Effectiveness of smoking cessation intervention based on the ABC Approach in patients with TB.

SETTING: Urban setting in the Philippines. OBJECTIVE: To assess the effectiveness of the ABC Approach developed by The Union as a tobacco-smoking cessation intervention for TB patients at a primary healthcare level in an urban setting in the Philippines. DESIGN: We set up an intervention group whose patients with TB received the ABC approach and a control group of patients with TB receiving only routine health education in Manila, The Philippines. We collected smoking status and the domestic secondhand-smoking (SHS) status data from patients with TB at months 0, 2, 4, 6, 8, and 12. TB treatment outcome data were also collected. RESULTS: Patients with TB (n = 2,174) were enrolled upon TB registration. Smoking rates were consistently low in the intervention group (3.9% vs. 8.7% at Month 6). The odds ratios of both tobacco-smoking status and domestic SHS status in the intervention group were significantly lower than those in the control group (tobacco-smoking status: P < 0.001, domestic SHS status: P < 0.01). TB treatment success rates were similar between the groups (85.0% vs. 87.3%; P = 0.201). CONCLUSION: The ABC approach successfully reduced tobacco-smoking rates, maintained low domestic SHS rates and TB treatment success rates in the Philippines.

CADRE: Cadre urbain aux Philippines. OBJECTIF: Évaluer l'efficacité de l'approche ABC développée par L'Union en tant qu'intervention de sevrage tabagique pour les patients atteints de TB au niveau des soins de santé primaires en milieu urbain aux Philippines. MÉTHODE: Nous avons mis en place un groupe d'intervention dont les patients atteints de TB ont reçu l'approche ABC et un groupe témoin de patients atteints de TB ne recevant qu'une éducation sanitaire de routine à Manille, aux Philippines. Nous avons recueilli des données sur le statut tabagique et le statut de tabagisme passif (SHS, pour l'anglais « secondhand-smoking ¼) domestique des patients atteints de TB aux mois 0, 2, 4, 6, 8 et 12. Des données sur les résultats du traitement de la TB ont également été recueillies. RÉSULTATS: Les patients atteints de TB (n = 2 174) ont été recrutés lors de l'enregistrement de la TB. Les taux de tabagisme étaient constamment faibles dans le groupe d'intervention (3,9% contre 8,7% au 6e mois). Les rapports de cotes du tabagisme et du statut SHS canadien dans le groupe d'intervention étaient significativement inférieurs à ceux du groupe témoin (tabagisme : P < 0,001, statut SHS national : P < 0,01). Les taux de réussite du traitement de la TB étaient similaires entre les groupes (85,0% contre 87,3% ; P = 0,201). CONCLUSION: L'approche ABC a permis de réduire les taux de tabagisme, de maintenir de faibles taux nationaux de SHS et de taux de réussite du traitement de la TB aux Philippines.

Changes in the Location of Cutaneous Melanoma Over the Past 30 Years. A Retrospective Observational Study. / Cambios en la localización del melanoma cutáneo en los últimos 30 años. Estudio observacional retrospectivo.

BACKGROUND: The location of cutaneous melanoma is associated with photoexposure. OBJECTIVES: To retrospectively analyze changes in the location of cutaneous melanoma over the past 30 years. PATIENTS AND METHODS: All patients treated at our hospital for cutaneous melanoma from 1988 through 2017 were prospectively collected. Data obtained in cases diagnosed from 1988 through June 2006 were compared to those diagnosed from July 2006 through 2017. RESULTS: A total of 1,937 patients (876 men and 1061 women; median age, 57 years; interquartile range 27) were diagnosed with primary cutaneous melanoma. The location of melanoma was head and neck (470 cases), trunk (745 cases), upper limbs (239 cases), and lower limbs (483 cases). From July 2006 through 2017 we detected an increase in the incidence of head and neck melanomas (19.9% vs 28.6%, p <0.001). A drop in the incidence of melanomas located in the lower extremities was also seen in women (39.8% vs 30.4%, p <0.001), and in the trunk men (57.5% vs 47.3%, p=0.003). In the multivariate analyses, only the decrease in melanomas located in lower extremities in women remained significant. CONCLUSION: The increased incidence of head and neck melanomas in both sexes and the decrease in trunk melanomas in men can be attributed to the aging of our population. The reduction in the incidence of melanomas in the lower extremities in women could be associated with changes in photoexposure patterns. Analyzing the factors possibly associated with these changes would contribute to better understanding the pathogenesis of cutaneous melanoma for prevention purposes.

Influence of lymphopenia on long-term mortality in septic shock, a retrospective observational study.

BACKGROUND AND OBJECTIVE: The diagnosis of infection, to diagnose septic shock, has been qualified by leukocyte counts and protein biomarkers. Septic shock mortality is persistently high (20%-50%), and rising in the long term. The definition of sepsis does not include leukocyte count, and lymphopenia has been associated with its mortality in the short term. Immunosuppression and increased mortality in the long term due to sepsis have not been demonstrated. The aim is to relate the occurrence of lymphopenia and its lack of recovery during septic shock with mortality at 2 years. PATIENTS AND METHODS: Cohort of 332 elderly patients diagnosed with septic shock. Mortality at 28 days and 2 years was analysed according to leukocyte, neutrophil, and lymphocyte counts, and the ability to recover from lymphopenia (LRec). RESULTS: A total of 74.1% of patients showed lymphopenia, and 73.5% did not improve during ICU stay. Mortality was 31.0% and 50.3% at 28 days and 2 years, respectively. Lymphopenia was a predictor of early mortality (OR 2.96) and LRec of late mortality (OR 3.98). Long-term mortality was associated with LRec (HR 1.69). CONCLUSIONS: In elderly patients with septic shock, 28-day mortality is associated with lymphopenia and neutrophilia, and LRec with 2-year mortality; this may represent 2 distinct phenotypes of behaviour after septic shock.

Efficient multi-fidelity computation of blood coagulation under flow.

Clot formation is a crucial process that prevents bleeding, but can lead to severe disorders when imbalanced. This process is regulated by the coagulation cascade, a biochemical network that controls the enzyme thrombin, which converts soluble fibrinogen into the fibrin fibers that constitute clots. Coagulation cascade models are typically complex and involve dozens of partial differential equations (PDEs) representing various chemical species' transport, reaction kinetics, and diffusion. Solving these PDE systems computationally is challenging, due to their large size and multi-scale nature. We propose a multi-fidelity strategy to increase the efficiency of coagulation cascade simulations. Leveraging the slower dynamics of molecular diffusion, we transform the governing PDEs into ordinary differential equations (ODEs) representing the evolution of species concentrations versus blood residence time. We then Taylor-expand the ODE solution around the zero-diffusivity limit to obtain spatiotemporal maps of species concentrations in terms of the statistical moments of residence time, , and provide the governing PDEs for . This strategy replaces a high-fidelity system of N PDEs representing the coagulation cascade of N chemical species by N ODEs and p PDEs governing the residence time statistical moments. The multi-fidelity order( p ) allows balancing accuracy and computational cost, providing a speedup of over N/p compared to high-fidelity models. Using a simplified coagulation network and an idealized aneurysm geometry with a pulsatile flow as a benchmark, we demonstrate favorable accuracy for low-order models of p = 1 and p = 2. These models depart from the high-fidelity solution by under 16% ( p = 1) and 5% ( p = 2) after 20 cardiac cycles. The favorable accuracy and low computational cost of multi-fidelity models could enable unprecedented coagulation analyses in complex flow scenarios and extensive reaction networks. Furthermore, it can be generalized to advance our understanding of other systems biology networks affected by blood flow.

Traditional sexing methods and external egg characteristics combination allow highly accurate early sex determination in an endangered native turkey breed.

Early sex determination methods are not only crucial in the worldwide massive poultry industry, but also for small-holder producers. The profitability of sexing techniques must be accounted for when aiming to boost management, nutrition, and conservation practices in endangered poultry breeds. This becomes pivotal when the local breed dealt with belongs to an understudied species, such as the turkey. So, the main objective of this study is to identify which method combination may report a higher likelihood of successful sex determination in poults across the three-pattern varieties of the Andalusian turkey breed. A total of 84 one to two days old Andalusian turkey poults (42 black, 28 black-roan, and 14 bronze-roan) were evaluated in this study. Sex determination was performed using 15 methods, which included testing external egg metrics and eggshell color, poult morphological appraisal and phaneroptics, and behavioral traits. Possible differences across plumage varieties and the interaction between sex and plumage were observed when external egg quality was measured. Sex determination through behavioral methods in black base feathered (black and black-roan) male sex individuals showed seven times higher sensitivity when compared to the rest of the studied individuals (χ2 = 7.14, df = 1, P < 0.01). In contrast, for the black-roan plumage females, the method based on the color of down feathers was approximately four times more sensitive (χ2 = 3.95, df = 1, P ≤ 0.05). For the bronze-roan pattern, none of the sexing techniques was reported to efficiently predict sex itself. However, the most proper method combination to determine sex, independent of plumage color, was physical external egg characteristics, the color of down feathers, and behavioral approaches ("English method" and "slap technique"). The specificity values were found to be 49.12, 93.33, and 100%, while the sensitivity values were observed to be 74.64, 91.03, and 100%, which translated into accuracy of 63.10, 92.26, and 100% in black, black-roan, and bronze-roan poults, respectively. Our results suggest that the method combination tested in this study could be considered a highly accurate, simple, and affordable alternative for sex determination in turkeys. This could mean a pivotal advance for small producers of turkeys, as early sex detection can help to plan timely conservational management strategies, which is of prominent importance in the context of endangered poultry breeds.

[Take-home messages from the COPD 2021 biennial of the French Society of Respiratory Diseases. Understanding to so as to better innovate]. / Principaux messages de la première Biennale BPCO 2021 de la SPLF. Mieux comprendre pour innover.

INTRODUCTION: The first COPD biennial organized by the French Society of Respiratory Diseases (SPLF) took place on 17 December 2021. STATE OF THE ART: The objective of the biennial was to discuss current knowledge regarding COPD pathophysiology, current treatments, research development, and future therapeutic approaches. PERSPECTIVES: The different lecturers laid emphasis on the complexity of pathophysiologic mechanisms including bronchial, bronchiolar and parenchymal alterations, and also dwelt on the role of microbiota composition in COPD pathenogenesis. They pointed out that addition to inhaled treatments, ventilatory support and endoscopic approaches have been increasingly optimized. The development of new therapeutic pathways such as biotherapy and cell therapy (stem cells…) call for further exploration. CONCLUSIONS: The dynamism of COPD research was repeatedly underlined, and needs to be further reinforced, the objective being to "understand so as to better innovate" so as to develop effective new strategies for treatment and management of COPD.

Proposals from a French expert panel for respiratory care in ALS patients.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive diaphragm weakness and deteriorating lung function. Bulbar involvement and cough weakness contribute to respiratory morbidity and mortality. ALS-related respiratory failure significantly affects quality of life and is the leading cause of death. Non-invasive ventilation (NIV), which is the main recognized treatment for alleviating the symptoms of respiratory failure, prolongs survival and improves quality of life. However, the optimal timing for the initiation of NIV is still a matter of debate. NIV is a complex intervention. Multiple factors influence the efficacy of NIV and patient adherence. The aim of this work was to develop practical evidence-based advices to standardize the respiratory care of ALS patients in French tertiary care centres. METHODS: For each proposal, a French expert panel systematically searched an indexed bibliography and prepared a written literature review that was then shared and discussed. A combined draft was prepared by the chairman for further discussion. All of the proposals were unanimously approved by the expert panel. RESULTS: The French expert panel updated the criteria for initiating NIV in ALS patients. The most recent criteria were established in 2005. Practical advice for NIV initiation were included and the value of each tool available for NIV monitoring was reviewed. A strategy to optimize NIV parameters was suggested. Revisions were also suggested for the use of mechanically assisted cough devices in ALS patients. CONCLUSION: Our French expert panel proposes an evidence-based review to update the respiratory care recommendations for ALS patients in daily practice.

Tumor de células granulares. Estudio clínico de 81 pacientes / Granular Cell Tumor: A Clinical Study of 81 Patients

Introducción: El tumor de células granulares (TCG) suele desarrollarse en la piel o en la mucosa oral, pero se ha descrito en muchos otros órganos. Suele ser único, pero puede ser múltiple y asociarse a otras enfermedades. Objetivos: Analizar las características clínicas de nuestros pacientes con TCG en la piel y la mucosa oral y su posible asociación con otras afecciones. Material y métodos: Estudio retrospectivo de los pacientes con TCG diagnosticados entre 1995-2019. Se revisaron las historias clínicas para obtener los siguientes datos: edad, sexo, localización, número de lesiones, diámetro, tiempo de evolución, diagnóstico clínico de sospecha, estado de los márgenes de resección, desarrollo de recidiva, tiempo de seguimiento y enfermedades asociadas. Resultados: Ochenta y un pacientes presentaron 89 TCG en la piel y la mucosa oral (43 mujeres/38 varones, edad media 40,21años). El diámetro medio fue de 1,34cm. Contabilizando los tumores extracutáneos 5 de los 81 pacientes presentaban TCG múltiple (6,2%). La edad media de los pacientes con TCG múltiple fue significativamente inferior a la de los pacientes con un único tumor (p=0,004). Solamente un paciente presentó recidiva local y ninguno desarrolló metástasis a distancia. No hemos detectado ningún caso asociado a otras enfermedades. Conclusiones: La mayoría de TCG son benignos, y a pesar de tener los márgenes afectados no suelen presentar recidivas locales. Sin embargo, hay que tener en cuenta la posibilidad de presentar TCG múltiples, tanto en la piel y en la mucosa oral como en órganos internos, especialmente en pacientes jóvenes (AU)

Introduction: Although a granular cell tumor (GCT) usually develops on the skin or oral mucosa, it has been described in many other organs. GCT typically presents as a solitary tumor, but multiple lesions can occur. It has also been described in association with other diseases. Objective: To describe the clinical characteristics of cutaneous and oral mucosal GCTs and explore potential associations with other diseases. Material and methods: Retrospective study of patients diagnosed with GCT at our hospital between 1995 and 2019. The following information was collected from the patients’ medical records: age, sex, number of GCTs, location, diameter, time to diagnosis, tentative clinical diagnosis, surgical margin status, recurrence, follow-up time, and associated diseases. Results: We detected 89 cutaneous or oral mucosal GCTs in 81 patients (43 women, 38 men) with a mean age of 40.21 years. The mean tumor diameter was 1.34cm. Five of the 81 patients (6.2%) had multiple GCTs, including noncutaneous tumors. Patients with multiple GCTs were on average younger than those with a single tumor (P=.004). There was only a single case of local recurrence and no cases of distant metastasis. None of the patients had associated diseases. Conclusions: Most GCTs are benign and local recurrence is uncommon, even in patients with positive margins. Nevertheless, the possibility of multiple tumors affecting the skin, oral mucosa, or internal organs should be borne in mind, especially in young patients (AU)

Granular Cell Tumor: A Clinical Study of 81 Patients. / Tumor de células granulares. Estudio clínico de 81 pacientes.

INTRODUCTION: Although a granular cell tumor (GCT) usually develops on the skin or oral mucosa, it has been described in many other organs. GCT typically presents as a solitary tumor, but multiple lesions can occur. It has also been described in association with other diseases. OBJECTIVES: To describe the clinical characteristics of cutaneous and oral mucosal GCTs and explore potential associations with other diseases. MATERIAL AND METHODS: Retrospective study of patients diagnosed with GCT at our hospital between 1995 and 2019. The following information was collected from the patients' medical records: age, sex, number of GCTs, location, diameter, time to diagnosis, tentative clinical diagnosis, surgical margin status, recurrence, follow-up time, and associated diseases. RESULTS: We detected 89 cutaneous or oral mucosal GCTs in 81 patients (43 women, 38 men) with a mean age of 40.21 years. The mean tumor diameter was 1.34cm. Five of the 81 patients (6.2%) had multiple GCTs, including noncutaneous tumors. Patients with multiple GCTs were on average younger than those with a single tumor (P=.004). There was only a single case of local recurrence and no cases of distant metastasis. None of the patients had associated diseases. CONCLUSIONS: Most GCTs are benign and local recurrence is uncommon, even in patients with positive margins. Nevertheless, the possibility of multiple tumors affecting the skin, oral mucosa, or internal organs should be borne in mind, especially in young patients.

[Guide for management of patients with possible respiratory sequelae after a SARS-CoV-2 pneumonia. Support proposals developed by the French-speaking Respiratory Medicine Society. Version of 10 November 2020]. / Guide de prise en charge des séquelles respiratoires post infection à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de Pneumologie de Langue Française. Version du 10 novembre 2020.

The French-speaking Respiratory Medicine Society (SPLF) proposes a guide for the management of possible respiratory sequelae in patients who have presented with SARS-CoV-2 pneumonia (COVID-19). The proposals are based on known data from previous epidemics, preliminary published data on post COVID-19 follow-up and on expert opinion. The proposals were developed by a group of experts and then submitted, using the Delphi method, to a panel of 22 pulmonologists. Seventeen proposals were validated ranging from additional examinations after the minimum assessment proposed in the SPLF monitoring guide, to inhaled or systemic corticosteroid therapy and antifibrotic agents. These proposals may evolve over time as knowledge accumulates. This guide emphasizes the importance of multidisciplinary discussion.

Respiratory support in patients with COVID-19 (outside intensive care unit). A position paper of the Respiratory Support and Chronic Care Group of the French Society of Respiratory Diseases.

With first cases noted towards the end of 2019 in China, COVID-19 infection was rapidly become a devastating pandemic. Even if most patients present with a mild to moderate form of the disease, the estimated prevalence of COVID-19-related severe acute respiratory failure (ARF) is 15-20% and 2-12% needed intubation and mechanical ventilation. In addition to mechanical ventilation some other techniques of respiratory support could be used in some forms of COVID-19 related ARF. This position paper of the Respiratory Support and Chronic Care Group of the French Society of Respiratory Diseases is intended to help respiratory clinicians involved in care of COVID-19 pandemic in the rational use of non-invasive techniques such as oxygen therapy, CPAP, non-invasive ventilation and high flow oxygen therapy in managing patients outside intensive care unit (ICU). The aims are: (1) to focus both on the place of each technique and in describing practical tips (types of devices and circuit assemblies) aimed to limit the risk of caregivers when using those techniques at high risk spreading of viral particles; (2) to propose a step-by-step strategy to manage ARF outside ICU.

Enfermedad de Paget extramamaria / Extramammary Paget Disease

ANTECEDENTES Y OBJETIVOS: Existen pocos estudios sobre la enfermedad de Paget extramamaria (EPEM) en la población mediterránea. Nuestro objetivo fue revisar las características de nuestros pacientes con EPEM, su asociación con neoplasia en continuidad y su evolución a largo plazo. PACIENTES Y MÉTODOS: Realizamos un estudio observacional retrospectivo sobre 27 pacientes diagnosticados de EPEM entre 1990-2015. Las historias clínicas fueron revisadas retrospectivamente para obtener los datos clínico-patológicos y de seguimiento. RESULTADOS: Se trata de 20 mujeres y 7 varones de entre 42 y 88 años de edad (mediana de 76 años). Las lesiones se localizaron en la vulva (16 casos), en el pubis-región inguinal (5), en la región perianal (4) y en la axila (2). El tiempo de evolución al diagnóstico osciló entre 1 y 60 meses (mediana de 12 meses) y el diámetro máximo entre 20 y 140 mm (mediana de 55 mm). En 3 casos (11,1%) la EPEM fue secundaria. Ningún caso se desarrolló sobre adenocarcinoma anexial cutáneo previo. Diez de 24 EPEM primarias (41,7%) presentaban invasión de la dermis. Ocho de los 27 pacientes (29,6%) presentaron recidiva local tras el tratamiento quirúrgico inicial. Tres pacientes (11,1%) fallecieron a consecuencia de metástasis de la EPEM. CONCLUSIONES: La presencia de un adenocarcinoma anexial cutáneo subyacente es poco frecuente pero no es rara la existencia de un adenocarcinoma extracutáneo en continuidad. A pesar de que la EPEM suele evolucionar lentamente, es frecuente la invasión de la dermis y no son excepcionales las metástasis. Las recidivas locales son frecuentes a pesar de la extirpación con márgenes amplios y pueden ser tardías, por lo que es preciso un seguimiento a largo plazo

BACKGROUND AND OBJECTIVE: Extramammary Paget disease (EMPD) has seldom been studied in Mediterranean populations. We aimed to review the characteristics of our patients with EMPD, the presence of a neoplasm in continuity, and the long-term course of the disease. PATIENTS AND METHODS: Retrospective observational study of 27 patients diagnosed with EMPD between 1990 and 2015. All clinical and pathology findings related to clinical course and outcomes were retrieved for analysis. RESULTS: Twenty patients were women and 7 were men. Ages ranged from 42 to 88 years (median, 76 years). Lesions were in the following locations: vulva (16 cases), pubis-groin (5), perianal region (4), and axilla (2). Time from onset to diagnosis ranged from 1 to 60 months (median, 12 months) and maximum lesion diameter from 20 to 140 mm (median, 55 mm). In 3 cases (11.1%) EMPD was a secondary condition. None of the lesions developed on a previous cutaneous adnexal adenocarcinoma. Ten of the 24 primary EMPDs (41.7%) invaded the dermis. Eight of the 27 patients (29.6%) experienced local recurrence after the initial surgical treatment.Three patients (11.1%) died as a consequence of metastasis from the EMPD. CONCLUSIONS: The presence of an underlying cutaneous adnexal adenocarcinoma is uncommon, but it is not unusual to find an extracutaneous adenocarcinoma in continuity. Although EMPD is a slow-growing tumor, dermal invasion is frequent and metastasis is not uncommon. Local recurrence is common even after excision with wide margins and may be delated, so long term follow-up is essential

Extramammary Paget Disease. / Enfermedad de Paget extramamaria.

BACKGROUND AND OBJECTIVE: Extramammary Paget disease (EMPD) has seldom been studied in Mediterranean populations. We aimed to review the characteristics of our patients with EMPD, the presence of a neoplasm in continuity, and the long-term course of the disease. PATIENTS AND METHODS: Retrospective observational study of 27 patients diagnosed with EMPD between 1990 and 2015. All clinical and pathology findings related to clinical course and outcomes were retrieved for analysis. RESULTS: Twenty patients were women and 7 were men. Ages ranged from 42 to 88 years (median, 76 years). Lesions were in the following locations: vulva (16 cases), pubis-groin (5), perianal region (4), and axilla (2). Time from onset to diagnosis ranged from 1 to 60 months (median, 12 months) and maximum lesion diameter from 20 to 140mm (median, 55mm). In 3 cases (11.1%) EMPD was a secondary condition. None of the lesions developed on a previous cutaneous adnexal adenocarcinoma. Ten of the 24 primary EMPDs (41.7%) invaded the dermis. Eight of the 27 patients (29.6%) experienced local recurrence after the initial surgical treatment.Three patients (11.1%) died as a consequence of metastasis from the EMPD. CONCLUSIONS: The presence of an underlying cutaneous adnexal adenocarcinoma is uncommon, but it is not unusual to find an extracutaneous adenocarcinoma in continuity. Although EMPD is a slow-growing tumor, dermal invasion is frequent and metastasis is not uncommon. Local recurrence is common even after excision with wide margins and may be delated, so long term follow-up is essential.

European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD

While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients. The European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients. The task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode. Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

Genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying drug-induced arrhythmia and sudden unexplained deaths

ABSTRACT: Drug-induced arrhythmia is an adverse drug reaction that can be potentially fatal since it is mostly related to drug-induced QT prolongation, a known risk factor for Torsade de Pointes and sudden cardiac death (SCD). Several risk factors have been described in association to these drug-induced events, such as preexistent cardiac disease and genetic variation. Our objective was to study the genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying suspected drug-induced arrhythmias and sudden unexplained deaths in 32 patients. The genetic component in the pharmacodynamic pathway was studied by analysing 96 genes associated with higher risk of SCD through massive parallel sequencing. Pharmacokinetic-mediated genetic susceptibility was investigated by studying the genes encoding cytochrome P450 enzymes using mediumthroughput genotyping. Pharmacodynamic analysis showed three probably pathogenic variants and 45 variants of uncertain significance in 28 patients, several of them previously described in relation to mild or late onset cardiomyopathies. These results suggest that genetic variants in cardiomyopathy genes, in addition to those related with channelopathies, could be relevant to drug-induced cardiotoxicity and contribute to the arrhythmogenic phenotype. Pharmacokinetic analysis showed three patients that could have an altered metabolism of the drugs they received involving CYP2C19 and/or CYP2D6, probably contributing to the arrhythmogenic phenotype. The study of genetic variants in both pharmacodynamic and pharmacokinetic pathways may be a useful strategy to understand the multifactorial mechanism of drug-induced events in both clinical practice and forensic field. However, it is necessary to comprehensively study and evaluate the contribution of the genetic susceptibility to drug-induced cardiotoxicity. (AU)

Genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying drug-induced arrhythmia and sudden unexplained deaths.

Drug-induced arrhythmia is an adverse drug reaction that can be potentially fatal since it is mostly related to drug-induced QT prolongation, a known risk factor for Torsade de Pointes and sudden cardiac death (SCD). Several risk factors have been described in association to these drug-induced events, such as preexistent cardiac disease and genetic variation. Our objective was to study the genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying suspected drug-induced arrhythmias and sudden unexplained deaths in 32 patients. The genetic component in the pharmacodynamic pathway was studied by analysing 96 genes associated with higher risk of SCD through massive parallel sequencing. Pharmacokinetic-mediated genetic susceptibility was investigated by studying the genes encoding cytochrome P450 enzymes using medium-throughput genotyping. Pharmacodynamic analysis showed three probably pathogenic variants and 45 variants of uncertain significance in 28 patients, several of them previously described in relation to mild or late onset cardiomyopathies. These results suggest that genetic variants in cardiomyopathy genes, in addition to those related with channelopathies, could be relevant to drug-induced cardiotoxicity and contribute to the arrhythmogenic phenotype. Pharmacokinetic analysis showed three patients that could have an altered metabolism of the drugs they received involving CYP2C19 and/or CYP2D6, probably contributing to the arrhythmogenic phenotype. The study of genetic variants in both pharmacodynamic and pharmacokinetic pathways may be a useful strategy to understand the multifactorial mechanism of drug-induced events in both clinical practice and forensic field. However, it is necessary to comprehensively study and evaluate the contribution of the genetic susceptibility to drug-induced cardiotoxicity.

[Transanal irrigations in patients with constipation and fecal incontinence: results, indications and follow up in our center]. / Irrigación transanal en pacientes con estreñimiento e incontinencia orgánica refractaria. Resultados, indicaciones y seguimiento en nuestro centro.

AIM OF THE STUDY: To present our results with transanal irrigation (TAI) for management of fecal incontinence and fecal constipation without response to other treatments. METHODS: Retrospective study of patients with fecal constipation and/or fecal incontinence treated with TAI between 2013 and 2017. A Rintala questionnaire(1) was carried out comparing pre and post-treatment results. This study was approved by the ethical committee. MAIN RESULTS: Twenty-five patients were included with a median age of 13 years old (range 6-44 years). Nineteen patients had spinal pathology (76%), four colorectal surgery (16%) and two functional constipation (8%). They presented fecal incontinence in 20% of cases, 12% of fecal constipation and 68% both conditions. After a mean follow-up of 1.5 years (1 month-4 years), 52% of the patients abandoned the treatment. The mean Rintala score was 6.8±4 before treatment, and after, resulted to 11.42±2.75 (p=0.001). The main complications throughout the treatment were pain (68%) and balloon leaks (28%). The patients declared as cause of treatment cessation: reduced mobility (15%), fear or misinformation (32%) and pain (76%). All patients with reduced mobility (n=3) left treatment, versus 45% (n=12) of the patients that had full mobility (p=0.17, OR 8.3 [IC95% 0.3-38]). Complementary treatments such as laxatives, enemas or digital extraction were abandoned in 55% of the patients. CONCLUSIONS: Using TAI seems to improve quality of life in patients with fecal constipation and fecal incontinence refractory compared to other treatments. Our abandonment rate was higher than expected, so we believe it is necessary to create a support group to improve follow-ups.

OBJETIVOS: Presentar nuestros resultados con el uso del irrigador transanal (IT) en el manejo intestinal de pacientes con incontinencia fecal o estreñimiento sin respuesta a otros tratamientos. METODOS: Estudio retrospectivo de pacientes con estreñimiento y/o incontinencia fecal refractaria tratados con IT (2013-2017) con el sistema Peristeen® (Coloplast). Se realizó cuestionario Rintala(1), comparando resultados pre y postratamiento. La realización del estudio fue aprobada por el comité de investigación clínica. RESULTADOS: Fueron incluidos en el estudio veinticinco pacientes, mediana de edad 13 años (6-44 años), cuatro no localizables. Diecinueve presentaban patología medular (76%), cuatro cirugías colorrectales (16%) y dos estreñimiento funcional (8%). El 20% aquejaba incontinencia, 12% estreñimiento y 68% ambas condiciones. Tras una mediana de seguimiento de 1,5 años (1 mes-4 años), el 52% abandonó el tratamiento. La puntuación media pretratamiento fue 6,8±4, frente a 11,42±2,75 tras su empleo (p=0,001), disminuyendo el número de escapes con repercusión positiva en actividades diarias. Las complicaciones principales fueron dolor (68%) y expulsión del balón (28%). Refirieron como causa de abandono: dificultad de uso por movilidad reducida (15%), miedo o desinformación (32%) y dolor (76%). El 100% de pacientes con movilidad reducida (n=3) abandonó el tratamiento, frente al 45% (n=12) en el resto (p=0,17, OR 8.3 [IC95% 0,3-38]). El 55% de los pacientes dejaron de utilizar laxantes, enemas o extracción digital. CONCLUSIONES: El uso de IT parece mejorar la calidad de vida en pacientes con estreñimiento e incontinencia de causa orgánica refractaria. La tasa de abandono fue mayor de la esperada, por lo que creemos necesaria la creación de un grupo de apoyo que mejore el seguimiento.