Analysis of ballistic trajectories and its association with clinical outcomes in civilian penetrating brain injury.

PURPOSE: Civilian penetrating brain injuries (PBI) caused by firearms are a medical emergency with high rates of morbidity and mortality. The aim of this study was to evaluate the association between trajectory vectors in CT brain angiography and clinical outcomes in patients with civilian gunshots. METHODS: This is a retrospective analytical cross-sectional study that includes patients over 15 years of age with PBI due to firearms, admitted from January 2019 to December 2021 at a University Hospital in Cali, Colombia. A brain CT with angio-CT was performed the first day of admission. An XYZ coordinate system centered on the Turk's saddle was developed. Trajectories of projectiles were plotted and compared to a patient 0 in a 3D-Slicer software. A bivariate analysis of the clinical and geometric characteristics of the trajectory was performed. Primary outcomes include mortality and disability at 6 months. RESULTS: Twenty-eight patients with a mean age of 27.39 ± 11.66 years were included. The vectors of non-survivors show a trend, crossing at a specific area. This area was designated as a "potential lethal zone" and inside this area, injuries around 25.3 mm from the circle of Willis, were associated with greater mortality (p < 0.005). CONCLUSIONS: In our study PBI avoiding the ventricular system, brain stem, dorsum sellae and the circle of Willis were associated with more survivability. A "potential lethal zone" was detected and associated with poor outcome after civilian PBI due to firearms. A better evaluation of the performance of this "potential lethal zone" in larger studies will be required.

Quality of Life of the Primary Caregivers of Children with Cleft Lip and Palate in Guanajuato, Mexico: A Cross-Sectional Study.

Comprehensive treatment is crucial for patients with a cleft lip/palate. While studies have investigated its impact on children's quality of life, few have examined the effects on primary caregivers. The aim of the study was to compare the quality of life of caregivers of children with cleft lip/palate to a control group at the National School for Higher Studies, National Autonomous University of Mexico, Guanajuato. A cross-sectional study was conducted at a teaching dental clinic of the National School of Higher Studies, National Autonomous University of Mexico, Guanajuato, México, from May to December 2021 involving 140 caregivers (70 in each group). The WHOQoL Bref instrument assessed the quality of life. In addition to the descriptive analysis, a binary logistic regression analysis was carried out, taking dichotomized reported quality of life as the dependent variable. Among the caregivers, 88.6% were female (p > 0.05), and 45 (64.8%) from the study group reported poor quality of life (p < 0.05). A multivariate analysis indicated that caring for a child with cleft lip/palate raised the likelihood of poor quality of life (p < 0.05). The findings emphasize the need for comprehensive support for both patients and caregivers, as their well-being affects patient outcomes.

Clinical Pharmacokinetic and Pharmacodynamic Profile of Vericiguat.

Vericiguat is an oral soluble guanylate cyclase stimulator and enhances the cyclic guanosine monophosphate pathway independently of nitric oxide as well as synergistically in normal- and low-nitric oxide conditions. This review describes the pharmacokinetic and pharmacodynamic profile of vericiguat and summarizes the effect of vericiguat on cardiac electrophysiology and population pharmacokinetic/pharmacodynamic relationships. Vericiguat demonstrates virtually complete absorption and increased exposure with food. Vericiguat has high oral bioavailability when taken with food (93.0%) with dose-proportional pharmacokinetics in healthy volunteers. Vericiguat has slightly less than dose-proportional pharmacokinetics with a slight decrease in bioavailability at higher doses in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Vericiguat is a low-clearance drug, with a half-life of approximately 20 h in healthy volunteers and 30 h in patients with HFrEF. Most drug metabolism is achieved by glucuronidation. Vericiguat has pharmacodynamic effects as expected from its pharmacological mechanism of action (i.e., relaxation of the smooth muscles in the vasculature leading to changes in hemodynamics). In the VICTORIA trial (NCT02861534), which enrolled patients with HFrEF, no meaningful exposure-response relationships for the incidence of symptomatic hypotension or syncope were evident. There were no significant imbalances in the incidence of undesirable hemodynamic-related effects (symptomatic hypotension and syncope) in subgroups with HFrEF defined by sex, age, race, and renal impairment. In addition, most patients achieved the 10-mg target dose per the blood pressure-guided titration regimen. No dose adjustments due to body weight, age, sex, race, or hepatic/renal impairment are necessary in adult patients with HFrEF. Observed and predicted changes in vericiguat exposure when co-administered with perpetrator drugs were small and not clinically meaningful. In addition, vericiguat has low potential as a perpetrator to affect exposure and/or pharmacodynamic effects of drugs commonly prescribed in patients with heart failure; therefore, no dose adjustment of these drugs is required in patients taking vericiguat. There is limited experience on the combined use of vericiguat with long-acting nitrates in patients with HFrEF. The ongoing VICTOR trial (NCT05093933), which is investigating vericiguat in patients with HFrEF, permits the co-administration of long-acting nitrates. Combined use of vericiguat and phosphodiesterase type-5 inhibitors has not been studied in patients with HFrEF and is therefore not recommended because of the potential increased risk for symptomatic hypotension. Vericiguat was not associated with electrophysiological abnormalities in preclinical and clinical studies up to the approved dose of 10 mg at steady state. Vericiguat is approved for the treatment of recently decompensated patients with worsening HFrEF. Vericiguat's safety and efficacy profile in patients with HFrEF will be further characterized by the VICTOR trial (NCT05093933) in adults without recent decompensation and in a pediatric population with HF due to left ventricular systolic dysfunction (VALOR trial, NCT05714085).

Exploring the influence of dietary habits on foot risk in type 2 diabetes patients: An observational study.

BACKGROUND & AIM: To date, there are no studies demonstrating the impact of the Mediterranean diet on the risk of diabetic foot ulcer. The aim of this research was to examine the connection between adherence to the Mediterranean diet and the level of risk of diabetic foot ulcers in individuals with type 2 diabetes. METHODS: Observational pilot study collecting sociodemographic, anthropometric, lifestyle, and type 2 diabetes-related data. Loss of protective sensation was assessed using the Semmes Weinstein 5.07-10 g monofilament, considered altered when not perceived in four points. Vascular status was assessed by palpating pulses and ankle-brachial index, indicating peripheral arterial disease if ankle-brachial index was less than 0.9 or if both pulses were absent. Foot deformities were recorded. The risk of diabetic foot ulcers was stratified into two categories: no risk and risk of diabetic foot ulcers. Adherence to the Mediterranean diet was evaluated using the Mediterranean Diet Adherence Screener-14 questionnaire (good adherence with score >7). RESULTS: Of the 174 patients with type 2 diabetes mellitus who participated (61.5% men and 38.5% women) with a mean age of 69.56 ± 8.86 years and a mean duration of type 2 diabetes of 15.34 ± 9.83 years. Non-adherent patients to the Mediterranean diet exhibited a higher association of diabetic foot ulcers (p = 0.030) and a lower average score on the Mediterranean Diet Adherence Screener-14 (p = 0.011). Additionally, a lower incidence of diabetic foot ulcers was observed in those who consumed nuts three or more times a week (p = 0.003) and sautéed foods two or more times a week (p = 0.003). Multivariate analysis highlighted the importance of physical activity (OR = 0.25, 95% CI 0.11-0.54; p < 0.001), podiatric treatment (OR = 2.59, 95% CI 1.21-5.56; p = 0.014), and duration of type 2 diabetes (OR = 3.25, 95% CI 1.76-5.99; p < 0.001) as significantly associated factors related to the risk of diabetic foot ulcers. CONCLUSIONS: Adhering to the Mediterranean diet correlates with a lower incidence of diabetic foot ulcers in individuals diagnosed with type 2 diabetes mellitus. Furthermore, factors such as regular physical activity, podiatric treatment, and the duration of type 2 diabetes mellitus emerge as pivotal in preventing diabetic foot ulcers.

Sociodemographic and obstetric factors may affect breastfeeding attitudes, self-efficacy, and knowledge in women with rheumatic diseases: a retrospective analysis of self-reported surveys.

Women with autoimmune rheumatic disease (ARDs) experience difficulties with BF in addition to those concerning their own disease. The aim of this study is to identify the impact factors as infant feeding attitude, the level of BF knowledge, BF self-efficacy, and the sociodemographic have in the intention to BF in women with ARDs. We performed an observational, retrospective, and analytical study. Reproductive-age women (18-50 years old) with ARDs with prior pregnancy history and who filled out self-reported BF surveys as part of the Rheumatology Integral Care Program were included. Sociodemographic and clinical characteristics were retrieved from medical charts. We analyzed three validated BF questionnaires. Sixty-five participants with a mean age of 41.32 ± 7.48 were evaluated. Of these, 63 (97%) women agreed with BF in the first 6 months. The most prevalent infant feeding attitude was neutral with 42 (64.6%) women. The most common level of BF knowledge was poor with 45 (69.2%) patients. There were significant correlations of BF knowledge with education years (p = < 0.001, r = 0.464) and age (p = 0.049, r=-0.245). A significant correlation was found between BF self-efficacy and age (p = 0.039, r = 0.257). Attitude toward BF was significantly associated with education level > 9 years (OR = 3.400; 95% CI = 1.091-10.593) and a history of miscarriage (OR = 3.670; 95% CI = 1.051-12.813). Although most women with ARDs agreed with BF, we identified a poor level of BF knowledge and a neutral infant feeding attitude as the most predominant. By identifying this data in women with ARDs, BF practices may be improved.

Epidemiology of Hepatitis C Virus in HIV Patients from West Mexico: Implications for Controlling and Preventing Viral Hepatitis.

The complex epidemiology of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV) patients in West Mexico remains poorly understood. Thus, this study aimed to investigate the HCV prevalence, HCV-associated risk factors, and HCV genotypes/subtypes and assess their impacts on liver fibrosis in 294 HIV patients (median age: 38 years; 88.1% male). HCV RNA was extracted and amplified by PCR. Hepatic fibrosis was assessed using three noninvasive methods: transient elastography (TE), the aspartate aminotransferase (AST)-to-platelets ratio index score (APRI), and the fibrosis-4 score (FIB4). Patients with liver stiffness of ≥9.3 Kpa were considered to have advanced liver fibrosis. HCV genotypes/subtypes were determined by line probe assay (LiPA) or Sanger sequencing. The prevalence of HIV/HCV infection was 36.4% and was associated with injection drug use (odds ratio (OR) = 13.2; 95% confidence interval (CI) = 5.9-33.6; p < 0.001), imprisonment (OR = 3.0; 95% CI = 1.7-5.4; p < 0.001), the onset of sexual life (OR = 2.6; 95% CI = 1.5-4.5; p < 0.001), blood transfusion (OR = 2.5; 95% CI = 1.5-4.2; p = 0.001), tattooing (OR = 2.4; 95% CI = 1.4-3.9; p = 0.001), being a sex worker (OR = 2.3; 95% CI = 1.0-5.4; p = 0.046), and surgery (OR = 1.7; 95% CI = 1.0-2.7; p = 0.042). The HCV subtype distribution was 68.2% for 1a, 15.2% for 3a, 10.6% for 1b, 3.0% for 2b, 1.5% for 2a, and 1.5% for 4a. The advanced liver fibrosis prevalence was highest in patients with HIV/HCV co-infection (47.7%), especially in those with HCV subtype 1a. CD4+ counts, albumin, direct bilirubin, and indirect bilirubin were associated with liver fibrosis. In conclusion, HCV infection had a significant impact on the liver health of Mexican HIV patients, highlighting the need for targeted preventive strategies in this population.

Real-life experience after 3 months with tezepelumab before marketing approval / Experiencia de la vida real después de 3 meses con tezepelumab antes de la aprobación de comercialización

Background: Tezepelumab is a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), implicated in asthma pathogenesis, and that has been approved for patients with severe uncontrolled asthma in Spain in October 2023. This study evaluates our experience with Tezepelumab for those patients who received the indicated drug off-label prior to its commercialization. Methods: We conducted a real-life observational study on three patients from the Severe Asthma Unit of the Hospital Universitario de Fuenlabrada, Spain, who received Tezepelumab off-label before its official approval. We analyzed symptoms control based on ACT, exacerbations, reductions in the doses of oral corticosteroid, lung function, blood changes and safety at 3 months of treatment. Results: Tezepelumab demonstrated efficacy in improving asthma control and a notable reduction in emergency department visits. OCS use decreased, with one patient halving their prednisone dose. Lung function, particularly FEV1 and FEV1/FVC parameters, improved, but no significant changes were observed in FeNO levels, blood eosinophil counts and total IgE. The treatment exhibited a favorable safety profile with no reported adverse effects during the study period. Conclusions: In this preliminary real-world experience prior to the official approval of tezepelumab in Spain, this monoclonal antibody showed promising results and suggests its potential as a valuable alternative for the treatment of severe asthma.(AU)

Entrevista motivacional como estrategia de mejoramiento de la salud bucal de niños y cuidadores. Revisión en sombrilla / Motivational interviewing as a strategy to improve the oral health of children and caregivers. Umbrella review

Objetivo: demostrar la efectividad de la entrevista motivacional (EM) en el mejoramiento de algunos indicadores de salud bucal en niños de 0 a 12 años y sus cuidadores. Material y métodos: estudio de revisión en sombrilla (umbrella review). Se realizó búsqueda en bases de datos electrónicas (PubMed, MEDLINE, SCOPUS, EBSCO) y Google Scholar desde el año 2010 hasta el año 2020, con las siguientes palabras clave: ('motivational interviewing' OR 'motivational interview' OR 'motivational interviewing style' OR 'motivational intervention' OR 'motivational counseling' OR 'brief motivational counseling' OR 'maternal counseling' OR 'behavioral intervention') AND (“caries” OR 'dental caries' OR 'tooth decay' OR 'dental decay' OR 'carious lesions' OR 'DMFT index' OR “ICDAS”) AND ('gingival diseases' OR “gingivitis” OR “CPITN” OR 'gingival bleeding' OR 'dental calculus') AND (“children” OR “families” OR “caregivers”). Se incluyeron artículos originales sobre la efectividad de la entrevista motivacional en salud bucal (EMSB) en niños de hasta 12 años y cuidadores, tipo revisión sistemática de la literatura y metanálisis, desde el año 2010 hasta el 2020. Resultados: 69 artículos (2 revisiones sistemáticas y 4 metanálisis). Los indicadores encontrados fueron: cambios en la presentación de caries de la infancia temprana, higiene bucal, condiciones gingivales y frecuencia de visitas a la consulta odontológica, con resultados alentadores y, en otros, contradictorios. Conclusiones: la evidencia sobre la efectividad de la entrevista motivacional en comparación con la educación convencional muestra cambios positivos en indicadores de salud bucal, como mejoramiento de la higiene dental y de la presentación de la caries en la primera infancia. (AU)

Objective: to demonstrate, the effectiveness of motivational interviewing in improving oral health indicators in children aged 0 to 12 years and their caregivers. Material and method: an umbrella review design. Search in electronic databases (PubMed, MEDLINE, SCOPUS, EBSCO) and Google Scholar since 2010 to 2020, with the following keywords: ('Motivational interviewing' OR 'motivational interview' OR 'motivational interviewing style' OR 'motivational intervention' OR 'motivational counseling' OR 'brief motivational counseling' OR 'maternal counseling' OR 'behavioral intervention') AND (“caries” OR 'dental caries' OR 'tooth decay' OR 'dental decay' OR 'carious lesions' OR 'DMFT index' OR “ICDAS”) AND ('gingival diseases' OR “gingivitis” OR “CPITN” OR 'gingival bleeding' OR 'dental calculus') AND (“children” OR “families” OR “caregivers”), original articles on the effectiveness of motivational interviewing in oral health (EMSB) in children between 0 and 12 years of age and caregivers, type systematic review of the literature and metaanalysis. Results: 69 articles were found (2 systematic reviews and 4 metaanalysis). The indicators found: change in early childhood caries, oral hygiene, gingival conditions and frequency of visits to the dental office with promise results and others contradictories. Conclusion: the evidence on the effectiveness of motivational interviewing compared to conventional education shows positive changes in oral health indicators such as improvement in dental hygiene and the presentation of caries in early childhood, among others. (AU)

In Vitro Anti-Toxoplasma Activity of Extracts Obtained from Tabebuia rosea and Tabebuia chrysantha: The Role of ß-Amyrin.

Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii that is highly prevalent worldwide. Although the infection is asymptomatic in immunocompetent individuals, it severely affects immunocompromised individuals, causing conditions such as encephalitis, myocarditis, or pneumonitis. The limited therapeutic efficacy of drugs currently used to treat toxoplasmosis has prompted the search for new therapeutic alternatives. The aim of this study was to determine the anti-Toxoplasma activity of extracts obtained from two species of the genus Tabebuia. Twenty-six extracts, 12 obtained from Tabebuia chrysantha and 14 from Tabebuia rosea, were evaluated by a colorimetric technique using the RH strain of T. gondii that expresses ß-galactosidase. Additionally, the activity of the promising extracts and their active compounds was evaluated by flow cytometry. ß-amyrin was isolated from the chloroform extract obtained from the leaves of T. rosea and displayed important anti-Toxoplasma activity. The results show that natural products are an important source of new molecules with considerable biological and/or pharmacological activity.

Real-life experience after 3 months with tezepelumab before marketing approval.

BACKGROUND: Tezepelumab is a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), implicated in asthma pathogenesis, and that has been approved for patients with severe uncontrolled asthma in Spain in October 2023. This study evaluates our experience with Tezepelumab for those patients who received the indicated drug off-label prior to its commercialization. METHODS: We conducted a real-life observational study on three patients from the Severe Asthma Unit of the Hospital Universitario de Fuenlabrada, Spain, who received Tezepelumab off-label before its official approval. We analyzed symptoms control based on ACT, exacerbations, reductions in the doses of oral corticosteroid, lung function, blood changes and safety at 3 months of treatment. RESULTS: Tezepelumab demonstrated efficacy in improving asthma control and a notable reduction in emergency department visits. OCS use decreased, with one patient halving their prednisone dose. Lung function, particularly FEV1 and FEV1/FVC parameters, improved, but no significant changes were observed in FeNO levels, blood eosinophil counts and total IgE. The treatment exhibited a favorable safety profile with no reported adverse effects during the study period. CONCLUSIONS: In this preliminary real-world experience prior to the official approval of tezepelumab in Spain, this monoclonal antibody showed promising results and suggests its potential as a valuable alternative for the treatment of severe asthma.

Motivational interviewing for preventing oral morbidities in adults: Systematic review and meta-analysis.

OBJECTIVE: This systematic review with meta-analysis was performed to assess whether motivational interviewing (MI) effectively prevents oral morbidities in adults. METHODS: Studies considered were randomized controlled trials, cluster-randomized controlled trials and community-based randomized trials assessing interventions based on MI or indicating that a counselling technique based on the principles developed by Miller and Rollnick was used. Controls were any type of oral health education or negative controls. Participants were 18-60 years old. The main outcome was any oral morbidity. From 602 studies identified in MEDLINE, Scopus, Web of Science and LILACS databases, seven studies were included in the synthesis. RESULTS: Studies included only evaluated periodontal outcomes, no studies were found for other oral morbidities. Patients' mean age was 43.7 years, and the follow-up time after MI or MI-based intervention varied between 1 month and 1 year. The total study population was 272 people with moderate-to-severe periodontitis; other groups analysed were pregnant women (n = 112) and patients with mental disorders and alcohol problems (n = 60). Meta-analysis for the plaque index (four studies, n = 267), bleeding on probing (two studies, n = 177) and gingival index (two studies, n = 166) were carried out. The summary effects for the random-effects model were estimated respectively as -3.59 percentage points (CI: [-11.44; 4.25] for plaque index, -6.41 percentage points (CI: [-12.18, -0.65]) for bleeding on probing and -0.70 (CI: [-1.87; 0.48]) for gingival index, marginally favouring the MI group. The reduced number of studies, the non-disclosure of some aspects of the data and the heterogeneity among them undermine the precision of the estimates. CONCLUSION: The current evidence available is limited to periodontal outcomes, and it is not possible to determine whether MI effectively prevents oral morbidities in adults.

Applied physiologically-based pharmacokinetic modeling to assess uridine diphosphate-glucuronosyltransferase-mediated drug-drug interactions for Vericiguat.

Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate-glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug-drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically-based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling. A PBPK model of vericiguat was developed based on in vitro and clinical data, verified against data from the mefenamic acid DDI study, and applied to assess the UGT1A1 DDI liability by running an in silico DDI study with the UGT1A1 inhibitor atazanavir. A minor effect with an area under the plasma concentration-time curve (AUC) ratio of 1.12 and a peak plasma concentration ratio of 1.04 was predicted, which indicates that there is no clinically relevant DDI interaction anticipated. Additionally, the effect of potential genetic polymorphisms of UGT1A1 and UGT1A9 was evaluated, which showed that an average modest increase of up to 1.7-fold in AUC may be expected in the case of concomitantly reduced UGT1A1 and UGT1A9 activity for subpopulations expressing non-wild-type variants for both isoforms. This study is a first cornerstone to qualify the PK-Sim platform for use of UGT-mediated DDI predictions, including PBPK models of perpetrators, such as mefenamic acid and atazanavir, and sensitive UGT substrates, such as dapagliflozin and raltegravir.

MRI and CT Fusion in Stereotactic Electroencephalography (SEEG).

Epilepsy is a neurological disorder characterized by spontaneous recurrent seizures. While 20% to 30% of epilepsy cases are untreatable with Anti-Epileptic Drugs, some of these cases can be addressed through surgical intervention. The success of such interventions greatly depends on accurately locating the epileptogenic tissue, a task achieved using diagnostic techniques like Stereotactic Electroencephalography (SEEG). SEEG utilizes multi-modal fusion to aid in electrode localization, using pre-surgical resonance and post-surgical computer tomography images as inputs. To ensure the absence of artifacts or misregistrations in the resultant images, a fusion method that accounts for electrode presence is required. We proposed an image fusion method in SEEG that incorporates electrode segmentation from computed tomography as a sampling mask during registration to address the fusion problem in SEEG. The method was validated using eight image pairs from the Retrospective Image Registration Evaluation Project (RIRE). After establishing a reference registration for the MRI and identifying eight points, we assessed the method's efficacy by comparing the Euclidean distances between these reference points and those derived using registration with a sampling mask. The results showed that the proposed method yielded a similar average error to the registration without a sampling mask, but reduced the dispersion of the error, with a standard deviation of 0.86 when a mask was used and 5.25 when no mask was used.

Vericiguat, a novel sGC stimulator: Mechanism of action, clinical, and translational science.

Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, is approved for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF). Decreased nitric oxide (NO) availability, sGC desensitization to NO, sGC deficiency, and reduced cyclic guanosine monophosphate (cGMP) signaling are potential contributing factors for HF disease progression. Vericiguat works via stimulation of sGC in the critical NO-sGC-cGMP pathway. Vericiguat is primarily metabolized by glucuronidation via uridine diphosphate-glucuronosyltransferase (UGT) isoforms UGT1A1 and UGT1A9. Urinary excretion and renal clearance of vericiguat are low. No intrinsic factor had a clinically relevant effect on vericiguat exposure. Vericiguat has low drug-drug interaction potential with no clinically relevant pharmacokinetic or pharmacodynamic interactions observed with warfarin, digoxin, aspirin, or sacubitril/valsartan. The global phase III study VICTORIA included patients with HFrEF who had a recent HF hospitalization or intravenous diuretic treatment for HF. Treatment with vericiguat on top of standard of care resulted in a 10% relative reduction in the primary composite outcome of death from cardiovascular causes or first hospitalization for HF. Vericiguat was well-tolerated with low incidence of symptomatic hypotension and syncope compared to placebo. Given its positive benefit-risk profile, vericiguat is an important option for high-risk patients with HFrEF who are already on guideline-directed medical therapy and had recent worsening of HF. Future efforts to develop additional effective therapies are needed to further reduce morbidity and mortality in patients with HF.

Compartment syndrome of the foot: A case report.

Background: Exercise-induced compartment syndrome is a condition characterized by elevated pressure within a muscle compartment, resulting from repetitive loading or participation in sports activities. Primarily affecting the medial compartment of the foot, this rare condition manifests as sudden-onset pain in the medial aspect of the foot, without a discernible history of trauma, occurring during or after physical exertion. Diagnosis is primarily clinical in nature, as diagnostic imaging techniques provide limited utility. Conclusions: Exercise-induced compartment syndrome is a rare syndrome with prolonged implications such as contractures, claw toes, muscle weakness, and sensory neuropathy. Hence, it is imperative for orthopedic surgeons to be familiar with this condition in order to facilitate timely diagnosis and treatment.

Consulta enfermera de Educación Terapéutica en asma grave / Outpatient nurse clinic on Therapeutic Education for severe asthma

La enfermera de la Unidad de Alergología del Hospital Universitario Puerta de Hierro Majadahonda (Madrid) propuso al equipo crear una consulta monográfica de educación en asma dada la alta prevalencia, consiguiendo el consenso del equipo interdisciplinar, y la acreditación de la Sociedad Española de Alergología e Inmunología Clínica. El proyecto de creación de la nueva consulta surgió al finalizar la pandemia de COVID-19, debido a la necesidad de mejorar la educación y el seguimiento de estos pacientes crónicos para reducir las recidivas. La Consulta de Educación en Asma Grave se puso en marcha en marzo de 2022. La educación terapéutica, como proceso continuo de cuidados centrado en el paciente, es una de las claves para mejorar el control de la enfermedad y la calidad de vida del paciente-familia. La enfermera es el profesional esencial que interviene en todos los procesos asistenciales, que puede conseguir promover el empoderamiento del paciente frente a su enfermedad, así como su rol activo en autocuidados. (AU)

The nurses from the Allergology Unit of the Hospital Universitario Puerta de Hierro, Majadahonda (Madrid) put forward to the team the idea of creating a specialized outpatient clinic on asthma education, given its high prevalence, and obtained consensus by the interdisciplinary team and accreditation by the Spanish Society of Allergology and Clinical Immunology. The project for creating this new outpatient clinic came up at the end of the COVID-19 pandemic, due to the need to improve the education and follow-up of these chronic patients in order to reduce relapses. The Outpatient Clinic for Education on Severe Asthma was launched in March 2022. Therapeutic education, as an ongoing process of patient-centred care, is one of the keys to improve disease control and the quality of life of patients and their families. The nurse is the key professional involved in all processes of care, who can achieve the promotion of patient empowerment regarding their disease, as well as an active role in self-care. (AU)

Assessing QTc Effects of Vericiguat Using Two Different Concentration-QTc Modeling Approaches.

BACKGROUND AND OBJECTIVES: Vericiguat is a soluble guanylate cyclase stimulator indicated to reduce the risk of cardiovascular death and hospitalization due to heart failure. A dedicated QTc study in patients with chronic coronary syndromes demonstrated no clinically relevant QTc effect of vericiguat for exposures across the therapeutic dose range (2.5-10 mg). Interval prolongation concentration-QTc (C-QTc) modeling was performed to complement the statistical evaluations of QTc in the dedicated QTc study. METHODS: Individual time-matched, baseline- and placebo-corrected Fridericia-corrected QT interval values (ΔΔQTcF) were derived. Two approaches for ΔΔQTcF calculation were investigated: (1) ΔΔQTcF correction with data from a single baseline (as in the primary statistical analysis); and (2) ΔΔQTcF correction with a modeled baseline (considering all available individual non-treatment baselines). The ΔΔQTcF values were related to observed vericiguat concentrations with linear mixed-effects modeling. RESULTS: For both modeling approaches, a positive relationship was found between ΔΔQTcF and vericiguat concentration; however, the slope for the single-baseline approach was not statistically significant, whereas the slope from the modeled-baseline approach was statistically significant. The upper bound of the two-sided 90% confidence interval for model-derived QTc was < 10 ms at the highest observed exposure (745 µg/L; investigated dose range 2.5-10 mg). CONCLUSION: By applying a single-baseline approach and a modeled-baseline approach that integrated all available QTc data across doses to characterize the QTc prolongation potential, this study showed that vericiguat 2.5-10 mg is not associated with clinically relevant QTc effects, in line with the conclusion from the primary statistical analysis. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov NCT03504982.

Plasticity of Cortico-striatal Neurons of the Caudal Anterior Cingulate Cortex During Experimental Neuropathic Pain.

Maladaptive neuronal plasticity is a main mechanism for the development and maintenance of pathological pain. Affective, motivational and cognitive deficits that are comorbid with pain involve cellular and synaptic modifications in the anterior cingulate cortex (ACC), a major brain mediator of pain perception. Here we use a model of neuropathic pain (NP) in male mice and ex-vivo electrophysiology to investigate whether layer 5 caudal ACC (cACC) neurons projecting to the dorsomedial striatum (DMS), a critical region for motivational regulation of behavior, are involved in aberrant neuronal plasticity. We found that while the intrinsic excitability of cortico-striatal cACC neurons (cACC-CS) was preserved in NP animals, excitatory postsynaptic potentials (EPSP) induced after stimulation of distal inputs were enlarged. The highest synaptic responses were evident both after single stimuli and in each of the EPSP that compose responses to trains of stimuli, and were accompanied by increased synaptically-driven action potentials. EPSP temporal summation was intact in ACC-CS neurons from NP mice, suggesting that the plastic changes were not due to alterations in dendritic integration but rather through synaptic mechanisms. These results demonstrate for the first time that NP affects cACC neurons that project to the DMS and reinforce the notion that maladaptive plasticity of the cortico-striatal pathway may be a key factor in sustaining pathological pain.