Post-operative Opioid Reduction Protocol Reduces Racial Disparity in Clinical Outcomes in Children.

INTRODUCTION: Racial disparities in health outcomes continue to exist for children requiring surgery. Previous investigations suggest that clinical protocols may reduce racial disparities. A post-operative opioid reduction protocol was implemented in children undergoing abdominal surgery who were less than 1 years old at a tertiary level hospital. The purpose of this investigation was to determine if the clinical protocol was associated with a reduction in racial disparity in post-operative opioid prescribing patterns and associated clinical outcomes. METHODS: A post-operative opioid reduction protocol based on standing intravenous acetaminophen, educational sessions with nursing staff, and standardized post-operative sign-out between the surgical and NICU teams was implemented in children under 1 year old in 2016. A time series and before and after analysis was conducted using a historical pre-intervention cohort (Jan 2011-Dec 2015) and prospectively collected post-intervention cohort (Jan 2016-Jan 2021). Primary outcomes included post-operative opioid use and post-operative pain scores stratified by race. Secondary outcomes included associated clinical outcomes also stratified by race. RESULTS: A total of 249 children were included in the investigation, 117 in the pre-intervention group and 132 in the post intervention group. The majority of patients in both cohorts were either White or Black. The two cohorts were equally matched in terms of pre-operative clinical variables. In the pre-intervention cohort, the median post-operative morphine equivalents in White children was 2.1 mg/kg (IQR 0.2, 11.1) while in Black children it was 13.1 mg/kg (IQR 2.4, 65.3), p-value = 0.0352. In the post-intervention cohort, the median value for White children and Black children was statistically identical (0.05 mg/kg (IQR 0, 0.5) and 0.0 mg/kg (IQR 0, 0.3), respectively, p-value = 0.237). This pattern was also demonstrated in clinical variables including length of stay, intubation length and total parenteral nutrition use. In the pre-intervention cohort, the total length of stay for white children was 16 days while for black children it was 45 days (p = 0.007). In the postintervention cohort the length of stay for both White and Black children were identical at 8 days (p = 0.748). CONCLUSION: The use of a clinical opioid reduction protocol implemented at a tertiary medical center was associated with a reduction in racial disparity in opioid prescribing habits in children. Prior to the protocol, there was a racial disparity in clinical variables associated with prolonged opioid use including length of stay, TPN use, and intubation length. The clinical protocol reduced variability in opioid prescribing patterns in all racial groups which was associated with a reduction in variability in associated clinical variables. LEVEL OF EVIDENCE: Level III.

Associations of Race, Ethnicity, and Social Determinants of Health With Colorectal Cancer Screening.

BACKGROUND: Racial and ethnic disparities in receipt of recommended colorectal cancer screening exist; however, the impact of social determinants of health on such disparities has not been recently studied in a national cohort. OBJECTIVE: This study aimed to determine whether social determinants of health attenuate racial disparities in receipt of colorectal cancer screening. DESIGN: This was a cross-sectional telephone survey of self-reported race and ethnicity and up-to-date colorectal cancer screening. Associations between race/ethnicity and colorectal cancer screening were tested before and after adjustment for demographics, behavioral factors, and social determinants of health. SETTING: This was a nationally representative telephone survey of US residents in 2018. PATIENTS: The patients included were US residents aged 50 to 75 years. MAIN OUTCOME MEASURES: The primary outcome was up-to-date colorectal cancer screening status, according to 2008 US Preventive Services Task Force recommendations. RESULTS: This study included 226,106 respondents aged 50 to 75 years. Before adjustment, all minority racial and ethnic groups demonstrated a significantly lower odds of screening than those of non-Hispanic white respondents. After adjustment for demographics, behavioral factors, and social determinants of health, compared to non-Hispanic white respondents, odds of screening were found to be increased among non-Hispanic black respondents (OR, 1.10; p = 0.02); lower but attenuated among Hispanic respondents (OR, 0.73; p < 0.001), non-Hispanic American Indian/Alaskan Native respondents (OR, 0.85; p = 0.048), and non-Hispanic respondents of other races (OR, 0.82; p = 0.01); and lower but not attenuated among non-Hispanic Asian respondents (OR, 0.68; p < 0.001). LIMITATIONS: Recall bias, participant bias, and residual confounding. CONCLUSIONS: Adjustment for social determinants of health reduced racial and ethnic disparities in colorectal cancer screening among all minority racial and ethnic groups except non-Hispanic Asian individuals; however, other unmeasured confounders likely exist. See Video Abstract at http://links.lww.com/DCR/B977 . ASOCIACIN DE RAZA, ETNICIDAD Y DETERMINANTES SOCIALES DE LA SALUD CON LA DETECCIN DEL CNCER COLORRECTAL: ANTECEDENTES: Existen disparidades raciales y étnicas en la recepción de las pruebas recomendadas de detección de cáncer colorrectal; sin embargo, el impacto de los determinantes sociales de la salud en dichas disparidades no se ha estudiado recientemente en una cohorte nacional.OBJETIVO: El objetivo de este estudio fue determinar si los determinantes sociales de la salud atenúan las disparidades raciales en la recepción de pruebas de detección del cáncer colorrectal.DISEÑO: Encuesta telefónica transversal de raza y etnia autoinformada y detección actualizada de cáncer colorrectal. Las asociaciones entre la raza/etnicidad y la detección del cáncer colorrectal se probaron antes y después del ajuste por demografía, factores conductuales y determinantes sociales de la salud.ESCENARIO: Esta fue una encuesta telefónica representativa a nivel nacional de los residentes de EE. UU. en 2018.PACIENTES: Los pacientes eran residentes de EE. UU. de 50 a 75 años.PRINCIPALES MEDIDAS DE RESULTADO: Estado actualizado de detección de cáncer colorrectal, según las recomendaciones del Grupo de Trabajo de Servicios Preventivos de EE. UU. de 2008.RESULTADOS: Este estudio incluyó a 226.106 encuestados de 50 a 75 años. Antes del ajuste, todos los grupos étnicos y raciales minoritarios demostraron probabilidades significativamente más bajas de detección en comparación con los encuestados blancos no hispanos. Después del ajuste por demografía, factores conductuales y determinantes sociales de la salud, en comparación con los encuestados blancos no hispanos, las probabilidades de detección aumentaron entre los encuestados negros no hispanos (OR 1,10, p = 0,02); más bajo pero atenuado entre los encuestados hispanos (OR 0,73, p < 0,001), los encuestados indios americanos/nativos de Alaska no hispanos (OR 0,85, p = 0,048) y los encuestados no hispanos de otras razas (OR 0,82, p = 0,01); y menor pero no atenuado entre los encuestados asiáticos no hispanos (OR 0,68, p < 0,001).LIMITACIONES: Sesgo de recuerdo y sesgo de participante, así como confusión residual.CONCLUSIONES: El ajuste para los determinantes sociales de la salud redujo las disparidades raciales y étnicas en la detección del cáncer colorrectal entre todos los grupos étnicos y raciales minoritarios, excepto las personas asiáticas no hispanas; sin embargo, es probable que existan otros factores de confusión no medidos. Consulte Video Resumen en http://links.lww.com/DCR/B977 . (Traducción-Dr. Felipe Bellolio ).

A dual-institutional study on first-year practice outcomes of pediatric surgeons who trained in the era of work hour restrictions.

BACKGROUND: In July 2003, an 80-h work week restriction for residencies was mandated. This was met with skepticism regarding its potential impact on operative training. We hypothesized no difference in outcomes for pediatric surgeons who trained under duty hour restrictions compared to historical complication rates. METHODS: Dual-institutional review of pediatric patients who underwent five of the most common operations (2013-2018) by first-year pediatric surgeons who trained under duty hour restrictions was performed. Tests of proportions were used to compare complication rates to published rates on data collected prior to 2003. RESULTS: Patient mean age was 10.1 years. No significant differences (p values > 0.05) were found in laparoscopic appendectomy rates of infection, bleeding or intra-abdominal abscess compared to previously published rates. Pyloromyotomy rates of infection or duodenal perforation were not different. No differences were detected in rates of infection, recurrence or testicular atrophy for inguinal hernia repair. Umbilical hernia rates of infection, bleeding, and recurrence were also not different. There was no difference in CVC rates of hemopneumothoraces; significantly more bleeding events were detected (1.2% vs. 0.1%; p value = 0.04). CONCLUSION: In this study, first-year complication rates of pediatric surgeons who trained under duty hour restrictions were not significantly different when compared to published rates.

Pediatric surgical errors: A systematic scoping review.

BACKGROUND: Medical errors were largely concealed prior to the landmark report "To Err Is Human". The purpose of this systematic scoping review was to determine the extent pediatric surgery defines and studies errors, and to explore themes among papers focused on errors in pediatric surgery. METHODS: The methodological framework used to conduct this scoping study has been outlined by Arksey and O'Malley. In January 2020, PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Oxford Level of Evidence was assigned to each study; only studies rated Level 3 or higher were included. RESULTS: Of 3,064 initial studies, 12 were included in the final analysis: 4 cohort studies, and 8 outcome/audit studies. This data represented 5,442,000 aggregate patients and 8,893 errors. There were 6 different error definitions and 5 study methods. Common themes amongst the studies included a systems-focused approach, an increase in errors seen with increased complexity, and studies exploring the relationship between error and adverse events. CONCLUSIONS: This study revealed multiple error definitions, multiple error study methods, and common themes described in the pediatric surgical literature. Opportunities exist to improve the safety of surgical care of children by reducing errors. Original Scientific Research Type of Study: Systematic Scoping Review Level of Evidence Rating: 1.

Disparities in telemedicine utilization among surgical patients during COVID-19.

BACKGROUND: Telemedicine has been rapidly adopted in the wake of the COVID-19 pandemic. There is limited work surrounding demographic and socioeconomic disparities that may exist in telemedicine utilization. This study aimed to examine demographic and socioeconomic differences in surgical patient telemedicine usage during the COVID-19 pandemic. METHODS: Department of Surgery outpatients seen from July 1, 2019 to May 31, 2020 were stratified into three visit groups: pre-COVID-19 in-person, COVID-19 in-person, or COVID-19 telemedicine. Generalized linear models were used to examine associations of sex, race/ethnicity, Distressed Communities Index (DCI) scores, MyChart activation, and insurance status with telemedicine usage during the COVID-19 pandemic. RESULTS: 14,792 patients (median age 60, female [57.0%], non-Hispanic White [76.4%]) contributed to 21,980 visits. Compared to visits before the pandemic, telemedicine visits during COVID-19 were more likely to be with patients from the least socioeconomically distressed communities (OR, 1.31; 95% CI, 1.08,1.58; P = 0.005), with an activated MyChart (OR, 1.38; 95% CI, 1.17-1.64; P < .001), and with non-government or commercial insurance (OR, 2.33; 95% CI, 1.84-2.94; P < .001). Adjusted comparison of telemedicine visits to in person visits during COVID-19 revealed telemedicine users were more likely to be female (OR, 1.38, 95% CI, 1.10-1.73; P = 0.005) and pay with non-government or commercial insurance (OR, 2.77; 95% CI, 1.85-4.16; P < .001). CONCLUSIONS: During the first three months of the COVID-19 pandemic, telemedicine was more likely utilized by female patients and those without government or commercial insurance compared to patients who used in-person visits. Interventions using telemedicine to improve health care access might consider such differences in utilization.

Racial and Gender Discrimination in Hand Surgery Letters of Recommendation.

PURPOSE: We sought to evaluate hand surgery applicants' letters of recommendations to understand whether applicant and letter writer demographics contribute to racial and gender bias. METHODS: All applications submitted through the American Society for Surgery of the Hand match to a single institution fellowship program for the 2017 to 2019 application cycles were analyzed using validated text analysis software. Race/ethnicity information was derived from an analysis of applicant photos using the Face Secret Pro software. Primary outcome measures were differences in communal and agentic language used in letters of recommendation, stratified by both race/ethnicity and gender. RESULTS: A total of 912 letters of recommendation were analyzed for 233 applicants (51 female and 172 male). Of these, 88 were written by female letter writers and 824 were written by male letter writers. There were 8 Black, 12 Hispanic, 36 Asian, and 167 White applicants. Letter writers used more agentic language with Asian applicants and non-White applicants overall. Female letter writers used more communal terms and were not associated with applicant race or gender. CONCLUSIONS: Letters of recommendation in hand surgery demonstrate disparities in language based on race and gender. CLINICAL RELEVANCE: Alerting letter writers to the role of implicit bias will hopefully spur a discussion on tools to mitigate the use of biased language and provide a foundation for an equitable selection process. Efforts to improve policies and procedures pertaining to diversity and inclusion are paramount to ensuring that fellows more completely represent the population hand surgeons wish to serve.

Clinical regression of inguinal hernias in premature infants without surgical repair.

BACKGROUND: The incidence of inguinal hernias in premature infants is approximately 30%. Due to concerns about a high risk of incarceration, early repair is commonly performed. We present a series of patients whose families opted to delay repair until after 55 weeks corrected gestational age (GA) and experienced safe clinical regression of their hernias. METHODS: Between June 2015 and July 2020, premature infants (< 37 weeks GA) diagnosed with inguinal hernias on physical examination were identified. Families of eligible infants were offered either immediate or delayed repair after 55 weeks corrected GA. Infants whose families elected to delay were followed until their hernia(s) clinically regressed, or until older than 55 weeks. RESULTS: Families of 68 infants consented to delay repair. 23 infants (33.8%) had hernias that clinically regressed at median follow up from diagnosis of 14.1 weeks. Univariate analysis demonstrated female sex as a significant predictor of hernia clinical regression (OR: 3.08; p = 0.046). Of the 45 infants who underwent repair, 84.4% safely progressed to 55 weeks corrected GA prior to. CONCLUSION: Delaying inguinal hernia repair in this series of premature infants until after 55 weeks corrected GA revealed that one third of hernias, especially in females, safely regressed upon follow-up examination.

Childhood cancer survivors face markedly worse overall survival after diagnosis with breast cancer, melanoma, or colorectal cancer.

BACKGROUND: Childhood cancer survivors (CCS) are at elevated risk of secondary malignancies (SM). Enhanced screening for SM is recommended, but compliance is poor. We hypothesized that CCS with adult-onset SM (colorectal cancer [CRC], melanoma, or breast cancer [BC]) would present with more advanced disease and have decreased overall survival (OS). METHODS: The Surveillance, Epidemiology, and End Results Program was queried for patients diagnosed with cancer at age less than or equal to 18 also diagnosed with adult-onset CRC, melanoma, or BC. A cohort without a history of prior malignancy was likewise identified. Tumor features and clinical outcomes were compared. RESULTS: CCS with a SM (n = 224) were compared with patients without a childhood cancer history (n = 1,392,670). CCS were diagnosed younger (BC = 37.6 vs. 61.3, p < 0.01, CRC = 35.0 vs. 67.1, p < 0.01, melanoma = 29.6 vs. 61.3 years old, p < 0.01). CCS with BC were more likely to have Stage III or IV disease (25.2% vs. 16.5%, p = 0.01). Hormone-receptor expression also differed; CCS were less likely to develop Luminal A-type tumors (48.6% vs. 66.9%, p = 0.01). After age-adjustment, CCS had worse OS (Hazard ratio: CRC = 2.449, p < 0.01, melanoma = 6.503, p < 0.01, BC = 3.383, p < 0.01). CONCLUSION: CCS were younger when diagnosed with a SM. After age-adjustment, OS was diminished. Heightened surveillance may be necessary for CCS diagnosed with SM.

Intestinal crypt-derived enteroid coculture in presence of peristaltic longitudinal muscle myenteric plexus.

The role of enteric neurons in driving intestinal peristalsis has been known for over a century. However, in recent decades, scientists have begun to unravel additional complex interactions between this nerve plexus and other cell populations in the intestine. Investigations into these potential interactions are complicated by a paucity of tractable models of these cellular relationships. Here, we describe a novel technique for ex vivo coculture of enteroids, so called "mini-guts," in juxtaposition to the longitudinal muscle myenteric plexus (LMMP). Key to this system, we developed a LMMP culture media that: (i) allows the LMMP to maintain ex vivo peristalsis for 2 weeks along with proliferation of neurons, glia, smooth muscle and fibroblast cells, and (ii) supports the proliferation and differentiation of the intestinal stem cells into enteroids complete with epithelial enterocytes, Paneth cells, goblet cells, and enteroendocrine cells. Importantly, this technique identifies a culture condition that supports both the metabolic needs of intestinal epithelium as well as neuronal elements, demonstrating the feasibility of maintaining these two populations in a single culture system. This sets the stage for experiments to better define the regulatory interactions of these two important intestinal cell populations.

The Risk and Reward of Speaking Out for Racial Equity in Surgical Training.

In order to maintain productivity and career advancement, Black and Brown individuals often find themselves downplaying persistent elements of bias and racism experienced in predominantly white fields. These elements are commonly reinforced by institutional and departmental policies that hinder the creation of an equitable and inclusive environment for all. In this manuscript, we outline specific challenges faced by Black and Brown trainees and faculty that are perpetuated by such policies. The challenges are followed by specific recommendations for change as they may apply to faculty, staff and trainees. The outlined recommendations or "action items" may be enacted by any residency program or department based on perceived timeliness and should serve as a foundation for change-one that is intently created through a lens of anti-racism. The risk of speaking up for racial equity is outweighed by the potential rewards of building an environment that is diverse, inclusive and better for everyone.

Food Insecurity and Obesity in US Adolescents: A Population-Based Analysis.

Background: Food insecurity and obesity are significant problems affecting adolescents. There is a paucity of recent data examining this relationship. This study utilizes a recent nationally representative sample of US adolescents to examine the relationship between obesity and food security status, as well as other risk factors. Methods: A cross-sectional analysis of 4777 US adolescents (13-18 years old) was performed using data from the National Health and Nutrition Examination Surveys 2007-2016. Prevalence of obesity based on food security status was calculated. Multivariable logistic regression was performed to examine characteristics of adolescents in relationship to obesity. Results: The prevalence of obesity among adolescents from food insecure households was significantly higher compared to those who were not, with a prevalence ratio of 1.3 (95% CI: 1.2-1.5, p < 0.0001). Food insecurity was associated with a higher unadjusted rate of obesity, with an odds ratio of 1.4 (95% CI: 1.2-1.7, p = 0.0002). After adjustment for potential confounding factors, food insecurity was no longer significantly associated with obesity (OR 1.19, 95% CI: 1.0-1.4, p = 0.08). However, other factors such as black race, Hispanic ethnicity, male sex, and households with a monthly income ≤185% of the poverty line were associated with increased odds of obesity. Conclusions: While the prevalence of obesity in adolescents from food insecure households was higher compared to those who were not, no association between the two was found when accounting for other risk factors. Data on independent food-seeking behaviors of adolescents may help clarify this complex relationship in future work.

Lung surgery in children and their post-operative risk of respiratory infection.

PURPOSE: Pediatric surgeons at our institution are often asked by families about a theoretical increased risk of severe common upper respiratory infections in children status post lung resection. No data exist on this topic. We, therefore, aimed to examine the risk of severe respiratory infection in children after pulmonary resection. METHODS: A chart review was conducted on all pediatric patients who underwent pulmonary resection between August 1st, 2009 and January 31st, 2019. Collected data included patient characteristics, operation, complications and any admission for respiratory infection. RESULTS: Fifty-seven patients met inclusion criteria. Resections included lobectomy (45.6%), segmentectomy (14.0%), and wedge resection (40.4%). Twelve (21.1%) were immunocompromised and 6 (10.5%) had post-operative complications. Within 1 year of surgery, 2 (3.5%) patients were hospitalized for a viral upper respiratory illness (URI), 1 (1.8%) for bacterial pneumonia, and none due to influenza. CONCLUSION: In the general pediatric population, the risk of admission for respiratory illness is 3-21%. At this institution, overall risk of respiratory infection after lung resection appears comparable to baseline community risk. Our findings could aid counseling pediatric patients and their families regarding the 1-year risk of infection after lung resection.

The Enteric Nervous System and Its Emerging Role as a Therapeutic Target.

The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation, and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection, or inflammation of the ENS highlight its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI diseases including short bowel syndrome with neuronal pathophysiology and current therapies. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances and ultimately change our treatment approach.

Total knee replacement for tricompartmental arthritis in a patient with a below-knee amputation after a previous closing wedge high tibial osteotomy.

This is a report of a 64-year-old man who had undergone a high tibial osteotomy (HTO) 17 years ago of his right knee for medial compartment osteoarthritis; 5 days later, he received a below-knee amputation owing to a missed popliteal artery injury at the time of the HTO. We elected to perform a total knee replacement (TKR) for progressive arthritis of the ipsilateral knee 17 years after the transtibial amputation. Although there is a plethora of literature regarding TKR in the contralateral knee of amputees, there is a paucity of data of TKR in the ipsilateral knee. Using medical search engines including Google Scholar and PubMed, we were only able to identify 4 case reports of TKR in the ipsilateral knee of below-knee amputees. This is the first description in the English literature that has the following rare pathology list: tricompartmental arthritis with a previous closing wedge HTO with a resultant truncated valgus tibia and short transtibial amputation.

Total elbow arthroplasty: outcomes after triceps-detaching and triceps-sparing approaches.

BACKGROUND: Total elbow arthroplasty (TEA) is associated with high complication rates compared with other large-joint arthroplasties. The frequency and type of complication may differ, depending on the surgical approach. A comparison of outcomes with triceps-off and triceps-on approaches was investigated. METHODS: Seventy-three patients underwent 83 primary TEAs between 2003 and 2012. Forty-six elbows had a triceps-off approach, and 37 had a triceps-on approach. Results were reviewed at a mean of 4.2 years. Cementing technique was graded according to Morrey's criteria, and clinical outcomes were assessed by means of the Mayo Elbow Performance Score. RESULTS: There was no statistically significant difference between the triceps-off and triceps-on groups with regard to the patient's age, gender, preoperative Mayo Elbow Performance Score or range of motion, or previous surgery on the affected elbow. Among patients who underwent a TEA for an inflammatory arthropathy, there was a significant difference in outcome between groups with regard to final flexion, extension, arc of motion, and pronation. Cementing technique in the triceps-off group was adequate in 70%. In the triceps-on group, cementing technique was adequate in 92%. The complication rate in the triceps-off group was 32.6% and included 7 triceps ruptures. Three patients who had attempted repairs of the triceps rupture developed deep infections requiring multiple further surgeries. The complication rate in the triceps-on group was 8.1%. CONCLUSION: A triceps-on approach in TEA results in consistently good clinical outcomes with no risk of triceps rupture, and the approach does not compromise the cement mantle. We believe that this approach will reduce complication rates in TEA.

Angular stable fixation of displaced distal-third clavicle fractures with superior precontoured locking plates.

HYPOTHESIS: We reviewed the outcome of angular stable plates in addressing displaced lateral-third clavicle fractures. We investigated union, shoulder function, request for implant removal, and return to sport. Our hypothesis was that these implants provide predictable union and return to sports without the negative consequence of leaving plates in situ, reducing the requirement for a second surgery. METHODS: We undertook a retrospective review of a consecutive series of patients who underwent this surgery between 2007 and 2010. Nineteen patients with a mean follow-up of 25 months were included. Postoperative follow-up was performed at 2 weeks and monthly thereafter until union was assessed as achieved clinically and radiographically. Two telephone interviews at a mean of 7 months and 25 months postoperatively assessed shoulder function by Oxford Shoulder Score, presence of any plate or scar discomfort, need for implant removal, and return to sport. RESULTS: Nineteen patients achieved union by 4 months (median, 12 weeks; range, 6-16 weeks). The mean Oxford Shoulder Score was 46 (range, 41-48) at a mean of 7 months (range, 3-18 months) and 47 (range, 44-48) at 25 months (range, 18-48 months). Initially, 2 patients requested implant removal; later, however, both declined surgery. No plates have been removed. Four patients complained of mild plate discomfort but did not wish removal. All patients had returned to sporting activities. CONCLUSION: Angular stable plate fixation of Neer group II, type II clavicle fractures resulted in a 100% union rate with excellent return of function with no mandatory need for removal.

Crystal structures of interleukin-2 tyrosine kinase and their implications for the design of selective inhibitors.

Interleukin-2 tyrosine kinase, Itk, is an important member of the Tec family of non-receptor tyrosine kinases that play a central role in signaling through antigen receptors such as the T-cell receptor, B-cell receptor, and Fcepsilon. Selective inhibition of Itk may be an important way of modulating many diseases involving heightened or inappropriate activation of the immune system. In addition to an unliganded nonphophorylated Itk catalytic kinase domain, we determined the crystal structures of the phosphorylated and nonphosphorylated kinase domain bound to staurosporine, a potent broad-spectrum kinase inhibitor. These structures are useful for the design of novel, highly potent and selective Itk inhibitors and provide insight into the influence of inhibitor binding and phosphorylation on the conformation of Itk.