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.

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.

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.

Assessment of Medical Industry Compensation to US Physicians by Gender.

Importance: It has been well established that female physicians earn less than their male counterparts in all specialties and ranks despite controlling for confounding variables. Objective: To investigate payments made from highest-grossing medical industry companies to female and male physicians and to assess compensation and engagement disparities based on gender. Design, Setting, and Participants: This retrospective, population-based cross-sectional study used data from the Open Payments database for the 5 female and 5 male physicians who received the most financial compensation from each of the 15 highest-grossing medical supply companies in the US from January 2013 to January 2019. Main Outcomes and Measures: The primary outcome was total general payments received by female and male physicians from medical industry over time and across industries. The secondary outcome was trends in industry payment to female and male physicians from 2013 to 2019. Results: Among the 1050 payments sampled, 1017 (96.9%) of the 5 highest earners were men and 33 (3.1%) were women. Female physicians were paid a mean (SD) of $41 320 ($88 695), and male physicians were paid a mean (SD) of $1 226 377 ($3 377 957) (P < .001). On multivariate analysis, male gender was significantly associated with higher payment after adjusting for rank, h-index, and specialty (mean [SD], $1 025 413 [$162 578]; P < .001). From 2013 to 2019, the payment gap between female and male physicians increased from $54 343 to $166 778 (P < .001). Conclusions and Relevance: This study found that male physicians received significantly higher payments from the highest-grossing medical industry companies compared with female physicians. This disparity persisted across all medical specialties and academic ranks. The health care industry gender payment gap continued to increase from 2013 to 2019, with a wider compensation gap in 2019.

Prevalence of Primary Liver Cancer is Affected by Place of Birth in Hispanic People Residing in the United States: All of Us Research Program Report.

BACKGROUND: Hispanic individuals have a disproportionately higher incidence and mortality for stomach, cervix, and liver cancers compared to Non-Hispanic White people. Since disparities in cancer incidence are influenced by multiple factors including immigration, elucidating the effect of birthplace and exposure to risk factors on the prevalence of these cancers is crucial for identifying high-risk populations and target risk reduction interventions. METHODS: The National Institutes of Health All of Us Research Program is a prospective, multidimensional biomedical data resource of underrepresented, minoritized people. The Registered Tier Dataset v5 was utilized to evaluate the prevalence and risk of stomach, cervix, and liver cancers among United States (US) born and non-US born Hispanic participants. RESULTS: Of over 434 000 current participants, 60 540 are Hispanic; 30 803 (50.9%) reported being US born and 29 294 (48.4%) non-US born. Non-US born Hispanic participants had significantly higher prevalence (.39% vs .21%, P < .001) and associated risk (OR 1.84, 95% CI 1.29-2.64, P < .001) of liver cancer, and trend towards higher prevalence of stomach (.14% vs .09%, P = .076) and cervix cancers (.27% vs .20%, P = .083) compared to US born counterparts. US born Hispanic patients with these 3 cancers were significantly younger than non-US born cohort (mean age 56.8 vs 61.7 years, P < .001). DISCUSSION: This is the first report using All of Us data to show that non-US born Hispanic participants have a higher risk of liver cancer compared to US born participants. Further analyses, including genomic studies, are necessary to understand these differences and identify targets for risk reduction interventions.

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.

Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E.

Macrophages play a key role in the development of atherosclerosis. Murine noroviruses (MNV) are highly prevalent in research mouse colonies and infect macrophages and dendritic cells. Our laboratory found that MNV4 infection in mice lacking the LDL receptor alters the development of atherosclerosis, potentially confounding research outcomes. Therefore, we investigated whether MNV4 likewise altered atherosclerosis in ApoE(-/-) mice. In the presence of oxidized LDL, MNV4 infection of ApoE(-/-) bone marrow-derived macrophages increased the gene expression of the inflammatory markers inducible nitric oxide synthase, monocyte chemoattractant protein 1, and IL6. In addition, proteins involved in cholesterol transport were altered in MNV4-infected ApoE -/- bone marrow-derived macrophages and consisted of increased CD36 and decreased ATP-binding cassette transporter A1. MNV4 infection of ApoE(-/-) mice at 12 wk of age (during the development of atherosclerosis) had a variable effect on atherosclerotic lesion size. In one study, MNV4 significantly increased atherosclerotic plaque area whereas in a second study, no effect was observed. Compared with controls, MNV4-infected mice had higher circulating Ly6C-positive monocytes, and viral RNA was detected in the aortas of some mice, suggesting potential mechanisms by which MNV4 alters disease progression. Plaque size did not differ when ApoE -/- mice were infected at 4 wk of age (early during disease development) or in ApoE -/- mice maintained on a high-fat, high-cholesterol diet. Therefore, these data show that MNV4 has the potential to exert a variable and unpredictable effect on atherosclerosis in ApoE(-/-) mice. We therefore propose that performing experiments in MNV-free mouse colonies is warranted.