Azathioprine in refractory sprue: results from a prospective, open-label study

OBJECTIVE: Refractory sprue is a rare and severe malabsorptive disorder that mimics celiac disease but is refractory to a gluten-free diet and is without initial evidence of overt lymphoma. Treatment is largely empiric and often ineffective, with steroids and immunosuppression being the mainstream therapeutic options. The aim of this study was to evaluate prospectively the effect of azathioprine on a group of patients diagnosed with refractory sprue. METHODS: We studied seven consecutive patients (five women and two men) with a well-defined diagnosis of refractory sprue and a lack of response to oral or parenteral steroids. At diagnosis, five patients had endoscopic evidence of ulcerative jejunitis, and five underwent exploratory laparotomy for exclusion of malignancies. The characteristic monoclonal TCR gene rearrangement was shown in five of six patients studied. Patients were treated for a mean of 11 months (range 8–12 months), and clinical, biochemical, molecular, and histological parameters were reassessed at the end of the trial. The study was a prospective, open-label, non–placebo-controlled study using azathioprine (2 mg/kg/ day) plus oral prednisone (1 mg/kg/day). A gluten-free diet (n 7) as well as enteral (n 6) and parenteral nutrition (n 5) were administered during the trial. RESULTS: After treatment, five patients had a complete clinical remission, and biochemical and nutritional parameters were significantly improved. Steroids were tapered after the onset of azathioprine, and no patient was on steroids at the end of the trial. Intestinal histology improved significantly in all cases (normal histology in three cases and minor infiltration in the lamina propria in two). Two patients did not respond to treatment at any time and died in months 10 and 9, of an irreversible ventricular fibrillation and sepsis, respectively. No overt lymphoma was demonstrated during the follow-up. CONCLUSIONS: The present study confirms earlier anecdotal reports on the efficacy of azathioprine in refractory sprue, with clear clinical and histological improvement shown in most patients. However, monoclonality persisted after treatment. We consider that a larger number of patients should be evaluated before a definitive recommendation is adopted for use of this drug in refractory sprue.Fil: Maurino, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina. Universidad del Salvador; ArgentinaFil: Niveloni, Sonia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Cherñavsky, Alejandra Claudia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Pedreira, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Mazure, Roberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Vazquez, Daniel Horacio. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Reyes, Hugo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Fiorini, Alcira. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Smecuol, Edgardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Cabanne, Ana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Capucchio, Monica. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; ArgentinaFil: Kogan, Zulema. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Bai, Julio C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina. Universidad del Salvador; Argentin

Ciencias Sociales: Economía y Humanidades

Este volumen I contiene 29 capítulos arbitrados que se ocupan de estos asuntos en Tópicos Selectos de Ciencias Sociales: Economía y Humanidades, elegidos de entre las contribuciones, reunimos algunos investigadores y estudiantes.Gómez, presenta un breve examen de la producción y comercialización de rosa en México; Arpi y Portillo realiza un estudio en México sobre el ingreso mínimo de las familias que identifica la línea de pobreza alimentaria en el área rural del sur de México, 2012; Bravo realiza un pequeño estudio donde hablará sobre el análisis comparado del Sector Gubernamental y la Economía Mexicana desde la perspectiva de los eslabonamientos productivos Hirshman-Rasmuss; Caamal, Pat, Jerónimo y Romero realizan un estudio sobre los canales de comercialización de limón persa en el municipio de Martínez de la Torre, Veracruz; Macías y Perales nos hablarán sobre una análisis del comercio estratégico en el TLCAN: El Estado en la política agrícola de biocombustibles; Figueroa, Pérez y Godínez se expresan acerca de la importancia de la comercialización del café en México; Sepúlveda, Sepúlveda y Pérez realizan un diagnóstico, retos del comercio electrónico en el Sector Agroindustrial Mexicano; Duana mediante su trabajo nos muestra y habla sobre la inversión extranjera directa y su impacto en crecimiento de México, un análisis en prospectiva: 1999-2010; Figueroa, Pérez y Ramírez hacen un estudio acerca sobre la importancia de la Banca en México; Pérez, Figueroa, Godínez y Pérez presenta un trabajo acerca de la competitividad de la producción agrícola en México, un análisis regional; Rodríguez, Espinosa y Márquez analizan todo acerca de el SIAL productor de quesos en Poxtla, competividad y territorio; Garza nos habla acerca de la intermediación financiera al servicio de la comunidad indígena: el fondo regional indígena Tarhiata Keri; Arroyo, Aguilar, Santoyo y Muñoz realizan un estudio acerca de la demanda de Importaciones de durazno (Prunus pérsica L. Batsch) en México procedentes de Estados Unidos de América (1982-2011); Loera y Sepúlveda analizan los parámetros de la productividad forestal en la producción de madera en rollo; Pérez, Morett y Tecpan realizan un análisis de factores sociales, ambientales y económicos del territorio rural cercano a la ciudad de México; Godínez, Figueroa y Pérez realizan un estudio acerca de la crisis económica mundial y su efecto sobre los flujos migratorios de América Latina; Magadán, Hernández y Escalona presentan la tipología de los sujetos sociales que intervienen en el mercado campesino de Ocotlán Oaxaca; Tavera y Cobos nos hablan de la normalización del proceso de compostaje: una opción para desarrollar el mercado de la composta; Piña y Pérez hablan acerca de la reestructuración del capitalismo y crisis política en México; Gonzáles, Rucoba y Ramírez realizan un estudio de la rentabilidad de la producción de miel en el municipio de León, Guanjuato; Ramírez, Gutiérrez y Figueroa realizan un estudio acerca de la economía del maíz en la región metropolitana, Chiapas, 2014; Bueno, Méndez y Cruz realizan un estudio y análisis de los centros de educación y cultura ambiental, necesidad de profesionalización Pedagógica de facilitadores ambientales; Pat, Caamal, Jerónimo y Mendoza presentan un estudio acerca de los Costos y competitividad de la producción del limón persa en el municipio de Martínez de la Torre, Veracruz. Vizuet presenta un trabajo de la construcción polisémica e histórica del concepto de la pobreza; Navarrete, Ríos y Arévalo presentan un estudio acerca de la producción ejidal de tomate rojo (Lycopersicum esculentum) en el DR-017, y su huella hídrica; Pérez y Piña hablan acerca de la productividad e inversión extranjera: La industria de Alimentos; Pérez, Figueroa, Godínez y Gómez presentan el trabajo sobre el sector primario en México; Pérez, Figueroa, Godínez y Gómez presentan acerca de los subsidios al campo como instrumento de política económica en México; Venegas, Perales y Del Valle realizan un estudio de rentabilidad de biodigestores y motogeneradores para diferentes tamaños de granjas porcinas en Michoacán

Ciencias Sociales: Economía y Humanidades HANDBOOK T-I

Se presenta un breve examen de la producción y comercialización de rosa en México; un estudio en México sobre el ingreso mínimo de las familias que identifica la línea de pobreza alimentaria en el área rural del sur de México, 2012; un pequeño estudio donde hablará sobre el análisis comparado del Sector Gubernamental y la Economía Mexicana desde la perspectiva de los eslabonamientos productivos Hirshman-Rasmuss; un estudio sobre los canales de comercialización de limón persa en el municipio de Martínez de la Torre, Veracruz; una análisis del comercio estratégico en el TLCAN: El Estado en la política agrícola de biocombustibles; también se expresan acerca de la importancia de la comercialización del café en México; un diagnóstico, retos del comercio electrónico en el Sector Agroindustrial Mexicano; trabajo nos muestra y habla sobre la inversión extranjera directa y su impacto en crecimiento de México, un análisis en prospectiva: 1999-2010; un estudio acerca sobre la importancia de la Banca en México; un trabajo acerca de la competitividad de la producción agrícola en México, un análisis regional; se analizan todo acerca de el SIAL productor de quesos en Poxtla, competividad y territorio; se habla acerca de la intermediación financiera al servicio de la comunidad indígena: el fondo regional indígena Tarhiata Keri; ademas un estudio acerca de la demanda de Importaciones de durazno (Prunus pérsica L. Batsch) en México procedentes de Estados Unidos de América (1982-2011); Loera y Sepúlveda analizan los parámetros de la productividad forestal en la producción de madera en rollo; un análisis de factores sociales, ambientales y económicos del territorio rural cercano a la ciudad de México; un estudio acerca de la crisis económica mundial y su efecto sobre los flujos migratorios de América Latina; Magadán, Hernández y Escalona presentan la tipología de los sujetos sociales que intervienen en el mercado campesino de Ocotlán Oaxaca; la normalización del proceso de compostaje: una opción para desarrollar el mercado de la composta; acerca de la reestructuración del capitalismo y crisis política en México; la rentabilidad de la producción de miel en el municipio de León, Guanjuato; la economía del maíz en la región metropolitana, Chiapas, 2014; análisis de los centros de educación y cultura ambiental, necesidad de profesionalización Pedagógica de facilitadores ambientales; los Costos y competitividad de la producción del limón persa en el municipio de Martínez de la Torre, Veracruz

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Expert Consensus Guidelines: How to safely perform minimally invasive anatomic liver resection

Background: The concept of minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). Methods: Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. Results: Seven clinical questions were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. Conclusions: The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR