Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis.

INTRODUCTION: Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma-peritoneal barrier. METHODS: We conducted a retrospective analysis of patients with stage II-IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360TM). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites. RESULTS: Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC: n = 61; visceral metastases: n = 138; other metastases: n = 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51; p < 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%; p < 0.01). In a subset of patients (n = 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue. CONCLUSIONS: PC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.

Plasma Exosome Gene Signature Differentiates Colon Cancer from Healthy Controls.

BACKGROUND: Liquid biopsies have become an integral part of cancer management as minimally invasive options to detect molecular and genetic changes. However, current options show poor sensitivity in peritoneal carcinomatosis (PC). Novel exosome-based liquid biopsies may provide critical information on these challenging tumors. In this initial feasibility analysis, we identified an exosome gene signature of 445 genes (ExoSig445) from colon cancer patients, including those with PC, that is distinct from healthy controls. METHODS: Plasma exosomes from 42 patients with metastatic and non-metastatic colon cancer and 10 healthy controls were isolated and verified. RNAseq analysis of exosomal RNA was performed and differentially expressed genes (DEGs) were identified by the DESeq2 algorithm. The ability of RNA transcripts to discriminate control and cancer cases was assessed by principal component analysis (PCA) and Bayesian compound covariate predictor classification. An exosomal gene signature was compared with tumor expression profiles of The Cancer Genome Atlas. RESULTS: Unsupervised PCA using exosomal genes with greatest expression variance showed stark separation between controls and patient samples. Using separate training and test sets, gene classifiers were constructed capable of discriminating control and patient samples with 100% accuracy. Using a stringent statistical threshold, 445 DEGs fully delineated control from cancer samples. Furthermore, 58 of these exosomal DEGs were found to be overexpressed in colon tumors. CONCLUSIONS: Plasma exosomal RNAs can robustly discriminate colon cancer patients, including patients with PC, from healthy controls. ExoSig445 can potentially be developed as a highly sensitive liquid biopsy test in colon cancer.

The Five-4-Life Quality Improvement Program: Improving Frontline Nurses' Cardiopulmonary Resuscitation Leadership and Team Management Skills.

BACKGROUND: Poor leadership and teamwork in cardiopulmonary resuscitation (CPR) are associated with poor patient outcomes. PROBLEM: Frontline nursing staff frequently identify patients in cardiac arrest but may not have the initial leadership and teamwork skills to organize their initial rescue response. APPROACH: The Five-4-Life Quality Improvement (QI) program was pilot tested in a pediatric unit within a 510-bed acute care hospital in 2 phases: first, an educational program focused on leadership, team dynamics, and CPR skills, followed by sustaining interventions in the unit. Video recordings of 12 mock codes (4 pre-, 4 post-, 4 follow-up) were analyzed by trained observers. OUTCOMES: Descriptive statistical tests indicated a significant improvement in leadership, teamwork, and task management scores pre- and post-program, and sustained after the program. CONCLUSION: Implementing the Five-4-Life QI program is feasible in improving leadership, teamwork, and task management of first responding frontline nurses.

Comparison of Same and Different Level Height Falls on Subsequent Midline Shift in Pediatric Traumatic Brain Injury.

OBJECTIVES: Up to 44% of pediatric traumatic brain injury occurs as a result of a fall. We hypothesized that a fall from height is associated with higher risk for subsequent midline shift in pediatric traumatic brain injury compared with a fall from same level. METHODS: The Pediatric Trauma Quality Improvement Program 2016 was queried for kids younger than 16 years with an injury in the abbreviated injury scale for the head after a fall. Patients with midline shift were identified. A logistic regression model was used for analysis. RESULTS: The risk of a midline shift was lower in those with a fall from a height (odds ratio, 0.64; 95% confidence interval, 0.46-0.91, P = 0.01). In kids older than 4 years, there was no association between the level of height of the fall and subsequent midline shift (P = 0.62). The risk for midline shift in kids younger than 4 years after a fall from same level was lower (odds ratio, 0.40; 95% confidence interval, 0.24-0.67; P = 0.001). CONCLUSIONS: In kids with traumatic brain injury, trauma activations due to falls from the same level are associated with a 2.5-fold higher risk of subsequent midline shift, compared with falling from height.

User-Centered Development and Patient Acceptability Testing of a Health-Coaching Intervention to Enhance Cancer Survivorship Follow-up in Primary Care.

We describe an iterative three-phase approach used to develop a cancer survivorship health-coaching intervention to guide self-management and follow-up care for post-treatment breast, colorectal, and prostate cancer survivors. Informed by theory (e.g., Cognitive-Social Health Information Processing Model (C-SHIP)), relevant literature, and clinical guidelines, we engaged in a user-centered design process. In phase I, we conducted depth interviews with survivors of breast (n = 34), prostate (n = 4), and colorectal (n = 6) cancers to develop a health coaching prototype. In phase II, we utilized user-testing interviews (n = 9) to test and refine the health coaching prototype. For both phases, we used a template analysis independently coding each interview. In phase I, majority (n = 34, 81%) of survivors were positive about the utility of health coaching. Among these survivors (n = 34), the top areas of identified need were emotional support (44%), general health information (35.3%), changes in diet and exercise (29.3%), accountability and motivation (23.5%), and information about treatment effects (17.7%). The prototype was developed and user-tested and refined in phase III to address the following concerns: (1) the amount of time for calls, (2) density of reading materials, (3) clarity about health coaches' role, (4) customization. Collectively, this resulted in the development of the Extended Cancer Educational for Long-Term Cancer Survivors health-coaching (EXCELSHC) program, which represents the first cancer survivorship follow-up program to support follow-up care designed-for-dissemination in primary care settings. EXCELSHC is being tested in a clinical efficacy trial. Future research will focus on program refinement and testing for effectiveness in primary care.

Analysis of COVID-19 Patients With Acute Respiratory Distress Syndrome Managed With Extracorporeal Membrane Oxygenation at US Academic Centers.

OBJECTIVE: This study analyzed the outcomes of COVID-19 patients with ARDS who were managed with extracorporeal membrane oxygenation (ECMO) across 155 US academic centers. SUMMARY BACKGROUND DATA: ECMO has been utilized in COVID-19 patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Early case series with the use of ECMO in these patients reported high mortality exceeding 90%. METHODS: Using ICD-10 codes, data of patients with COVID-19 with ARDS, managed with ECMO between April and September 2020, were analyzed using the Vizient clinical database. Outcomes measured included in-hospital mortality, hospital and ICU length of stay, and direct cost. For comparative purposes, the outcome of a subset of COVID-19 patients aged between 18 and 64 years and managed with versus without ECMO were examined. RESULTS: 1,182 patients with COVID-19 and ARDS received ECMO. In-hospital mortality was 45.9%, mean length of stay was 36.8 ±â€Š24.9 days, and mean ICU stay was 29.1 ±â€Š17.3 days. In-hospital mortality according to age group was 25.2% for 1 to 30 years; 42.2% for 31 to 50 years; 53.2% for 51 to 64 years; and 73.7% for ≥65 years. A subset analysis of COVID-19 patients, aged 18 to 64 years with ARDS requiring mechanical ventilation and managed with (n = 1113) vs without (n = 16,343) ECMO, showed relatively high in-hospital mortality for both groups (44.6% with ECMO vs 37.9% without ECMO). CONCLUSIONS: In this large US study of patients with COVID-19 and ARDS managed with ECMO, the in-hospital mortality is high but much lower than initial reports. Future research is needed to evaluate which patients with COVID-19 and ARDS would benefit from ECMO.

Analysis of Unintentional Falls in Pediatric Population and Predictors of Morbidity.

INTRODUCTION: Unintentional falls are a leading cause of pediatric traumatic injury. This study evaluates clinical outcomes of fall-related injuries in children under the age of 10. METHODS: The National Trauma Database was queried for children who experienced an unintentional fall. Patients were stratified by age in two groups: 1-5 and 6-10 years old. The primary outcome was post discharge extension of care, defined as transfer to skilled nursing facility or rehabilitation center after discharge from the hospital. Descriptive statistics and a multivariable logistic regression analysis were used to compare the two groups. RESULTS: From 2009 to 2016, a total of 8,277 pediatric patients experienced an unintentional fall, with 93.6% of patients being discharged home. Falls were more common in younger children, with greater odds of post discharge extension of care. Predictors of increased associated risk of extended medical care included intracranial hemorrhage (OR 1.05, 95% CI 1.03-1.06) and thoracic injuries (OR 1.03, 95% CI 1.00-1.1.05) (P< 0.05). Mortality in pediatric patients suffering unintentional falls was a rare event occurring in 0.7% of cases in children 1-5 years old and 0.4% of children 6-10 years old. CONCLUSION: The majority of children experiencing an unintentional fall are discharged home, with mortality being very rare. However, younger age is prone to more severe and serious injury patterns. Intracranial hemorrhage and thoracic injury were a predictor of need for extended medical care.

Development and usability testing of the e-EXCELS tool to guide cancer survivorship follow-up care.

OBJECTIVE: The aim of this study is to describe a user-centered (e.g., cancer survivors and clinicians) development process of an eHealth tool designed to facilitate self-management of cancer survivorship follow-up care. METHODS: Guided by Cognitive-Social Health Information Processing (C-SHIP) model and informed by core self-management skills, we engaged in a user-centered design process. In phase I, we conducted in-depth interviews with survivors of breast (n = 33), prostate (n = 4), and colorectal (n = 6) cancers, and (n = 9) primary care providers to develop content and design of the web tool. Phase II utilized iterative user testing interviews (n = 9) to test the web-based tool prototype. Data from both phases were independently coded using a template/content analytic approach. RESULTS: The top 5 functions identified in phase I for the web-based platform included: (a) educational materials to learn and prepare for health encounters (80%); (b) questions for health providers (74%); (c) ability to track contact information of providers (67%); (d) provide general information (64%); and, (e) support information (62%). Users of the prototype reported patient burden, tool fatigue, introduction timing of the tool, relevance, and security/privacy as concerns in phase II. CONCLUSIONS: This study demonstrates the value of using a theoretically informed and user-centered design process to develop relevant and patient-centered eHealth resources to support cancer survivorship. A larger study is needed to establish the efficacy of this eHealth tool as an intervention to improve adherence to follow-up care guidelines.

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.

The ethical perspectives of using animals in pediatric health.

While there are ethical standards for human biomedical research, animals have historically not benefitted from the same levels of protection. Cultural shifts in response to studies demonstrating animal capacity to suffer have resulted in laws defining minimum ethical standards for the treatment of various animal populations. However, none of these pertain to service or therapy animals nor do they define ethical considerations regarding training, placement, environment, and duty limitations specific to this population. The potential for harm and inability to provide consent should raise ethical questions of animal assisted interventions (AAI), including how to best balance the risk: benefit ratio for both animal and human participants. While service animals have specific definitions, therapy and emotional support animals are much less clearly defined and therefore have far less standardized practices regarding their training, certification, and process for matching to handlers. This can lead to animals being inadequately trained to cope with the stresses of their jobs or being placed in incompatible environments. Meanwhile, service animals' duties are constant, and the animal has little ability to consent to or withdraw from participation, leading to overwork, without the opportunity to engage in activities that align with the animals' natural preferences. Emotional support animals are the least defined of these populations, receive no formal training, and are at increased risk of inadequate care, unstable housing, and abuse from handlers who may also be poorly prepared to properly handle their needs. To uphold our moral obligations to the animals that serve to improve our own mental wellness and physical independence, urgent actions are needed to improve the protections in place for these populations.

Impact of COVID-19 Pandemic on Management and Outcomes of Acute Cholecystitis at US Academic Centers.

BACKGROUND: The COVID-19 pandemic has had wide-ranging effects on management of medical conditions. Many hospitals encountered staffing shortages, limited operating room availability, and shortage of hospital beds. There was increased psychological stress and fear of contracting COVID-19 infection, leading to delay in medical care for various disease processes. The objective of this study was to examine changes in management and outcomes attributed to the COVID-19 pandemic in patients presenting with acute calculus cholecystitis at US academic centers. STUDY DESIGN: Using the Vizient database, patients with the diagnosis of acute calculus cholecystitis who underwent intervention during the 15 months before the pandemic (prepandemic, October 2018 to December 2019) were compared with 15 months during the pandemic (pandemic, March 2020 to May 2021). Outcomes measures included demographics, characteristics, type of intervention, length of stay, in-hospital mortality, and direct cost. RESULTS: There were 146,459 patients with acute calculus cholecystitis identified (prepandemic: 74,605 vs pandemic: 71,854). Patients in the pandemic group were more likely to undergo medical management (29.4% vs 31.8%; p < 0.001) or percutaneous cholecystostomy tube placement (21.5% vs 18%; p < 0.001) and less likely to undergo laparoscopic cholecystectomy (69.8% vs 73.0%; p < 0.001). Patients in the pandemic group who underwent procedural intervention had longer length of stay (6.5 days vs 5.9 days; p < 0.001), higher in-hospital death (3.1% vs 2.3%; p < 0.001), and higher cost ($14,609 vs $12,570; p < 0.001). CONCLUSIONS: In this analysis of patients with acute calculus cholecystitis, there were distinct changes in the management and outcomes of patients due to the COVID-19 pandemic. Changes in the type of intervention and outcomes are likely related to delayed presentation with increases in the severity and complexity of the disease.

Readmission and Disposition in Patients With Malignant Bowel Obstructions Following Gastrostomy Tube.

BACKGROUND: Patients with peritoneal carcinomatosis (PC) can develop malignant bowel obstructions (MBOs) requiring inpatient admission and nasogastric tube decompression. Palliative decompressive gastrostomy tubes (G-tubes) may affect patient disposition, allowing for self-management and reduction in inpatient services. Therefore, we sought to assess disposition and inpatient readmission rates in patients admitted with PC and MBO following G-tube placement. METHODS: The Vizient® Clinical Data Base was queried for inpatient admissions from October 2018 to May 2022 utilizing ICD-10 codes to identify patients admitted with PC and bowel obstruction, with or without G-tube placement. Demographics and hospital outcomes were recorded. Descriptive statistics and multivariate logistic regression analysis were performed. RESULTS: From 750 patients, 59 (7.9%) had a G-tube placed. Compared to patients without G-tubes, those with G-tubes had lower rates of disposition to home (32.2% vs 70.0%, P < .001) and higher rates of disposition to hospice (home: 30.5% vs 7.8%, P < .001, facility: 10.2% vs 3.9%, P = .02). There was no significant difference in the rate (17.3% vs 22.3%, P = .40) or risk (OR = 1.44, 95% CI .69-3.01) of 30-day readmissions with G-tubes. However, palliative care consultation (OR 33.77, 95% CI 19.16-59.52) and G-tube placement (OR 5.82, 95% CI 2.56-13.25) were independent predictors for hospice. DISCUSSION: Placement of G-tubes in patients with PC and MBO was associated with higher rates of disposition to hospice but there is no difference in 30-day readmission rates compared to those without G-tubes. Further prospective studies are needed to understand the role of G-tube placement in patients with MBO in relation to outcomes and disposition.

Confusion and anxiety in between abnormal cervical cancer screening results and colposcopy: "The land of the unknown".

OBJECTIVE: Attendance to colposcopy after abnormal cervical cancer screening is essential to cervical cancer prevention. This qualitative study explored patients' understanding of screening results, their experiences of the time leading up to the colposcopy appointment, and colposcopy. METHODS: We recruited women referred for colposcopy from two urban practices in an academic health system. Individual interviews (N = 15) with participants were conducted after colposcopy appointments about their cervical cancer screening histories, current results, and colposcopy experiences. A team analyzed and summarized interviews and coded transcripts in Atlas.ti. RESULTS: We found that most women were confused about their screening results, did not know what a colposcopy was before being referred for one, and experienced anxiety in the interval between receiving their results and having their colposcopy. Most women searched for information online, but found "misinformation," "worst-case scenarios" and generic information that did not resolve their confusion. CONCLUSION: Women had little understanding of their cervical cancer risk and experienced anxiety looking for information and waiting for the colposcopy. Educating patients about cervical precancer and colposcopy, providing tailored information about their abnormal screening test results and potential next steps, and helping women manage distress may alleviate uncertainty while waiting for follow-up appointments. PRACTICE IMPLICATIONS: Interventions to manage uncertainty and distress in the interval between receiving an abnormal screening test result and attending colposcopy are needed, even among highly adherent patients.

Connect: Cultivating Academic-Community Partnerships to Address Our Communities' Complex Needs During Public Health Crises.

BACKGROUND: Black and Latino communities have been disproportionately impacted by coronavirus disease 2019 and we sought to understand perceptions and attitudes in four heavily impacted New Jersey counties to develop and evaluate engagement strategies to enhance access to testing. OBJECTIVE: To establish a successful academic/community partnership team during a public health emergency by building upon longstanding relationships and using principles from community engaged research. METHODS: We present a case study illustrating multiple levels of engagement, showing how we successfully aligned expectations, developed a commitment of cooperation, and implemented a research study, with community-based and health care organizations at the center of community engagement and recruitment. LESSONS LEARNED: This paper describes successful approaches to relationship building including information sharing and feedback to foster reciprocity, diverse dissemination strategies to enhance engagement, and intergenerational interaction to ensure sustainability. CONCLUSIONS: This model demonstrates how academic/community partnerships can work together during public health emergencies to develop sustainable relationships.

Development and validation of machine learning models for the prediction of blunt cerebrovascular injury in children.

BACKGROUND: Blunt cerebrovascular injury (BCVI) is a rare finding in trauma patients. The previously validated BCVI (Denver and Memphis) prediction model in adult patients was shown to be inadequate as a screening option in injured children. We sought to improve the detection of BCVI by developing a prediction model specific to the pediatric population. METHODS: The National Trauma Databank (NTDB) was queried from 2007 to 2015. Test and training datasets of the total number of patients (885,100) with complete ICD data were used to build a random forest model predicting BCVI. All ICD features not used to define BCVI (2268) were included within the random forest model, a machine learning method. A random forest model of 1000 decision trees trying 7 variables at each node was applied to training data (50% of the dataset, 442,600 patients) and validated with test data in the remaining 50% of the dataset. In addition, Denver and Memphis model variables were re-validated and compared to our new model. RESULTS: A total of 885,100 pediatric patients were identified in the NTDB to have experienced blunt pediatric trauma, with 1,998 (0.2%) having a diagnosis of BCVI. Skull fractures (OR 1.004, 95% CI 1.003-1.004), extremity fractures (OR 1.001, 95% 1.0006-1.002), and vertebral injuries (OR 1.004, 95% CI 1.003-1.004) were associated with increased risk for BCVI. The BCVI prediction model identified 94.4% of BCVI patients and 76.1% of non-BCVI patients within the NTDB. This study identified ICD9/ICD10 codes with strong association to BCVI. The Denver and Memphis criteria were re-applied to NTDB data to compare validity and only correctly identified 13.4% of total BCVI patients and 99.1% of non BCVI patients. CONCLUSION: The prediction model developed in this study is able to better identify pediatric patients who should be screened with further imaging to identify BCVI. LEVEL OF EVIDENCE: Retrospective diagnostic study-level III evidence.

Conflict of Interest Disclosure Among the Highest Earning Physicians Receiving Compensation From Vascular Device Companies.

OBJECTIVE: To characterize the association between payments made by vascular device companies to clinicians, and the conflict of interest (COI) declarations on relevant publications. SUMMARY BACKGROUND DATA: Close association between medical device companies and clinicians is essential in the advancement of surgical technology. When evaluating the efficacy of novel equipment, identification of these relationships can minimize the risk of bias in relevant studies. METHODS: Using the Open Payments Database (OPD), the 10 highest compensated clinicians from 10 vascular device companies were identified. In the population based bibliometric analysis, general payments, number of payments, h-index, and academic rank were identified. PubMed and Scopus were queried to identify author publications. Relevance to payment received and COI disclosures were identified for each article. RESULTS: The physicians identified earned $33,442,266.74 with a median of $92,500 in 2017. The authors published an average of 6.46+/-9.08 articles in 2018. Relevant COI was identified in 74%. In 50.5% of the relevant publications was a COI declared. The median h index of authors was 18+/-23. Community based physicians had a higher rate of COI disclosure (65.6%) compared to academic physicians (47.6%) (P = .008). Low h-index authors had a higher rate of COI declaration (71.4%) compared to high h-index (43.6%) (P = .001). CONCLUSION: A high degree of inconsistency was found between self-declared COI and relevant articles published by the highest compensated physicians. We propose a policy of full disclosure and the addition of a link to each author's OPD page on all publications to increase access to potential COI.