A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis.

Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk.

Dose-Intensified Infliximab Rescue Therapy for Severe Ulcerative Colitis Does Not Reduce Short-term Colectomy Rates or Increase Postoperative Complications.

BACKGROUND: Dose-intensified rescue therapy with infliximab for hospitalized patients with ulcerative colitis has become increasingly popular in recent years. However, there is ongoing debate about both the efficacy of these regimens to reduce the rate of colectomy and the associated risks of increased infliximab exposure. OBJECTIVE: The purpose of this study was to compare the colectomy and postoperative complication rates in hospitalized patients with severe ulcerative colitis receiving standard infliximab induction therapy (3 doses of 5 mg/kg at weeks 0, 2, and 6) and dose-intensified regimens including a higher weight-based dosing or more rapid interval. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at an academic tertiary care hospital. PATIENTS: A total of 145 adult patients received inpatient rescue infliximab therapy for the treatment of ulcerative colitis between 2008 and 2020. MAIN OUTCOME MEASURES: The primary outcome was colectomy rate within 3 months of rescue therapy. Secondary outcomes include mid-term colectomy rates, as well as perioperative complications in patients receiving colectomy within 3 months of rescue infliximab initiation. RESULTS: The proportion of dose-intensified regimens increased over time. Unadjusted 3-month colectomy rates were 14% in patients who received standard rescue infliximab dosing, 16% in patients given a single dose-escalated dose, and 24% in patients given multiple inpatient dose-escalated doses. These rates were not statistically significantly different. Of the patients requiring colectomy within 3 months of infliximab rescue, those who received multiple inpatient doses of dose-escalated therapy had a higher percentage of colectomy during the initial hospitalization but a lower rate of perioperative complications. LIMITATIONS: This study was limited by the use of retrospective data and the limited power to account for the heterogeneity of disease. CONCLUSIONS: No significant difference was found in colectomy rates between patients receiving standard or dose-intensified regimens. However, dose-intensified regimens, including multiple inpatient doses given to patients with more severe disease, were not associated with a greater risk of perioperative complications. See Video Abstract at http://links.lww.com/DCR/B864 . LA TERAPIA DE RESCATE CON DOSIS INTENSIFICADA DE INFLIXIMAB EN COLITIS ULCEROSA GRAVE NO REDUCE LAS TASAS DE COLECTOMA A CORTO PLAZO NI AUMENTA LAS COMPLICACIONES POSOPERATORIAS: ANTECEDENTES:La terapia de rescate de dosis intensificada con infliximab para pacientes hospitalizados con colitis ulcerosa se ha vuelto cada vez más popular en los últimos años. Sin embargo, existe un debate en curso sobre la eficacia de estos regímenes para reducir la tasa de colectomía y los riesgos asociados a una mayor exposición al infliximab.OBJETIVO:El propósito de este estudio fue comparar las tasas de colectomía y complicaciones posoperatorias en pacientes hospitalizados con colitis ulcerosa grave que recibieron terapia estándar de inducción de infliximab (3 dosis de 5 mg/kg en las semanas 0, 2, 6) y regímenes de dosis intensificada que incluyen una dosificación más alta basada en el peso o intervalo más rápido.DISEÑO:Fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un hospital académico de tercer nivel.PACIENTES:Un total de 145 pacientes adultos que recibieron terapia de rescate con infliximab para el tratamiento de la colitis ulcerosa entre 2008 y 2020.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado principal fue la tasa de colectomía dentro de los 3 meses posteriores a la terapia de rescate. Los resultados secundarios incluyen tasas de colectomía a mediano plazo, así como las complicaciones perioperatorias en pacientes que reciben colectomía dentro de los 3 meses posteriores al inicio de infliximab de rescate.RESULTADOS:La proporción de regímenes de dosis intensificada aumentó con el tiempo. Las tasas de colectomía de 3 meses no ajustadas fueron del 14% en los pacientes que recibieron dosis estándar de infliximab de rescate, del 16% en los pacientes que recibieron una dosis única escalonada y del 24% en los pacientes que recibieron múltiples dosis hospitalarias escalonadas. Estas tasas no fueron estadísticamente significativas. De los pacientes que requirieron colectomía dentro de los 3 meses posteriores al rescate de infliximab, aquellos que recibieron terapia de múltiples dosis hospitalarias escalonadas tuvieron un mayor porcentaje de colectomía durante la hospitalización inicial pero una menor tasa de complicaciones perioperatorias.LIMITACIONES:Datos retrospectivos y poder limitado para explicar la heterogeneidad de la enfermedad.CONCLUSIONES:No se encontraron diferencias significativas en las tasas de colectomía entre los pacientes que recibieron regímenes estándar o de dosis intensificada. Sin embargo, los regímenes de dosis intensificadas, incluidas múltiples dosis hospitalarias administradas a pacientes con enfermedad más grave, no se asociaron con un mayor riesgo de complicaciones perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B864 . (Traducción-Dr. Ingrid Melo ).

Preventable Emergency Department Visits After Colorectal Surgery.

BACKGROUND: The emergency department plays a common and critical role in the treatment of postoperative patients. However, many quality improvement databases fail to record these interactions. As such, our understanding of the prevalence and etiology of postoperative emergency department visits in contemporary colorectal surgery is limited. Visits with potentially preventable etiologies represent a significant target for quality improvement, particularly in the current era of rapidly evolving postoperative and ambulatory care patterns. OBJECTIVE: We aimed to characterize postoperative emergency department visits and identify factors associated with these visits for potential intervention. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at an academic medical center. PATIENTS: Consecutive patients undergoing colectomy or proctectomy within the division of colorectal surgery at an academic medical center between 2014 and 2018 were included. MAIN OUTCOME MEASURES: Frequency and indication for emergency department visits, as well as clinical and sociodemographic factors associated with emergency department visits in the postoperative period, were included measures. RESULTS: From the 1763 individual operations, there were 207 emergency department visits from 199 patients (11%) within 30 days of discharge. Two thirds of emergency department visits led to readmission. Median (interquartile range) time to presentation was 8 days (4-16 d). Median time in the emergency department was 7.8 hours (6.0-10.1 h). One third of visits were identified as potentially preventable, most commonly for pain (17%) and stoma complications (excluding dehydration; 13%). A primary language other than English was associated with any postoperative emergency department visit risk ratio of 2.7 (95% CI, 1.3-5.3), as well as a preventable visit risk ratio of 3.6 (95% CI, 1.7-8.0). LIMITATIONS: This was a single-center study and a retrospective review. CONCLUSIONS: One third of emergency department visits after colorectal surgery are potentially preventable. Special attention should be directed toward those patients who do not speak English as a primary language. See Video Abstract at http://links.lww.com/DCR/B648. SE PUEDEN EVITAR LAS VISITAS AL SERVICIO DE URGENCIA DESPUS DE UNA CIRUGA COLORECTAL: ANTECEDENTES:Las unidades de emergencia tienen un rol fundamental en el periodo posterior a una cirugía. Sin embargo muchos de los registros en las bases de datos de estas secciones no son de buena calidad. Por esto analizar la prevalencia y etiología de las visitas postoperatorias en cirugía colorectal resulta ser bastante limitada. Para lograr una mejoría en la calidad es fundamental analizar las causas potencialmente evitables, especialmente al considerer la rapida evolucion de los parametros de medición actuales.OBJETIVO:Nuestro objetivo es caracterizar las visitas postoperatorias al servicio de urgencias e identificar los factores asociados potencialmente evitables.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Centro médico académico, 2014-2018.PACIENTES:Pacientes consecutivos sometidos a colectomía o proctectomía dentro de la división de cirugía colorrectal en un centro médico académico entre 2014 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:Frecuencia e indicación de las visitas al servicio de urgencias en el period postoperatorio: factores clínicos y sociodemográficos.RESULTADOS:De 1763 operaciones individuales, hubo 207 visitas al departamento de emergencias de 199 pacientes (11%) en los 30 días posteriores al alta. Dos tercios de las visitas al servicio de urgencias dieron lugar a readmisiones. La mediana [rango intercuartílico] de tiempo hasta la presentación fue de 8 [4-16] días. La mediana de tiempo en el servicio de urgencias fue de 7,8 [6-10,1] horas. Un tercio de las visitas se identificaron como potencialmente evitables, más comúnmente dolor (17%) y complicaciones del estoma (excluida la deshidratación) (13%). En los pacientes con poco manejo del inglés se asoció con una mayor frecuencia razón de visitas al departamento de emergencias posoperatorias [IC del 95%] 2,7 [1,3-5,3], así como opetancialmente evitables con un RR de 3,6 [1,7-8,0].LIMITACIONES:Estudio de un solo centro y revisión retrospectiva.CONCLUSIÓN:Al menos un tercio de las visitas al servicio de urgencias después de una cirugía colorrectal son potencialmente evitables. Se debe prestar especial atención a los pacientes que no hablan inglés como idioma materno. Consulte Video Resumen en http://links.lww.com/DCR/B648.

Correction to: Surgeon-delivered laparoscopic transversus abdominis plane blocks are non-inferior to anesthesia-delivered ultrasound-guided transversus abdominis plane blocks: a blinded, randomized non-inferiority trial.

The following text should have been included in the Acknowledgments.

Surgeon-delivered laparoscopic transversus abdominis plane blocks are non-inferior to anesthesia-delivered ultrasound-guided transversus abdominis plane blocks: a blinded, randomized non-inferiority trial.

BACKGROUND: The transversus abdominis plane (TAP) block is an important non-narcotic adjunct for post-operative pain control in abdominal surgery. Surgeons can use laparoscopic guidance for TAP block placement (LTAP), however, direct comparisons to conventional ultrasound-guided TAP (UTAPs) have been lacking. The aim of this study is to determine if surgeon placed LTAPs were non-inferior to anesthesia placed UTAPs for post-operative pain control in laparoscopic colorectal surgery. METHODS: This was a prospective, randomized, patient and observer blinded parallel-arm non-inferiority trial conducted at a single tertiary academic center between 2016 and 2018 on adult patients undergoing laparoscopic colorectal surgery. Narcotic consumption and pain scores were compared for LTAP vs. UTAP for 48 h post-operatively. RESULTS: 60 patients completed the trial (31 UTAP, 29 LTAP) of which 25 patients were female (15 UTAP, 10 LTAP) and the mean ages (SD) were 60.0 (13.6) and 61.5 (14.3) in the UTAP and LTAP groups, respectively. There was no significant difference in post-operative narcotic consumption between UTAP and LTAP at the time of PACU discharge (median [IQR] milligrams of morphine, 1.8 [0-4.5] UTAP vs. 0 [0-8.7] LTAP P = .32), 6 h post-operatively (5.4 [1.8-17.1] UTAP vs. 3.6 [0-12.6] LTAP P = .28), at 12 h post-operatively (9.0 [3.6-29.4] UTAP vs. 7.2 [0.9-22.5] LTAP P = .51), at 24 h post-operatively (9.0 [3.6-29.4] UTAP vs. 7.2 [0.9-22.5] LTAP P = .63), and 48 h post-operatively (39.9 [7.5-70.2] UTAP vs. 22.2 [7.5-63.8] LTAP P = .41). Patient-reported pain scores as well as pre-, intra-, and post-operative course were similar between groups. Non-inferiority criteria were met at all post-op time points up to and including 24 h but not at 48 h. CONCLUSIONS: Surgeon-delivered LTAPs are safe, effective, and non-inferior to anesthesia-administered UTAPs in the immediate post-operative period. TRIAL REGISTRY: The trial was registered at clinicaltrials.gov Identifier NCT03577912.

Ephrin type-B receptor 4 activation reduces neointimal hyperplasia in human saphenous vein in vitro.

BACKGROUND: Vein bypass is an essential therapy for patients with advanced peripheral and coronary artery disease despite development of neointimal hyperplasia. We have shown that stimulation of the receptor tyrosine kinase ephrin type-B receptor 4 (Eph-B4) with its ligand ephrin-B2 prevents neointimal hyperplasia in murine vein grafts. This study determines whether Eph-B4 in adult human veins is capable of phosphorylation and activation of downstream signaling pathways, as well as functional to release nitric oxide (NO) and prevent neointimal hyperplasia in vitro. METHODS: Discarded human saphenous veins were taken from the operating room and placed in organ culture without or with ephrin-B2/Fc (2 µg/mL) for 14 days, and the neointima/media ratio was measured in matched veins. Primary human umbilical vein endothelial cells were treated with ephrin-B2/Fc (2 µg/mL) and examined with quantitative polymerase chain reaction, Western blot, immunoassays, and for release of NO. Ephrin-B2/Fc (2 µg/mL) was placed on the adventitia of saphenous veins treated with arterial shear stress for 24 hours in a bioreactor and activated Eph-B4 examined with immunofluorescence. RESULTS: The baseline intima/media ratio in saphenous vein rings was 0.456 ± 0.097, which increased to 0.726 ± 0.142 in untreated veins after 14 days in organ culture but only to 0.630 ± 0.132 in veins treated with ephrin-B2/Fc (n = 19, P = .017). Ephrin-B2/Fc stimulated Akt, endothelial NO synthase and caveolin-1 phosphorylation, and NO release (P = .007) from human umbilical vein endothelial cells (n = 6). Ephrin-B2/Fc delivered to the adventitia stimulated endothelial Eph-B4 phosphorylation after 24 hours of arterial stress in a bioreactor (n = 3). CONCLUSIONS: Eph-B4 is present and functional in adult human saphenous veins, with intact downstream signaling pathways capable of NO release and prevention of neointimal hyperplasia in vitro. Adventitial delivery of ephrin-B2/Fc activates endothelial Eph-B4 in saphenous veins treated with arterial shear stress in vitro. These results suggest that stimulation of Eph-B4 function may be a candidate strategy for translation to human clinical trials designed to inhibit venous neointimal hyperplasia.

Late onset venous thoracic outlet syndrome following clavicle non-union fracture: A case report.

A 59-year-old woman was admitted three times over a six-month period with recurrent upper extremity deep venous thrombosis (UEDVT). It was determined that this patient was suffering from an unusual presentation of Paget-Schröetter syndrome secondary to a 20-year-old non-union of a midshaft clavicle fracture. Following thrombolysis the patient underwent resection and plate fixation of the clavicle fracture non-union. Despite the anatomic proximity of the subclavian vessels to the clavicle, vascular complications from fracture are rare. Treatment of midshaft clavicle fractures is often non-operative. Non-union rates are generally less than 10%, and easily treated secondarily without complication. Clavicular pseudo-arthroses from trauma have been implicated in the development of the thoracic outlet syndromes, however, onset 20 years after fracture has never before been reported.

Metabolic syndrome is associated with type II endoleak after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Type II endoleak is usually a benign finding after endovascular abdominal aortic aneurysm repair (EVAR). In some patients, however, type II endoleak leads to aneurysm sac expansion and the need for further intervention. We examined which factors, in particular the components of metabolic syndrome (MetS), would lead to an increase risk of endoleak after EVAR. METHODS: The medical records of all patients who underwent EVAR between 2002 and 2011 at the Veterans Affairs Connecticut Healthcare System were reviewed. MetS was defined as the presence of three or more of the following: hypertension (blood pressure ≥130 mm Hg/≥90 mm Hg), serum triglycerides ≥150 mg/dL, serum high-density lipoproteins ≤50 mg/dL for women and ≤40 mg/dL for men, body mass index ≥30 kg/m(2), and fasting blood glucose ≥110 mg/dL. Development of endoleak, including specific endoleak type, was determined by review of standard radiologic surveillance. RESULTS: During a 9-year period, 79 male patients (mean age, 73.5 years), underwent EVAR for infrarenal abdominal aortic aneurysm (mean 6.2 cm maximal transverse diameter). MetS was present in 52 patients (66%). The distribution of MetS factors among all patients was hypertension in 86%, hypertriglyceridemia in 72%, decreased high-density lipoprotein in 68%, diabetes in 37%, and a body mass index of ≥30 kg/m(2) in 30%. No survival difference was found between the MetS and non-MetS groups (P = .66). There was no difference in perioperative myocardial infarction or visceral ischemia immediately postoperatively between the two groups. Patients with MetS had a significant increase in acute kidney injury (n = 7, P = .0128). Endoleaks of all types were detected in 26% (n = 20) of all patients; patients with MetS had more endoleaks than patients without MetS (35% vs 7.4%, P = .0039). Of the 19 type II endoleaks, 79% were present at the time of EVAR and only 21% developed during surveillance; 95% had MetS (P = .0007). CONCLUSIONS: Type II endoleak after EVAR for abdominal aortic aneurysm is associated with MetS. Whether these patients are subject to more subsequent intervention due to sac expansion is unclear. MetS may be a factor to consider in the treatment of type II endoleak.

Vein graft adaptation and fistula maturation in the arterial environment.

Veins are exposed to the arterial environment during two common surgical procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both cases, veins adapt to the arterial environment that is characterized by different hemodynamic conditions and increased oxygen tension compared with the venous environment. Successful venous adaptation to the arterial environment is critical for long-term success of the vein graft or AVF and, in both cases, is generally characterized by venous dilation and wall thickening. However, AVF are exposed to a high flow, high shear stress, low-pressure arterial environment and adapt mainly via outward dilation with less intimal thickening. Vein grafts are exposed to a moderate flow, moderate shear stress, high-pressure arterial environment and adapt mainly via increased wall thickening with less outward dilation. We review the data that describe these differences, as well as the underlying molecular mechanisms that mediate these processes. Despite extensive research, there are few differences in the molecular pathways that regulate cell proliferation and migration or matrix synthesis, secretion, or degradation currently identified between vein graft adaptation and AVF maturation that account for the different types of venous adaptation to arterial environments.

Arterial shear stress reduces eph-b4 expression in adult human veins.

Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

Safety and Efficacy of Inpatient Infliximab Rescue Therapy for Acute Crohn's Disease Flares.

PURPOSE: Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare. BACKGROUND: Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear. METHODS: A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery. RESULTS: 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P = .01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3 days, P = .04). CONCLUSION: Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage.

The mouse aortocaval fistula recapitulates human arteriovenous fistula maturation.

Several models of arteriovenous fistula (AVF) have excellent patency and help in understanding the mechanisms of venous adaptation to the arterial environment. However, these models fail to exhibit either maturation failure or fail to develop stenoses, both of which are critical modes of AVF failure in human patients. We used high-resolution Doppler ultrasound to serially follow mice with AVFs created by direct 25-gauge needle puncture. By day 21, 75% of AVFs dilate, thicken, and increase flow, i.e., mature, and 25% fail due to immediate thrombosis or maturation failure. Mature AVF thicken due to increased amounts of smooth muscle cells. By day 42, 67% of mature AVFs remain patent, but 33% of AVFs fail due to perianastomotic thickening. These results show that the mouse aortocaval model has an easily detectable maturation phase in the first 21 days followed by a potential failure phase in the subsequent 21 days. This model is the first animal model of AVF to show a course that recapitulates aspects of human AVF maturation.

Delivery of ERAS Care in an Academic Hospital: An Analysis of Pathway Deviations and Obstacles to Adherence.

Enhanced Recovery after Surgery (ERAS) pathways in colorectal surgery improve outcomes and reduce disparities, but pathway adherence rates are variable. Sustainability of adherence following initial implementation, particularly in academic settings with trainee involvement, is underexplored. This study measures and describes ERAS adherence for 163 consecutive patients undergoing elective colorectal resection in an academic colorectal surgery department with a well-established ERAS pathway. Providers, including residents and nursing staff, were surveyed regarding pathway knowledge and obstacles to adherence. Adherence was higher preoperatively (80%) and intraoperatively (93%) than postoperatively (61%). Opioid-sparing analgesia and bowel motility agents were underdosed on up to 63% of hospital days, without clinical rationale in ≥50% of cases. Providers cited peer teaching (71%) as the primary source of pathway knowledge and identified individual surgeon preferences as an obstacle to adherence. Formalized ERAS pathway education, communication, and coordination among attending physicians are needed to reduce provider-driven deviation in an academic setting.

The Surgical Program in Innovation (SPIN): A Design and Prototyping Curriculum for Surgical Trainees.

PROBLEM: Health professions education does not routinely incorporate training in innovation or creative problem solving. Although some models of innovation education within graduate medical education exist, they often require participants' full-time commitment and removal from clinical training or rely upon participants' existing expertise. There is a need for curricula that teach innovation skills that will enable trainees to identify and solve unmet clinical challenges in everyday practice. To address this gap in surgical graduate education, the authors developed the Surgical Program in Innovation (SPIN). APPROACH: SPIN, a 6-month workshop-based curriculum, was established in 2016 in the Beth Israel Deaconess Medical Center Department of Surgery to teach surgical trainees the basics of the innovation process, focusing on surgeon-driven problem identification, product design, prototype fabrication, and initial steps in the commercialization process. Participating surgical residents and graduate students attend monthly workshops taught by medical, engineering, and medical technology (MedTech) industry faculty. Participants collaborate in teams to develop a novel device, fabricate a protype, and pitch their product to a panel of judges. OUTCOMES: From academic years 2015-2016 to 2017-2018, 49 trainees, including 41 surgical residents, participated in SPIN. Across this period, 13 teams identified an unmet need, ideated a solution, and designed and pitched a novel device. Ten teams fabricated prototypes. The 22 SPIN participants who responded to both pre- and postcourse surveys reported significant increases in confidence in generating problem statements, computer-aided design, fabrication of a prototype, and initial commercialization steps (product pitching and business planning). NEXT STEPS: Incorporating innovation education and design thinking into clinical training will prove essential in preparing future physicians to be lifelong problem finders and solvers. The authors plan to expand SPIN to additional clinical specialties, as well as to assess its impact in fostering future innovation and collaboration among program participants.

Modulation of lymphocyte-mediated tissue repair by rational design of heterocyclic aryl hydrocarbon receptor agonists.

Aryl hydrocarbon receptor (AHR) is an essential regulator of gut immunity and a promising therapeutic target for inflammatory bowel disease (IBD). Current AHR agonists are inadequate for clinical translation due to low activity, inadequate pharmacokinetics, or toxicity. We synthesized a structurally diverse library and used integrated computational and experimental studies to discover mechanisms governing ligand-receptor interaction and to design potent drug leads PY109 and PY108, which display physiochemical drug-likeness properties, desirable pharmacokinetic profiles, and low toxicity. In a murine model of dextran sulfate sodium-induced colitis, orally administered compounds increase interleukin-22 (IL-22) production and accelerate mucosal healing by modulating mucosal adaptive and innate lymphoid cells. AHR and IL-22 pathway induction was confirmed using RNA sequencing and characterization of the lymphocyte protein-protein interaction network. Significant induction of IL-22 was also observed using human T cells from patients with IBD. Our findings support rationally designed AHR agonists for IBD therapy.

Surgery in the age of biologics.

Since the introduction of the first anti-tumor necrosis factor antibodies in the late 1990s, biologic therapy has revolutionized the medical treatment of patients with inflammatory bowel disease (IBD). Nevertheless, surgery continues to play a significant role in treating IBD patients. Rates of intestinal resection in patients with Crohn's disease or colectomy in ulcerative colitis are reducing but not substantially over the long term. An increasing variety of biologic medications are now available to treat IBD patients in various clinical situations. Consequently, a number of questions persist about how biologic medications affect the need for surgery and overall course in IBD patients. Given the trend for earlier and more frequent use of biologic medications in IBD patients, a working knowledge of the effects of these medications on surgical decision-making and outcomes is essential for the practicing colorectal surgeon and gastroenterologist. This review seeks to summarize the relevant literature surrounding biologic use and IBD surgery with a focus on the effect of biologics on the frequency, type and complications of surgery in this 'age of biologics'.