Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: A case series.

OBJECTIVE: Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications. METHODS: This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®. RESULTS: All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24-26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported. SIGNIFICANCE: This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases.

Evolutionary analysis of indeterminate cytology and risk of malignancy in a thyroid nodule unit.

OBJECTIVE: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. METHODS: 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed. RESULTS: only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively. All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. CONCLUSION: Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

Dual FGFR-targeting and pH-activatable ruthenium-peptide conjugates for targeted therapy of breast cancer.

Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.8 and pH 7.4 aimed at mimicking the tumor microenvironment and normal tissues/bloodstream pHs, respectively. The RuPCs showed higher cytotoxicity in cells with higher level of FGFR expression at acidic pH. Additionally, RuPCs showed up to 6-fold higher activity in the FGFR(+) breast cancer lines compared to the normal cell line. The release profile of Ru complexes from RuPCs corroborates the antiproliferative effects observed. Remarkably, the cytotoxicity and releasing ability of RuPCs were shown to be strongly dependent on the conjugation of the peptide position in the Ru complex. Complementary molecular dynamic simulations and computational calculations were performed to help interpret these findings at the molecular level. In summary, we identified a lead bi-functional RuPC that holds strong potential as a FGFR-targeted chemotherapeutic agent.

Effectiveness of an Interactive mHealth App (EVITE) in Improving Lifestyle After a Coronary Event: Randomized Controlled Trial.

BACKGROUND: Coronary heart disease is one of the leading causes of mortality worldwide. Secondary prevention is essential, as it reduces the risk of further coronary events. Mobile health (mHealth) technology could become a useful tool to improve lifestyles. OBJECTIVE: This study aimed to evaluate the effect of an mHealth intervention on people with coronary heart disease who received percutaneous coronary intervention. Improvements in lifestyle regarding diet, physical activity, and smoking; level of knowledge of a healthy lifestyle and the control of cardiovascular risk factors (CVRFs); and therapeutic adherence and quality of life were analyzed. METHODS: This was a randomized controlled trial with a parallel group design assigned 1:1 to either an intervention involving a smartphone app (mHealth group) or to standard health care (control group). The app was used for setting aims, the self-monitoring of lifestyle and CVRFs using measurements and records, educating people with access to information on their screens about healthy lifestyles and adhering to treatment, and giving motivation through feedback about achievements and aspects to improve. Both groups were assessed after 9 months. The primary outcome variables were adherence to the Mediterranean diet, frequency of food consumed, patient-reported physical activity, smoking, knowledge of healthy lifestyles and the control of CVRFs, adherence to treatment, quality of life, well-being, and satisfaction. RESULTS: The study analyzed 128 patients, 67 in the mHealth group and 61 in the control group; most were male (92/128, 71.9%), with a mean age of 59.49 (SD 8.97) years. Significant improvements were observed in the mHealth group compared with the control group regarding adherence to the Mediterranean diet (mean 11.83, SD 1.74 points vs mean 10.14, SD 2.02 points; P<.001), frequency of food consumption, patient-reported physical activity (mean 619.14, SD 318.21 min/week vs mean 471.70, SD 261.43 min/week; P=.007), giving up smoking (25/67, 75% vs 11/61, 42%; P=.01), level of knowledge of healthy lifestyles and the control of CVRFs (mean 118.70, SD 2.65 points vs mean 111.25, SD 9.05 points; P<.001), and the physical component of the quality of life 12-item Short Form survey (SF-12; mean 45.80, SD 10.79 points vs mean 41.40, SD 10.78 points; P=.02). Overall satisfaction was higher in the mHealth group (mean 48.22, SD 3.89 vs mean 46.00, SD 4.82 points; P=.002) and app satisfaction and usability were high (mean 44.38, SD 6.18 out of 50 points and mean 95.22, SD 7.37 out of 100). CONCLUSIONS: The EVITE app was effective in improving the lifestyle of patients in terms of adherence to the Mediterranean diet, frequency of healthy food consumption, physical activity, giving up smoking, knowledge of healthy lifestyles and controlling CVRFs, quality of life, and overall satisfaction. The app satisfaction and usability were excellent. TRIAL REGISTRATION: Clinicaltrials.gov NCT04118504; https://clinicaltrials.gov/study/NCT04118504.

Nivel de ansiedad y miedo al covid-19 en médicos de la contingencia respiratoria del Hospital de Clínicas, durante la pandemia por el SARS-COV-2 / Anxiety and covid-19 fear in respiratory contingency of Clinical Hospital physicians during SARS-COV-2 pandemic

Introducción: Como ocurrió en todos los hospitales, los profesionales del Hospital de Clínicas sufrieron elevada presión física y psicológica. Estudios previos, sobre todo realizados en China, ya sugerían que los profesionales sanitarios eran especialmente vulnerables al malestar psicológico derivado de la pandemia. Objetivos: Determinar el nivel de ansiedad y miedo al COVID 19 en los médicos del área de Contingencia respiratoria del Hospital de Clínicas. Materiales y métodos: Se realizó un estudio observacional, descriptivo, de corte transverso, de muestreo no probabilístico por conveniencia, en individuos de ambos sexos, mayores de 18 años, en médicos del área de Contingencia respiratoria del Hospital de Clínicas de San Lorenzo durante la pandemia por el SARS-COV2. Resultados: Fueron encuestados 68 médicos, de los cuales el 63% fueron del sexo femenino, la edad promedio de los participantes fue de 31 años (±4,48). La mayoría de los encuestados fueron residentes. El 75% pertenecen a la especialidad de Medicina Interna. El 30.8% cuenta con 4 dosis de vacuna contra el SARSCOV 2. Presentaron síntomas de miedo al COVID-19 el 44,1%, de los cuales, los síntomas más frecuentes fueron: miedo a infectarse con el COVID-19 48,5%; incomodidad al pensar en el COVID19 39,7%; perder la vida a causa del COVID-19 el 30,8%. El 66,1% tiene criterios de Trastorno de Ansiedad Generalizada, de los cuales la mayoría sufre de Ansiedad Leve. Conclusión: Se observa una alta prevalencia de síntomas de Ansiedad y Miedo al COVID-19 en médicos de la Contingencia Respiratoria del Hospital de Clínicas.

Introduction: As happened in all hospitals, the professionals at the Hospital de Clínicas suffered high physical and psychological pressure. Previous studies, especially carried out in China, already suggested that health professionals were especially vulnerable to psychological distress derived from the pandemic. Objectives: Determine the level of anxiety and fear of COVID 19 in doctors of the Respiratory Contingency area of the Hospital de Clínicas. Materials and methods: An observational, descriptive, cross-sectional, non-probabilistic convenience sampling study was carried out in individuals of both sexes, over 18 years of age, in doctors from the Respiratory Contingency area of the Hospital de Clínicas de San Lorenzo during the SARS-COV2 pandemic. Results: 68 doctors were surveyed, of which 63% were female; the average age of the participants was 31 years (±4.48). The majority of respondents were residents. 75% belong to the specialty of Internal Medicine. 30.8% have 4 doses of vaccine against SARSCOV 2. 44.1% presented symptoms of fear of COVID-19, of which the most frequent symptoms were: fear of becoming infected with COVID-19 48. 5%; discomfort when thinking about COVID19 39.7%; 30.8% lose their lives due to COVID-19. 66.1% have criteria for Generalized Anxiety Disorder, of which the majority suffer from Mild Anxiety. Conclusion: A high prevalence of symptoms of Anxiety and Fear of COVID-19 is observed in Respiratory Contingency doctors at the Hospital de Clínicas.

Impact of mHealth application on adherence to cardiac rehabilitation guidelines after a coronary event: Randomised controlled clinical trial protocol.

Background: Coronary disease is the main cause of death around the world. mHealth technology is considered attractive and promising to promote behavioural changes aimed at healthy lifestyle habits among coronary patients. The purpose of this study is to evaluate the efficacy of an mHealth intervention regarding improved results in secondary prevention in patients after an acute myocardial infarction (AMI) or angina in terms of lifestyle, clinical variables and therapeutic compliance. Methods: Randomised clinical trial with 300 patients who underwent a percutaneous coronary intervention (PCI) with stent implant. They will be assigned to either the mHealth group, subject to a self-monitored educational intervention involving an internet application installed on their mobile phone or tablet, or to a control group receiving standard healthcare (150 patients in each arm). The primary outcome variables will be adherence to the Mediterranean diet, physical activity, smoking, therapeutic compliance, knowledge acquired, user-friendliness and satisfaction with the application. Measurements of blood pressure, heart rate, body weight, waist circumference (WC) and the 6-min walk test will be taken. Furthermore, the blood lipid profile, glucose and HbA1c will be evaluated. Clinical interview will be conducted, and validated questionnaires completed. The primary quantitative results will be compared using an analysis of covariance adjusted for age and sex. A multivariate analysis will be performed to examine the association of the intervention with lifestyle habits, the control of cardiovascular risk factors (CDRFs) and the results after the hospital discharge (major adverse events, treatment compliance and lifestyle). Conclusions: The study will provide evidence about the effectiveness of an mHealth intervention at improving the lifestyle of the participants and could be offered to patients with coronary disease to complement existing services. Trial registration: NCT05247606. [https://ClinicalTrials.gov]. 21/02/2022.

Cáncer incidental de vesícula: incidencia y factores asociados en pacientes de una institución de la ciudad de Medellín / Incidental gallbladder cancer: Incidence and associated factors in patients from an institution in the city of Medellín

Introducción. El cáncer de vesícula biliar es una de las neoplasias más frecuentes de la vía biliar y la mayoría de los casos se diagnostican de forma incidental o en estadios avanzados. En Colombia existen pocas publicaciones acerca de la prevalencia y características clínicas de pacientes con cáncer insospechado de vesícula biliar. El objetivo de este trabajo fue actualizar la información existente. Métodos. Estudio de tipo transversal basado en registros médicos. Como variable de resultado se definió el hallazgo incidental de patología maligna reportado por un patólogo y el subtipo histológico. Se midieron variables demográficas, clínicas y quirúrgicas. Se calcularon OR con sus respectivos intervalos de confianza (IC95%). Resultados. De los 2630 casos analizados, en cuatro se hizo diagnóstico de cáncer incidental de vesícula, con una prevalencia del 0,15 %. Se encontraron como características asociadas al cáncer incidental de vesícula, la edad, el antecedente de cáncer y la presencia de pólipos. Conclusiones. Esta es una patología poco frecuente en la población evaluada, lo que permite afirmar que no es necesario realizar estudios prequirúrgicos más amplios de forma rutinaria, a menos que el paciente presente alguno de los factores asociados.

Introduction. Gallbladder cancer is one of the most common neoplasms of the bile duct and most cases are diagnosed incidentally or in advanced stages. In Colombia, there are few publications about the prevalence and clinical characteristics of patients with unsuspected gallbladder cancer. The objective of this work was to update the existing information. Methods. Cross-sectional study based on medical records. The incidental finding of malignant pathology reported and the histological subtype were defined as the outcome variable. Demographic, clinical and surgical variables were measured. ORs were calculated with their respective 95% CI. Results. Of the 2630 cases analyzed, four were diagnosed with incidental gallbladder cancer, with a prevalence of 0.15%. Characteristics associated with incidental gallbladder cancer were age, history of cancer and the presence of polyps. Conclusions. This is a rare pathology in the population evaluated, which allows us to recommend that it is not necessary to routinely perform more extensive presurgical studies, unless the patient presents any of the associated factors.

Robotic surgery in the management of synchronous esophageal and gastric perforation after endoscopic dilation.

Upper gastrointestinal perforation is a feared complication of diagnostic and therapeutic endoscopy, with an incidence of perforation between 0.3% and 5%. Even though is rare, the mortality rate can be as high as 40%. Currently, there is no consensus on the best therapeutic strategy and it usually depends on patient stability, the extent of perforation, time to diagnosis, surgeon experience and available resourcesWe present a case of a patient who presented to our institution to undergo an ambulatory oesophageal dilation. After dilation, the patient developed two full-thickness gastric perforations and a full-thickness oesophageal perforation without haemodynamic instability. All perforations were diagnosed and treated with a combination of intraoperative endoscopy and robotic surgery with excellent outcomes.We demonstrate that a robotic approach combined with intraoperative diagnostic endoscopy is a safe and feasible treatment option for esophageal and gastric perforations in a stable patient without large extraluminal contamination.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Mitochondrial Functionality Is Regulated by Alkylphospholipids in Human Colon Cancer Cells.

Alkylphospholipids (APLs) have been studied as anticancer drugs that interfere with biological membranes without targeting DNA. Although their mechanism of action is not fully elucidated yet, it is known that they disrupt the intracellular trafficking of cholesterol and its metabolism. Here, we analyzed whether APLs could also interfere with mitochondrial function. For this purpose, we used HT29 colorectal cancer cells, derived from a primary tumor, and SW620 colorectal cancer cells, derived from a metastasis site. After treatment with the APLs miltefosine and perifosine, we analyzed various mitochondrial parameters, including mitochondrial mass, cardiolipin content, mitochondrial membrane potential, H2O2 production, the levels of oxidative phosphorylation (OXPHOS) complexes, metabolic enzymes activity, the oxygen consumption rate, and the levels of apoptosis and autophagy markers. APLs, especially perifosine, increased mitochondrial mass while OXPHOS complexes levels were decreased without affecting the total oxygen consumption rate. Additionally, we observed an increase in pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH) levels and a decrease in lactate dehydrogenase (LDH) activity, suggesting a metabolic rewiring induced by perifosine. These alterations led to higher mitochondrial membrane potential, which was potentiated by decreased uncoupling protein 2 (UCP2) levels and increased reactive oxygen species (ROS) production. Consequently, perifosine induced an imbalance in mitochondrial function, resulting in higher ROS production that ultimately impacted cellular viability.

Standards for psychosocial care in pediatric cancer: adapted proposal for Latin American and Caribbean countries.

Objective: To highlight the objectives, achievements, challenges, and next steps for the World Health Organization's Global Initiative for Childhood Cancer (GICC) framework, a project designed to improve psychosocial care (PSC) in pediatric cancer centers across Latin America and the Caribbean (LAC). Methods: The project was launched in Peru, the first GICC focal country, in November 2020. The diagnosis phase included a survey and a semistructured interview with health professionals to assess PSC practices in institutions, and a needs assessment survey for caregivers. In the second phase, a strategic plan was developed to address the identified needs, including the adaptation of PSC standards, the establishment of multicenter working groups, the expansion of the proposal, and the development of materials. Results: The study found that PSC was not being adequately provided in accordance with international standards. Six adapted standards were proposed and validated, and more than 50 regional health professionals participated in online activities to support the project. The implementation process is currently ongoing, with the establishment of five multidisciplinary working groups, one regional committee, and the production of 16 technical outputs. Conclusion: This project represents a substantial step forward to improve PSC for pediatric patients with cancer and their families in LAC countries. The establishment of working groups and evidence-based interventions strengthen the proposal and its implementation. Development of health policies that include PSC according to standards is needed to achieve sustainable results in the quality of life of children with cancer and their families.

Evaluation of factors associated with recruitment rates in early phase clinical trials based on the European Clinical Trials Register data.

Effective participant recruitment is a critical challenge in clinical trials. Inadequate enrollment of participants can precipitate delays, escalated costs, and compromise scientific integrity. Despite its relevance, particularly during the early phases, it persists as an obstacle in the field of clinical research. The primary aim of this study was to analyze the recruitment rates of early-phase clinical trials and evaluate their potential associations with key trial characteristics. Using a descriptive and statistical analysis, a research study was conducted based on the early-phase trials registered at the European Clinical Trials Register (EU-CTR), spanning the timeframe from January 2017 to December 2021. Among the 194 trials examined, we found median recruitment rates of 68%. A more detailed exploration revealed a greater level of success in terms of recruitment achievement in pediatric trials when compared to trials involving adults, non-oncologic trials, or those also developed in non-European countries. It is important to underscore that only 69 trials out of the total managed to conclude recruitment, with the most prevalent reason for premature cessation being the presence of efficacy and safety issues or sponsor's strategy. This number can be greatly improved. Despite certain disparities observed in the information within EU-CTR, we have successfully determined the recruitment rates of the studies and established associations with some of the clinical trial characteristics analyzed. Owing to the inherent constraints of this study, further research is warranted to gain a comprehensive understanding of the intricate interplay between trial characteristics and their impact on recruitment rates in early-phase studies.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Lack of associations of microRNAs with severe NAFLD in people living with HIV: discovery case-control study.

Background & objective: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people living with HIV (PLWH) and the expression of some microRNAs could be useful as biomarkers for the diagnosis of NAFLD. The aim of this study was to identify patterns of differential expression of microRNAs in PLWH and assess their diagnostic value for NALFD. Methods: A discovery case-control study with PLWH was carried out. The expression of miRNAs was determined using HTG EdgeSeq technology. Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, BMI, CD4+ lymphocyte count, active HCV infection, and ART regimen. Results: Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study. Conclusion: Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.

Side effects screening and early intervention to impact in quality of life of patients with gynecological cancers (HALIS study).

BACKGROUND: Advances in the treatment of gynecological cancers have led to increased survival in patients with gynecological cancers. Nevertheless, patients may still experience prevalent long term consequences, including lower limb lymphedema, depression, anxiety, sexual dysfunction, malnutrition, and sarcopenia, that negatively impact their quality of life. PRIMARY OBJECTIVE: To assess the impact on self-perceived quality of life of systematic screening and early treatment of lower limb lymphedema, anxiety and depression, sexual dysfunction, and sarcopenia and malnutrition compared with standard practice. STUDY HYPOTHESIS: Systematic screening with validated questionnaires leading to early diagnosis and treatment of side effects will have a positive impact on quality of life. TRIAL DESIGN: This prospective clinical trial will randomize candidates for surgery to either standard of care or systematic screening every 2 months for 2 years. Quality of life data will be collected every 4 months. After randomization, patients in the control group will follow standard usual care. Their screening scales will not be considered. In the experimental group, positive screenings will generate an alert to the physician, and patients will be referred to the corresponding specific area (rehabilitation unit, psycho-oncology unit, sexual health unit, or nutrition unit). MAJOR INCLUSION AND XCLUSION CRITERIA: Patients aged ≥18 years with ovarian, cervical, or endometrial cancer who are candidates for surgery will be included. PRIMARY ENDPOINT: Self-reported quality of life questionnaire score. SAMPLE SIZE: 168 patients will be randomized to detect a difference of 6 points in the questionnaires. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Study completion is estimated for January 2026 and the results will be presented in May 2026. TRIAL REGISTRATION NUMBER: NCT05918770.

Soluble Transferrin Receptor as Iron Deficiency Biomarker: Impact on Exercise Capacity in Heart Failure Patients.

The soluble transferrin receptor (sTfR) is a marker of tissue iron status, which could indicate an increased iron demand at the tissue level. The impact of sTfR levels on functional capacity and quality of life (QoL) in non-anemic heart failure (HF) patients with otherwise normal systemic iron status has not been evaluated. We conducted an observational, prospective, cohort study of 1236 patients with chronic HF. We selected patients with normal hemoglobin levels and normal systemic iron status. Tissue iron deficiency (ID) was defined as levels of sTfR > 75th percentile (1.63 mg per L). The primary endpoints were the distance walked in the 6 min walking test (6MWT) and the overall summary score (OSS) of the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The final study cohort consisted of 215 patients. Overall QoL was significantly worse (51 ± 27 vs. 39 ± 20, p-value = 0.006, respectively), and the 6 MWT distance was significantly worse in patients with tissue ID when compared to patients without tissue ID (206 ± 179 m vs. 314 ± 155, p-value < 0.0001, respectively). Higher sTfR levels, indicating increased iron demand, were associated with a shorter distance in the 6 MWT (standardized ß = -0.249, p < 0.001) and a higher MLHFQ OSS (standardized ß = 0.183, p-value = 0.008). In this study, we show that in patients with normal systemic iron parameters, higher levels of sTfR are strongly associated with an impaired submaximal exercise capacity and with worse QoL.

Uremic Toxins Induce THP-1 Monocyte Endothelial Adhesion and Migration through Specific miRNA Expression.

Atherosclerosis is initiated by the activation of endothelial cells that allows monocyte adhesion and transmigration through the vascular wall. The accumulation of uremic toxins such as indoxyl sulphate (IS) and p-cresol (PC) has been associated with atherosclerosis. Currently, miRNAs play a crucial role in the regulation of monocyte activation, adhesion, and trans-endothelial migration. The aim of the present study is to evaluate the effect of IS and PC on monocyte adhesion and migration processes in monocytes co-cultured with endothelial cells as well as to determine the underlying mechanisms. The incubation of HUVECs and THP-1 cells with both IS and PC toxins resulted in an increased migratory capacity of THP-1 cells. Furthermore, the exposure of THP-1 cells to both uremic toxins resulted in the upregulation of BMP-2 and miRNAs-126-3p, -146b-5p, and -223-3p, as well as the activation of nuclear factor kappa B (NF-κB) and a decrease in its inhibitor IĸB. Uremic toxins, such as IS and PC, enhance the migratory and adhesion capacity of THP-1 cells to the vascular endothelium. These toxins, particularly PC, contribute significantly to uremia-associated vascular disease by increasing in THP-1 cells the expression of BMP-2, NF-κB, and key miRNAs associated with the development of atherosclerotic vascular diseases.

Consent document translation expense hinders inclusive clinical trial enrolment.

Patients from historically under-represented racial and ethnic groups are enrolled in cancer clinical trials at disproportionately low rates in the USA1-3. As these patients often have limited English proficiency4-7, we hypothesized that one barrier to their inclusion is the cost to investigators of translating consent documents. To test this hypothesis, we evaluated more than 12,000 consent events at a large cancer centre and assessed whether patients requiring translated consent documents would sign consent documents less frequently in studies lacking industry sponsorship (for which the principal investigator pays the translation costs) than for industry-sponsored studies (for which the translation costs are covered by the sponsor). Here we show that the proportion of consent events for patients with limited English proficiency in studies not sponsored by industry was approximately half of that seen in industry-sponsored studies. We also show that among those signing consent documents, the proportion of consent documents translated into the patient's primary language in studies without industry sponsorship was approximately half of that seen in industry-sponsored studies. The results suggest that the cost of consent document translation in trials not sponsored by industry could be a potentially modifiable barrier to the inclusion of patients with limited English proficiency.

Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study.

PURPOSE: To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice. METHODS: Observational, retrospective, phase 4 study on subjects receiving cenobamate in three Spanish centers. The primary endpoint was the retention rate at the last follow-up. The main secondary endpoints were the 50%-responder  and seizure-free rates at three months and the last follow-up. Other secondary endpoints were Global Clinical Impressions-Improvement (CGI-I) scores and treatment-emergent adverse events (TEAEs). RESULTS: Fifty-one patients with highly refractory focal epilepsy with 24.7 years of disease evolution, ten previously tried ASM, and a 23.5% of previous epilepsy surgery were included. The retention rate at the last follow-up was 80.4%. The 50% responder rate in focal seizures at three months was 56.5% (median reduction per month 51%, 0-74.6; p < 0.0001) and in focal to bilateral tonic-clonic seizures was 63.6% (median reduction per month 89%, 0-100; p = 0.022). A total of 54.3% of subjects reported a reduction in the intensity of focal seizures, and 66% manifested clinically significant satisfaction. Cenobamate allowed a significant decrease in concomitant ASM, especially sodium channel blockers. TEAEs were reported in 43.1% of individuals, 85% of whom resolved or improved, with no new safety findings. CONCLUSION: In this analysis of patients with highly refractory focal epilepsy treated with cenobamate according to standard clinical practice, there was evidence of a high reduction in both seizure frequency and intensity, with a manageable safety profile.

Autonomy with responsibility ¿Is informed consent just a signature on a paper? Evaluation in patients who underwent spine's surgery.

PURPOSE: To evaluate the information that patients undergoing spine surgery truly receive and assimilate when they sign their informed consent documents. METHODS: This was a retrospective study on patients who underwent spine arthrodesis or spine discectomy. Patients were given a full explanation of the surgical technique to be employed and its potential risks before they were included on the surgical waiting list. Before surgery, they were asked to sign an informed consent form. The studied variables included whether patients read the informed consent form, whether they recalled the surgical technique used or the spinal segment operated, whether they were aware of the surgical risks involved, and if they had looked for information about their procedure elsewhere. Answers were analyzed by age and educational level. RESULTS: Of a total of 458 total patients, only 51.9% answered all the questions. Sixty-three percent of patients said they had read the informed consent document before surgery. Although 91.6% of patients were aware of the spine segment operated, only 73.5% remembered the surgical technique employed. A total of 63.9% of patients could recall the vertebral levels operated. 39.1% were not aware of the surgical risks involved, and only 16.0% of patients admitted having looked for additional information. A statistically significant correlation was found between the search for additional information and young age (p < 0.001) on the one hand, and high educational level on the other (p = 0.023). CONCLUSION: Even though obtaining informed consent is an important procedure before spinal surgery, almost 40% of the patients in this study underwent surgery without reading the informed consent document or being aware of the risks posed by the procedure.