Preoperative Opioid Prescription Is Associated With Major Complications in Patients With Crohn's Disease Undergoing Elective Ileocolic Resection.

BACKGROUND: Opioid use has grown exponentially over the last decade. The effect of preoperative opioid prescription in patients with Crohn's disease undergoing surgery is unknown. OBJECTIVE: The purpose of this study was to identify whether preoperative opioid prescription is associated with adverse postoperative outcomes in Crohn's disease. DESIGN: This is a single-institution retrospective observational study. SETTINGS: This study was performed at an academic tertiary care center. Details of preoperative opioid prescription were collected from the Kentucky All-Schedule Prescription Electronic Reporting database and the electronic databases of bordering states. PATIENTS: Consecutive patients undergoing ileocolic resection for Crohn's disease from 2014 to 2018 were included. MAIN OUTCOME MEASURES: The outcomes examined were major complications (Clavien-Dindo ≥3a), length of stay, and 30-day hospital readmission. RESULTS: Fifty one of 118 patients were prescribed opioids within 6 months preoperatively (range, 0-33,760 morphine milligram equivalents). Patients with preoperative opioid prescription compared with no preoperative opioid prescription required more daily opioids during hospital admission (p = 0.024). Nineteen patients had a major postoperative complication (preoperative opioid prescription: 26% (13/51) vs no preoperative opioid prescription: 9% (6/67)). On multivariable analysis, preoperative opioid prescription (OR = 2.994 (95% CI, 1.024-8.751); p = 0.045) was a significant risk factor for a major complication. Preoperative opioid prescription was associated with increased length of stay (p < 0.001) and was a risk factor for readmission (OR = 2.978 (95% CI, 1.075-8.246); p = 0.036). Twenty-four patients were readmitted. Using a cutoff for higher opioid prescription of 300 morphine milligram equivalents within 6 months preoperation (eg, 60 tablets of hydrocodone/acetaminophen 5/325), preoperative opioid prescription remained a risk factor for major postoperative complications (OR = 3.148 (95% CI, 1.110-8.928); p = 0.031). LIMITATIONS: This was a retrospective study and could not assess nonprescribed opioid use. CONCLUSIONS: Preoperative opioid prescription was a significant risk factor for adverse outcomes in patients with Crohn's disease undergoing elective ileocolic resection. See Video Abstract at http://links.lww.com/DCR/B113. LA PRESCRIPCIÓN PREOPERATORIA DE OPIOIDES SE ASOCIA CON COMPLICACIONES MAYORES EN PACIENTES CON ENFERMEDAD DE CROHN SOMETIDOS A RESECCIÓN ILEOCÓLICA ELECTIVA: El uso de opioides ha crecido exponencialmente en la última década. Se desconoce el efecto de la prescripción preoperatoria de opioides en pacientes con enfermedad de Crohn sometidos a cirugía.Identificar si la prescripción preoperatoria de opioides está asociada con resultados postoperatorios adversos en la enfermedad de Crohn.Este es un estudio observacional retrospectivo de una sola institución.Este estudio se realizó en un centro académico de atención terciaria. Los detalles de la prescripción preoperatoria de opiáceos se recopilaron de la base de datos de "Kentucky All-Schedule Prescription Electronic Reporting" y de las bases de datos electrónicas de los estados fronterizos.Pacientes consecutivos sometidos a resección ileocólica por enfermedad de Crohn entre 2014-2018.Los resultados examinados fueron complicaciones mayores (Clavien-Dindo ≥3a), duración de la estancia y el reingreso hospitalario de 30 días.A cincuenta y uno de 118 pacientes se le recetaron opioides dentro de los 6 meses preoperatorios (rango, 0 a 33,760 equivalentes de miligramos de morfina). Los pacientes con prescripción preoperatoria de opioides en comparación con ninguna prescripción preoperatoria de opioides requirieron más opioides diarios durante el ingreso hospitalario (p = 0,024). Diecinueve pacientes tuvieron una complicación postoperatoria importante (prescripción preoperatoria de opioides: 26% [13/51] frente a ninguna prescripción preoperatoria de opioides: 9% [6/67]). En el análisis multivariable, la prescripción de opioides preoperatorios (OR = 2.994, IC 95%: 1.024-8.751, p = 0.045) fueron factores de riesgo significativos para una complicación mayor. La prescripción preoperatoria de opioides se asoció con un aumento de la duración de la estadía (p <0.001) y fue un factor de riesgo para el reingreso (OR = 2.978, IC 95%: 1.075-8.246, p = 0.036). Veinticuatro pacientes fueron readmitidos. Utilizando un límite para una mayor prescripción de opioides de 300 miligramos equivalentes de morfina dentro de los 6 meses previos a la operación (p. Ej., 60 tabletas de hidrocodona / acetaminofén 5/325), la prescripción preoperatoria de opioides siguió siendo un factor de riesgo para complicaciones postoperatorias mayores (OR = 3.148 IC 95%: 1.110-8.928, p = 0.031).Este fue un estudio retrospectivo y no pudo evaluar el uso de opioides no prescritos.La prescripción preoperatoria de opioides fue un factor de riesgo significativo para los resultados adversos en pacientes con enfermedad de Crohn sometidos a resección ileocólica electiva. Consulte Video Resumen en http://links.lww.com/DCR/B113.

CRISPR-mediated gene editing for the surgeon scientist.

Tremendous advances have occurred in gene editing during the past 20 years with the development of a number of systems. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9) system represents an exciting area of research. This review examines both the relevant studies pertaining to the history, current status, and modifications of this system, in comparison with other gene-editing systems and future applications, and limitations of the CRISPR-Cas9 gene-editing system, with a focus on applications of relevance to the surgeon scientist. The CRISPR-Cas9 system was described initially in 2012 for gene editing in bacteria and then in human cells, and since then, a number of modifications have improved the efficiency and specificity of gene editing. Clinical studies have been limited because further research is required to verify its safety in patients. Some clinical trials in oncology have opened, and early studies have shown that gene editing may have a particular role in the field of organ transplantation and in the care of trauma patients. Gene editing is likely to play an important role in future research in many aspects of the surgery arena.

Long-term outcomes following ileal pouch-anal anastomosis in patients with indeterminate colitis.

BACKGROUND: The advisability of performing ileal pouch-anal anastomosis for patients with indeterminate colitis is debated. Indeterminate colitis is found in up to 15% of inflammatory bowel disease colectomy specimens. We determined long-term outcomes in patients diagnosed with indeterminate colitis undergoing ileal pouch-anal anastomosis. METHODS: Fifty-six patients were included with a mean follow-up of 14 ± 7 years. Long-term behavior was defined based on surgeon assessment as "Crohn disease-like" in patients who subsequently developed clear signs of Crohn disease and as "non-Crohn disease-like." Long-term function was assessed using the Cleveland Global Quality of Life and Pouch Functional Score. RESULTS: Thirty-nine percent of patients developed Crohn disease-like behavior, and 61% developed non-Crohn disease-like behavior. Both groups experienced a high rate of pouchitis (57%). Crohn disease-like patients required more anti-inflammatory/immunomodulatory medications (95% vs 18%, P < .001), dilatations for afferent-limb strictures (41% vs 0%, P < .001), and pouch reoperations (32% vs 6%, P = .02). Eight patients required pouch excision or diversion (7 with Crohn disease-like behavior). The Pouch Functional Score was equivalent between groups. CONCLUSION: Long-term function after ileal pouch-anal anastomosis for the majority of indeterminate colitis patients was good. Approximately 40% eventually exhibited Crohn disease-like behavior, but the majority had acceptable function and quality of life. Ileal pouch-anal anastomosis is an appropriate surgical option for indeterminate colitis patients after informed consent.

The effect of IκK-16 on lipopolysaccharide-induced impaired monocytes.

This study focuses on impaired monocyte function, which occurs in some patients after trauma, major elective surgery, or sepsis. This monocyte impairment increases the risk of secondary infection and death. We aimed to determine the influence IκK-16 had on monocytes using an ex-vivo model of human monocyte impairment. We included the effects of the well-studied comparators interferon-gamma (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on impaired monocytes. Primary human monocytes were stimulated with 10ng/mL of lipopolysaccharide (LPS) for 16h and then challenged with 100ng/mL LPS to assess the monocyte inflammatory response. Treatment regimens, consisting of either IκK-16, IFN-γ, or GM-CSF, were administered to impaired monocytes near the time of initial LPS stimulation. Stimulation with 10ng/mL LPS initially promoted a pro-inflammatory response but subsequently impaired production of both tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) and decreased HLA-DR expression. IκK-16 treatment attenuated TNF-α production and programmed death-ligand 1 (PD-L1) expression and increased IL-10 and CD14 expression. IFN-γ treatment increased TNF-α production as well as PD-L1 and HLA-DR expression. In conclusion, limiting early inflammation with IκK-16 suppresses TNF-α production and PD-L1 expression but enhances IL-10 production and preserves CD14 expression for potential future exposure to infective stimuli.

IκK-16 decreases miRNA-155 expression and attenuates the human monocyte inflammatory response.

Excessive inflammatory responses in the surgical patient may result in cellular hypo-responsiveness, which is associated with an increased risk of secondary infection and death. microRNAs (miRNAs), such as miR-155, are powerful regulators of inflammatory signalling pathways including nuclear factor κB (NFκB). Our objective was to determine the effect of IκK-16, a selective blocker of inhibitor of kappa-B kinase (IκK), on miRNA expression and the monocyte inflammatory response. In a model of endotoxin tolerance using primary human monocytes, impaired monocytes had decreased p65 expression with suppressed TNF-α and IL-10 production (P < 0.05). miR-155 and miR-138 levels were significantly upregulated at 17 h in the impaired monocyte (P < 0.05). Notably, IκK-16 decreased miR-155 expression with a corresponding dose-dependent decrease in TNF-α and IL-10 production (P < 0.05), and impaired monocyte function was associated with increased miR-155 and miR-138 expression. In the context of IκK-16 inhibition, miR-155 mimics increased TNF-α production, while miR-155 antagomirs decreased both TNF-α and IL-10 production. These data demonstrate that IκK-16 treatment attenuates the monocyte inflammatory response, which may occur through a miR-155-mediated mechanism, and that IκK-16 is a promising approach to limit the magnitude of an excessive innate inflammatory response to LPS.