Prognostic Role of Tissue Iron Deficiency Measured by sTfR Levels in Heart Failure Patients without Systemic Iron Deficiency or Anemia.

Background. Iron deficiency (ID) is a significant, high-prevalence comorbidity in chronic heart failure (HF) that represents an independent predictor of a worse prognosis. However, a clear-cut diagnosis of ID in HF patients is not assured. The soluble transferrin receptor (sTfR) is a marker that reflects tissue-level iron demand and may be an early marker of ID. However, the impact of sTfR levels on clinical outcomes in non-anemic HF patients with a normal systemic iron status has never been evaluated. Methods. This is a post hoc analysis of an observational, prospective cohort study of 1236 patients with chronic HF of which only those with normal hemoglobin levels and a normal systemic iron status were studied. The final cohort consisted of 215 patients. Tissue ID was defined as levels of sTfR > 75th percentile (1.65 mg/L). Our aim was to describe the association between sTfR and clinical outcomes (all-cause death and HF hospitalization) and to explore its association with a wide array of serum biomarkers. Results. The sTfR level (HR 1.48, 95% CI 1.13-1.96, p = 0.005) and tissue ID (HR 2.14, 95% CI 1.22-3.75, p = 0.008) was associated with all-cause death. However, we found no association between sTfR levels and the risk of HF hospitalization. Furthermore, high sTfR levels were associated with a worse biomarker profile indicating myocardial damage (troponin and NT-proBNP), systemic inflammation (CRP and albumin), and impaired erythropoiesis (erythropoietin). Conclusions. In this cohort, the presence of tissue ID defined by sTfR levels is an independent factor for all-cause death in patients with normal systemic iron parameters.

Directing novel ChoKα1 inhibitors using MamC-mediated biomimetic magnetic nanoparticles: a way to improve specificity and efficiency.

Targeting phospholipid biosynthesis, specifically phosphatidylcholine (PC), which is enhanced in tumor cells, has been proven a suitable antitumor strategy. In fact, the overexpression of the choline kinase α1 (ChoKα1) isoform has been found in malignant cells and tumors, thus becoming an excellent antitumor target. ChoKα1 inhibitors are being synthesized at the present that show a large inhibitory activity. Two of them have been chosen in this study as representatives of different structural families: a biscationic biphenyl derivative of thieno[3,2-d]pyrimidinium substituted with a cyclic amine (here referred to as Fa22) and a biscationic biphenyl thioethano derivative of 7-chloro-quinolinium substituted with a pyrrolidinic moiety (here referred to as PL48). However, the potential use of these types of compounds in systemic treatments is hampered because of their low specificity. In fact, to enter the cell and reach their target, these inhibitors use choline transporters and inhibit choline uptake, being that one of the causes of their toxicity. One way to solve this problem could be allowing their entrance into the cells by alternative ways. With this goal, MamC-mediated magnetic nanoparticles (BMNPs), already proven effective drug nanocarriers, have been used to immobilize Fa22 and PL48. The idea is to let BMNPs enter the cell (they enter the cell by endocytosis) carrying these molecules, and, therefore, offering another way in for these compounds. In the present study, we demonstrate that the coupling of Fa22 and PL48 to BMNPs allows these molecules to enter the tumoral cell without completely inhibiting choline uptake, so, therefore, the use of Fa22 and PL48 in these nanoformulations reduces the toxicity compared to that of the soluble drugs. Moreover, the nanoassemblies Fa22-BMNPs and PL48-BMNPs allow the combination of chemotherapy and local hyperthermia therapies for a enhanced cytotoxic effect on the tumoral HepG2 cell line. The consistency of the results, independently of the drug structure, may indicate that this behavior could be extended to other ChoKα1 inhibitors, opening up a possibility for their potential use in clinics.

Triple negative breast cancer migration is modified by mitochondrial metabolism alteration induced by natural extracts of C. spinosa and P. alliacea.

Tumor metabolism is a crucial aspect of cancer development, and mitochondria plays a significant role in the aggressiveness and metastasis of tumors. As a result, mitochondria have become a promising therapeutic target in cancer treatment, leading to the development of compounds known as mitocans. In our group, we have consolidated the search of anticancer therapies based on natural products derived from plants, obtaining extracts such as P2Et from Caesalpinia spinosa and Anamu-SC from Petiveria alliacea, which have been shown to have antitumor activities in different cancer models. These extracts, due to their complex molecular composition, can interfere with multiple functions during tumor progression. To better understand how these natural products operate (P2Et and Anamu-SC), we constructed a model using 4T1 murine breast cancer cells with reduced expression of genes associated with glycolysis (Hexokinase-2) and mitochondrial function (Cqbp). The results indicate that the cells were more sensitive to the Anamu-SC extract, showing significant decreases in glucose consumption, ATP production, and oxygen consumption rate. Additionally, we observed changes in mitochondrial function, which reduced the cells' ability to migrate, particularly when C1qbp was silenced. This triple-negative breast cancer model allows us to identify potential natural products that can modulate tumor cell metabolism.

Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic neoplasm: a HARMONY Alliance study.

Lenalidomide (LEN) can induce red blood cell-transfusion independence (RBC-TI) in 60-70% of del(5q) myelodysplastic neoplasm (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN while RBC-transfusion independent. We enrolled 118 patients with IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis, RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved again RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients who reached RBC-TI allows prolonged maintenance of TI in a large subset of patients.

The role of emotion regulation through mindfulness in oncological patients: A pilot study.

BACKGROUND: Traditional MBSR or MBTC programs do not delve deeply enough into emotional regulation, which is especially relevant in oncological patients. The aim of this study was to analyze the benefits of a mindfulness-based emotion regulation program in adult oncological patients. METHOD: Psycho-oncologists from the AECC developed a mindfulness-based emotion regulation program. The Five Facet Mindfulness Questionnaire (FFMQ), Trait Meta-Mood Scale (TMMS), and Hospital Anxiety and Depression Scale (HADS) were administered before and after the program. A single-group pre-post test design with repeated measures was employed, utilizing the General Linear Model. RESULTS: Ninety-seven adult cancer patients completed the pre- and post-program assessments. Statistically significant improvements were observed in all FFMQ subscales, increased clarity of emotional discrimination, mood repair, and statistically significant reductions in anxiety and depressive symptoms. CONCLUSIONS: Regardless of the phase of the disease, the results of this study suggest that emotional regulation may improve and anxiety and depressive symptomatology decrease after a mindfulness-based emotion regulation program in oncological patients.

Treatment characteristics and outcomes in lower-risk, non-del(5q) myelodysplastic syndromes: findings from a medical record review in the USA, Canada and Europe.

Aim: To assess treatment patterns and outcomes in patients with non-del(5q) lower-risk myelodysplastic syndromes. Methods: Patient medical records were reviewed in the USA, Canada (CAN), UK and the EU. Results: Analysis included 119 patients in the USA/CAN (median age, 61.5 years) and 245 patients in the UK/EU (median age, 67.3 years). Most patients received erythropoiesis-stimulating agents (ESAs) as first-line (1L) therapy (USA/CAN: 89.0%; UK/EU: 90.2%). A substantial proportion of 1L erythropoiesis-stimulating agent-treated patients were transfusion dependent before 1L (USA/CAN: 37.1%; UK/EU: 51.2%); a small percentage of these patients achieved transfusion independence during 1L therapy (USA/CAN: 2.8%; UK/EU: 14.4%). Conclusion: These findings highlight an unmet need for more effective treatments among patients with non-del(5q) lower-risk myelodysplastic syndromes.

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Efficacy of a Mobile Health App (eMOTIVA) Regarding Compliance With Cardiac Rehabilitation Guidelines in Patients With Coronary Artery Disease: Randomized Controlled Clinical Trial.

BACKGROUND: Cardiac rehabilitation is fundamental among patients recovering from a coronary event, and mHealth technology may constitute a useful tool that provides guidelines based on scientific evidence in an entertaining, attractive, and user-friendly format. OBJECTIVE: This study aimed to compare the efficacy of an mHealth intervention involving the eMOTIVA app and that of usual care regarding compliance with cardiac rehabilitation guidelines in terms of lifestyle, cardiovascular risk factors, and satisfaction among patients with acute coronary syndrome. METHODS: A randomized controlled clinical trial with a parallel group design was conducted. It included 300 patients (mHealth group, 150; control group, 150) who underwent percutaneous coronary intervention for acute coronary syndrome. Both groups underwent evaluations initially (during hospitalization) and after 3 and 6 months (face-to-face consultations). The eMOTIVA app incorporates a virtual classroom providing audio and video information about a healthy lifestyle, a section for self-recording cardiovascular risk factors, and a section for feedback messages and gamification. The primary outcome variables were (1) adherence to the Mediterranean diet and the frequency of consumption of food; (2) physical activity level, sedentary time, and exercise capacity; (3) smoking cessation and nicotine dependence; (4) level of knowledge about cardiovascular risk factors; and (5) app satisfaction and usability. RESULTS: The study analyzed 287 patients (mHealth group, 145; control group, 142). Most participants were male (207/300, 69.0%), and the mean age was 62.53 (SD 8.65) years. Significant improvements were observed in the mHealth group compared with the control group at 6 months in terms of (1) adherence to the Mediterranean diet (mean 11.92, SD 1.70 vs 8.92, SD 2.66 points; P<.001) and frequency of eating foods (red meat [≤1/week]: 141/143, 97.9% vs 96/141, 68.1%; industrial pastries [<2/week]: 129/143, 89.6% vs 80/141, 56.8%; oily fish [≥2/week]: 124/143, 86.1% vs 64/141, 41.4%; vegetables [≥2/day]: 130/143, 90.3% vs 78/141, 55.3%; fruit [≥2/day]: 128/143, 88.9% vs 85/141, 60.2%; all P<.001); (2) physical activity (mean 2112.66, SD 1196.67 vs 1372.60, SD 944.62 metabolic equivalents/week; P<.001) and sedentary time (mean 8.38, SD 1.88 vs 9.59, SD 2.09 hours; P<.001); (3) exercise capacity (distance: mean 473.49, SD 102.28 vs 447.25, SD 93.68 meters; P=.04); and (4) level of knowledge (mean 117.85, SD 3.83 vs 111.00, SD 7.11 points; P<.001). App satisfaction was high (mean 42.53, SD 6.38 points), and its usability was excellent (mean 95.60, SD 4.03 points). CONCLUSIONS: With the eMOTIVA app, favorable results were obtained in the intervention group in terms of adherence to the Mediterranean diet, frequency of eating certain foods, physical activity, sedentary time, exercise capacity, knowledge level, systolic blood pressure, heart rate, and blood sugar level. Furthermore, participants reported high app satisfaction and rated its usability as excellent. Thus, this innovative tool is very promising. TRIAL REGISTRATION: ClinicalTrials.gov NCT05247606; https://clinicaltrials.gov/study/NCT05247606.

The Weight of Bariatric Surgery: Wernicke-Korsakoff Syndrome after Vertical Sleeve Gastrectomy-A Case Series.

In this case series, the simultaneous occurrence of Wernicke's encephalopathy (WE) and dry beriberi was reported in three patients who underwent vertical sleeve gastrectomy (VSG) between May 2021 and May 2023. All patients were obese women who underwent vertical sleeve gastrectomy (VSG) without immediate postoperative complications, but two weeks later, hyperemesis and subsequent encephalopathy with ocular movement abnormalities and weakness were observed over the following thirty days. Patients were referred to neurology, where due to the high suspicion of WE, thiamine replacement therapy was initiated; meanwhile, diagnostic neuroimaging and blood tests were conducted. Neurological and psychiatric evaluations and neuroconduction studies were performed to assess the clinical evolution and present sequelae. One year after diagnosis, all patients exhibited affective and behavioral sequelae, anterograde memory impairment, and executive functioning deficits. Two patients met the criteria for Korsakoff syndrome. Additionally, peripheral nervous system sequelae were observed, with all patients presenting with sensorimotor polyneuropathy. In conclusion, Wernicke's encephalopathy requires a high diagnostic suspicion for timely intervention and prevention of irreversible sequelae, which can be devastating. Therefore, raising awareness among medical professionals regarding the significance of this disease is essential.

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.

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.

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.

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.

Análisis de conglomerados usando la distancia Euclidiana en el comportamiento de linfocitos T CD4

Introducción: La infección por el virus de inmunodeficiencia humana (VIH) y su evolución a través de cuatro décadas (crónica) ha orillado a médicos a estudiar el comportamiento de los linfocitos T CD4 con ayuda ramas como la estadística y matemáticas. Objetivo: Describir el comportamiento del conteo de linfocitos T CD4 en el tiempo a través del aprendizaje no supervisado. Métodos: Estudio tipo cohorte retrospectiva, se realizó una búsqueda de cuantificaciones de linfocitos T CD4 continuas a través del periodo de estudio establecido (2018-2022) en el expediente electrónico, en la presente investigación no se tuvo contacto con los pacientes. Resultados: Existe un ascenso en los valores numéricos promedio de linfocitos T CD4 a lo largo del estudio y se empieza a estabilizar entre los grupos hacia un recuento sobre los 500 linfocitos, lo cual refleja un estado inmunológico bueno a través del tiempo. Conclusión: Identificamos estabilidad en el seguimiento temporal, lo cual puede contribuir a un patrón de memoria por lo que sugerimos un análisis fractal extenso.

Introduction: Infection with the human immunodeficiency virus (HIV) and its evolution over four decades (chronic) has led doctors to study the behavior of CD4 T lymphocytes with the help of branches such as statistics and mathematics. Objective: To describe the behavior of the CD4 T lymphocyte count over time through unsupervised learning. Methods: Retrospective cohort type study, a search for continuous CD4 T lymphocyte quantifications throughout the established study period (2018-2022) was performed in the electronic file, in the present investigation there was no contact with the patients. Results: There is an increase in the average numerical values of CD4 T lymphocytes throughout the study and it begins to stabilize between the groups towards a count of over 500 lymphocytes, which reflects a good immune status over time. Conclusion: We identified stability in temporal tracking, which may contribute to a memory pattern, so we suggest an extensive fractal analysis.

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.