Modern Trends in Surgical Site Infection Rates for Colorectal Surgery: A National Surgical Quality Improvement Project Study 2013-2020.

BACKGROUND: Few studies have investigated trends in global surgical site infection rates in colorectal surgery in the past decade. OBJECTIVE: This study seeks to describe changes in rates of different surgical site infections from 2013 to 2020, identify risk factors for surgical site infection occurrence, and evaluate the association of minimally invasive surgery and infection rates in colorectal resections. DESIGN: A retrospective analysis of the National Surgical Quality Improvement Program database 2013-2020 identifying patients undergoing open or laparoscopic colorectal resections by procedure codes was performed. Patient demographic information, comorbidities, procedures, and complications data were obtained. Univariable and multivariable logistic regression analyses were performed. SETTING: This was a retrospective study. PATIENTS: A total of 279,730 patients received colorectal resections from 2013 to 2020. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of surgical site infection, divided into superficial, deep incisional, and organ space infections. RESULTS: There was a significant decrease in rates of superficial infections ( p < 0.01) and deep incisional infections ( p < 0.01) from 5.9% in 2013 to 3.3% in 2020 and from 1.4% in 2013 to 0.6% in 2020, respectively, but a rise in organ space infections ( p < 0.01) from 5.2% in 2013 to 7.1% in 2020. Minimally invasive techniques were associated with decreased odds of all surgical site infections compared to open techniques ( p < 0.01) in multivariate analysis, and adoption of minimally invasive techniques increased from 59% in 2013 to 66% in 2020. LIMITATIONS: The study is limited by its retrospective nature and variables available for analysis. CONCLUSIONS: Superficial and deep incisional infection rates have significantly decreased, likely secondary to improved adoption of minimally invasive techniques and infection prevention bundles. Organ space infection rates continue to increase. Additional research is warranted to clarify current recommendations for mechanical bowel preparation and oral antibiotic use as well as to study novel interventions to decrease postoperative infection occurrence. See Video Abstract . TENDENCIAS MODERNAS EN LAS TASAS DE INFECCIN DEL SITIO QUIRRGICO PARA CIRUGA COLORRECTAL UN ESTUDIO DEL PROYECTO NACIONAL DE MEJORA DE LA CALIDAD QUIRRGICA: ANTECEDENTES:Hay pocos estudios que investiguen las tendencias en las tasas globales de infección del sitio quirúrgico en cirugía colorrectal en la última década.OBJETIVO:Este estudio busca describir cambios en las tasas de diferentes infecciones del sitio quirúrgico entre 2013 y 2020, identificar factores de riesgo para la aparición de ISQ y evaluar la asociación de la cirugía mínimamente invasiva y las tasas de infección en resecciones colorrectales.DISEÑO:Se realizó un análisis retrospectivo de la base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica 2013-2020 que identifica a los pacientes sometidos a resecciones colorrectales abiertas o laparoscópicas mediante códigos de procedimiento. Se obtuvo información demográfica de los pacientes, comorbilidades, procedimientos y datos de complicaciones. Se realizó regresión logística univariable y multivariable.AJUSTE:Este fue un estudio retrospectivo.PACIENTES:Un total de 279,730 pacientes recibieron resección colorrectal entre 2013 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:La medida de resultado primaria fue la tasa de infección del sitio quirúrgico, dividida en infecciones superficiales, incisionales profundas y del espacio de órganos.RESULTADOS:Hubo una disminución significativa en las tasas de infecciones superficiales (p < 0,01) e infecciones incisionales profundas ( p < 0,01) del 5,9% en 2013 al 3,3% en 2020 y del 1,4% en 2013 al 0,6% en 2020, respectivamente. pero un aumento en las infecciones del espacio de los órganos ( p < 0,01) del 5,2 % en 2013 al 7,1 % en 2020. El uso de técnicas mínimamente invasivas se asoció con una disminución de las probabilidades de todas las infecciones del sitio quirúrgico en comparación con las técnicas abiertas ( p < 0,01) en el análisis multivariado y la adopción de técnicas mínimamente invasivas aumentó del 59% en 2013 al 66% en 2020.LIMITACIONES:El estudio está limitado por la naturaleza retrospectiva y las variables disponibles para el análisis.CONCLUSIONES:Las tasas de infección superficial y profunda han disminuido significativamente, probablemente debido a una mejor adopción de técnicas mínimamente invasivas y esquemas de prevención de infecciones. Las tasas de infección del espacio de los órganos continúan aumentando. Se justifica realizar investigaciones adicionales para aclarar las recomendaciones actuales para la preparación intestinal mecánica y el uso de antibióticos orales, así como para estudiar intervenciones novedosas para disminuir la aparición de infecciones posoperatorias. (Traducción-Dr. Yolanda Colorado ).

Cylindromatosis drives synapse pruning and weakening by promoting macroautophagy through Akt-mTOR signaling.

The lysine-63 deubiquitinase cylindromatosis (CYLD) is long recognized as a tumor suppressor in immunity and inflammation, and its loss-of-function mutations lead to familial cylindromatosis. However, recent studies reveal that CYLD is enriched in mammalian brain postsynaptic densities, and a gain-of-function mutation causes frontotemporal dementia (FTD), suggesting critical roles at excitatory synapses. Here we report that CYLD drives synapse elimination and weakening by acting on the Akt-mTOR-autophagy axis. Mice lacking CYLD display abnormal sociability, anxiety- and depression-like behaviors, and cognitive inflexibility. These behavioral impairments are accompanied by excessive synapse numbers, increased postsynaptic efficacy, augmented synaptic summation, and impaired NMDA receptor-dependent hippocampal long-term depression (LTD). Exogenous expression of CYLD results in removal of established dendritic spines from mature neurons in a deubiquitinase activity-dependent manner. In search of underlying molecular mechanisms, we find that CYLD knockout mice display marked overactivation of Akt and mTOR and reduced autophagic flux, and conversely, CYLD overexpression potently suppresses Akt and mTOR activity and promotes autophagy. Consequently, abrogating the Akt-mTOR-autophagy signaling pathway abolishes CYLD-induced spine loss, whereas enhancing autophagy in vivo by the mTOR inhibitor rapamycin rescues the synaptic pruning and LTD deficits in mutant mice. Our findings establish CYLD, via Akt-mTOR signaling, as a synaptic autophagy activator that exerts critical modulations on synapse maintenance, function, and plasticity.

Dorsomedial prefrontal hypoexcitability underlies lost empathy in frontotemporal dementia.

Empathic function is essential for the well-being of social species. Empathy loss is associated with various brain disorders and represents arguably the most distressing feature of frontotemporal dementia (FTD), a leading form of presenile dementia. The neural mechanisms are unknown. We established an FTD mouse model deficient in empathy and observed that aged somatic transgenic mice expressing GGGGCC repeat expansions in C9orf72, a common genetic cause of FTD, exhibited blunted affect sharing and failed to console distressed conspecifics by affiliative contact. Distress-induced consoling behavior activated the dorsomedial prefrontal cortex (dmPFC), which developed profound pyramidal neuron hypoexcitability in aged mutant mice. Optogenetic dmPFC inhibition attenuated affect sharing and other-directed consolation in wild-type mice, whereas chemogenetically enhancing dmPFC excitability rescued empathy deficits in mutant mice, even at advanced ages when substantial cortical atrophy had occurred. These results establish cortical hypoexcitability as a pathophysiological basis of empathy loss in FTD and suggest a therapeutic strategy.

C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo.

The GGGGCC repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, it is not known which dysregulated molecular pathways are primarily responsible for disease initiation or progression. We established an inducible mouse model of poly(GR) toxicity in which (GR)80 gradually accumulates in cortical excitatory neurons. Low-level poly(GR) expression induced FTD/ALS-associated synaptic dysfunction and behavioral abnormalities, as well as age-dependent neuronal cell loss, microgliosis and DNA damage, probably caused in part by early defects in mitochondrial function. Poly(GR) bound preferentially to the mitochondrial complex V component ATP5A1 and enhanced its ubiquitination and degradation, consistent with reduced ATP5A1 protein level in both (GR)80 mouse neurons and patient brains. Moreover, inducing ectopic Atp5a1 expression in poly(GR)-expressing neurons or reducing poly(GR) level in adult mice after disease onset rescued poly(GR)-induced neurotoxicity. Thus, poly(GR)-induced mitochondrial defects are a major driver of disease initiation in C9ORF72-related ALS/FTD.