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Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Objective: We aimed to determine a safe zone of intraoperative fluid management associated with the lowest postoperative complication rates without increased acute kidney injury (AKi) risk for elective colorectal surgery patients. Background: To date, standard practice within institutions, let alone national expectations related to fluid administration, are limited. This fact has perpetuated a quality gap. Methods: Elective colorectal surgeries between 2018 and 2020 were included. Unadjusted odds ratios (ORs) for postoperative ileus, prolonged LOS, and AKi were plotted against the rate of intraoperative RL infusion (mL/ kg/h) and total intraoperative volume. Binary logistic regression analysis, including fluid volumes as a confounder, was used to identify risk factors for postoperative complications. Results: A total of 2900 patients were identified. Of them, 503 (17.3%) patients had ileus, 772 (26.6%) patients had prolonged LOS, and 240 (8.3%) patients had AKI. The intraoperative fluid resuscitation rate (mg/kg/h) was less impactful on postoperative ileus, LOS, and AKI than the total amount of intraoperative fluid. A total fluid administration range between 300 mL and 2.7 L was associated with the lowest complication rate. Total intraoperative RL ≥2.7 L was independently associated with a higher risk of ileus (adjusted OR 1.465; 95% confidence interval 1.154–1.858) and prolonged LOS (adjusted OR 1.300; 95% confidence interval 1.047–1.613), but not AKI. Intraoperative RL ≤300 mL was not associated with an increased risk of AKI. Conclusion: Total intraoperative RL ≥2.7 L was independently associated with postoperative ileus and prolonged LOS in elective colorectal surgery patients. A new potential standard for intraoperative fluids will require anesthesia case planning (complexity and duration) to ensure total fluid volume meets this new opportunity to improve care.

BACKGROUND: Although the overall adoption of minimally invasive surgery in the nonemergent management of ulcerative colitis is established, little is known about its utilization in emergency settings. OBJECTIVE: The goal of this study was to assess rates of urgent and emergent surgery over time in the era of emerging biologic therapies and to highlight the current practice in the United States regarding the utilization of minimally invasive surgery for urgent and emergent indications for ulcerative colitis. DESIGN: This was a retrospective analysis study. SETTINGS: Data were collected from the American College of Surgeons National Quality Improvement Program database. PATIENTS: All adult patients who underwent emergent or urgent colectomy for ulcerative colitis were included. MAIN OUTCOME MEASURES: Rates of emergency operations over time and utilization trends of minimally invasive surgery in urgent and emergent settings were assessed. Unadjusted and adjusted overall, surgical, and medical 30-day complication rates were compared between open and minimally invasive surgery. RESULTS: A total of 2219 patients were identified. Of those, 1515 patients (68.3%) underwent surgery in an urgent setting and 704 (31.7%) as an emergency. Emergent cases decreased over time (21% in 2006 to 8% in 2018; p < 0.0001). However, the rate of urgent surgeries has not significantly changed (42% in 2011 to 46% in 2018; p = 0.44). Minimally invasive surgery was offered to 70% of patients in the urgent group (1058/1515) and 22.6% of emergent indications (159/704). Overall, minimally invasive surgery was increasingly utilized over the study period in urgent (38% in 2011 to 71% in 2018; p < 0.0001) and emergent (0% in 2005 to 42% in 2018; p < 0.0001) groups. Compared to minimally invasive surgery, open surgery was associated with a higher risk of surgical, septic, and overall complications, and prolonged hospitalization. LIMITATIONS: This study was limited by its retrospective nature of the analysis. CONCLUSION: Based on a nationwide analysis from the United States, minimally invasive surgery has been increasingly and safely implemented for emergent and urgent indications for ulcerative colitis. Although the sum of emergent and urgent cases remained the same over the study period, emergency cases decreased significantly over the study period, which may be related to improved medical treatment options and a collaborative, specialized team approach. See Video Abstract at http://links.lww.com/DCR/B847. CIRUGÍA DE URGENCIA Y EMERGENCIA PARA LA COLITIS ULCEROSA EN LOS ESTADOS UNIDOS EN LA ERA MÍNIMAMENTE INVASIVA Y DE TERAPIA BIOLÓGICA ANTECEDENTES: Si bien se ha establecido la adopción generalizada de la cirugía mínimamente invasiva en el tratamiento electivo de la colitis ulcerosa, se sabe poco sobre su utilización en situaciones de emergencia. OBJETIVO: Evaluar las tasas de cirugía de urgencia a lo largo del tiempo en la era de las terapias biológicas emergentes y destacar la práctica actual en los Estados Unidos con respecto a la utilización de la cirugía mínimamente invasiva para las indicaciones de urgencia y emergencia de la colitis ulcerosa. DISEÑO: Análisis retrospectivo. AJUSTES: Base de datos del Programa Nacional de Mejoramiento de la Calidad del Colegio Americano de Cirujanos. PACIENTES: Todos los pacientes adultos que se sometieron a colectomía de emergencia o urgencia por colitis ulcerosa. MEDIDAS DE RESULTADO: Se evaluaron las tasas de operaciones de emergencia a lo largo del tiempo y las tendencias de utilización de la cirugía mínimamente invasiva en entornos de urgencia y emergencia. Se compararon las tasas de complicaciones generales, quirúrgicas y médicas de 30 días no ajustadas y ajustadas entre la cirugía abierta y la mínimamente invasiva. RESULTADOS: Se identificaron un total de 2.219 pacientes. De ellos, 1.515 pacientes (68,3%) fueron intervenidos de urgencia y 704 (31,7%) de emergencia. Los casos emergentes disminuyeron con el tiempo (21% en 2006 a 8% en 2018; p <0,0001). Sin embargo, la tasa de cirugías urgentes no ha cambiado significativamente (42% en 2011 a 46% en 2018, p = 0,44). Se ofreció cirugía mínimamente invasiva al 70% de los pacientes del grupo urgente (1.058 / 1.515) y al 22,6% de las emergencias (159/704). En general, la cirugía mínimamente invasiva se utilizó cada vez más durante el período de estudio en grupos urgentes (38% en 2011 a 71% en 2018; p <0,0001) y emergentes (0% en 2005 a 42% en 2018; p <0,0001). En comparación con la cirugía mínimamente invasiva, la cirugía abierta se asoció con un mayor riesgo de complicaciones generales, quirúrgicas, sépticas y hospitalización prolongada. LIMITACIONES: Carácter retrospectivo del análisis. CONCLUSIÓNES: Basado en un análisis nacional de los Estados Unidos, la cirugía mínimamente invasiva se ha implementado de manera creciente y segura para las indicaciones emergentes y urgentes de la colitis ulcerosa. Si bien la suma de casos emergentes y urgentes permaneció igual durante el período de estudio, los casos de emergencia disminuyeron significativamente, lo que puede estar relacionado con mejores opciones de tratamiento médico y un enfoque de equipo colaborativo y especializado. Consulte Video Resumen en http://links.lww.com/DCR/B847. (Traducción—Dr. Felipe Bellolio)

BACKGROUND: The efficacy of preoperative oral antibiotics alone compared with mechanical and oral antibiotic bowel preparation in minimally invasive surgery is still a matter of debate. OBJECTIVE: This study aimed to assess the trend of surgical site infection rates in parallel to the utilization of bowel preparation modality over time for minimally invasive colorectal surgeries in the United States. DESIGN: This study is a retrospective analysis. SETTINGS: The American College of Surgeons National Surgical Quality Improvement Program database was the source of data for this study. PATIENTS: Adult patients who underwent elective colorectal surgery and reported bowel preparation modality were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the trends and the comparison of surgical site infection rates for mutually exclusive groups according to the underlying disease (colorectal cancer, IBD, and diverticular disease) who underwent bowel preparation using oral antibiotics or combined mechanical and oral antibiotic bowel preparation. Patients who underwent rectal surgery were analyzed separately. RESULTS: A total of 30,939 patients were included. Of them, 12,417 (40%) had rectal resections. Over the 7-year study period, mechanical and oral antibiotic bowel preparation utilization increased from 29.3% in 2012 to 64.0% in 2018; p < 0.0001 at the expense of no preparation and mechanical bowel preparation alone. Similarly, oral antibiotics utilization increased from 2.3% in 2012 to 5.5% in 2018; p < 0.0001. For patients with colon cancer, patients who had oral antibiotics alone had higher superficial surgical site infection rates than patients who had combined mechanical and oral antibiotic bowel preparation (1.9% vs 1.1%; p = 0.043). Superficial, deep, and organ space surgical site infection rates were similar for all other comparative colon surgery groups (cancer, IBD, and diverticular disease). Patients with rectal cancer who had oral antibiotics had higher rates of deep surgical site infection (0.9% vs 0.1%; p = 0.004). However, superficial, deep, and organ space surgical site infection rates were similar for all other comparative rectal surgery groups. LIMITATIONS: This study was limited by the retrospective nature of the analysis. CONCLUSION: This study revealed widespread adoption of mechanical and oral antibiotic bowel preparation and increased adoption of oral antibiotics over the study period. Surgical site infection rates are similar from a clinical relevance standpoint among most comparative groups, questioning the systematic preoperative addition of mechanical bowel preparation to oral antibiotics alone in all patients for minimally invasive colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B828. PREPARACIÓN INTESTINAL CON ANTIBIÓTICOS ORALES SIN PREPARACIÓN MECÁNICA EN CIRUGÍAS COLORRECTALES MÍNIMAMENTE INVASIVAS: PRÁCTICA ACTUAL Y PERSPECTIVAS FUTURAS ANTECEDENTES: La eficacia de los antibióticos orales preoperatorios solos en comparación con la preparación intestinal mecánica mas antibióticos orales en la cirugía mínimamente invasiva es un tema de debate que todavía esta en curso. OBJETIVO: Este estudio tuvo como objetivo evaluar la tendencia de las tasas de infección del sitio quirúrgico en relacion a la utilización de la modalidad de preparación intestinal a lo largo del tiempo en cirugías colorrectales mínimamente invasivas en los Estados Unidos. DISEÑO: Análisis retrospectivo. ENTORNO CLINICO: Base de datos del Programa Nacional de Mejoramiento de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos. PACIENTES: Pacientes adultos sometidos a cirugía colorrectal electiva y reportados con modalidad de preparación intestinal. PRINCIPALES MEDIDAS DE VALORACIÓN: Tendencias y comparacion de las tasas de infección del sitio quirúrgico para grupos mutuamente excluyentes según la enfermedad subyacente (cáncer colorrectal, enfermedad inflamatoria intestinal y enfermedad diverticular) que se sometieron a preparación intestinal usando antibióticos orales exclusivamente o preparación intestinal mecánica combinada con antibióticos orales. Los pacientes que se sometieron a cirugía rectal se analizaron por separado. RESULTADOS: Se incluyeron un total de 30.939 pacientes. De ellos, 12.417 (40%) se sometieron a resecciones rectales. Durante el período de estudio de siete años, la preparación mecánica del intestino y la utilización de antibióticos orales aumentó del 29,3% en 2012 al 64,0% en 2018; p < 0,0001 sobre la no preparación y de la preparación intestinal mecánica exclusivamente. De manera similar, la utilización de antibióticos orales ha aumentado del 2,3% en 2012 al 5,5% en 2018; p < 0,0001. Para los pacientes con cáncer de colon, los pacientes que recibieron antibióticos orales solos tuvieron mayores tasas de infección superficial del sitio quirúrgico en comparación con los pacientes que recibieron una preparación intestinal mecánica combinada con antibióticos orales (1,9% frente a 1,1%; p = 0,043). Las tasas de infección superficial, profundo del sitio quirúrgico y de los compartimientos intraabdominales fueron similares para todos los demás grupos de cirugía de colon (cáncer, enfermedad inflamatoria intestinal y enfermedad diverticular). Los pacientes con cáncer de recto que recibieron antibióticos orales tuvieron tasas más altas de infección profunda del sitio quirúrgico (0,9% frente a 0,1%; p = 0,004). Sin embargo, las tasas de infección del sitio quirúrgico superficial, profundo y de los compartimientos intraabdominales fueron similares comparativamente para todos los demás grupos de cirugía rectal. LIMITACIONES: Carácter retrospectivo del análisis. CONCLUSIONES: Este estudio reveló la adopción generalizada de preparación intestinal mecánica y antibióticos orales y una mayor aceptación de antibióticos orales durante el período de estudio. Las tasas de infección del sitio quirúrgico parecen ser similares desde un punto de vista de relevancia clínica entre la mayoría de los grupos comparados, lo que cuestiona la adición preoperatoria sistemática de preparación intestinal mecánica a antibióticos orales solos en todos los pacientes para cirugía colorrectal mínimamente invasiva. Consulte Video Resumen en http://links.lww.com/DCR/B828. (Traducción— Dr. Ingrid Melo)

Abstract Aims Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS. Methods and results We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65–0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96–1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments. Conclusion In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS. Study registration number This study is registered in PROSPERO (CRD42021258603). Key Question A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored. Key Finding In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality. Take Home Message A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome.

Abstract Context Pseudohypoparathyroidism type Ib (PHP1B) is characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone resistance in the proximal renal tubules. Maternal pathogenic STX16/GNAS variants leading to maternal epigenetic GNAS changes impair expression of the stimulatory G protein alpha-subunit (Gsα) thereby causing autosomal dominant PHP1B. In contrast, genetic defects responsible for sporadic PHP1B (sporPHP1B) remain mostly unknown. Objective Determine whether PHP1B encountered after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) causes GNAS remethylation defects similar to those in sporPHP1B. Design Retrospective analysis. Results Nine among 36 sporPHP1B patients investigated since 2000, all with loss of methylation (LOM) at the 3 maternal GNAS differentially methylated regions (DMRs) and gain of methylation at the paternal NESP DMR, had been conceived through IVF or ICSI. Besides abnormal GNAS methylation, IVF/ICSI PHP1B cases revealed no additional imprinting defects. Three of these PHP1B patients have dizygotic twins, and 4 have IVF/ICSI-conceived siblings, all with normal GNAS methylation; 2 unaffected younger siblings were conceived naturally. Conclusion Sporadic and IVF/ICSI-conceived PHP1B patients revealed indistinguishable epigenetic changes at all 4 GNAS DMRs, thus suggesting a similar underlying disease mechanism. Given that remethylation at the 3 maternal DMRs occurs during oogenesis, male factors are unlikely to cause LOM postfertilization. Instead, at least some of the sporPHP1B variants could be caused by a defect or defects in an oocyte-expressed gene that is required for fertility and for re-establishing maternal GNAS methylation imprints. It remains uncertain, however, whether the lack of GNAS remethylation alone and the resulting reduction in Gsα expression is sufficient to impair oocyte maturation.