Sex-Based Differences in IBD Surgical Outcomes.

BACKGROUND: Although there are discrepancies in the development and progression of IBD based on biologic sex, little is known about differences in postoperative outcomes between men and women undergoing surgery for this condition. OBJECTIVE: To compare rates of anastomotic leaks, wound complications, and serious adverse events between men and women undergoing surgery for IBD. DESIGN: This was a retrospective cohort study. SETTINGS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program IBD Collaborative database, which includes 15 high-volume IBD surgery centers. PATIENTS: All adult patients undergoing surgery for IBD were included. Participants with missing data for exposure or outcome variables were excluded. MAIN OUTCOME MEASURES: Rates of anastomotic leaks, wound complications, and serious adverse events were compared between women and men. RESULTS: A total of 3143 patients were included. There was a significant association between sex and BMI, IBD type, and preoperative medication use. Women had decreased odds of serious adverse events compared to men (OR 0.73; 95% CI, 0.55-0.96), but there was no significant association between sex and anastomotic leaks or wound complications. IBD type was found to be an effect measure modifier of the relationship between sex and serious adverse events. Among patients with ulcerative colitis, women had a 54% decrease in the odds of serious adverse events compared to men, whereas there was no significant difference between women and men with Crohn's disease. LIMITATIONS: This study was limited by capturing only 30 days of postoperative outcomes. CONCLUSIONS: Women undergoing surgery for ulcerative colitis had decreased odds of serious adverse events compared to men. Understanding sex-based differences in outcomes allows clinicians to make patient-centered decisions regarding surgical planning and perioperative management for patients with IBD. See Video Abstract . DIFERENCIAS BASADAS EN EL SEXO EN LOS RESULTADOS QUIRRGICOS DE LA ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:Aunque existen discrepancias en el desarrollo y la progresión de la enfermedad inflamatoria intestinal según el sexo biológico, se sabe poco sobre las diferencias en los resultados postoperatorios entre hombres y mujeres sometidos a cirugía por esta afección.OBJETIVO:Nuestro objetivo fue comparar las tasas de fugas anastomóticas, complicaciones de las heridas y eventos adversos graves entre hombres y mujeres sometidos a cirugía por enfermedad inflamatoria intestinal.DISEÑO:Este fue un estudio de cohorte retrospectivo.AJUSTES:Los datos se obtuvieron de la base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Americano de Cirujanos para la Enfermedad Inflamatoria Intestinal, que incluye 15 centros de cirugía de enfermedad inflamatoria intestinal de alto volumen.PACIENTES:Se incluyeron todos los pacientes adultos sometidos a cirugía por enfermedad inflamatoria intestinal. Se excluyeron los sujetos a los que les faltaban datos sobre exposición o variables de resultado.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon las tasas de fugas anastomóticas, complicaciones de las heridas y eventos adversos graves entre mujeres y hombres.RESULTADOS:Se incluyeron un total de 3.143 pacientes. Hubo una asociación significativa entre el sexo y el índice de masa corporal, el tipo de enfermedad inflamatoria intestinal y el uso de medicación preoperatoria. Las mujeres tuvieron menores probabilidades de sufrir eventos adversos graves en comparación con los hombres (OR = 0,73; IC del 95 %: 0,55 a 0,96), pero no hubo una relacion significativa entre el sexo y las fugas anastomóticas o las complicaciones de las heridas. Se encontró que el tipo de enfermedad inflamatoria intestinal era un modificador de la medida del efecto de la relación entre el sexo y los eventos adversos graves. Entre los pacientes con colitis ulcerosa, las mujeres tuvieron una disminución del 54 % en las probabilidades de sufrir eventos adversos graves en comparación con los hombres, mientras que no hubo diferencias significativas entre mujeres y hombres con enfermedad de Crohn.LIMITACIONES:Este estudio estuvo limitado al capturar solo 30 días de resultados posoperatorios.CONCLUSIONES:Las mujeres sometidas a cirugía por colitis ulcerosa tuvieron menores probabilidades de sufrir eventos adversos graves en comparación con los hombres. Comprender las diferencias en los resultados basadas en el sexo permite a los médicos tomar decisiones centradas en el paciente con respecto a la planificación quirúrgica y el manejo perioperatorio de los pacientes con enfermedad inflamatoria intestinal. (Traducción-Dr Yolanda Colorado).

Association of Race and Postoperative Outcomes in Patients with Inflammatory Bowel Disease.

BACKGROUND: Previous literature suggests that rates of postoperative complications following inflammatory bowel disease (IBD) surgery differ based on race. AIMS: The purpose of this study was to examine the association between race and adverse events and wound complications in patients with IBD. METHODS: This was a retrospective cohort study of the American College of Surgeons National Surgery Quality Improvement Program Inflammatory Bowel Disease Collaborative from 2017 to 2022. The data was collected from 15 high-volume IBD centers across the United States. The data was analyzed using crude and multivariable logistic regressions. RESULTS: 4284 patients were included in the study. Overall rates of adverse events and wound complications were 20.3% and 11.3%, respectively, and did not differ based on race on bivariate analysis. Rates of adverse events were 20.0% vs 24.6% vs 22.1%, p = 0.13 for white, black and other minority subjects, respectively. The adjusted odds of adverse events were higher for black subjects (1.46 [95%CI 1.0-2.1], p = 0.03) compared to white subjects. No difference in adverse events was found between other minority subjects and either black or white subjects (1.29 [0.7-2.3], p = 0.58). Race was not associated with likelihood of wound complications in the final analysis. CONCLUSIONS: We found that a subset of black patients with IBD continue to experience more adverse events compared to white patients, primarily driven by a higher need for postoperative blood transfusion. Nonetheless, known risk factors, including comorbid conditions, decreased BMI, open surgery, and emergency surgery have a stronger association with postoperative complications than race alone.

Differential Actions of Muscarinic Receptor Subtypes in Gastric, Pancreatic, and Colon Cancer.

Cancers arising from gastrointestinal epithelial cells are common, aggressive, and difficult to treat. Progress in this area resulted from recognizing that the biological behavior of these cancers is highly dependent on bioactive molecules released by neurocrine, paracrine, and autocrine mechanisms within the tumor microenvironment. For many decades after its discovery as a neurotransmitter, acetylcholine was thought to be synthesized and released uniquely from neurons and considered the sole physiological ligand for muscarinic receptor subtypes, which were believed to have similar or redundant actions. In the intervening years, we learned this former dogma is not tenable. (1) Acetylcholine is not produced and released only by neurons. The cellular machinery required to synthesize and release acetylcholine is present in immune, cancer, and other cells, as well as in lower organisms (e.g., bacteria) that inhabit the gut. (2) Acetylcholine is not the sole physiological activator of muscarinic receptors. For example, selected bile acids can modulate muscarinic receptor function. (3) Muscarinic receptor subtypes anticipated to have overlapping functions based on similar G protein coupling and downstream signaling may have unexpectedly diverse actions. Here, we review the relevant research findings supporting these conclusions and discuss how the complexity of muscarinic receptor biology impacts health and disease, focusing on their role in the initiation and progression of gastric, pancreatic, and colon cancers.

Frailer Patients Undergoing Robotic Colectomies for Colon Cancer Experience Increased Complication Rates Compared With Open or Laparoscopic Approaches.

BACKGROUND: Minimally invasive surgical techniques are routinely promoted as alternatives to open surgery because of improved outcomes. However, the impact of robotic surgery on certain subsets of the population, such as frail patients, is poorly understood. OBJECTIVE: The purpose of our study was to examine the association between frailty and minimally invasive surgical approaches with colon cancer surgery. DESIGN: This is a retrospective study of prospectively collected outcomes data. Thirty-day surgical outcomes were compared by frailty and surgical approach using doubly robust multivariable logistic regression with propensity score weighting, and testing for interaction effects between frailty and surgical approach. SETTING: Patients undergoing an open, laparoscopic, or robotic colectomy for primary colon cancer, 2012 to 2016, were identified from the American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Patients undergoing a colectomy with an operative indication for primary colon cancer were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were 30-day postoperative complications. RESULTS: After propensity score weighting of patients undergoing colectomy, 33.8% (n = 27,649) underwent an open approach versus 34.3% (n = 28,058) underwent laparoscopic surgery versus 31.9% (n = 26,096) underwent robotic surgery. Robotic (OR, 0.53; 95% CI, 0.42-0.69, p < 0.001) and laparoscopic (OR, 0.58; 95% CI, 0.52-0.66, p < 0.001) surgeries were independently associated with decreased rates of major complications. Frailer patients had increased complication rates (OR, 1.56; 95% CI, 1.07-2.25, p = 0.018). When considering the interaction effects between surgical approach and frailty, frailer patients undergoing robotic surgery were more likely to develop a major complication (combined adjusted OR, 3.15; 95% CI, 1.34-7.45, p = 0.009) compared with patients undergoing open surgery. LIMITATIONS: Use of the modified Frailty Index as an associative proxy for frailty was a limitation of this study. CONCLUSIONS: Although minimally invasive surgical approaches have decreased postoperative complications, this effect may be reversed in frail patients. These findings challenge the belief that robotic surgery provides a favorable alternative to open surgery in frail patients. See Video Abstract at http://links.lww.com/DCR/B163. LOS PACIENTES MÁS FRÁGILES SOMETIDOS A COLECTOMÍA ROBÓTICA POR CÁNCER DE COLON EXPERIMENTAN MAYORES TASAS DE COMPLICACIONES EN COMPARACIÓN CON ABORDAJES LAPAROSCÓPICO O ABIERTO: Las técnicas quirúrgicas mínimamente invasivas estan frecuentement promovidas como alternativas a la cirugía abierta debido a sus mejores resultados. Sin embargo, el impacto de la cirugía robótica en ciertos subgrupos de población, como el caso de los pacientes endebles, es poco conocido.El propósito de nuestro estudio fue examinar la asociación entre la fragilidad de los pacientes y el aborgaje quirúrgico mínimamente invasivo para la cirugía de cáncer de colon.Estudio retrospectivo de datos de resultados recolectados prospectivamente. Los resultados quirúrgicos a 30 días se compararon entre fragilidad y abordaje quirúrgico utilizando la regresión logística multivariable doblemente robusta con ponderación de puntaje de propensión y pruebas de efectos de interacción entre fragilidad y abordaje quirúrgico.Los pacientes identificados en la base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos, que fueron sometidos a una colectomía abierta, laparoscópica o robótica por cáncer de colon primario, de 2012 a 2016.Todos aquellos pacientes seleccionados con indicación quirúrgica de cáncer primario de colon que fueron sometidos a una colectomía.Las complicaciones postoperatorias a 30 días.Luego de ponderar el puntaje de propensión de los pacientes colectomizados, el 33.8% (n = 27,649) fué sometido a laparotomía versus el 34.3% (n = 28,058) operados por laparoscopía versus el 31.9% (n = 26,096) operados con tecnica robótica. Las cirugías robóticas (OR 0.53, IC 95% 0.42-0.69, p < 0.001) y laparoscópicas (OR 0.58, IC 95% 0.52-0.66, p < 0.001) se asociaron de forma independiente con una disminución de las tasas de complicaciones mayores. Los pacientes más delicados tenían mayores tasas de complicaciones (OR 1.56, IC 95% 1.07-2.25, p = 0.018). Al considerar los efectos de interacción entre el abordaje quirúrgico y la fragilidad, los pacientes más débiles sometidos a cirugía robótica tenían más probabilidades de desarrollar una complicación mayor (OR ajustado combinado 3.15, IC 95% 1.34-7.45, p = 0.009) en comparación con los pacientes sometidos a cirugía abierta.El uso del índice de fragilidad modificado como apoderado asociativo de la fragilidad.Si bien los abordajes quirúrgicos mínimamente invasivos han disminuido las complicaciones postoperatorias, este efecto puede revertirse en pacientes lábiles. Estos hallazgos desafían la creencia de que la cirugía robótica proporciona una alternativa favorable a la cirugía abierta en pacientes frágiles. Consulte Video Resumen en http://links.lww.com/DCR/B163. (Traducción-Dr. Xavier Delgadillo).

Outcomes for Ulcerative Colitis With Delayed Emergency Colectomy Are Worse When Controlling for Preoperative Risk Factors.

BACKGROUND: Increasing evidence supports immediate colectomy in acute fulminant ulcerative colitis in comparison with ongoing medical management. Prior studies have been limited to inpatient-only administrative data sets or single-institution experiences. OBJECTIVE: The purpose of this study was to compare outcomes of early versus delayed emergency colectomy in patients admitted with ulcerative colitis flares while controlling for known preoperative risks and acuity. DESIGN: This is a cohort study of patients undergoing emergent total abdominal colectomies for ulcerative colitis compared by the timing of surgery. SETTING: Adult patients undergoing an emergent total abdominal colectomy for ulcerative colitis, 2005 to 2015, were identified in the American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Patients undergoing total abdominal colectomy with an operative indication of ulcerative colitis admitted on a nonelective basis were selected. MAIN OUTCOME MEASURE: The primary outcomes measured were 30-day National Surgical Quality Improvement Program-reported mortality and postoperative complications, and early operation within 2 days of admission. RESULTS: We identified 573 total abdominal colectomies after propensity score matching. Median time to surgery was 1 hospital day in the early group versus 6 hospital days in the delayed group (p < 0.001). Early operation was associated with a lower mortality rate (4.9% versus 20.3% in matched groups, p < 0.001) and lower complication rate (64.5% versus 72.0%, p = 0.052). Multivariable logistic regression with propensity weighting of mortality on preoperative risk factors demonstrated that early surgery is associated with an 82% decrease in the odds of death compared with delayed surgery (p < 0.001). Regression of morbidity on preoperative risk factors demonstrated that early surgery is associated with a 35% decrease in the odds of a complication with delayed surgery (p = 0.034). LIMITATIONS: Quality improvement data were used for clinical research questions. CONCLUSIONS: Patients undergoing immediate surgical intervention for acute ulcerative colitis have decreased postoperative complications and mortality rates. Rapid and early transitioning from medical to surgical management may benefit those expected to require surgery on the same admission. See Video Abstract at http://links.lww.com/DCR/A800.

Cutting Ties: General Surgery Residents Have Higher Attrition Rates Than Residents in Other Surgical Training Programs.

OBJECTIVE: Attrition rates among general surgery residents are notoriously high relative to other specialties. The aim of this study was to compare annual resident attrition rates between general surgery and other surgical subspecialties and to examine these trends in recent years. DESIGN: This was a retrospective study performed using Accreditation Council for Graduate Medical Education (ACGME) Data Resource Books from 2012-2022. Annual attrition rate and average ten-year attrition rate were calculated for general surgery and surgical specialties. Differences were assessed by Pearson chi-square test. SETTING: All ACGME accredited residency programs in the United States were included. RESULTS: General surgery residencies had a significantly higher average annual attrition rate (3.3%) than all other surgical specialties studied except thoracic surgery. Most attrition among general surgery residents was voluntary and these rates did not appear to be affected by the COVID-19 pandemic. CONCLUSIONS: Attrition among general surgery residents is higher than in other surgical specialties, suggesting that early specialization may be protective against resident attrition.

Parental leave policies in general surgery residencies.

BACKGROUND: Prospective residents use program websites to glean information regarding parental leave policies. This study investigates the online availability and content of parental leave policies for general surgery residency programs. METHODS: Parental leave policy information was collected from general surgery residency program and Graduate Medical Education (GME) websites. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of the 344 general surgery residency programs, parental leave policies were found on 6% of program and 52% of GME websites. Family Medical Leave Act policies were reported the most, followed by maternity, then paternity, and then adoption/other clauses. Academic programs, program location in the Southeastern US and larger program size were all significant predictors of online policy availability. CONCLUSIONS: General surgery parental leave policies vary and are not readily available online. These findings identify a significant opportunity for surgery residency programs to improve the disclosure of parental leave policy information.

Early Implementation of Robotic Training in Surgical and Surgical Subspecialty Residency.

BACKGROUND: Robotic surgery has emerged as an operative tool for many elective and urgent surgical procedures. The purpose of this study was to evaluate early surgical trainees' experiences and opinions of robotic surgery. METHODS: An introductory robotic training course consisting of online da Vinci Xi/X training and in-person, hands on training was implemented for residents and medical students across surgical subspecialties at a single institution. A voluntary survey evaluating perceptions of and interest in robotic surgery and prior robotic surgery experience, as well as a basics of robotics quiz, was distributed to participants prior to the start of the in-person session. Descriptive statistics were used to evaluate the cohort. RESULTS: 85 trainees participated in the course between 2020 and 2023, including 58 first- and second-year surgical residents (general surgery, urology, OB/GYN, and thoracic surgery) and 27 fourth-year medical students. 9.4% of participants reported any formal robotic surgery training prior to the session, with only 19% of participants reporting robotic operative experience. 52% of the participants knew of and/or had completed the da Vinci online course modules prior to the scheduled training session. Participants unanimously (100%) agreed that robotic surgery should be implemented into surgical training. CONCLUSIONS: There is rising enthusiasm for robotic surgery, yet early exposure and training remain infrequent and inconsistent amongst medical students and new surgical residents. A standardized introduction of multi-disciplinary robotic surgery training should be incorporated into medical school and/or early residency education to ensure surgical residents receive appropriate exposure and training to achieve competency.

An Abdominal Seat Belt Sign is Associated With Similar Incidence of Hollow Viscus Injury but Increased In-Hospital Mortality in Older Adult Trauma Patients: A PCSA Multicenter Study.

BACKGROUND: The abdominal seat belt sign (SBS) is associated with an increased risk of hollow viscus injury (HVI). Older age is associated with worse outcomes in trauma patients. Thus, older trauma patients ≥65 years of age (OTPs) may be at an increased risk of HVI with abdominal SBS. Therefore, we hypothesized an increased incidence of HVI and mortality for OTPs vs younger trauma patients (YTPs) with abdominal SBS. STUDY DESIGN: This post hoc analysis of a multi-institutional, prospective, observational study (8/2020-10/2021) included patients >18 years old with an abdominal SBS who underwent abdominal computed tomography (CT) imaging. Older trauma patients were compared to YTPs (18-64 years old) with bivariate analyses. RESULTS: Of the 754 patients included in this study from nine level-1 trauma centers, there were 110 (14.6%) OTPs and 644 (85.4%) YTPs. Older trauma patients were older (mean 75.3 vs 35.8 years old, P < .01) and had a higher mean Injury Severity Score (10.8 vs 9.0, P = .02). However, YTPs had an increased abdominal abbreviated-injury scale score (2.01 vs 1.63, P = .02). On CT imaging, OTPs less commonly had intraabdominal free fluid (21.7% vs 11.9%, P = .02) despite a similar rate of abdominal soft tissue contusion (P > .05). Older trauma patients also had a statistically similar rate of HVI vs YTPs (5.5% vs 9.8%, P = .15). Despite this, OTPs had increased mortality (5.5% vs 1.1%, P < .01) and length of stay (LOS) (5.9 vs 4.9 days P < .01). CONCLUSION: Despite a similar rate of HVI, OTPs with an abdominal SBS had an increased rate of mortality and LOS. This suggests the need for heightened vigilance when caring for OTPs with abdominal SBS.

Lessons in liability: Examining medical malpractice suits against general surgeons in Maryland.

BACKGROUND: Although medical malpractice lawsuits pose a significant burden, there is a paucity of research on physician-specific characteristics influencing lawsuits against surgeons. Our objective was to identify factors associated with general surgeons being named in malpractice cases. METHODS: This was a cross sectional study of Maryland general surgeons, using malpractice data from a publicly accessible judiciary database. Case number per decade and lifetime lawsuit status were modeled with linear and logistic regression. RESULTS: Male surgeons had a higher average lawsuit volume (p = 0.002) and were more likely to be named in a malpractice case (p < 0.001). In regression analysis, a second graduate degree was a predictor of average cases per 10 years (p = 0.008) and male gender predicted lifetime lawsuit status (OR = 1.73, p = 0.046). CONCLUSIONS: Male gender was associated with increased odds of being named in a malpractice lawsuit. Identifying this difference is a preliminary step in developing interventions to reduce lawsuits amongst surgeons.

Selective Activation of M1 Muscarinic Receptors Attenuates Human Colon Cancer Cell Proliferation.

M3 muscarinic receptor (M3R) activation stimulates colon cancer cell proliferation, migration, and invasion; M3R expression is augmented in colon cancer and ablating M3R expression in mice attenuates colon neoplasia. Several lines of investigation suggest that in contrast to these pro-neoplastic effects of M3R, M1R plays an opposite role, protecting colon epithelial cells against neoplastic transformation. To pursue these intriguing findings, we examined the relative expression of M1R versus M3R in progressive stages of colon neoplasia and the effect of treating colon cancer cells with selective M1R agonists. We detected divergent expression of M1R and M3R in progressive colon neoplasia, from aberrant crypt foci to adenomas, primary colon cancers, and colon cancer metastases. Treating three human colon cancer cell lines with two selective M1R agonists, we found that in contrast to the effects of M3R activation, selective activation of M1R reversibly inhibited cell proliferation. Moreover, these effects were diminished by pre-incubating cells with a selective M1R inhibitor. Mechanistic insights were gained using selective chemical inhibitors of post-muscarinic receptor signaling molecules and immunoblotting to demonstrate M1R-dependent changes in the activation (phosphorylation) of key downstream kinases, EGFR, ERK1/2, and p38 MAPK. We did not detect a role for drug toxicity, cellular senescence, or apoptosis in mediating M1R agonist-induced attenuated cell proliferation. Lastly, adding M1R-selective agonists to colon cancer cells augmented the anti-proliferative effects of conventional chemotherapeutic agents. Collectively, these results suggest that selective M1R agonism for advanced colon cancer, alone or in combination with conventional chemotherapy, is a therapeutic strategy worth exploring.

Muscarinic receptor agonist-induced ßPix binding to ß-catenin promotes colon neoplasia.

M3 muscarinic receptors (M3R) modulate ß-catenin signaling and colon neoplasia. CDC42/RAC guanine nucleotide exchange factor, ßPix, binds to ß-catenin in colon cancer cells, augmenting ß-catenin transcriptional activity. Using in silico, in vitro, and in vivo approaches, we explored whether these actions are regulated by M3R. At the invasive fronts of murine and human colon cancers, we detected co-localized nuclear expression of ßPix and ß-catenin in stem cells overexpressing M3R. Using immunohistochemistry, immunoprecipitation, proximity ligand, and fluorescent cell sorting assays in human tissues and established and primary human colon cancer cell cultures, we detected time-dependent M3R agonist-induced cytoplasmic and nuclear association of ßPix with ß-catenin. ßPix knockdown attenuated M3R agonist-induced human colon cancer cell proliferation, migration, invasion, and expression of PTGS2, the gene encoding cyclooxygenase-2, a key player in colon neoplasia. Overexpressing ßPix dose-dependently augmented ß-catenin binding to the transcription factor TCF4. In a murine model of sporadic colon cancer, advanced neoplasia was attenuated in conditional knockout mice with intestinal epithelial cell deficiency of ßPix. Expression levels of ß-catenin target genes and proteins relevant to colon neoplasia, including c-Myc and Ptgs2, were reduced in colon tumors from ßPix-deficient conditional knockout mice. Targeting the M3R/ßPix/ß-catenin axis may have therapeutic potential.

Development and Validation of a Novel Hollow Viscus Injury Prediction Score for Abdominal Seatbelt Sign: A Pacific Coast Surgical Association Multicenter Study.

BACKGROUND: High-quality CT can exclude hollow viscus injury (HVI) in patients with abdominal seatbelt sign (SBS) but performs poorly at identifying HVI. Delay in diagnosis of HVI has significant consequences necessitating timely identification. STUDY DESIGN: This multicenter, prospective observational study conducted at 9 trauma centers between August 2020 and October 2021 included adult trauma patients with abdominal SBS who underwent abdominal CT before surgery. HVI was determined intraoperatively and physiologic, examination, laboratory, and imaging findings were collected. Least absolute shrinkage and selection operator- and probit regression-selected predictor variables and coefficients were used to assign integer points for the HVI score. Validation was performed by comparing the area under receiver operating curves (AUROC). RESULTS: Analysis included 473 in the development set and 203 in the validation set. The HVI score includes initial systolic blood pressure <110 mmHg, abdominal tenderness, guarding, and select abdominal CT findings. The derivation set has an AUROC of 0.96, and the validation set has an AUROC of 0.91. The HVI score ranges from 0 to 17 with score 0 to 5 having an HVI risk of 0.03% to 5.36%, 6 to 9 having a risk of 10.65% to 44.1%, and 10 to 17 having a risk of 58.59% to 99.72%. CONCLUSIONS: This multicenter study developed and validated a novel HVI score incorporating readily available physiologic, examination, and CT findings to risk stratify patients with an abdominal SBS. The HVI score can be used to guide decisions regarding management of a patient with an abdominal SBS and suspected HVI.

Excluding Hollow Viscus Injury for Abdominal Seat Belt Sign Using Computed Tomography.

Importance: Abdominal seat belt sign (SBS) has historically entailed admission and observation because of the diagnostic limitations of computed tomography (CT) imaging and high rates of hollow viscus injury (HVI). Recent single-institution, observational studies have questioned the utility of this practice. Objective: To evaluate whether a negative CT scan can safely predict the absence of HVI in the setting of an abdominal SBS. Design, Setting, and Participants: This prospective, observational cohort study was conducted in 9 level I trauma centers between August 2020 and October 2021 and included adult trauma patients with abdominal SBS. Exposures: Inclusion in the study required abdominal CT as part of the initial trauma evaluation and before any surgical intervention, if performed. Results of CT scans were considered positive if they revealed any of the following: abdominal wall soft tissue contusion, free fluid, bowel wall thickening, mesenteric stranding, mesenteric hematoma, bowel dilation, pneumatosis, or pneumoperitoneum. Main Outcomes and Measures: Presence of HVI diagnosed at the time of operative intervention. Results: A total of 754 patients with abdominal SBS had an HVI prevalence of 9.2% (n = 69), with only 1 patient with HVI (0.1%) having a negative CT (ie, none of the 8 a priori CT findings). On bivariate analysis comparing patients with and without HVI, there were significant associations between each of the individual CT scan findings and the presence of HVI. The strongest association was found with the presence of free fluid, with a more than 40-fold increase in the likelihood of HVI (odds ratio [OR], 42.68; 95% CI, 20.48-88.94; P < .001). The presence of free fluid also served as the most effective binary classifier for presence of HVI (area under the receiver operator characteristic curve [AUC], 0.87; 95% CI, 0.83-0.91). There was also an association between a negative CT scan and the absence of HVI (OR, 41.09; 95% CI, 9.01-727.69; P < .001; AUC, 0.68; 95% CI, 0.66-0.70). Conclusions and Relevance: The prevalence of HVI among patients with an abdominal SBS and negative findings on CT is extremely low, if not zero. The practice of admitting and observing all patients with abdominal SBS should be reconsidered when a high-quality CT scan is negative, which may lead to significant resource and cost savings.

Potential Role for Combined Subtype-Selective Targeting of M1 and M3 Muscarinic Receptors in Gastrointestinal and Liver Diseases.

Despite structural similarity, the five subtypes comprising the cholinergic muscarinic family of G protein-coupled receptors regulate remarkably diverse biological functions. This mini review focuses on the closely related and commonly co-expressed M1R and M3R muscarinic acetylcholine receptor subtypes encoded respectively by CHRM1 and CHRM3. Activated M1R and M3R signal via Gq and downstream initiate phospholipid turnover, changes in cell calcium levels, and activation of protein kinases that alter gene transcription and ultimately cell function. The unexpectedly divergent effects of M1R and M3R activation, despite similar receptor structure, distribution, and signaling, are puzzling. To explore this conundrum, we focus on the gastrointestinal (GI) tract and liver because abundant data identify opposing effects of M1R and M3R activation on the progression of gastric, pancreatic, and colon cancer, and liver injury and fibrosis. Whereas M3R activation promotes GI neoplasia, M1R activation appears protective. In contrast, in murine liver injury models, M3R activation promotes and M1R activation mitigates liver fibrosis. We analyze these findings critically, consider their therapeutic implications, and review the pharmacology and availability for research and therapeutics of M1R and M3R-selective agonists and antagonists. We conclude by considering gaps in knowledge and other factors that hinder the application of these drugs and the development of new agents to treat GI and liver diseases.

Process measures facilitate maturation of pediatric enhanced recovery protocols.

BACKGROUND/PURPOSE: The role of process measures used to predict quality in pediatric colorectal surgery enhanced recovery protocols has not been described. The purpose of this study was to demonstrate the feasibility of abstracting and monitoring process measures over protocol improvement iteration. METHODS: Patients enrolled in the Pediatric Colorectal Enhanced Recovery After Surgery pathway at our institution were grouped by stage of implementation. We used a quality improvement database to compare multistage enhanced recovery process measures and 30-day patient outcomes. RESULTS: We identified 58 surgical patients with 28(48%) cases enrolled in the pathway. There was increased use of regional anesthesia techniques in pathway patients (83% versus 20%, p < 0.001). All preoperative process measures clinically improved between early and full implementation. Improvements included a dramatic increase in formal preoperative education (56% versus 0%, p = 0.004) and administration of preoperative medication (p = 0.025). Overall, 12 (21%) patients experienced postoperative complications, which were similarly distributed between implementation groups. Readmissions were highest during the early implementation phase (40%, p = 0.029). Children in the late implementation group experienced fewer complications, which clinically correlated with process measure adherence. CONCLUSIONS: Process measures complement outcome measures in assessing quality and effectiveness of a pediatric colorectal recovery protocol. Adherence to processes may reduce complications. LEVEL OF EVIDENCE: Treatment study, Level III.

A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry.

Targeted α-particle therapy is a promising treatment modality for cancer. Due to the short path-length of α-particles, the potential efficacy and toxicity of these agents is best evaluated by microscale dosimetry calculations instead of whole-organ, absorbed fraction-based dosimetry. Yet time-integrated activity (TIA), the necessary input for dosimetry, can still only be quantified reliably at the organ or macroscopic level. We describe a nephron- and cellular-based kidney dosimetry model for α-particle radiopharmaceutical therapy, more suited to the short range and high linear energy transfer of α-particle emitters, which takes as input kidney or cortex TIA and through a macro to micro model-based methodology assigns TIA to micro-level kidney substructures. We apply a geometrical model to provide nephron-level S-values for a range of isotopes allowing for pre-clinical and clinical applications according to the medical internal radiation dosimetry (MIRD) schema. We assume that the relationship between whole-organ TIA and TIA apportioned to microscale substructures as measured in an appropriate pre-clinical mammalian model also applies to the human. In both, the pre-clinical and the human model, microscale substructures are described as a collection of simple geometrical shapes akin to those used in the Cristy-Eckerman phantoms for normal organs. Anatomical parameters are taken from the literature for a human model, while murine parameters are measured ex vivo. The murine histological slides also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus versus proximal tubule versus distal tubule. Monte Carlo simulations are run with activity placed in the different nephron compartments for several α-particle emitters currently under investigation in radiopharmaceutical therapy. The S-values were calculated for the α-emitters and their descendants between the different nephron compartments for both the human and murine models. The renal cortex and medulla S-values were also calculated and the results compared to traditional absorbed fraction calculations. The nephron model enables a more optimal implementation of treatment and is a critical step in understanding toxicity for human translation of targeted α-particle therapy. The S-values established here will enable a MIRD-type application of α-particle dosimetry for α-emitters, i.e. measuring the TIA in the kidney (or renal cortex) will provide meaningful and accurate nephron-level dosimetry.