor that is overexpressed in approximately 20% of breast cancers. The use of the anti-HER2 monoclonal antibodies Pertuzumab and Trastuzumab in association with chemotherapy has achieved a higher percentage of pathologic complete response (pCR) than conventional chemotherapy. The purpose of our study was to identify factors that could affect the therapeutic response of patients with breast cancer and HER2 overexpression treated with cytotoxic chemotherapy plus double HER2 blockade in neoadjuvant setting at Fundación Arturo López Pérez (FALP). A case-control study was designed to evaluate the effect of clinical and histopathological variables on the response to neoadjuvant therapy. Ninety-four women with non-metastatic breast cancer and HER2 overexpression received neoadjuvant combination chemotherapy with Trastuzumab and Pertuzumab at FALP during the period 2017-2020. Seventy percent of patients achieved pCR, and in the group of hormone receptor negative patients, 89% of patients achieved pCR. Different variables were analysed trying to look for clinicopathological predictors of complete response. This study provides us with real-world data on the efficacy of using this treatment combination in our population of HER2-overexpressing breast cancer patients.