Developing Cardio-Oncology Programs in the New Era: Beyond Ventricular Dysfunction Due to Cancer Treatments.

Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.

Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver.

INTRODUCTION: Previous work suggests the existence of a paracrine signaling mechanism in which histamine released from visceral mast cells into the portal circulation contributes to fasting-induced ketogenesis by stimulating biosynthesis of the endogenous high-affinity PPAR-α agonist oleoylethanolamide (OEA). METHODS: Male C57Bl/6J mice were rendered obese by exposure to a high-fat diet (HFD; 60% fat). We measured histamine, OEA, and other fatty-acid ethanolamides by liquid-chromatography/mass spectrometry, gene transcription by RT-PCR, protein expression by ELISA, neutral lipid accumulation in the liver using Red Oil O and BODIPY staining, and collagen levels using picrosirius red staining. RESULTS: Long-term exposure to HFD suppressed both fasting-induced histamine release into portal blood and histamine-dependent OEA production in the liver. Additionally, subchronic OEA administration reduced lipid accumulation, inflammatory responses, and fibrosis in the liver of HFD-exposed mice. DISCUSSION: The results suggest that disruption of histamine-dependent OEA signaling in the liver might contribute to pathology in obesity-associated liver steatosis.

Thymic Polypeptide Fraction Biomodulina T Decreases Exhausted and Terminally Differentiated EMRA T Cells in Advanced Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

Lung cancer is the second cause of cancer related deaths worldwide. Chemotherapy and immunotherapy represent the current standard of care for advanced NSCLC. Platinum-based chemotherapy expands late-differentiated T cell populations. Therefore, immune restoration after chemotherapy to adjuvate the immunotherapeutic potential could be crucial. The aim of this study was to evaluate the effect of Biomodulina T (BT), a thymic polypeptide fraction, on peripheral lymphocytes subpopulations in the context of cancer disease. Additionally, whether these effects might induce a better response to CIMAvax-EGF, an epidermal growth factor (EGF) depleting immunotherapy. Eighteen advanced NSCLC patients were evaluated after being treated with platinum-based chemotherapy. We found that the frequency of terminally differentiated effector T cells re-expressing CD45RA (EMRA) CD4+ (p=0.0031) and CD8+ (p=0.0372) T cells decreased with the administration of BT, whereas CD4+ naive T cells increase in more than 70% of the patients. Remarkably, CD4+ and CD8+ T lymphocytes expressing programmed cell death receptor-1 (PD1) significantly decreased after BT administration (p=0.0005 and p<0.0001, respectively). We also found an enhancement of the anti-EGF antibody response with a large percentage of patients treated with CIMAvax-EGF reaching the good antibody response condition after four vaccine doses. Moreover, the median overall survival of patients treated with CIMAvax-EGF was 16.09 months. In conclusion, our results suggest that the immunorestoration generated by the administration of BT after first-line chemotherapy may induce a better immune response to CIMAvax-EGF that could translate into the clinical benefit of patients diagnosed with advanced NSCLC.

Social Restrictions versus Testing Campaigns in the COVID-19 Crisis: A Predictive Model Based on the Spanish Case.

The global COVID-19 spread has forced countries to implement non-pharmacological interventions (NPI) (i.e., mobility restrictions and testing campaigns) to preserve health systems. Spain is one of the most severely impacted countries, both clinically and economically. In an effort to support policy decision-making, we aimed to assess the impacts of different NPI on COVID-19 epidemiology, healthcare costs and Gross Domestic Product (GDP). A modified Susceptible-Exposed-Infectious-Removed epidemiological model was created to simulate the pandemic evolution. Its output was used to populate an economic model to quantify healthcare costs and GDP variation through a regression model which correlates NPI and GDP change from 42 countries. Thirteen scenarios combining different NPI were consecutively simulated in the epidemiological and economic models. Both increased testing and stringency could reduce cases, hospitalizations and deaths. While policies based on increased testing rates lead to higher healthcare costs, increased stringency is correlated with greater GDP declines, with differences of up to 4.4% points. Increased test sensitivity may lead to a reduction of cases, hospitalizations and deaths and to the implementation of pooling techniques that can increase throughput testing capacity. Alternative strategies to control COVID-19 spread entail differing economic outcomes. Decision-makers may utilize this tool to identify the most suitable strategy considering epidemiological and economic outcomes.

[What are the epidemiological characteristics of patients with work incapacity as a result of fibromyalgia who return to work?] / ¿Qué características epidemiológicas tienen los pacientes con fibromialgia e incapacidad laboral que se reincorporan a un puesto de trabajo?

OBJECTIVE: To ascertain what epidemiological variables determine whether a patient with work incapacity as a result of fibromyalgia returns to work. MATERIAL AND METHODS: A retrospective cohort study was carried out that included 412 patients with fibromyalgia under 54 years of age and classified as having a total permanent disability by the National Institute of Social Security in Madrid in 2005. Follow-up from 2005 to 2019. We studied the variables of age, sex, marital status, CFS/MCS, psychiatric diagnosis, type of social security affiliation, occupation (CNO-11) and economic amount of the disability benefit in euros/month (4 tranches are established of <500, 500-750, 750-1000 and> 1000). We analyse the impact of these variables on return to work using a binary logistic regression model. RESULT: The mean age was 45+/-7. A total of 44% did not return to another job. The variables that were significant in the multivariate study were age (OR 0.93, CI 0.90 - 0.97), association with CFS and/or MCS (OR 0.07, CI 0.02 - 0.24), occupation (OR 0, 82; IC 0.73 - 0.92) and the amount of the disability benefit (OR 0.26; IC 0.19 - 0.35). CONCLUSION: The probability of returning to another job decreases with age (1.07 times for each year), as the amount of the disability benefit increases (3.85 times for each successive tranche), as the level of qualification required for the occupation decreases (1.21 times for each successive CON-11 code) or if there is CFS and/or MCS (12.9 times).

Duodenoyeyunostomía laparoscópica en el Síndrome de la Arteria Mesentérica Superior / Laparoscopic duodenojejunostomy for Superior Mesenteric Artery Syndrome

Introducción: El Síndrome de la Arteria Mesentérica Superior es causa poco frecuente de obstrucción duodenal. Los síntomas varían desde una obstrucción leve hasta emergencias agudas. El examen físico no siempre ayuda al diagnóstico, que se basa en los hallazgos imagenológicos. Objetivo: preconizar, recomendar el uso de las técnicas mínimamente invasivas en el manejo quirúrgico del Síndrome de la Arteria Mesentérica Superior. Presentación del caso: Mujer de 49 años de edad, antecedentes de pérdida de peso después de quimioterapia con náuseas, vómitos y dolor abdominal posprandial de dos años de evolución. Tratada exitosamente con duodenoyeyunostomía laparoscópica. El tratamiento inicial suele ser conservador. Publicaciones recientes respaldan que la duodenoyeyunostomía laparoscópica es un método seguro y efectivo para su tratamiento. Conclusiones: El tratamiento quirúrgico es cada vez más exitoso, la mayoría de los pacientes no presenta síntomas después de la cirugía(AU)

Introduction: Superior Mesenteric Artery Syndrome is an uncommon cause of duodenal obstruction. Symptoms may vary from mild obstruction to acute life-threatening emergencies. Physical examination does not always help in establishing the diagnosis which is based on findings from imaging studies. Objective: To recommend the laparoscopic approach for the surgical treatment of this entity. Case presentation: A 49-year old female patient with prior history of weight loss after chemotherapy and a two-year history of postprandial nausea, vomiting, and abdominal pain who was successfully treated by laparoscopic duodenojejunostomy is presented. Discussion: Initial treatment is usually conservative. Recently published studies support that laparoscopic duodenojejunostomy is a safe and effective method of treatment. Conclusions: Surgical treatment is becoming more successful and the majority of patients are symptom-free after surgery(AU)

Evaluation of Anti-Cytotoxic and Anti-Genotoxic Effects of Nigella sativa through a Micronucleus Test in BALB/c Mice.

Nigella sativa (N. sativa) is a medicinal plant used for its therapeutic pharmacological effects such as anti-inflammatory, antioxidant, anticancer, antidiabetic, and immunomodulation. This study explored the anti-cytotoxic and anti-genotoxic effect of N. sativa through a micronucleus test (MNT) of BALB/c mice peripheral blood. Using 6-to-8-week-old healthy male BALB/c mice, four groups were formed: (1) Control (sterile water), single-dose 2 mg/kg/intraperitoneal (i.p); (2) N. sativa oil, 500 mg/kg/24 h/7 days/i.p; (3) Cisplatin (CP), single-dose 2 mg/kg/subcutaneous (s.c); (4) N. sativa + CP with their respective dosage. When evaluating polychromatic erythrocytes (PCE), a biomarker of cytotoxicity, the group treated with N. sativa + CP experienced an increase in the frequency of PCE, which demonstrated the recovery of bone marrow and modulation of cell proliferation. The analysis of micronucleated polychromatic erythrocytes (MNPCE), an acute genotoxicity biomarker, showed similar frequency of MNPCE within the groups except in CP, but, in the N. sativa + CP group, the frequency of MNPCE decreased and then regulated. Finally, the frequency of micronucleated erythrocytes (MNE), a biomarker of genotoxicity, the supplementation of N. sativa oil did not induce genotoxic damage in this model. Thus, we conclude that N. sativa has both cytoprotective, genoprotective effects and modulates cell proliferation in BALB/c mice.

Teleophthalmology: a strategy for timely diagnosis of sight-threatening diabetic retinopathy in primary care, Concepción, Chile.

AIM: To estimate the prevalence of diabetic retinopathy (DR) in a diabetic population of the public health system. METHODS: This non-experimental, descriptive and cross-sectional study, with no direct control over the variables analysed, was carried out by the Telemedicine Unit of the University of Concepción (TELMED) and the Family Health Centers (CESFAM) of the Health Service Concepción, Chile, among a population of 7382 diabetic patients of the public health system, from October 2014 to June 2015. Two digital images for each patient's eyes were obtained and uploaded to the TELMED tele-ophthalmology platform. The images were remotely evaluated by a retina expert ophthalmologist for diagnosis. Treatment and a referral (if required) were recommended, and an individualised report for each patient was sent to the place of origin. RESULTS: The prevalence of DR in this study was 14.9%. Of these, 48.7% had mild non-proliferative DR (NPDR), 30.8% moderate NPDR, 15.9% severe NPDR, and 4.6% proliferative DR. Of the patients with DR, 17.8% were referred for fluorescein angiography, 4.3% for panretinal photocoagulation, 1.2% for vitrectomy, and 0.4% for cataract surgery. CONCLUSION: The use of telemedicine allowed an increased screening coverage for DR in diabetic patients. The different types of DR were detected in a timely manner, decreasing waiting times due to the lack of specialists in ophthalmology in the public health system.

Fructanos tipo inulina: efecto en la microbiota intestinal, la obesidad y la saciedad / Inulin-type fructans: effect on gut microbiota, obesity and satiety

RESUMEN Fundamento: Los fructanos tipo inulina de cadena corta se nombran fructooligosacáridos (FOS) y son considerados prebióticos al beneficiar la salud del huésped. Objetivo: Analizar tres de los más importantes beneficios a la salud de los fructanos tipo inulina como prebióticos. Metodología: Se revisaron documentos publicados en diferentes bases de datos (PubMed, Medline, NCBI) en idioma inglés. Se escogieron los que aportaron datos sobre la influencia de los prebióticos en la microbiota intestinal, la obesidad y la saciedad. Se utilizó el método de análisis documental para evaluar los resultados de diferentes ensayos clínicos. Resultados: Se revisaron un total de 70 artículos, de los cuales se seleccionaron 49 que contenían ensayos clínicos controlados y evidencias sobre los efectos beneficiosos en la salud de los fructanos tipo inulina. Conclusiones: Los fructanos tipo inulina en general, y los fructooligosacáridos en particular, al ser fermentados en el tracto gastrointestinal producen ácidos grasos de cadena corta; estos productos de la fermentación favorecen el desarrollo de microorganismos beneficiosos en detrimento de otros perjudiciales. De igual forma los ácidos grasos de cadena corta pueden regular el metabolismo de los lípidos y la sensación de saciedad.

ABSTRACT Background: Short-chain inulin-type fructans (ITF) are named fructooligosaccharides (FOS) and considered prebiotics to benefit the health of the host. Objective: To analyze three of the most important health benefits of inulin-type fructans as prebiotics. Methodology: Documents published in different databases (PubMed, Medline, NCBI) in English were reviewed. Those which provided data on the influence of prebiotics on the gut microbiota, obesity and satiety were chosen. The documentary analysis method was used to evaluate the results of different clinical trials. Results: A total of 70 articles were reviewed, of which 49 were selected and contained controlled clinical trials and evidence of the beneficial health effects of inulin-type fructans. Conclusions: Inulin-type fructans in general, and fructooligosaccharides (FOS) in particular, when fermented in the gastrointestinal tract produce short-chain fatty acids (SCFA); these fermentation products favor the development of beneficial microorganisms to the detriment of other harmful ones. Similarly, short chain fatty acids can regulate lipid metabolism and satiety.

Spectrophotometric, fluorimetric and electrochemical selective pyrophosphate/ATP sensing based on the dimethyltin(IV)-tiron system.

Sensing of pyrophosphate anion (PPi) in the presence of nucleotide triphosphates allows the real time monitoring of the polymerase chain reaction. To get a deeper understanding of the factors involved in PPi/nucleotide triphosphate discrimination, a detailed study on the performance of a dimethyltin (IV)-catecholate complex capable of both separate fluorimetric or electrochemical detection of PPi in the presence of adenosine triphosphate (ATP) has been undertaken. Dimethyltin (IV) tightly binds PPi or ATP, and forms a stable 1:1 complex with tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) in water. The complexation equilibria with all components are characterized quantitatively by potentiometric and spectroscopic titrations. Pyrophosphate anion can be detected owing to its ability to release free tiron from the complex by measuring either a fluorimetric or an electrochemical signal. On the contrary, ATP does not displace tiron but causes an interference with PPi in the fluorimetric detection method due to the formation of a ternary Me2Sn(IV)-tiron-ATP complex with optical properties intermediate between those of free and bound tiron. In the electrochemical (square wave voltammetry) method, the ternary ATP complex shows a separate peak which does not coincide with the peaks of neither free nor bound tiron, thus making possible the simultaneous detection of ATP in addition to PPi.

Reintervenciones por fallo de la cirugía antirreflujo / Reinterventions for Failed Antireflux Surgery

RESUMEN Introducción: En la actualidad, la fundoplicatura laparoscópica se considera el tratamiento de elección para la enfermedad por reflujo gastroesofágico con resultados excelentes en más del 90 por ciento de los pacientes. Sin embargo, a pesar de estos resultados, el 30 % de los pacientes presentan persistencia de los síntomas y del 3 por ciento al 10 por ciento requieren reintervención por fallo de la cirugía antirreflujo. Objetivo: Describir las causas del fracaso de la cirugía antirreflujo y las técnicas realizadas en la reintervención. Método: Se realizó un estudio descriptivo, retrospectivo y longitudinal, de una serie de pacientes a los cuales se les realizo cirugía antirreflujo en el Centro Nacional de Cirugía de Mínimo Acceso desde enero de 1994 hasta diciembre de 2016. Las variables analizadas fueron: reintervenciones y sus causas, tratamiento quirúrgico, morbilidad y el índice de conversión. Resultados: De un total de 1 550 pacientes operados, 37 (2,3 por ciento) fueron reintervenidos. Las causas más frecuentes de reintervención fueron la recidiva de los síntomas y la presencia de disfagia. La herniación de la fundoplicatura fue el hallazgo transoperatorio más frecuente. El índice de conversión fue bajo y no hubo fallecidos en las reintervenciones. La morbilidad triplicó la del total de la serie, así como la estadía hospitalaria. Conclusiones: Las reintervenciones por fallo de la cirugía antirreflujo resultan de gran complejidad pues aumentan considerablemente la morbilidad y la estadía hospitalaria. Debe realizarse en centros que acumulen una alta experiencia en estas técnicas(AU)

ABSTRACT Introduction: Nowadays, laparoscopic fundoplication is considered the treatment of choice for gastroesophageal reflux disease, showing excellent results in more than 90 percent of patients. However, despite these results, 30 percent of patients present with persistent symptoms, while 3 percent to 10 percent require reintervention for failed antireflux surgery. Objective: To describe the causes of failed antireflux surgery and the techniques performed in the reintervention. Method: A descriptive, retrospective and longitudinal study was conducted with a series of patients who underwent antireflux surgery at the National Center for Minimally Access Surgery, from January 1994 to December 2016. The variables analyzed were reinterventions and their causes, surgical treatment, morbidity and the conversion rate. Results: From among 1550 patients operated on, 37 (2.3 percent) were reintervened. The most frequent causes of reintervention were the recurrence of symptoms and the occurrence of dysphagia. The fundoplication herniation was the most frequent transoperative finding. The conversion rate was low and there were no deaths in the reinterventions. The morbidity tripled that of the total of the series, as well as hospital stay. Conclusions: Reinterventions for failed antireflux surgery are very complex, since they increase morbidity and hospital stay considerably. It must be performed in centers that accumulate a high experience in these techniques(AU)

Calidad de vida y evolución clínica después de miotomía de Heller con fundoplicatura de Dor / Quality of Life and Clinical Evolution after Heller Myotomy plus Dor fundoplication

RESUMEN Introducción: La miotomía de Heller laparoscópica es considerada en la actualidad el tratamiento de elección para el alivio de la disfagia. Se ha demostrado que gracias a ella se logra una baja incidencia de reflujo gastroesofágico y una mejoría evidente de la calidad de vida Objetivo: Evaluar la calidad de vida y evolución clínica de los pacientes después de la miotomía de Heller con fundoplicatura de Dor. Método: Estudio observacional descriptivo longitudinal prospectivo mediante la aplicación del cuestionario de índice de calidad de vida gastrointestinal a pacientes operados de acalasia esofágica desde enero del 2010 hasta diciembre del 2017 en el Centro Nacional de Cirugía de Mínimo Acceso. Se aplicó un cuestionario en el preoperatorio y al año de operados. Análisis estadístico: Porcentajes para variables cualitativas, media ± desviación estándar o mediana y rango según corresponda para las cuantitativas, para la comparación de los resultados del cuestionario se emplearon pruebas de hipótesis de comparación de medias, con nivel de significación estadística α= 0,05. Resultados: Fueron incluidos en el estudio 101 pacientes. Las edades oscilaban entre 18 y 78 años con una media de 47 años. El tiempo medio de evolución de los síntomas fue de 62 meses, con una media de 3,3 en la escala de disfagia y una presión de reposo del esfínter esofágico inferior (mmHg) 38,7 ± 16,8, se obtuvo un GIQLI inicial de 85,3 ± 20,4 que aumentó al año a 131,6 ± 10,5 Conclusiones: La miotomía de Heller con fundoplicatura de Dor, mejora la calidad de vida de los pacientes con acalasia esofágica con una evolución clínica excelente(AU)

ABSTRACT Introduction: Laparoscopic Heller myotomy is now considered the treatment of choice for the relief of dysphagia. It has been shown that thanks to it a low incidence of gastroesophageal reflux and evident improvement in the quality of life is achieved. Objective: To evaluate the quality of life and clinical evolution of patients after Heller myotomy plus Dor fundoplication. Method: Prospective, longitudinal, descriptive, observational study carried out by applying the Gastrointestinal Quality of Life Index (GIQLI) questionnaire to patients operated on for esophageal achalasia, from January 2010 to December 2017, at the National Center for Minimum Access Surgery. The questionnaire was applied preoperatively and one year after surgery. Statistical analysis: Percentages for qualitative variables, mean and standard deviation, or median and range, as appropriate for quantitative variables. For the comparison of the results of the questionnaire, we used tests of hypothesis of comparison of means, with statistical significance level of 0.05. Results: The ages ranged between 18 and 78 years, with an average of 47 years. The mean time of evolution of symptoms was 62 months, with an average of 3.3 on the dysphagia scale and a resting pressure of the lower esophageal sphincter (mmHg) 38.7±16.8. An initial gastrointestinal quality of life index of 85.3±20.4 was obtained, which increased to 131.6±10.5 per year. Conclusions: Heller myotomy plus Dor fundoplication improves the quality of life of patients with esophageal achalasia and guarantees an excellent clinical evolution(AU)

Calidad de vida antes y después de la cirugía videolaparoscópica en la acalasia esofágica / Quality of live before and after videolaparoscopic surgery in esophageal achalasia

Introducción: la acalasia esofágica es el más frecuente de los trastornos motores. Origina disfagia, regurgitaciones y pérdida de peso con deterioro marcado de la calidad de vida. El tratamiento quirúrgico videolaparoscópico es el de elección para el alivio de la disfagia. Objetivo: evaluar la calidad de vida relacionada con la salud en pacientes con acalasia esofágica operados por videolaparoscopia. Método: se realizó estudio observacional descriptivo longitudinal prospectivo, mediante la aplicación del cuestionario GIQLI (en la consulta de preoperatorio, a los tres meses y al año del posoperatorio) a los pacientes operados de acalasia esofágica desde enero hasta diciembre del año 2015 en el Centro Nacional de Cirugía de Mínimo Acceso. Análisis estadístico: porcentajes para variables cualitativas, media ± desviación estándar para las cuantitativas. Para evaluar el comportamiento de la calidad de vida relacionada con la salud se realizó análisis de varianza (ANOVA) de medidas repetidas con nivel de significación estadística α= 0,05. Resultados: 34 pacientes fueron incluidos, se excluyeron tres, 41,2 por ciento del sexo masculino, 58,8 por ciento del femenino, predominó color de la piel blanca (66,7 por ciento), media de edad de 44,8 años, GIQLI inicial 85,6 (± 20,9) puntos, a los tres meses 125,2 (± 12,4) puntos, al año 134,0 (± 9,6) puntos, p= 0,000. Conclusiones: la esofagocardiomiotomía de Heller laparoscópica mejora la calidad de vida relacionada con la salud de los pacientes con acalasia esofágica(AU)

Introduction: Achalasia is the most frequent of motor disorders of the esophagus, producing dysphagia, regurgitation and weight loss, with a marked deterioration of the quality of life. ideolaparoscopic surgery remains the gold standard for dysphagia relief. However, the health-related quality of live measurement is still necessary to assess treatment outcome and the impact on the patients' lives. Objective: To assess the health-related quality of live in patients with esophageal achalasia who received videolaparoscopic surgery. Methods: An observational, descriptive, longitudinal and prospective study was carried out, using the questionnaire GIQLI, in the preoperative interview, three months and then a year following videolaparoscopic surgery, in patients who received achalasia surgery from January to December 2015 in the National Center for Minimally Invasive Surgery. The statistical analysis considered percentages for qualitative variables and mean standard deviation for quantitative variables. In order to assess the actual state of the health-related quality of live, a variance analysis of repetitive measures (ANOVA) was made, with a level of statistical significance α=0.05. Results: 34 patients were included, three were excluded, 41.2 percent of male sex, 58.8 percent of female sex, the white skin predominated (66.7 percent), average age of 44.8 years, baseline GIQLI score 85.6 (±20.9), after three months 125.2 (±12.4), and after one year 134.0 (±9.6), p=0,000. Conclusions: The laparoscopic Heller's esophageal cardiomyotomy improves the health-related quality of live in patients with esophageal achalasia(AU)

Reintervenciones por fracaso de la miotomía de Heller por acalasia esofágica / Reintervention after failed Heller myotomy for esophageal achalasia

Introducción: la cardiomiotomía de Heller asociada al proceder antirreflujo descrito por Dor constituye el tratamiento de elección en los pacientes con acalasia esofágica; sin embargo, las causas del fracaso del tratamiento aún son controversiales. Objetivo: describir las causas del fracaso de la miotomía de Heller en pacientes operados por acalasia esofágica y la evolución clínica de los pacientes reintervenidos. Métodos: se realizó un estudio descriptivo, retrospectivo y longitudinal de una serie de pacientes reintervenidos por fracaso de la miotomía de Heller en el Centro Nacional de Cirugía de Mínimo Acceso desde enero de 2010 hasta diciembre de 2016. Resultados: se les realizó miotomía de Heller a 253 pacientes con diagnóstico de acalasia esofágica. De ellos, 7 (2,7 por ciento) fueron reintervenidos por recurrencia de los síntomas, 4 (1,5 por ciento) fueron operados inicialmente en la institución y el resto fueron remitidos de otras instituciones del país. La edad media fue de 41 ± 15 años (rango 20-59). Los síntomas más frecuentes fueron la disfagia posoperatoria y la pérdida de peso (100 por ciento). El tiempo de recurrencia de los síntomas después de la primera operación fue de 6-12 meses en 4 (57 por ciento), de 12 a 18 meses en 1 (16 por ciento) y de 18 a 24 en 2 (33 por ciento) pacientes. Conclusiones: la miotomía incompleta fue la causa principal de reintervención. La remiotomia laparoscópica con o sin fundoplicatura fue la técnica quirúrgica de elección para estos pacientes los cuales tuvieron una evolución clínica excelente o buena en el posoperatorio(AU)

Introduction: Heller's cardiomyotomy associated with the antireflux procedure described by Dor is the treatment of choice in patients with esophageal achalasia. However, the causes of treatment failure are still controversial. Objective: To describe the causes of failure of Heller's myotomy in patients operated for esophageal achalasia and the clinical progress of patients who required another surgery. Methods: A descriptive, retrospective and longitudinal study was performed in a series of patients who required another surgery due to failed Heller's myotomy at the National Center for Minimally Invasive Surgery from January 2010 to December 2016. Results: Heller's myotomy was performed in 253 patients diagnosed with esophageal achalasia. Among these patients, 7 (2.7 percent) required another surgery due to the relapse of symptoms, 4 (1.5 percent) were initially operated at the institution, and the rest were referred from other institutions in the country. The average age was 41±15 years (range 20-59). The most frequent symptoms were postoperative dysphagia and weight loss (100 percent). The time of symptoms relapse after the first surgery was 6-12 months in 4 patients (57 percent), 12-18 months in 1 (16 percent) and 18-24 months in 2 (33 percent) patients. Conclusions: Incomplete myotomy was the main cause of reintervention, laparoscopic myotomy with or without fundoplication being the surgical technique of choice for these patients, who had an excellent or good postoperative clinical evolution(AU)

Calidad de vida en pacientes con acalasia esofágica operados por videolaparoscopia / Quality of life in patients with esophageal achalasia after video-laparoscopic surgery

Introducción: la acalasia esofágica se asocia con un marcado deterioro de la calidad de vida, el tratamiento quirúrgico videolaparoscópico es el de elección. Sin embargo, es necesario medir la calidad de vida relacionada con la salud para evaluar los resultados del tratamiento y el impacto sobre su vida. Objetivos: evaluar la calidad de vida relacionada con la salud en pacientes con acalasia esofágica operados por videolaparoscopia. Método: estudio observacional, descriptivo, longitudinal prospectivo, mediante la aplicación del cuestionario de índice gastrointestinal de calidad de vida a pacientes operados de acalasia esofágica desde enero hasta diciembre de 2015 en el Centro Nacional de Cirugía de Mínimo Acceso. Se incluyeron en el estudio 34 pacientes y se excluyeron tres. El cuestionario se aplicó en el preoperatorio y a los tres meses de operados. El análisis estadístico expresa porcentajes para variables cualitativas, media ± desviación estándar o mediana y rango según corresponda para las cuantitativas, para la comparación de los resultados del cuestionario se emplearon pruebas de hipótesis de comparación de medias, con nivel de significación estadística α= 0,05. Resultados: hubo u total de 41,2 por ciento, 14 del sexo masculino, 58,8 por ciento, 20 del sexo femenino. Predominó color de la piel blanca (66,7 por ciento), media de edad de 44,8 años, GIQLI inicial 85,6 (± 20,9), GIQLI trimestral 125,2 (± 12,4) p= 0,000. Conclusiones: la esofagocardiomiotomía de Heller videolaparoscópica mejora la calidad de vida relacionada con la salud de los pacientes con acalasia esofágica(AU)

Introduction: Esophageal achalasia is associated with a marked decay in quality of life, treatment with video-laparoscopic surgery is the chosen one. However, it is necessary to measure their health-related quality of life, in order to evaluate the results after treatment and the impact on their lives. Objective: To evaluate health-related quality of life in patients with esophageal achalasia after video-laparoscopic surgery. Methods: Observational, descriptive, longitudinal and prospective study using the questionnaire for Gastrointestinal Quality of Life Index (GIQLI) in patients who had esophageal achalasia operation from January to December 2015 at the National Center for Minimal Invasive Surgery. The study included 34 patients and excluded 3. The questionnaire was applied in the preoperatory and three months after. The statistical analysis expresses percentages for qualitative variables, mean ± average or standard deviation, and range by correspondence for the quantitative ones, to compare the questionnaire results, hypothetical tests for means comparison were used, with a level of statistical significance ?=0.05. Results: There was a total of 41.2 por ciento, 14 of male sex, 58.8 por ciento, 20 of female sex. There was a predominance of white skin color (66.7 por ciento), mean age of 44.8 years, initial GIQLI of 85.6 (± 20.9), quarterly GIQLI of 125.2 (± 12.4) p= 0.000. Conclusions: Video-laparoscopic Heller's esophagocardiomyotomy improves health-related quality of life of the patients with esophageal achalasia(AU)

Assessment three constitutive promoters for GUS expression in rice (Oryza sativa L., var. J-104) / Evaluación de tres promotores constitutivos para la expresión GUS en arroz (Oryza sativa L., cv. J-104)

This work analyzed the constitutive expression of the ß-Glucuronidase (GUS) reporter gene fused to three promoters: the cauliflower mosaic virus (CaMV) 35S, the chimerical A9 promoter which contains rice Act1, and the Ubiquitine-1 promoter from maize. The activity of the promoters was qualitative and quantitatively obtained in different tissues and various growth stages of rice plants (cv J-104) transformed by biolistic. All the promoters were found to be active, with distinct patterns of relative activity in leaves, stem and roots from in vitro and ex vitro plants, and in plants of T1 progeny. The chimerical A9 promoter increased significantly levels of GUS expression in all the tissues and at all growth stages of the plants.

Se analizó la expresión constitutiva del gen reportero de la ß-Glucuronidasa (GUS) fusionado a tres promotores: el 35S del virus del mosaico de la coliflor (CaMV), el promotor quimérico A9 que contiene la actina-1 de arroz y el promotor ubiquitina-1 de maíz. La actividad de los promotores fue analizada cualitativa y cuantitativamente en diferentes tejidos y estadíos de crecimiento de plantas de arroz (variedad J-104) transformadas mediante biobalística. Se demostró la expresión constitutiva de GUS bajo los promotores estudiados, con distintos patrones de actividad relativa en hojas, tallos y raíces de plantas in vitro y ex vitro, y en plantas de la progenie T1. Bajo el promotor quimérico A9 se lograron los mayores niveles de expresión GUS en todos los tejidos y fases de crecimiento de las plantas.

Estrategias terapéuticas en el tratamiento de la acalasia esofágica / Therapeutical strategies in the treatment of esophageal achalasia

Introducción: la acalasia es un trastorno degenerativo de la motilidad esofágica cuyo resultado es la ausencia o pobre relajación del esfínter esofágico inferior a la deglución asociado a trastorno motor del cuerpo esofágico. Afecta a ambos sexos con una incidencia de 1/100 000 y una prevalencia de 10/100 000. En su fisiopatología se han involucrado factores inmunológicos, genéticos, infecciosos y neurodegenerativos, que conllevan a pérdida selectiva de las neuronas inhibitorias del plexo mientérico e infiltrado inflamatorio en el esfínter esofágico inferior. Objetivo: revisar las modalidades terapéuticas en el tratamiento de la acalasia con un análisis a corto y largo plazo de las opciones de tratamiento. Métodos: con la introducción para su diagnóstico de la manometría de alta resolución se ha creado un novedoso sistema de clasificación que puede evaluar el pronóstico para el paciente y predecir la respuesta al tratamiento. La terapéutica descansa sobre la base de: tratamiento médico, procederes endoscópicos y tratamiento quirúrgico, siendo éste el estándar terapéutico, aunque continúa el debate sobre qué método es mejor, si la dilatación neumática, o la miotomía de Heller. Resultados: la miotomía laparoscópica de Heller (MLH) ha emergido en los últimos años como el tratamiento de elección, particularmente en pacientes jóvenes (≤ 45 años). Desde noviembre del 2012 hasta septiembre del 2015 se han realizado 27 dilataciones endoscópicas,15 mujeres (55,6 por ciento) y 12 hombres (44,4 por ciento), sin reportar complicaciones. Desde enero 2010 hasta diciembre 2014 se realizaron 188 miotomías de Heller por abordaje laparoscópico, el promedio de estadía hospitalaria fue de un día, no hubo conversión ni reintervención y la mortalidad fue nula(AU)

Introduction: Achalasia is a neurodegenerative motility disorder of the esophagus resulting in failure of the lower esophageal sphincter to relax properly in response to swallowing and associated to motor disorder of the esophageal body. It affects both sex with an incidence rate of 1/100 000 and a prevalence of 10/100 000. Its pathophysiology includes immune, genetics, infectious and neurodegenerative factors that result in a selective loss of inhibitory neurons of the myenteric plexus and inflammatory infiltrate in the lower esophageal sphincter. Objective: Objectives: To review the therapeutic modalities in the treatment of achalasia with short- and long-term analysis of treatment options. Methods: Through the introduction of high resolution manometry, a novel classification system for achalasia has been created to evaluate the prognosis of a patient and to predict response to treatment. Therapeutics is based on medical treatment, endoscopic procedures and surgery, being the latter the gold standard; however there is currently much debate over whether pneumatic dilation is better than Heller myotomy procedure in the treatment of achalasia. Results: Laparoscopic Heller myotomy has emerged in the last few years as the treatment of choice, particularly for young patients 45 years of age or younger. From November 2012 to September 2015, 27 endoscopic dilations have been perfomed in 15 women (55.6 percent) and 12 men (44.4 percent) with no reported complications. From January 2010 to December 2014, one hundred and eighty eight laparoscopic Heller myotomies were performed; the hospital stay was one day, neither conversion nor reoperation was necessary and the mortality rate was zero(AU)

Organ-level quorum sensing directs regeneration in hair stem cell populations.

Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair plucking, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Plucking hair at different densities leads to a regeneration of up to five times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α-secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells.