Humanized mouse models for immuno-oncology research.

Immunotherapy has emerged as a promising treatment paradigm for many malignancies and is transforming the drug development landscape. Although immunotherapeutic agents have demonstrated clinical efficacy, they are associated with variable clinical responses, and substantial gaps remain in our understanding of their mechanisms of action and specific biomarkers of response. Currently, the number of preclinical models that faithfully recapitulate interactions between the human immune system and tumours and enable evaluation of human-specific immunotherapies in vivo is limited. Humanized mice, a term that refers to immunodeficient mice co-engrafted with human tumours and immune components, provide several advantages for immuno-oncology research. In this Review, we discuss the benefits and challenges of the currently available humanized mice, including specific interactions between engrafted human tumours and immune components, the development and survival of human innate immune populations in these mice, and approaches to study mice engrafted with matched patient tumours and immune cells. We highlight the latest advances in the generation of humanized mouse models, with the aim of providing a guide for their application to immuno-oncology studies with potential for clinical translation.

Use of In-Situ Simulation Based Clinical Systems Test of Thoracic Robotic Surgery Emergencies.

INTRODUCTION: With the advancement of robotic surgery, some thoracic surgeons have been slow to adopt to this new operative approach, in part because they are un-scrubbed and away from the patient while operating. Aiming to allay surgeon concerns of intra-operative emergencies, an insitu simulation-based clinical system's test (SbCST) can be completed to test the current clinical system, and to practice low-frequency, high-stakes clinical scenarios with the entire operating room (OR) team. METHODS: Six different OR teams completed an insitu SbCST of an intra-operative pulmonary artery injury during a robot-assisted thoracic surgery at a single tertiary care center. The OR team consisted of an attending thoracic surgeon, surgery resident, anesthesia attending, anesthesia resident, circulating nurse, and a scrub technician. This test was conducted with an entire OR team along with study observers and simulation center staff. Outcomes included the identified latent safety threats (LSTs) and possible solutions for each LST, culminating in a complete failure mode and effects analysis (FMEA). A Risk Priority Number (RPN) was determined for each LST identified. Pre- and post-simulation surveys using Likert scales were also collected. RESULTS: The six FMEAs identified 28 potential LSTs in four categories. Of these 28 LSTs, nine were considered high priority based on their Risk Priority Number (RPN) with seven of the nine being repeated multiple times. Pre- and post-simulation survey responses were similar, with the majority of participants (94%) agreeing that high fidelity simulation of intra-operative emergencies is helpful and provides an opportunity to train for high-stakes, low-frequency events. After completing the SbCST, more participants felt confident that they knew their role during an intra-operative emergency than their pre-simulation survey responses. All participants agreed that simulation is an important part of continuing education and is helpful for learning skills that are infrequently used. Following the SbCST, more participants agreed that they knew how to safely undock the da Vinci robot during an emergency. CONCLUSIONS: SbCSTs provide an opportunity to test the current clinical system with a low-frequency, high-stakes event and allow medical personnels to practice their skills and teamwork. By completing multiple SbCSTs, we were able to identify multiple LSTs within different OR teams, allowing for a broader review of the current clinical systems in place. The use of these SbCSTs in conjunction with debriefing sessions and FMEA completion allows for the most significant potential improvement of the current system. This study shows that SbCST with FMEA completion can be used to test current systems and create better systems for patient safety.

Venous thromboembolism risk stratification in trauma using the Caprini risk assessment model.

INTRODUCTION: The Caprini risk assessment model is widely used for venous thromboembolism (VTE) but has limited data in trauma. The study objective was to determine if the Caprini risk assessment model could effectively risk stratify trauma patients. MATERIALS AND METHODS: We performed a retrospective review of trauma patients aged ≥18 years, admitted for greater than 24 h at a level one trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Multiple logistic regression assessed odds of inpatient VTE. RESULTS: A total of 1279 patients met study eligibility, with a total of 33 VTE (2.6%). When comparing those with VTE to those without, the mean age was lower (52.5 vs 59.5, p = 0.06, respectively), sex distribution was similar, but mean body mass index was higher (30.2 vs 27.4, p = 0.019, respectively). The mean Caprini score was 9.9, and 75.5% had a score >4, the traditional Caprini high-risk cutoff. The VTE group had a higher mean Injury Severity Score (17.8 vs 12.6, p = 0.011), and mean Caprini score (16.4 vs 9.8, p < 0.001). Multiple logistic regression found Caprini score, not Injury Severity Score, was associated with higher odds of VTE (adjusted odds ratio 1.06, 95% confidence interval 1.02-1.10), after adjusting for Injury Severity Score, any missed doses of VTE chemoprophylaxis, and VTE prophylaxis type. CONCLUSIONS: Higher Caprini scores are associated with elevated odds of inpatient VTE within hospitalized trauma patients. These data support using the Caprini risk assessment model in the trauma population, which may aid in risk stratification.

Patterns of General Surgery Residency Social Media Use in the Age of COVID-19.

OBJECTIVE: The role for social media use by General Surgery departments continues to expand and social media accounts have been increasingly implemented as a tool for residency program for promotion and engagement. The importance of these accounts appears to have increased given the unprecedented changes with COVID-19 and the dramatic and unpredictable change to the application cycle including the use of virtual interviews, suggesting a perceived need for increased online engagement with applicants. The purpose of this study was to determine the patterns of creation and usage of Twitter and Instagram accounts of Accreditation Council for Graduate Medical Education (ACGME)-accredited General Surgery residency programs and their associated surgical departments. METHORDS: A cross-sectional study of the use of Twitter and Instagram by the 332 ACGME-accredited General Surgery residency programs and their associated departments was conducted in February 2021. Twitter and Instagram accounts were identified by accessing program/department websites as well as social media platform and internet searches. Year of creation, number of followers, and number of posts (July 1, 2018-December 31, 2020) were collected. Trends in usage were compared across years stratified by platform and by account owner (department vs. residency). RESULTS: Instagram accounts are more than five-times greater for residencies compared to departments (42% vs 8%, p < 0.001). There was not a significant difference between the number of department and residency Twitter accounts (26% vs 23%, p = 0.37). Significantly more residency Instagram and Twitter accounts were created or first posted in 2020 compared to department accounts (Instagram: 100 vs 7, p < 0.001; Twitter: 31 vs 6, p = 0.001). Over 18% of residency programs had both Twitter and Instagram accounts compared to only 6% of departments (p < 0.001). However, department Twitter and Instagram accounts had significantly higher median total posts from 7/1/2018-12/31/2020 (Twitter: p = 0.0001, Instagram p = 0.004). While the number of Instagram followers and accounts being followed were similar between residencies and departments, department Twitter accounts had a larger median number of followers (1141 vs. 430, p=0.003) and account followings (308 vs. 192, p = 0.001) compared to residency accounts. CONCLUSIONS: The number of residency social media accounts has significantly increased in 2020 compared to account creation of departments, with Instagram account creation exceeding that of Twitter and of departments. The opposite pattern in usage was seen related to number of posts, and with Twitter, followers, and number of followings, with departments outpacing residencies. This significant increase in account creation may have been influenced by the COVID-19 pandemic and the change to a virtual interview season, suggesting an unprecedented need for online engagement with applicants. As the increased social media presence will likely persist in future application cycles, further study about the impact of residency social media use on recruitment and applicant decision-making as well as effective strategies, is needed.

Unique surgical approach to a twisted ileal-anal pouch.

Total proctocolectomy with ileal pouch-anal anastomosis can restore gastrointestinal continuity in patients requiring colectomy for ulcerative colitis, however, it can be associated with high morbidity. Reoperation for pouch-related complications is technically challenging and often leads to deterioration of pouch function or need for permanent stoma. We report a case of acute on chronic small bowel obstruction secondary to a 360-degree twist in the small bowel introduced during creation of the ileal-anal pouch. Our novel approach at repair has not been reported in past literature which included resection and re-anastomosis of the small bowel proximal to the pouch allowing for pouch salvage with return to function.

Field Synopsis of the Role of Sex in Stroke Prediction Models.

BACKGROUND: Guidelines for stroke prevention recommend development of sex-specific stroke risk scores. Incorporating sex in Clinical Prediction Models (CPMs) may support sex-specific clinical decision making. To better understand their potential to guide sex-specific care, we conducted a field synopsis of the role of sex in stroke-related CPMs. METHODS AND RESULTS: We identified stroke-related CPMs in the Tufts Predictive Analytics and Comparative Effectiveness CPM Database, a systematic summary of cardiovascular CPMs published from January 1990 to May 2012. We report the proportion of models including the effect of sex on stroke incidence or prognosis, summarize the directionality of the predictive effects of sex, and explore factors influencing the inclusion of sex. Of 92 stroke-related CPMs, 30 (33%) contained a coefficient for sex or presented sex-stratified models. Only 12/58 (21%) CPMs predicting outcomes in patients included sex, compared to 18/30 (60%) models predicting first stroke (P<0.0001). Sex was most commonly included in models predicting stroke among a general population (69%). Female sex was consistently associated with reduced mortality after ischemic stroke (n=4) and higher risk of stroke from arrhythmias or coronary revascularization (n=5). Models predicting first stroke versus outcomes among patients with stroke (odds ratio=5.75, 95% CI 2.18-15.14, P<0.001) and those developed from larger versus smaller sample sizes (odds ratio=4.58, 95% CI 1.73-12.13, P=0.002) were significantly more likely to include sex. CONCLUSIONS: Sex is included in a minority of published CPMs, but more frequently in models predicting incidence of first stroke. The importance of sex-specific care may be especially well established for primary prevention.

Recent Marijuana Use and Associations With Exhaled Nitric Oxide and Pulmonary Function in Adults in the United States.

BACKGROUND: The medical and recreational use of marijuana is now legal in some parts of the United States; the health effects are unknown. We aimed to evaluate associations between recent marijuana use and exhaled nitric oxide (eNO) and pulmonary function. METHODS: We performed a cross-sectional study of 10,327 US adults participating in the National Health and Nutrition Examination Survey in the years 2007 to 2012. We examined associations between marijuana use and eNO, FEV1, FVC, the FEV1/FVC ratio, and forced expiratory flow (midexpiratory phase) (FEF25%-75%) by weighted linear regression. RESULTS: In the study population, there were 4,797 never users, 4,084 past marijuana users, 555 participants who used marijuana 5 to 30 days before the examination, and 891 participants who used marijuana 0 to 4 days before the examination. Current marijuana use in the past 4 days was associated with 13% lower eNO (95% CI, -18% to 8%). FVC was higher in past users (75 mL; 95% CI, 38-112) and current users in the past 5 to 30 days (159 mL; 95% CI, 80-237) and in users within 0 to 4 days of the examination (204 mL; 95% CI, 139-270) compared with never users. All associations remained unchanged and statistically significant in sensitivity analyses excluding current and past tobacco users. CONCLUSIONS: Current marijuana use was associated with lower levels of eNO and higher FVC. The lower eNO in marijuana smokers suggests that short-term exposure to marijuana may, like tobacco, acutely affect the pulmonary vascular endothelium and impair airflow through the small airways.

The impact of marijuana use on glucose, insulin, and insulin resistance among US adults.

BACKGROUND: There are limited data regarding the relationship between cannabinoids and metabolic processes. Epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in marijuana users compared with people who have never used marijuana, suggesting a relationship between cannabinoids and peripheral metabolic processes. To date, no study has investigated the relationship between marijuana use and fasting insulin, glucose, and insulin resistance. METHODS: We included 4657 adult men and women from the National Health and Nutrition Examination Survey from 2005 to 2010. Marijuana use was assessed by self-report in a private room. Fasting insulin and glucose were measured via blood samples after a 9-hour fast, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance. Associations were estimated using multiple linear regression, accounting for survey design and adjusting for potential confounders. RESULTS: Of the participants in our study sample, 579 were current marijuana users and 1975 were past users. In multivariable adjusted models, current marijuana use was associated with 16% lower fasting insulin levels (95% confidence interval [CI], -26, -6) and 17% lower HOMA-IR (95% CI, -27, -6). We found significant associations between marijuana use and smaller waist circumferences. Among current users, we found no significant dose-response. CONCLUSIONS: We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.