First consensus document of waiting list prioritization for liver transplantation by the Spanish Society of Liver Transplantation (SETH).

Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.

Comparison of flipped learning and traditional lecture method for teaching digestive system diseases in undergraduate medicine: A prospective non-randomized controlled trial.

INTRODUCTION: This study examined the effects of a large-scale flipped learning (FL) approach in an undergraduate course of Digestive System Diseases. METHODS: This prospective non-randomized trial recruited 404 students over three academic years. In 2016, the course was taught entirely in a Traditional Lecture (TL) style, in 2017 half of the course (Medical topics) was replaced by FL while the remaining half (Surgical topics) was taught by TL and in 2018, the whole course was taught entirely by FL. Academic performance, class attendance and student's satisfaction surveys were compared between cohorts. RESULTS: Test scores were higher in the FL module (Medical) than in the TL module (Surgical) in the 2017 cohort but were not different when both components were taught entirely by TL (2016) or by FL (2018). Also, FL increased the probability of reaching superior grades (scores >7.0) and improved class attendance and students' satisfaction. CONCLUSION: The holistic FL model is more effective for teaching undergraduate clinical gastroenterology compared to traditional teaching methods and has a positive impact on classroom attendances.

[Effects of pharmaceutical counseling on the effectiveness of anticoagulation in patients with atrial fibrillation]. / Impacto de la atención farmacéutica en la calidad del tratamiento con acenocumarol en pacientes con fibrilación auricular.

BACKGROUND: Vitamin K antagonists such as acenocoumarol and warfarin are usually indicated for the treatment of Atrial Fibrillation (AF). The Therapeutic Range Time (TRT) is a quality of treatment indicator. Values greater than 65% are associated with significantly lower stroke and bleeding rates. Proper pharmaceutical care improves TRT. AIM: To evaluate the impact of pharmaceutical care in patients with AF treated with acenocoumarol. MATERIAL AND METHODS: We studied 41 patients using acenocoumarol for AF aged 71 ± 11 years (43% women). They received pharmaceutical counseling during 12 weeks. TRT was calculated retrospectively for the year before counseling and prospectively during the intervention period. RESULTS: After receiving pharmaceutical counseling TRT improved from 29% at baseline to 46% at the end of the intervention (p < 0.01). After pharmaceutical care, the adherence of patients to drug treatment improved from 27% at baseline to 85% at the end of the study. The user satisfaction survey of the pharmaceutical care received showed a high degree of patient satisfaction. CONCLUSIONS: Pharmaceutical care in patients with oral anticoagulant treatment improves TRT of anticoagulation. It is accepted and positively evaluated by patients.

[Anticoagulant efficacy of different pharmacological presentations of vitamin K antagonists]. / Eficacia en el control de la anticoagulación de los diferentes fármacos antagonistas de la vitamina K disponibles en Chile.

BACKGROUND: Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen. AIM: To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile. To contrast the overall anticoagulant control efficacy between acenocoumarol and warfarin. MATERIAL AND METHODS: The results of 69333 outpatient oral anticoagulation controls were analyzed. Patient were separated in groups according to the drug that they used. Subsequently, the proportions of controls outside the range for each of acenocoumarol and warfarin bioequivalent drugs were compared. Acenocoumarol non-bioequivalent drugs were also compared with the reference drug. Acenocoumarol was compared with warfarin. RESULTS: Acenocoumarol bioequivalent drugs and the reference drug had a similar proportion of controls outside the range (Odds ratios (OR) 0.812; 0.969; 0.974 and 0.963). Non-bioequivalent drugs had a higher proportion than the reference drug (OR 1.561 and 2.037). Both warfarin brands have a similar proportion of controls outside of the range (OR 1.050). Acenocoumarol compared to warfarin had a significant higher proportion of controls outside the range (OR 1.191). CONCLUSIONS: The pharmacological presentation of vitamin K antagonists could influence anticoagulant control. Therefore, it is not prudent to switch these presentations frequently.

[Comparison of point of care capillary international normalized ratio (INR) with INR measured in venous samples]. / Estudio comparativo de equipos INR capilar "point of care" versus INR venoso, en pacientes en tratamiento con antagonistas de vitamina K.

BACKGROUND: INR is used to monitor the treatment with vitamin K antagonists. A strategy to reduce waiting times for sampling is to measure INR in a capillary sample using a portable point of care (POC) type coagulometer. AIM: To evaluate the correlation of CoaguChek Pro II™, Xprecia™ and microINR™ with venous INR measured at the clinical laboratory and their ease of use. MATERIALS AND METHODS: Patients provided capillary and venous blood samples for parallel tests comparing Xprecia™ Stride with CoaguChek Pro II™ and with venous INR, microINR™ with CoaguChek Pro IITM and with venous INR. The devices' ease of use was assessed surveying the sampling staff. RESULTS: The three tested devices had good correlation coefficients with venous INR: CoaguChek Pro IITM 0.953 and 0.962; Xprecia™ of 0.912 and microINR™ of 0.932. The correlation coefficient of Xprecia™ with CoaguChek Pro IITM was 0.937 and microINR™ with CoaguChek Pro IITM was 0.976. CONCLUSIONS: CoaguChek Pro IITM, Xprecia™ and microINR™ results had a good correlation coefficient with INR measured at the laboratory. Our results indicate that, in the hands of trained users, POC-type coagulometers are reliable and acceptable for routine use in anticoagulant treatment control.

[Intravenous thrombolysis for ischemic stroke: Experience in 54 patients]. / Trombolisis intravenosa en accidente cerebro vascular isquémico agudo en un hospital público de Chile: Análisis prospectivo de 54 casos.

BACKGROUND: Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) reduces disability in patients with ischemic stroke. However, its implementation in Chilean public general hospitals has been slow and faces some difficulties. AIM: To analyze the results of an intravenous thrombolysis protocol implementation in a public general hospital. MATERIAL AND METHODS: During a lapse of 28 months a standardized protocol for intravenous thrombolysis implemented in the emergency room of a public hospital, was prospectively evaluated. Fifty four patients with ischemic stroke were treated and assessed three months later as outpatients. RESULTS: At three months of follow-up, 66.4% of patients subjected to thrombolysis had a favorable evolution, defined as having 0 to 1 points in the modified Rankin scale. Intracerebral hemorrhage rate was 11.1%, including 5.5% of symptomatic intracerebral hemorrhage. Four percent of patients had systemic bleeding complications after thrombolysis. The mortality rate was 14.8%. CONCLUSIONS: The success rates, mortality, and complications rate were comparable to the results obtained in international studies, despite of the absence of a stroke unit to manage stroke and its complications.

[Effect of VKORC1 and CYP2C9 variants on dosage of oral anticoagulants in Chilean individuals]. / Efecto de las variantes de VKORC1 y CYP2C9 sobre la dosis de anticoagulantes orales en individuos chilenos.

BACKGROUND: The dose of oral anticoagulants (OAC) shows great variability among patients. Pharmacogenetic studies have shown that common variants in genes CYP2C9 (*2 and *3) and VKORC1 (-1639G>A) are associated with lower requirements of OAC. AIM: To study the association between average maintenance doses of oral anticoagulant therapy required to maintain a stable INR and CYP2C9 and VKORC1 gene variants in Chilean adults. MATERIAL AND METHODS: Prospective study of patients on anticoagulant treatment and with a stable international normalized ratio (INR) for prothrombin time for at least three months. Patients were classified as having high or low acenocoumarol or warfarin requirements. Peripheral blood DNA genotyping was performed by polymerase chain reaction and restriction fragment polymorphism or sequencing and electrophoresis. RESULTS: The study included 185 patients, 125 on acenocoumarol and 60 on warfarin. Patients with VKORC1-1639A allele were more likely to require lower doses of both drugs than patients with the G allele (Odds ratio [OR] for acenocoumarol 9.06, and OR for warfarin = 18.7). There was no association between CYP2C9*2 and*3 and acenocoumarol or warfarin requirements. CONCLUSIONS: There is an association between VKORC1-1639A variant and anticoagulant doses.

[Management of ischemic strokes derived from intraventricular thrombi: report of two cases]. / Accidente cerebrovascular isquémico en pacientes con trombo intracavitario: experiencia con tratamientos distintos en fase aguda.

The origin of 20% of ischemic strokes is a left ventricular thrombus. We report two patients with strokes originating from cardiac thrombi, treated in two different ways. A 42-year-old diabetic man admitted with a left parietal and occipital stroke. An echocardiogram showed a left ventricular thrombus. The patient was subjected to a surgical cardiac revascularization procedure and left ventricular thrombectomy. The postoperative evolution was uneventful and the patient was discharged on oral anticoagulation. On ambulatory follow up, no neurological deterioration was evidenced. A 38-year-old male admitted with an acute ischemic stroke, was subjected to thrombolysis with human plasminogen activator. An echocardiogram showed a left ventricular thrombus, considered the cause of the stroke. The patient was anticoagulated with heparin and discharged ten days after admission with oral anticoagulation. A new echocardiogram performed one month later, did not show the left ventricular thrombus.

Educational agents and institutions called into action in suicide prevention, intervention, and postvention.

Introduction: Suicide is the second leading cause of death in the 15 to 29 age group worldwide, and is a severe public health problem. Adolescent and young adult individuals attend educational institutions which can play an essential role in detecting and preventing suicide. For this reason, the purpose of this research is to identify what educational institutions and agents are called into action in suicide prevention, intervention, and postvention. Methods: The method of systematic review of the literature based on the PRISMA protocol was used. The review protocol was registered in PROSPERO (PROSPERO 2020 CRD42020189127). The systematic review yielded 66 articles published between 1990 and February 2023. Results: The results show that a wide variety of educational stakeholders are required to intervene for suicide prevention, interventions and postvention between primary education and college. The study describes the different programs that have been provided, the countries in which they have been implemented and the agents who have been targeted. It also identifies gaps in the research on suicide in the educational field. Discussion: Overall, educational suicide initiatives report positive effects on participants' understanding, attitudes, and beliefs regarding suicide and suicide prevention, although some studies have expressed some caution.

Our experience in the short-term diagnostic-therapeutic management of the patient with anal dysplasia.

INTRODUCTION: Anal intraepithelial neoplasia (AIN) is a premalignant lesion of anal squamous cell carcinoma. HIV-positive males who have sex with males, are the most affected at-risk population. Cytology and anuscopy are the best accepted methods for its diagnosis, although it is controversial which patients should complete it with a biopsy. Neither which patients should undergo treatment nor which is the best treatment is not well established. With this study, we would like to present our experience in the diagnostic-therapeutic management of AIN in the short term. METHODS: Retrospective observational study of patients at risk of AIN with altered anal cytology who underwent high-resolution anuscopy with biopsy. After histological confirmation of dysplasia, they started treatment with trichloroacetic acid. Its effectiveness was verified by subsequent cytology. The demographic variables of the sample and the results of both diagnostic and treatment tests were analyzed. RESULTS: The majority were HIV-positive males (104/115) and 50% had sexual relations with other men. We included 115 patients with altered anal cytology, of whom 92% had dysplasia on biopsy. 97% with atypia of uncertain significance on cytology had histological dysplasia. Cytology normalized after treatment in 60% of patients. CONCLUSION: Early detection of AIN should be routinely considered in known at-risk populations. Any cytological abnormality should be biopsied. Tricholoroacetic acid can be an effective treatment achieving a high percentage of regression, although currently, the information we have is of low level of evidence.

Immunomodulatory Role of CB2 Receptors in Emotional and Cognitive Disorders.

Emotional behavior, memory, and learning have been associated with alterations in the immune system in neuropsychiatric and neurodegenerative diseases. In recent years, several studies pointed out the involvement of the cannabinoid receptor 2 (CB2r) in the immune system and the regulation of inflammation. This receptor is widely distributed in different tissues and organs with higher expression in spleen and immune system cells. However, CB2r has also been detected in several brain areas and different brain cell types, such as neurons and glia. These findings suggest that CB2r may closely relate the immune system and the brain circuits regulating inflammation, mood, and cognitive functions. Therefore, we review the studies that may help elucidate the molecular bases of CB2r in regulating inflammation in different brain cells and its role in the pathophysiology of psychiatric and neurodegenerative disorders.

Inflammatory Biomarkers in Addictive Disorders.

Substance use disorders are a group of diseases that are associated with social, professional, and family impairment and that represent a high socio-economic impact on the health systems of countries around the world. These disorders present a very complex diagnosis and treatment regimen due to the lack of suitable biomarkers supporting the correct diagnosis and classification and the difficulty of selecting effective therapies. Over the last few years, several studies have pointed out that these addictive disorders are associated with systemic and central nervous system inflammation, which could play a relevant role in the onset and progression of these diseases. Therefore, identifying different immune system components as biomarkers of such addictive disorders could be a crucial step to promote appropriate diagnosis and treatment. Thus, this work aims to provide an overview of the immune system alterations that may be biomarkers of various addictive disorders.

Sexual orientation, gender identity and gender expression-based violence in Catalan universities: qualitative findings from university students and staff.

BACKGROUND: Hate crimes have raised in Spain and the gender and sexuality-based conflicts persist worldwide which leads to this problem having an effect on health and wellbeing. Following a focus of transforming Higher Education Institutions, this research analysed the problem that affects undergraduate students in six Spanish universities. The research goal is to improve the life quality of lesbian, gay, bisexual, transgender, queer and intersex university students, breaking the silence that exists around the violence that this group suffer in Catalonia, Spain. METHODS: Following the Communicative Methodology, this study has identified violence based on sexual orientation, gender identity or gender expression in the target universities and provided guidelines to improve anti-discrimination protocols. A qualitative method has reached experiences of university students, heads of equality commissions, professors and administrative staff regarding this conflict. Focussing on the qualitative research tools, 30 semi-structured interviews were conducted with university students and staff around issues related to the violence against lesbian, gay, bisexual transgender, queer and intersex students: 1) perception of violence and discrimination, 2) institutional measures, 3) actions against violence. An analysis of exclusionary and transformative dimensions was used to identify emergent themes. RESULTS: We have identified two dimensions for the analysis given their impact in contributing or overcoming violence: exclusionary and transformative. A wide range of forms of violence on the grounds of sexual orientation, gender identity and gender expression perpetrated at universities have been identified as exclusionary facts and described by participants in the study. Equality commissions have not received reports of violence based on sexual orientation, gender identity or gender expression, and university staff shows certain unfamiliarity regarding the measures and politics to prevent and intervene in cases of violence against the lesbian, gay, bisexual, transgender, queer and intersex community. Among the results identified as transformative are the ways through which actions of lesbian, gay, bisexual, transgender, queer and intersex groups against violence and the professors' commitment to intervene have a relevant impact on student's wellbeing. An improvement and implementation of anti-discrimination protocols with mandatory applicability has also been documented. CONCLUSIONS: Findings highlight the need of collecting more evidence that contributes to the improvement of protocols, measures and politics to protect all the members of the university community. A better understanding of violence based on sexual orientation, gender identity and gender expression in HEI's may guide national and international governments to improve the health and well-being of lesbian, gay, bisexual, transgender, queer and intersex persons.

Identification of Occult Adenomas in Primary Hyperparathyroidism With 18F-fluorocholine PET/CT. / Identificación de adenomas ocultos en hiperparatiroidismo primario con PET-TC 18F-fluorocolina.

INTRODUCTION: Single parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHP) in our population. Parathyroidectomy is still the only potentially curative treatment and requires preoperative localization imaging studies to perform selective surgery. In patients with negative results on conventional tests, PET/CT has demonstrated higher sensitivity rates. METHODS: A prospective cohort study was designed, including 34 patients diagnosed with PHP between 2017 and 2019, candidates for surgery with negative preoperative localization tests with scintigraphy and MIBI SPECT/CT. All patients underwent PET/CT with 18F-Fluorocholine. The clinical, biochemical and postoperative outcome results were compared with a control group of 30 patients with positive standard tests. RESULTS: Hyperfunctional parathyroid tissue was detected in 85% of the patients that had undergone choline PET/CT. The selective resection of the adenoma identified in these patients achieved curative criteria in 87% of the cases without undergoing bilateral cervical surgical exploration. The preoperative levels of PTH, calcemia and gland weight were significantly lower in this group compared to the control group. No differences were identified in cure criteria or approach between the 2groups. CONCLUSION: In our study, choline PET/CT showed higher detection rates compared to the gold standard. The increase provides the opportunity to perform unilateral selected adenoma resection, especially in patients with smaller adenomas associated with lower calcemia and PTH levels and patients with previous cervical surgery.

A Pharmacogenetically Guided Acenocoumarol Dosing Algorithm for Chilean Patients: A Discovery Cohort Study.

BACKGROUND: Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables. OBJECTIVE: The authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patients. METHODOLOGY: DNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0-3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for VKORC1 (rs9923231), VKORC1 (rs7294), GGCx (rs11676382), CYP4F2 (rs2108622), ABCB1 (rs1045642), CYP2C9*2 (rs1799853), ApoE (rs429358), and CYP2C9*3 (rs1057910). RESULTS: The clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were VKORC1 (rs9923231), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), explaining for another 37% of the variability. CONCLUSION: We developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included VKORC1, CYP2C9*2, and CYP2C9*3 polymorphisms, as well as age, sex, BMI, and initial INR.

Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients.

Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. It is well known that polymorphisms in pharmacokinetic and pharmacodynamic proteins related to coumarins (especially warfarin) influence response to these drugs. This work analyzed the impact of CYP2C19*2 (rs4244285), CYP1A2*1F (rs762551), GGCx (rs11676382), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), CYP4F2 (rs2108622), VKORC1 (rs9923231), VKORC1 (rs7294), CYP3A4*1B (rs2740574), and ABCB1 (rs1045642) polymorphisms on time to therapeutic range for oral anticoagulants in 304 Chilean patients. CYP2C9*3 polymorphisms were associated with time to therapeutic range for acenocoumarol in Chilean patients, and the CYP4F2 TT genotype, MDR1 A allele, CYP1A2 A allele, and CYP3A4T allele are promising variants that merit further analysis. The presence of polymorphisms explained only 4.1% of time to therapeutic range for acenocoumarol in a multivariate linear model. These results improve our understanding of the basis of ethnic variations in drug metabolism and response to oral anticoagulant therapy. We hope that these findings will contribute to developing an algorithm for VKA dose adjustment in the Chilean population in the near future, decreasing the frequency of stroke, systemic embolism, and bleeding-related adverse events.

Anticoagulation Management With Coumarinic Drugs in Chilean Patients.

Warfarin and acenocoumarol are used in various cardiovascular disorders to improve the prognosis of patients with thromboembolic disease. However, there is a lack of substantial efficacy and safety data on antithrombotic prophylaxis in several countries, particularly in Latin America. The aim of this study was to provide information about the efficacy of anticoagulants in Chilean patients. Data were collected from databases of the Western Metropolitan Health Service, Santiago, Chile. We identified 6280 records of patients receiving anticoagulant treatment. The three most common diagnoses were rhythm disorder (43.7%), venous thrombosis (22%), and valvular prosthesis (10.7%). The majority of patients (98.5%) received acenocoumarol while 1.5% of patients received warfarin, at weekly therapeutic doses of 13.6 mg and 30.4 mg, respectively. For total diagnoses, the median time in the therapeutic range was 50%. However, better results, 66.7%, were observed when a telemedicine strategy was used only in Santiago Province. Our findings emphasize that in Chile, where the number of patients receiving anticoagulant treatment increases every year, telemedicine, by committed teams, improves the use of oral anticoagulants and is able to increase quality indicators of anticoagulant treatment care.

Dequalinium induces cell death in human leukemia cells by early mitochondrial alterations which enhance ROS production.

Dequalinium (DQA) has been proposed as a selective antitumoral agent due to its preferential accumulation in mitochondria of cancer cells. Our aim was a better understanding of DQA cytotoxicity. DQA-induced NB4 and K562 cell alterations are initiated within the first 30 min of treatment at a high DQA concentration with a mitochondrial membrane depolarization. Cytochrome c release to cytoplasm, superoxide anion overproduction and ATP depletion in NB4 cells induce, 16 h later, apoptosis by a typical caspase-9/caspase-3-dependent intrinsic pathway. K562 cells were more resistant to the DQA effect than NB4 cells, remaining viable for longer time periods.