Race, Ethnicity, and Socioeconomic Factors as Determinants of Cachexia Incidence and Outcomes in a Retrospective Cohort of Patients With Gastrointestinal Tract Cancer.

PURPOSE: Cachexia is a paraneoplastic syndrome of unintentional adipose and muscle tissue wasting with severe impacts to functionality and quality of life. Although health inequities across minority and socioeconomically disadvantaged groups are known, the role of these factors in cachexia progression is poorly characterized. This study aims to evaluate the relationship between these determinants and cachexia incidence and survival in patients with gastrointestinal tract cancer. METHODS: Through retrospective chart review from a prospective tumor registry, we established a cohort of 882 patients with gastroesophageal or colorectal cancer diagnosed between 2006 and 2013. Patient race, ethnicity, private insurance coverage, and baseline characteristics were evaluated through multivariate, Kaplan-Meier, and Cox regression analyses to determine associations with cachexia incidence and survival outcomes. RESULTS: When controlling for potentially confounding covariates (age, sex, alcohol and tobacco history, comorbidity score, tumor site, histology, and stage), Black (odds ratio [OR], 2.447; P < .0001) and Hispanic (OR, 3.039; P < .0001) patients are at an approximately 150% and 200%, respectively, greater risk of presenting with cachexia than non-Hispanic White patients. Absence of private insurance coverage was associated with elevated cachexia risk (OR, 1.439; P = .0427) compared to privately insured patients. Cox regression analyses with previously described covariates and treatment factors found Black race (hazard ratio [HR], 1.304; P = .0354) to predict survival detriments, while cachexia status did not reach significance (P = .6996). CONCLUSION: Our findings suggest that race, ethnicity, and insurance play significant roles in cachexia progression and related outcomes that are not accounted for by conventional predictors of health. Disproportionate financial burdens, chronic stress, and limitations of transportation and health literacy represent targetable factors for mitigating these health inequities.

Racial, Ethnic, and Socioeconomic Characteristics Independently Predict for Cachexia Risk and Associated Survival Outcomes in Stage IV NSCLC: A Brief Report.

Introduction: Cancer cachexia, found in more than a third of patients with NSCLC, directly leads to functional and survival detriments. As screening and interventions for cachexia and NSCLC improve, deficits in health care access and quality among patients disadvantaged by racial-ethnic and socioeconomic factors must be addressed. Methods: We retrospectively evaluated 957 patients diagnosed with having stage IV NSCLC between 2014 and 2020 in Dallas, Texas. Cachexia was retrospectively assessed by applying criteria for substantial unintentional weight loss in the time leading up to cancer diagnosis. Nonparametric, parametric, multivariate logistic regression, and Kaplan-Meier analyses were conducted to evaluate for variables potentially associated with cachexia incidence and survival. Results: In multivariate analysis including age, sex, comorbidities, body mass index, risk behaviors, and tumor characteristics, Black race and Hispanic ethnicity were independently associated with more than a 70% increased risk of presenting with cachexia at the time of NSCLC diagnosis (p < 0.05). When private insurance status was included as a covariate, this association was diminished for Hispanic patients only. Black patients presented with stage IV disease at an average of approximately 3 years younger than White patients (Kruskal-Wallis p = 0.0012; t test p = 0.0002). Cachexia status at diagnosis consistently predicted for survival detriments, further highlighting the importance of addressing differential cachexia risk across racial-ethnic groups. Conclusions: Fundamentally, our findings reveal elevated cachexia risk in Black and Hispanic patients with stage IV NSCLC with associated survival detriments. These differences are not fully accounted for by traditional determinants of health and suggest novel avenues for addressing oncologic health inequities.

Training Students as Navigators for Patients Experiencing Homelessness.

Background and Objectives: Despite the significant effects of homelessness on health, medical and health professions students rarely receive formal education in caring for individuals experiencing homelessness. We describe the implementation and evaluation of a novel student-run Patient Navigator Program (PNP) and its prerequisite elective that trains students in patient navigation principles specific to homelessness in the local community. METHODS: We analyzed pre- and postsurvey matched responses from students immediately before and after course completion. The survey utilizes the externally-validated instruments Health Professional Attitudes Toward the Homeless Inventory (HPATHI) and the Student-Run Free Clinic Project (SRFCP) survey. We examined differences using paired t tests and Wilcoxon signed-rank tests. Students also completed separate end-of-curriculum evaluation forms assessing satisfaction with the course. RESULTS: After completing the elective, students (n=45) demonstrated improvement in self-assessed attitude towards individuals experiencing homelessness (P=.03), specifically an increase in reported social advocacy (P<.001); and an increase in self-perceived knowledge about (P<.001), efficacy in working with (P=.01), and skills in caring for (P<.001) underserved groups. The elective also received high student satisfaction ratings. CONCLUSIONS: Formal education in patient navigation and caring for individuals experiencing homelessness improves self-assessed preparedness of future health care providers in serving homeless and underserved populations.

Association of Spinal Cord Stimulator Implantation With Persistent Opioid Use in Patients With Postlaminectomy Syndrome.

Importance: The results of studies evaluating spinal cord stimulation (SCS) for postlaminectomy syndrome (PLS) have yielded mixed results. This has led to an increased emphasis on objective outcome measures such as opioid prescribing. Objective: To determine the association between SCS and long-term opioid therapy (LOT) for PLS. Design, Setting, and Participants: In this cohort study, adults with PLS were identified using the TriNetx Diamond Network and separated based on whether they underwent SCS. Patients were stratified according to baseline opioid use (opioid-naive or receiving LOT) and subsequent opioid therapy over the 12-month period ranging from 3 to 15 months post-SCS implantation or post-PLS index date. Statistical analysis was performed from June to December 2021. Exposure: SCS. Main Outcomes and Measures: The main outcome was cessation of opioid use among patients receiving LOT or abstinence from opioids among opioid-naive patients. Opioid-naive patients were defined as those receiving at most 2 opioid prescriptions per year, and patients on LOT were those receiving at least 6 opioid prescriptions per year. Results: Among 552 937 eligible patients treated between December 2015 and May 2021, 26 179 with PLS received an SCS implant. The median (IQR) patient age was 60 (51-69) years; 305 802 patients (55.3%) were female. Among those reporting racial identify (37.0% [204 758 patients]), 9.3% (18 971 patients) were African American, 0.3% (648 patients) were Asian, and 90.4% (185 139 patients) were White. Compared with those who did not receive an SCS, individuals who received an SCS were more likely to be using opioids preimplantation (mean [SD] prescriptions: 4.3 [8.5] vs 4.1 [9.3]; P < .001) but less likely to be using opioids after SCS implantation (mean [SD] prescriptions: 3.8 [8.2] vs 4.0 [9.4]; P = .006). In the 12-month study period, similar proportions in the SCS and no-SCS groups receiving baseline LOT remained on LOT (70.3% [n = 74 585] vs 69.2% [n = 3882], respectively; P = .10). In opioid-naive patients, SCS was associated with a small decreased likelihood of patients subsequently receiving LOT (7.6% vs 7.0%; difference, -0.6% [95% CI, -1.0% to -0.2%]; P = .003). In multivariable analysis, SCS was associated with an increased likelihood of not being on opioids in both opioid-naive (adjusted odds ratio [OR], 0.90 [95% CI, 0.85-0.96]; P < .001) and LOT patients (adjusted OR, 0.93 [95% CI, 0.88-0.99]; P = .02). White patients were significantly more likely to be diagnosed with PLS (ie, underwent surgery) (90.4% vs 85.2%; difference, 5.2% [95% CI, 5.1%-5.4%]; P < .001) and receive an SCS (93.7% vs 90.3%; difference, 3.4% [95% CI, 2.9% to 4.0%]; P < .001) than patients of other racial identities. Conclusions and Relevance: These findings suggest that under real-life conditions, SCS was associated with small, clinically questionable associations with opioid discontinuation and not starting opioids in the context of PLS.

Tmprss6-ASO as a tool for the treatment of Polycythemia Vera mice.

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm resulting from an acquired driver mutation in the JAK2 gene of hematopoietic stem and progenitor cells resulting in the overproduction of mature erythrocytes and abnormally high hematocrit, in turn leading to thromboembolic complications. Therapeutic phlebotomy is the most common treatment to reduce the hematocrit levels and consequently decrease thromboembolic risk. Here we demonstrate that, by using the iron restrictive properties of the antisense oligonucleotides against Tmprss6 mRNA, we can increase hepcidin to achieve effects equivalent to therapeutic phlebotomy. We provide evidence that this less invasive approach could represent an additional therapeutic tool for the treatment of PV patients.

Variations in Presentation and Management of COVID-19 Inpatients by Race and Ethnicity in a Large Texas Metroplex.

OBJECTIVE: The aim of this study was to assess variations in presentation and outcomes of coronavirus disease 2019 (COVID-19) across race/ethnicity at a large Texas metroplex hospital. METHODS: A retrospective cohort study was performed. RESULTS: Although COVID-19 patients demonstrated significant socioeconomic disparities, race/ethnicity was not a significant predictor of intensive care unit (ICU) admission (P = 0.067) or case fatality (P = 0.078). Hospital admission varied by month, with incidence among Black/African-American and Hispanic/Latino patients peaking earlier in the pandemic timeline (P < 0.001). Patients reporting Spanish as their primary language were significantly more likely to be admitted to the ICU (odds ratio, 1.75; P = 0.007). CONCLUSIONS: COVID-19 patients do not demonstrate significant racial/ethnic disparities in case fatality, suggesting that state-wide disparities in mortality rate are rooted in infection risk rather than hospital course. Variations in admission rates by race/ethnicity across the timeline and increased ICU admission among Spanish-speaking patients demonstrate the need to pursue tailored interventions on both a community and structural level to mitigate further health disparities throughout the pandemic and after.

Oropharyngeal Bleeding Due to Cannabidiol Oil Vape Use.

Vaping has become an increasingly popular alternative to smoking in recent years. We present a rare and unusual case of upper airway bleeding caused by inhalation of a cannabidiol (CBD) oil-based vape due to a chemical burn. There are no case reports of this injury in the literature, and we discuss the clinical presentation, diagnosis and our management of this potentially life-threatening injury. A 27-year-old man presented to the accident and emergency department after using a CBD oil vape. After one inhalation of the CBD oil vape, the patient experienced immediate onset pain in the oropharynx, dyspnoea, expectoration of blood and hoarseness. The patient had used a CBD oil vape four hours earlier that evening for the first time, which was procured from an unregulated online source. The patient was referred to the Ear, Nose and Throat (ENT) team where the examination of oropharynx identified a posterior pharyngeal bleeding point. Flexible nasal endoscopy was undertaken showing profound erythema and inflammation throughout the oropharynx and posterior pharyngeal wall. The mucous membranes had been detached leaving an exposed bleeding submucosa. The patient was commenced on three cycles of back-to-back adrenaline nebulisers (1:1000 adrenaline in 5ml of 0.9% NaCl), 6.6mg dexamethasone intravenously and hydrogen peroxide gargles (5ml of 3% hydrogen peroxide in 10ml of water) three times a day. There were early involvement and review of the airway by the anaesthetic and intensive care teams, which was deemed safe at the time. A plan was made for a definitive airway if bleeding reoccurred. Upper airway bleeding can present as a rare form of vape-induced injury and should be considered part of the differential diagnosis particularly in those using CBD oil vapes. History taking is pertinent and patients should be questioned on the specific vape liquids used. Airway stabilisation is the priority with early involvement of the multi-disciplinary team including anaesthetists, intensive care specialists and ENT surgeons.

Haemorrhagic nasal polyp mimicking melanoma in an 83-year-old on rivaroxaban.

An 83-year-old woman presented with rapid onset unilateral nasal obstruction after sneezing. She had a history of hypertension and atrial fibrillation, and was on rivaroxaban. Examination revealed a dark red polypoidal lesion completely obstructing the left nostril. She underwent CT and MRI, and proceeded to urgent excision biopsy of the lesion. Intraoperative appearance was in keeping with a haemorrhagic polyp arising from the nasal septum. Histology revealed haematoma within a layer of nasal mucosa. There was no evidence of haemangioma underlying the polyp. Our literature search has identified this case as the first described haemorrhagic polyp of the nasal septum. It is likely that rivaroxaban contributed to the formation of this haemorrhagic polyp, and it is important to differentiate benign haemorrhagic lesions from malignant conditions such as melanoma. Similar cases may become more common in the future as the proportion of the population on anticoagulants increases.

Correcting ß-thalassemia by combined therapies that restrict iron and modulate erythropoietin activity.

ß-Thalassemia intermedia is a disorder characterized by ineffective erythropoiesis (IE), anemia, splenomegaly, and systemic iron overload. Novel approaches are being explored based on the modulation of pathways that reduce iron absorption (ie, using hepcidin activators like Tmprss6-antisense oligonucleotides [ASOs]) or increase erythropoiesis (by erythropoietin [EPO] administration or modulating the ability of transferrin receptor 2 [Tfr2] to control red blood cell [RBC] synthesis). Targeting Tmprss6 messenger RNA by Tmprss6-ASO was proven to be effective in improving IE and splenomegaly by inducing iron restriction. However, we postulated that combinatorial strategies might be superior to single therapies. Here, we combined Tmprss6-ASO with EPO administration or removal of a single Tfr2 allele in the bone marrow of animals affected by ß-thalassemia intermedia (Hbbth3/+). EPO administration alone or removal of a single Tfr2 allele increased hemoglobin levels and RBCs. However, EPO or Tfr2 single-allele deletion alone, respectively, exacerbated or did not improve splenomegaly in ß-thalassemic mice. To overcome this issue, we postulated that some level of iron restriction (by targeting Tmprss6) would improve splenomegaly while preserving the beneficial effects on RBC production mediated by EPO or Tfr2 deletion. While administration of Tmprss6-ASO alone improved the anemia, the combination of Tmprss6-ASO + EPO or Tmprss6-ASO + Tfr2 single-allele deletion produced significantly higher hemoglobin levels and reduced splenomegaly. In conclusion, our results clearly indicate that these combinatorial approaches are superior to single treatments in ameliorating IE and anemia in ß-thalassemia and could provide guidance to translate some of these approaches into viable therapies.

Discoidin domain receptor 1-deletion ameliorates fibrosis and promotes adipose tissue beiging, brown fat activity, and increased metabolic rate in a mouse model of cardiometabolic disease.

OBJECTIVE: Discoidin domain receptor 1 (DDR1) is a collagen binding receptor tyrosine kinase implicated in atherosclerosis, fibrosis, and cancer. Our previous research showed that DDR1 could regulate smooth muscle cell trans-differentiation, fibrosis and calcification in the vascular system in cardiometabolic disease. This spectrum of activity led us to question whether DDR1 might also regulate adipose tissue fibrosis and remodeling. METHODS: We have used a diet-induced mouse model of cardiometabolic disease to determine whether DDR1 deletion impacts upon adipose tissue remodeling and metabolic dysfunction. Mice were fed a high fat diet (HFD) for 12 weeks, followed by assessment of glucose and insulin tolerance, respiration via indirect calorimetry, and brown fat activity by FDG-PET. RESULTS: Feeding HFD induced DDR1 expression in white adipose tissue, which correlated with adipose tissue expansion and fibrosis. Ddr1-/- mice fed an HFD had improved glucose tolerance, reduced body fat, and increased brown fat activity and energy expenditure compared to Ddr1+/+ littermate controls. HFD-fed DDR1-/- mice also had reduced fibrosis, smaller adipocytes with multilocular lipid droplets, and increased UCP-1 expression characteristic of beige fat formation in subcutaneous adipose tissue. In vitro, studying C3H10T1/2 cells stimulated to differentiate, DDR1 inhibition caused a shift from white to beige adipocyte differentiation, whereas DDR1 expression was increased with TGFß-mediated pro-fibrotic differentiation. CONCLUSION: This study is the first to identify a role for DDR1 as a driver of adipose tissue fibrosis and suppressor of beneficial beige fat formation.

Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult ß-thalassemia major.

Minihepcidins are hepcidin agonists that have been previously shown to reverse iron overload and improve erythropoiesis in mice affected by non-transfusion-dependent thalassemia. Given the extreme anemia that occurred with the previous model of transfusion-dependent thalassemia, that model was inadequate for investigating whether minihepcidins can improve red blood cell quality, lifespan and ineffective erythropoiesis. To overcome this limitation, we generated a new murine model of transfusion-dependent thalassemia with severe anemia and splenomegaly, but sufficient red cells and hemoglobin production to test the effect of minihepcidins. Furthermore, this new model demonstrates cardiac iron overload for the first time. In the absence of transfusions, minihepcidins improved red blood cell morphology and lifespan as well as ineffective erythropoiesis. Administration of a minihepcidin in combination with chronic red blood cell transfusion further improved the ineffective erythropoiesis and splenomegaly and reversed cardiac iron overload. These studies indicate that drugs such as minihepcidins have therapeutic potential for patients with transfusion-dependent thalassemia.

Assessment of the Spatial Heterogeneity of Breast Cancers: Associations Between Computed Tomography and Immunohistochemistry.

BACKGROUND: Tumour heterogeneity is considered an important mechanism of treatment failure. Imaging-based assessment of tumour heterogeneity is showing promise but the relationship between these mathematically derived measures and accepted 'gold standards' of tumour biology such as immunohistochemical measures is not established. METHODS: A total of 20 women with primary breast cancer underwent a research dynamic contrast-enhanced computed tomography prior to treatment with data being available for 15 of these. Texture analysis was performed of the primary tumours to extract 13 locoregional and global parameters. Immunohistochemical analysis associations were assessed by the Spearman rank correlation. RESULTS: Hypoxia-inducible factor-1α was correlated with first-order kurtosis (r = -0.533, P = .041) and higher order neighbourhood grey-tone difference matrix coarseness (r = 0.54, P = .038). Vascular maturity-related smooth muscle actin was correlated with higher order grey-level run-length long-run emphasis (r = -0.52, P = .047), fractal dimension (r = 0.613, P = .015), and lacunarity (r = -0.634, P = .011). Micro-vessel density, reflecting angiogenesis, was also associated with lacunarity (r = 0.547, P = .035). CONCLUSIONS: The associations suggest a biological basis for these image-based heterogeneity features and support the use of imaging, already part of standard care, for assessing intratumoural heterogeneity.

Cervical Epidural Depth: Correlation Between Cervical MRI Measurements of the Skin-to-Cervical Epidural Space and the Actual Needle Depth During Interlaminar Cervical Epidural Injections.

Objective: The purpose of this study was to assess the correlation between skin-to-epidural space depth, as measured on cervical magnetic resonance imaging (MRI), and actual needle depth, as measured by Tuohy needle markings during cervical epidural steroid injections. Methods: We conducted a retrospective review of cervical MRI images to determine estimated depth from skin to epidural space. Of the 121 reviewed patients who underwent cervical epidural steroid injections, 81 met inclusion criteria and were retained for data analysis. Results: At the C6-C7 level, the estimated needle depth according to MRI images was 6.03 ± 1.15 cm (mean ± SD) and the actual needle depth was 5.62 ± 0.77 cm. At the C7-T1 level, the estimated needle depth based on MRI images was 5.90 ± 1.05 cm and the actual needle depth was 5.73 ± 0.98 cm. At both C6-C7 and C7-T1, MRI depth (P < 0.009, P < 0.001) and body mass index (P < 0.001, P < 0.002) were significantly associated with actual depth. Conclusions: Estimates of needle depth made with MRI were consistently slightly deeper than the actual loss-of-resistance needle depth, indicating that the provider should employ caution when using MRI predictive depths. Information garnered from preprocedure MRIs can be used to improve the safety of cervical epidural steroid injection procedures.