Simultaneous inhibition of two neutrophil serine proteases by the S. aureus innate immune evasion protein EapH2.

Extracellular adherence protein domain (EAP) proteins are high-affinity, selective inhibitors of neutrophil serine proteases (NSP), including cathepsin-G (CG) and neutrophil elastase (NE). Most Staphylococcus aureus isolates encode for two EAPs, EapH1 and EapH2, that contain a single functional domain and share 43% identity with one another. Although structure/function investigations from our group have shown that EapH1 uses a globally similar binding mode to inhibit CG and NE, NSP inhibition by EapH2 is incompletely understood due to a lack of NSP/EapH2 cocrystal structures. To address this limitation, we further studied NSP inhibition by EapH2 in comparison with EapH1. Like its effects on NE, we found that EapH2 is a reversible, time-dependent, and low nanomolar affinity inhibitor of CG. We characterized an EapH2 mutant which suggested that the CG binding mode of EapH2 is comparable to EapH1. To test this directly, we used NMR chemical shift perturbation to study EapH1 and EapH2 binding to CG and NE in solution. Although we found that overlapping regions of EapH1 and EapH2 were involved in CG binding, we found that altogether distinct regions of EapH1 and EapH2 experienced changes upon binding to NE. An important implication of this observation is that EapH2 might be capable of binding and inhibiting CG and NE simultaneously. We confirmed this unexpected feature by solving crystal structures of the CG/EapH2/NE complex and demonstrating their functional relevance through enzyme inhibition assays. Together, our work defines a new mechanism of simultaneous inhibition of two serine proteases by a single EAP protein.

Staphylococcal peroxidase inhibitor (SPIN): Investigation of the inhibitory N-terminal domain via a stabilizing disulfide insertion.

Staphylococcus aureus secretes an array of small proteins that inhibit key enzyme-catalyzed reactions necessary for proper function of the human innate immune system. Among these, the Staphylococcal Peroxidase Inhibitor, SPIN, blocks the activity of myeloperoxidase (MPO) and thereby disrupts the HOCl-generating system of neutrophils. Previous studies on S. aureus SPIN have shown that it relies on a C-terminal α-helical bundle domain to mediate initial binding to MPO, but requires a disordered N-terminal region to fold into a ß-hairpin conformation to inhibit MPO activity. To further investigate the structure/function relationship of SPIN, we introduced two cysteine residues into its N-terminal region to trap SPIN in its MPO-bound conformation and characterized the modified protein, which we refer to here as SPIN-CYS. Although control experiments confirmed the presence of the disulfide bond in SPIN-CYS, solution structure determination revealed that the N-terminal region of SPIN-CYS adopted a physically constrained series of lariat-like structures rather than a well-defined ß-hairpin. Nevertheless, SPIN-CYS exhibited a gain in inhibitory potency against human MPO when compared to wild-type SPIN. This gain of function persisted even in the presence of deleterious mutations within the C-terminal α-helical bundle domain. Surface plasmon resonance studies showed that the gain in potency arose through an increase in apparent affinity of SPIN-CYS for MPO, which was driven primarily by an increased association rate with MPO when compared to wild-type SPIN. Together, this work provides new information on the coupled binding and folding events required to manifest biological activity of this unusual MPO inhibitor.

Room for Improvement: The Impact of Guideline-Recommended Extended Thromboprophylaxis in Patients Undergoing Abdominal Surgery for Colorectal and Anal Cancer at a Tertiary Referral Center.

BACKGROUND: Venous thromboembolism occurs in approximately 2% of patients undergoing abdominal and pelvic surgery for cancers of the colon, rectum, and anus and is considered preventable. The American Society of Colon and Rectal Surgeons recommends extended prophylaxis in high-risk patients, but there is low adherence to the guidelines. OBJECTIVE: This study aims to analyze the impact of venous thromboembolism risk-guided prophylaxis in patients undergoing elective abdominal and pelvic surgeries for colorectal and anal cancers from 2016 to 2021. DESIGN: This was a retrospective analysis. SETTING: The study was conducted at a multisite tertiary referral academic health care system. PATIENTS: Patients who underwent elective abdominal or pelvic surgery for colon, rectal, or anal cancer. MAIN OUTCOME MEASURES: Receipt of Caprini-guided venous thromboembolism prophylaxis, 90-day postoperative rate of deep vein thrombosis, pulmonary embolism, venous thromboembolism, and bleeding events. RESULTS: A total of 3504 patients underwent elective operations, of whom 2224 (63%) received appropriate thromboprophylaxis in the inpatient setting. In the postdischarged cohort of 2769 patients, only 2% received appropriate thromboprophylaxis and no thromboembolic events were observed. In the group receiving inappropriate thromboprophylaxis, at 90 days postdischarge, the deep vein thrombosis, pulmonary embolism, and venous thromboembolism rates were 0.60%, 0.40%, and 0.88%, respectively. Postoperative bleeding was not different between the 2 groups. LIMITATIONS: Limitations to our study include its retrospective nature, use of aggregated electronic medical records, and single health care system experience. CONCLUSION: Most patients in our health care system undergoing abdominal or pelvic surgery for cancers of the colon, rectum, and anus were discharged without appropriate Caprini-guided venous thromboembolism prophylaxis. Risk-guided prophylaxis was associated with decreased rates of inhospital and postdischarge venous thromboembolism without increased bleeding complications. See Video Abstract . MARGEN DE MEJORA EL IMPACTO DE LA TROMBOPROFILAXIS RECOMENDADA POR LAS DIRECTRICES EN PACIENTES SOMETIDOS A CIRUGA ABDOMINAL POR CNCER COLORRECTAL Y ANAL EN UN CENTRO DE REFERENCIA TERCIARIO: ANTECEDENTES:El tromboembolismo venoso ocurre en aproximadamente el 2% de los pacientes sometidos a cirugía abdominal y pélvica por cánceres de colon, recto y ano, y se considera prevenible. La Sociedad Estadounidense de Cirujanos de Colon y Recto recomienda una profilaxis prolongada en pacientes de alto riesgo, pero el cumplimiento de las directrices es bajo.OBJETIVO:Este estudio tiene como objetivo analizar el impacto de la profilaxis guiada por el riesgo de tromboembolismo venoso (TEV) en pacientes sometidos a cirugías abdominales y pélvicas electivas por cáncer colorrectal y anal entre 2016 y 2021.DISEÑO:Este fue un análisis retrospectivo.AJUSTE:El estudio se llevó a cabo en un sistema de salud académico de referencia terciaria de múltiples sitios.PACIENTES:Pacientes sometidos a cirugía abdominal o pélvica electiva por cáncer de colon, recto o ano.PRINCIPALES MEDIDAS DE RESULTADO:Recepción de profilaxis de tromboembolismo venoso guiada por Caprini, tasa postoperatoria de 90 días de trombosis venosa profunda, embolia pulmonar, tromboembolismo venoso y eventos de sangrado.RESULTADOS:Un total de 3.504 pacientes se sometieron a operaciones electivas, de los cuales 2.224 (63%) recibieron tromboprofilaxis adecuada en el ámbito hospitalario. En el cohorte de 2.769 pacientes después del alta, solo el 2% recibió tromboprofilaxis adecuada en la que no se observaron eventos tromboembólicos. En el grupo que recibió tromboprofilaxis inadecuada, a los 90 días después del alta, las tasas de trombosis venosa profunda, embolia pulmonar y tromboembolia venosa fueron del 0,60%, 0,40% y 0,88%, respectivamente. El sangrado posoperatorio no fue diferente entre los dos grupos.LIMITACIONES:Las limitaciones de nuestro estudio incluyen su naturaleza retrospectiva, el uso de registros médicos electrónicos agregados y la experiencia de un solo sistema de atención médica.CONCLUSIÓN:La mayoría de los pacientes en nuestro sistema de salud sometidos a cirugía abdominal o pélvica por cánceres de colon, recto y ano fueron dados de alta sin una profilaxis adecuada de TEV guiada por Caprini. La profilaxis guiada por el riesgo se asoció con menores tasas de tromboembolismo venoso hospitalario y dado de alta sin un aumento de las complicaciones de sangrado. (Traducción-Dr. Aurian Garcia Gonzalez ).

Management of Acute Diverticulitis in Immunocompromised Patients-The Mayo Clinic Experience.

BACKGROUND: Acute diverticulitis in immunocompromised patients is associated with high morbidity and mortality rates with either medical or surgical treatment. Thus, management approach is controversial, especially for patients presenting with nonperforated disease. OBJECTIVE: This study aimed to report the Mayo clinic experience of acute diverticulitis management in immunocompromised patients. DESIGN: This design is based on a retrospective cohort study. SETTING: This study was conducted with institutional data composed from 3 tertiary referral centers. PATIENTS: Immunocompromised patients presenting with acute diverticulitis at 3 Mayo clinic sites between 2016 and 2020 were included. MAIN OUTCOME MEASURES: The main outcome measures were the management algorithm and short-term outcomes. RESULTS: Immunocompromised patients presenting with acute uncomplicated diverticulitis (86) were all managed nonoperatively at presentation with a success rate of 93% (80/86). Two patients (2.3%, 2/86) required surgery during the same admission, and 4 patients (4.8%, 4/84) had 30-day readmission. Complicated diverticulitis patients with abscess (22) were all managed nonoperatively first with a success rate of 95.4% (21/22). One patient (4.6%, 1/22) required surgery during the same admission. All the patients who presented with obstruction (2), fistula (1), or free perforation (11) underwent surgery except one who chose hospice. Overall, the major complication rate was 50% (8/16) and mortality rate was 18.8% (3/16) among patients who underwent surgery during the same admission. For patients who presented with perforated diverticulitis, the mortality rate was 27.3% (3/11), compared with 0% (0/111) for patients who presented with nonperforated disease. LIMITATIONS: This cohort was limited by its retrospective nature and heterogeneity of the patient population. CONCLUSIONS: Nonoperative management was safe and feasible for immunocompromised patients with colonic diverticulitis without perforation at our center. Perforated colonic diverticulitis in immunocompromised patients was associated with high morbidity and mortality rate. See Video Abstract at http://links.lww.com/DCR/B988 .MANEJO DE LA DIVERTICULITIS AGUDA EN PACIENTES INMUNOCOMPROMETIDOS: EXPERIENCIA DE LA CLINICA MAYOANTECEDENTES:La diverticulitis aguda en pacientes inmunocomprometidos se asocia con una alta tasa de morbilidad y mortalidad con el tratamiento médico o quirúrgico. Por lo tanto, el enfoque de manejo es controvertido, especialmente para pacientes que presentan enfermedad no perforada.OBJETIVO:El propósito fue informar la experiencia de la clínica Mayo en el manejo de la diverticulitis aguda en pacientes inmunocomprometidos.DISEÑO:Este es un estudio de cohorte retrospectivoENTORNO CLÍNICO:Este estudio se realizó con datos institucionales compuestos de tres centros de referencia terciarios.PACIENTES:Se incluyeron pacientes inmunocomprometidos que presentaron diverticulitis aguda en tres sitios de la clínica Mayo entre 2016 y 2020.RESULTADO PRINCIPAL:Algoritmo de gestión y resultados a corto plazo.RESULTADOS:Los pacientes inmunocomprometidos que presentaban diverticulitis aguda no complicada (86) fueron tratados de forma no quirúrgica en la presentación inicial con una tasa de éxito del 93 % (80/86). Dos pacientes (2,3%, 2/86) requirieron cirugía durante el mismo ingreso y cuatro pacientes (4,8%, 4/84) tuvieron reingreso a los 30 días. Todos los pacientes con diverticulitis complicada con absceso (22) fueron tratados primero de forma no quirúrgica con una tasa de éxito del 95,4 % (21/22). Un paciente (4,6%, 1/22) requirió cirugía durante el mismo ingreso. Todos los pacientes que presentaron obstrucción (2), fístula (1) o perforación libre (11) fueron intervenidos excepto uno que optó por hospicio. La tasa global de complicaciones mayores fue del 50 % (8/16) y la tasa de mortalidad fue del 18,8 % (3/16) entre los pacientes que se sometieron a cirugía durante el mismo ingreso. Para los pacientes que presentaban diverticulitis perforada, la tasa de mortalidad fue del 27,3 % (3/11), en comparación con el 0 % (0/111) de los pacientes que presentaban enfermedad no perforada.LIMITACIONES:Esta cohorte estuvo limitada por su naturaleza retrospectiva y la heterogeneidad de la población de pacientes. CONCLUSINES: El manejo no quirúrgico fue seguro y factible para pacientes inmunocomprometidos con diverticulitis colónica sin perforación en nuestro centro. La diverticulitis colónica perforada en pacientes inmunocomprometidos se asoció con una alta tasa de morbilidad y mortalidad. Consulte Video Resumen en http://links.lww.com/DCR/B988 . (Traducción- Dr. Ingrid Melo ).

Re-resection of Microscopically Positive Margins Found on Intraoperative Frozen Section Analysis Does Not Result in a Survival Benefit in Patients Undergoing Surgery and Intraoperative Radiation Therapy for Locally Recurrent Rectal Cancer.

BACKGROUND: Intraoperative frozen-section analysis provides real-time margin resection status that can guide intraoperative decisions made by the surgeon and radiation oncologist. For patients with locally recurrent rectal cancer undergoing surgery and intraoperative radiation therapy, intraoperative re-resection of positive margins to achieve negative margins is common practice. OBJECTIVE: This study aimed to assess whether re-resection of positive margins found on intraoperative frozen-section analysis improves oncologic outcomes. DESIGN: This is a retrospective cohort study. SETTINGS: This study was an analysis of a prospectively maintained multicenter database. PATIENTS: All patients who underwent surgical resection of locally recurrent rectal cancer with intraoperative radiation therapy between 2000 and 2015 were included and followed for 5 years. Three groups were compared: initial R0 resection, initial R1 converted to R0 after re-resection, and initial R1 that remained R1 after re-resection. Grossly positive margin resections (R2) were excluded. MAIN OUTCOME MEASURES: The primary outcome measures were 5-year overall survival, recurrence-free survival, and local re-recurrence. RESULTS: A total of 267 patients were analyzed (initial R0 resection, n = 94; initial R1 converted to R0 after re-resection, n = 95; initial R1 that remained R1 after re-resection, n = 78). Overall survival was 4.4 years for initial R0 resection, 2.7 years for initial R1 converted to R0 after re-resection, and 2.9 years for initial R1 that remained R1 after re-resection ( p = 0.01). Recurrence-free survival was 3.0 years for initial R0 resection and 1.8 years for both initial R1 converted to R0 after re-resection and initial R1 that remained R1 after re-resection ( p ≤ 0.01). Overall survival did not differ for patients with R1 and re-resection R1 or R0 ( p = 0.62). Recurrence-free survival and freedom from local re-recurrence did not differ between groups. LIMITATIONS: This study was limited by the heterogeneous patient population restricted to those receiving intraoperative radiation therapy. CONCLUSIONS: Re-resection of microscopically positive margins to obtain R0 status does not appear to provide a significant survival advantage or prevent local re-recurrence in patients undergoing surgery and intraoperative radiation therapy for locally recurrent rectal cancer. See Video Abstract at http://links.lww.com/DCR/B886 . LA RERESECCIN DE LOS MRGENES MICROSCPICAMENTE POSITIVOS ENCONTRADOS DE MANERA INTRAOPERATORIA MEDIANTE LA TCNICA DE CRIOSECCIN, NO DA COMO RESULTADO UN BENEFICIO DE SUPERVIVENCIA EN PACIENTES SOMETIDOS A CIRUGA Y RADIOTERAPIA INTRAOPERATORIA PARA EL CNCER RECTAL LOCALMENTE RECIDIVANTE: ANTECEDENTES:El análisis de la ténica de criosección para los margenes positivos encontrados de manera intraoperatoria proporciona el estado de la resección del margen en tiempo real que puede guiar las decisiones intraoperatorias tomadas por el cirujano y el oncólogo radioterapeuta. Para los pacientes con cáncer de recto localmente recurrente que se someten a cirugía y radioterapia intraoperatoria, la re-resección intraoperatoria de los márgenes positivos para lograr márgenes negativos es una práctica común.OBJETIVO:Evaluar si la re-resección de los márgenes positivos encontrados en el análisis de la ténica por criosecciónde manera intraoperatorios mejora los resultados oncológicos.DISEÑO:Estudio de cohorte retrospectivo.AJUSTES:Análisis de una base de datos multicéntrica mantenida de forma prospectiva.POBLACIÓN:Todos los pacientes que se sometieron a resección quirúrgica de cáncer de recto localmente recurrente con radioterapia intraoperatoria entre 2000 y 2015 fueron incluidos y seguidos durante 5 años. Se compararon tres grupos: resección inicial R0, R1 inicial convertido en R0 después de la re-resección y R1 inicial que permaneció como R1 después de la re-resección. Se excluyeron las resecciones de márgenes macroscópicamente positivos (R2).PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia global a cinco años, supervivencia sin recidiva y recidiva local.RESULTADOS:Se analizaron un total de 267 pacientes (resección inicial R0 n = 94, R1 inicial convertido en R0 después de la re-resección n = 95, R1 inicial que permaneció como R1 después de la re-resección n = 78). La supervivencia global fue de 4,4 años para la resección inicial R0, 2,7 años para la R1 inicial convertida en R0 después de la re-resección y 2,9 años para la R1 inicial que permaneció como R1 después de la re-resección ( p = 0,01). La supervivencia libre de recurrencia fue de 3,0 años para la resección inicial R0 y de 1,8 años para el R1 inicial convertido en R0 después de la re-resección y el R1 inicial que permaneció como R1 después de la re-resección ( p ≤ 0,01). La supervivencia global no difirió para los pacientes con R1 y re-resección R1 o R0 ( p = 0,62). La supervivencia libre de recurrencia y la ausencia de recurrencia local no difirieron entre los grupos.LIMITACIONES:Población de pacientes heterogénea, restringida a aquellos que reciben radioterapia intraoperatoria.CONCLUSIONES:La re-resección de los márgenes microscópicamente positivos para obtener el estado R0 no parece proporcionar una ventaja de supervivencia significativa o prevenir la recurrencia local en pacientes sometidos a cirugía y radioterapia intraoperatoria para el cáncer de recto localmente recurrente. Consulte Video Resumen en http://links.lww.com/DCR/B886 . (Traducción-Dr. Daniel Guerra ).

Risk of malignancy and outcomes of surgically resected presacral tailgut cysts: A current review of the Mayo Clinic experience.

AIM: The aim of this study was to describe the surgical management, outcomes and risk of malignancy of presacral tailgut cysts. METHOD: A retrospective analysis of all patients who underwent resection of tailgut cyst at Mayo Clinic in Arizona, Florida and Minnesota between 2008 and 2020 was performed. Demographics, presentation, evaluation, surgical approach, postoperative complications, pathology and recurrence rates were reviewed. RESULTS: Seventy-three patients were identified (81% female) with a mean age of 45 years. Thirty-nine patients (53%) were symptomatic, most commonly with pelvic pain (26 patients). Digital rectal examination identified a palpable mass in 68%. Mean tumour size was 6 cm. Resection was primarily performed through a posterior approach (77%, n = 56), followed by a transabdominal approach (18%, n = 13) and a combined approach (5%, n = 4). Six patients underwent a minimally invasive resection (laparoscopic/robotic). Coccygectomy or distal sacrectomy was performed in 41 patients (56%). Complete resection was achieved in 94% of patients. Thirty-day morbidity occurred in 18% and was most commonly wound related; there was no mortality. Malignancy was identified in six patients (8%). For the 30 patients with follow-up greater than 1 year, the median follow-up was 39 months (range 1.0-11.1 years). Local recurrence was identified in three patients and distant metastatic disease in one patient. CONCLUSION: The rate of malignancy in presacral tailgut cysts based on this current review was 8%. Overall recurrence was 5% at a median of 24 months.

Cost drivers of locally advanced rectal cancer treatment-An analysis of a leading healthcare insurer.

BACKGROUND: To evaluate the economic burden of locally advanced rectal cancer (LARC) treatment from a society perspective through analysis of health insurance-derived data of commercially insured and Medicare Advantage (MA) patients. METHODS: Retrospective cost analysis of patients undergoing rectal resection within a multimodal (neoadjuvant chemoradiation + adjuvant chemotherapy) treatment strategy between January 1, 2010 and October 31, 2018, using the claims OptumLabs Data Warehouse database. RESULTS: In total, 1738 (935 commercial and 803 MA) patients were included. Overall treatment costs totaled $230,881,746 (on average $183 653 ± 82 384 per commercially insured and $73 681 ± 32 917 per MA patient). Cost distribution according to category (commercially insured patients) was: 29.92% related to outpatient care (follow-up visits/diagnostics), radiotherapy: 21.83%, index resection: 20.62%, chemotherapy: 17.44%, surgical inpatient: 6.32%, medical inpatient: 3.28%, emergency room: 0.58%. Relative cost distribution of the index resection itself differed marginally between the three approaches and was 21.49% for open, 19.30% for laparoscopic, and 20.93% for robotic surgery. Relative cost distributions of neoadjuvant, adjuvant, and outpatient treatments remained unchanged, independently of the surgical approach. This representation was similar in MA patients. CONCLUSION: Index-surgery related costs were outweighed by costs related to oncological and outpatient workup/follow-up treatments independently of both surgical approach and insurance type.

Surgical Management of Recurrent Uncomplicated Diverticulitis.

Sigmoid diverticulitis represents a most common gastroenterological diagnosis in the western world. There has been a significant change in the management of recurrent uncomplicated diverticulitis in the last 10 to 15 years. The absolute number of previous episodes is not used as criteria to recommend surgery anymore. Young age is no longer considered to be an indication for more aggressive surgical treatment. It is accepted that subsequent episodes of diverticulitis are not significantly worse than the first episode. Laparoscopic surgery is now the standard of care for elective surgery for diverticulitis where expertise is available. There is a consensus that decision to perform sigmoid colectomy should be individualized, after careful risk benefit assessment.

Robotic Harvest of a Rectus Abdominis Muscle Flap After Abdominoperineal Resection.

INTRODUCTION: As multidisciplinary treatment modalities for rectal cancer continue to evolve, neoadjuvant chemoradiation then surgical resection is a common approach. Robotic-assisted abdominoperineal resection is becoming more prevalent in part because of better visualization and instrument mobility within the pelvis. After abdominoperineal resection, postoperative perineal wound complications remain a significant risk. Pelvic reconstruction lowers this risk, and a pedicled rectus abdominis muscle flap is frequently used to achieve this. Traditional flap harvest requires laparotomy, resulting in violation of both rectus sheaths and a large midline scar. Robotic harvest of the rectus abdominis muscle for pelvic reconstruction after abdominoperineal resection is a novel approach with foreseeable benefits. TECHNIQUE: After completion of abdominoperineal resection, 2 additional trocars are inserted in the lateral abdomen, and the robot is reoriented toward the posterior abdominal wall. The peritoneum and posterior rectus sheath are incised, and dissection is carried superiorly and inferiorly in a sagittal plane to reveal the rectus abdominis muscle. The muscle body is separated from the anterior rectus sheath. Once the inferior epigastric artery is identified, the superior pole of the muscle is transected. Continued lateral dissection ensures flap mobility for placement within the pelvis. After obtaining proper reach, the robot is undocked, and the flap is sutured in place through the perineal defect. RESULTS: After trocar placement and robot repositioning, both the colorectal and plastic surgeons trade places at the console. Robotic flap harvest precludes the need for laparotomy. The anterior rectus sheath remains unviolated and the patient avoids an additional midline scar. The aforementioned benefits of robot-assisted abdominoperineal resection, namely increased visualization and maneuverability, were also found applicable when robotically harvesting this flap. CONCLUSIONS: This technique exemplifies an additional minimally invasive technique for patients pursuing abdominoperineal resection. With knowledge of this novel approach, surgeons can better tailor their operations to benefit the patient.

Primary Colorectal Lymphoma: Institutional Experience and Review of a National Database.

BACKGROUND: Primary colorectal lymphoma is rare, representing 0.2% to 0.6% of all colorectal cancers. Because of its low incidence and histologic variety, no treatment guidelines exist. OBJECTIVE: The purpose was to report the experience of primary colorectal lymphoma in an institutional and a national cohort. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted with institutional data composed of 3 tertiary referral centers and national data. PATIENTS: Patients with primary colorectal lymphoma were identified within the Mayo Clinic (1990-2016) and the Surveillance, Epidemiology, and End Results database (1990-2014). MAIN OUTCOME MEASURES: Primary outcomes were overall and 5-year survival. RESULTS: For the institutional cohort (N = 82), 5-year survival was 79.9%. Five-year survival was higher for rectal (88.4%) than for colon tumors (77.2%; p = 0.004). On multivariable analysis, age <50 years was associated with higher overall survival (p = 0.04). Left-sided colon masses and aggressive histological subtypes were associated with worse survival (0.04 and 0.03). No effect of treatment modality on survival was noted. For the national cohort (N = 2942), 5-year survival was 58.4%. Five-year survival for rectal tumors was 61.0% and 57.8% for colon tumors. On multivariable analysis, factors associated with improved survival were age <70 y, (p < 0.0001), female sex (p = 0.005), right-sided masses (p = 0.02), and diagnoses after 2000 compared with 1990-1999 (p < 0.0001). Aggressive pathology (p < 0.0001) and stage III or stage IV presentation compared with stage I (p = 0.02 and p < 0.0001) were associated with worse survival. LIMITATIONS: The institutional cohort was limited by sample size to describe treatment effect on survival. A major limitation of the national cohort was the ability to describe treatment modalities other than surgery, including chemotherapy and/or no additional treatment. CONCLUSIONS: Poorer survival was noted in elderly patients and in those with aggressive pathology. An overall survival advantage was seen in women in the national cohort. Currently, optimal strategies should follow a patient-centered multidisciplinary approach. See Video Abstract at http://links.lww.com/DCR/A807. LINFOMA COLORECTAL PRIMARIO: EXPERIENCIA INSTITUCIONAL Y REVISIÓN DE UNA BASE DE DATOS NACIONAL: El linfoma colorectal primario es poco frecuente, representando del 0.2% al 0.6% de todos los cánceres colorectales. Debido a su baja incidencia y variedad histológica, no existen guías de tratamiento. OBJETIVO: El propósito fue reportar la experiencia en linfoma colorectal primario en una cohorte institucional y una nacional. DISEÑO:: Este fue un estudio de cohorte retrospectivo. ESCENARIO: El estudio se realizó con datos institucionales provenientes de 3 centros de referencia terciarios y datos nacionales. PACIENTES: Se identificaron pacientes con linfoma colorectal primario en la base de datos de la Clínica Mayo (1990-2016) y en la base de datos de vigilancia, epidemiología y resultados finales [Surveillance, Epidemiology, and End Results database (1990-2014)]. PRINCIPALES MEDIDAS DE RESULTADO: Los resultados primarios fueron la sobrevida general y a 5 años. RESULTADOS: Para la cohorte institucional (N = 82), la sobrevida a 5 años fue de 79.9%. La sobrevida a cinco años fue mayor en tumores rectales (88.4%) que en los de colon (77.2%; p = 0.004). En el análisis multivariable, la edad <50 años se asoció con una mayor sobrevida general (p = 0,04). Las masas de colon izquierdo y los subtipos histológicos agresivos se asociaron con una peor sobrevida (0.04 y 0.03). No se observó ningún efecto según la modalidad de tratamiento en la sobrevida. Para la cohorte nacional (N = 2942), la sobrevida a 5 años fue del 58.4%. La sobrevida a cinco años fue de 61.0% para los tumores rectales y 57.8% para los tumores de colon. En el análisis multivariable, los factores asociados con una mayor sobrevida fueron edad <70 años, (p <0.0001), sexo femenino (p = 0.005), masas derechas (p = 0.02) y los casos diagnósticados después del año 2000 comparados con los de 1990-1999 (p <0.0001). Histopatología agresiva (p <0.0001) y presentación en estadio III o estadio IV en comparación con estadio I (p = 0.02 y p <0.0001) se asociaron con una peor sobrevida. LIMITACIONES: La cohorte institucional estuvo limitada por el tamaño de la muestra para describir el efecto del tratamiento en la sobrevida. Una limitación mayor en la cohorte nacional fue la habilidad para describir modalidades de tratamiento distintas a la cirugía, incluyendo quimioterapia y/o ningún tratamiento adicional. CONCLUSIONES: Una menor sobrevida fue documentada en pacientes de edad avanzada y en aquellos con histopatología agresiva. Se observó ventaja en cuanto a sobrevida general en las mujeres de la cohorte nacional. Actualmente, las estrategias óptimas deben de seguir un abordaje multidisciplinario centrado en cada paciente. Vea el abstract en video en http://links.lww.com/DCR/A807.

Factors Influencing Colon and Rectal Surgery Residency Program Selection.

BACKGROUND: Little information exists to help colon and rectal surgery residency programs determine which factors applicants find important when selecting a training program. Our aim was to identify factors applicants find pertinent in the selection of their desired colon and rectal surgery residency program. METHODS: After the 2016 and 2017 National Resident Matching Program (The Match), a 58-question anonymous web-based survey was sent to all trainees who applied to our colon and rectal surgery residency program to determine factors applicants find important in selecting colon and rectal surgery residency training programs. RESULTS: Of 196 invitation emails sent, a total of five were returned with unidentifiable addresses leaving 191 surveys for possible completion. The survey response rate was 62.8% (n = 120). The top 10 areas identified as strongly to moderately influential in residency program selection included faculty experience, balanced training, operative volume, operative complexity, autonomy, faculty reputation, employment opportunities, Accreditation Council for Graduate Medical Education index case volumes, office/clinic complexity, and current resident/fellow input. CONCLUSIONS: Multiple elements were identified as strongly to moderately influential when selecting a training program. Training programs can use these named factors for resident recruitment, development, and self-assessment.

Infectious Surgical Complications are Not Dichotomous: Characterizing Discordance Between Administrative Data and Registry Data.

OBJECTIVE: To characterize reasons for discordance between administrative data and registry data in the determination of postoperative infectious complications. BACKGROUND: Data regarding the occurrence of postoperative surgical complications are identified through either administrative or registry data. Rates of complications vary significantly between these two types of data; the reasons for this are not well-understood. METHODS: The occurrence of 30-day inpatient infectious complications (pneumonia, sepsis, surgical site infection, and urinary tract infection) was compared between the NSQIP and administrative mechanisms at 4 academic hospitals between 2012 and 2014. In each situation where the NSQIP and administrative data were discordant regarding the occurrence of a specific complication, a 2-clinician chart abstraction was performed to characterize the reasons for discordance as (i) administrative coding error, (ii) NSQIP coding error, (iii) "question of criteria", where the discordance was the result of differences in criteria, or (iv) "dually incorrect", where both data sources coded the complication incorrectly. RESULTS: The cohort included 19,163 patients undergoing surgery in 4 different academic hospitals. Rates of infectious complications varied up to 5-fold between the two data sources. A total of 717 discordant complications were identified. Of these, the greatest portion (43%) was due to "question of criteria," followed by administrative coding error (37%), NSQIP error (15%), and dually incorrect (5%). CONCLUSIONS: With a goal of improving existing mechanisms for measuring surgical quality, definitions for the occurrence of a postoperative complication need to be developed and applied consistently. Progress toward this goal will enable patients and payers to better take advantage of recent advances in healthcare data transparency.

Colonoscopic Perforations.

Colonoscopy is the gold standard for colon cancer screening. It has led to a decrease in the incidence of colorectal cancer mortality. Colon perforation is a feared complication of this procedure with high morbidity and substantial mortality. Due to the high volume of colonoscopies performed, the absolute number of colonoscopic perforations is relatively high. It leads to a substantial cost to the patient and the health system. Understanding the mechanisms and the risk factors may help in preventing perforation. Traditionally, a laparotomy with creation of a stoma was used to address this complication. However, minimally invasive techniques such as laparoscopy and endoluminal repairs are being used more commonly now. More surgeons are favoring primary anastomosis (with or without a diverting loop ileostomy) than a Hartmann procedure.

Transanal Approach to Rectal Polyps and Cancer.

A transanal approach to rectal polyp and cancer excision is often an appropriate alternative to conventional rectal resection, and has a lower associated morbidity. There has been a steady evolution in the techniques of transanal surgery over the past 30 years. It started with traditional transanal excision and was revolutionized by introduction of transanal endoscopic microsurgery in early 1980s. Introduction of transanal minimally invasive surgery made it more accessible to surgeons around the world. Now robotic platforms are being tried in certain institutions. Concerns have been raised about recurrence rates of cancers with transanal approach and success of subsequent salvage operations.

Clinical efficacy of psoralen + sunlight vs. combination of isotretinoin and psoralen + sunlight for the treatment of chronic plaque-type psoriasis vulgaris: a randomized hospital-based study.

BACKGROUND: Isotretinoin has been used in combination with oral psoralen + UVA (PUVA) and narrowband UVB (NBUVB) for treating psoriasis, especially in women of child-bearing age. The efficacy of oral psoralen + sun exposure (PUVAsol) is comparable to that of PUVA. This study was planned to compare the efficacy of oral PUVAsol with that of the combination of oral isotretinoin and PUVAsol in patients with chronic plaque psoriasis. METHODS: Forty patients with psoriasis vulgaris were randomized to two groups. Group A (control group) received PUVAsol only. Group B (intervention group) received PUVAsol + isotretinoin (0.5 mg/kg/day). Psoriasis Area Severity Index (PASI) score was recorded at baseline and weeks 4, 8 and 12. Dermatology Life Quality Index was assessed at baseline and 12 weeks. The end point of the study was PASI 75 or 12 weeks, whichever came earlier. RESULTS: Thirty-five patients completed the study. There were statistically significant differences between the two study groups for the number of patients achieving the endpoint of PASI 75, PASI scores at the end of 12 weeks, mean duration to achieve PASI 75, number of PUVAsol sessions needed to achieve PASI75 and mean cumulative dosage of 8-methoxypsoralen needed to achieve PASI 75. CONCLUSION: The combination of isotretinoin with PUVAsol is more effective compared with PUVAsol alone for treating chronic plaque psoriasis.

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics.

Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs' potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.

Use of intra-abdominal drains.

The use of drains in colorectal surgery has been a subject of debate for several decades. Prophylactic drainage of the peritoneal cavity has become less popular in recent years. This change is due to several studies demonstrating that intraperitoneal drains do not adequately drain the peritoneal cavity and do not prevent or contain anastomotic leaks. Percutaneous drain placement has become the standard of care for patients with intra-abdominal abscesses. Selected anastomotic leaks in the stable patient can also be managed with percutaneous drains. In this article, the authors review in detail the use of drains and the literature to support their use in our everyday practice.

Pressure Therapy for Pyogenic Granuloma.

Pyogenic granuloma is a benign vascular tumor, with a tendency to bleed on manipulation. A young female presented to us with a disfiguring facial pyogenic granuloma. We adopted a novel approach using pressure therapy to treat the same. The use of an elastic adhesive bandage reduced the size and vascularity of the lesion, following which laser ablation was done with minimal bleeding and scarring. This is a simple, inexpensive method to approach large and disfiguring pyogenic granulomas.