Treating black patients as "knowers".

Recent trends in healthcare policy from high-volume service models to "high-value" delivery systems have refocused the need for patient-centered approaches to quality care. However, benchmarks of how to define and evaluate successful patient-centeredness have not been sufficiently established. Such ill-defined evaluation criteria can further exacerbate systemic inequities in maximum quality health care delivery, especially based on the intersectional diversity of various patient populations. In this context, applying a phenomenology of medicine framework or perspective-driven analysis is useful in defining cross-cultural patient-centeredness. This reframing from a naturalistic or objective/biological viewpoint to a phenomenological viewpoint may aid in placing greater epistemic or knowledge authority in the hands of vulnerable and/or marginalized patients- allowing these patients to become key "knowers" in the clinical interaction. Moreover, treating Black patients as "knowers" emphasizes the prioritization of patient values at the core of providing valuable healthcare. Such an academic, policy, and clinical approach to medicine agrees with well-established principles of medical ethics. In addition, the framework of a phenomenology of medicine can better facilitate physician-patient communication and interaction by delineating often muddled hermeneutics.

Predictors of follow-up non-compliance after definitive radiotherapy for locally advanced cervical cancer at a community cancer center.

Introduction: Non-compliance to post-treatment cancer surveillance can lead to late detection of recurrence. This study aims to identify patients at high risk for loss of follow-up after radiotherapy for locally advanced cervical cancer. Methods: Consecutive patients with locally advanced cervical cancer treated with definitive chemoradiotherapy (2013-2020) at a community cancer center were retrospectively reviewed. The main outcome was overall follow-up compliance rate over time. Additionally, specialist-specific follow-up times, reasons for discontinuation and predictors of loss of follow-up events were evaluated. Results: The median age of the 154 patients included was 46.5 years (range: 26-84). The 6-month, 1-, 3-, and 5-year overall loss of follow-up rates were: 5.3%, 15.3%, 33.6%, and 48.2%, respectively. After a median overall follow-up time of 21.0 months, the median specialist-specific surveillance times were 17 months and 6 months with gynecologic and radiation oncologists, respectively (p < 0.01). Overall, the most common reasons for loss of follow-up were financial (21.7%) and relocation to another city (28.3%). By specialty, the most common reasons were relocation of care (56.5%, gynecologic oncologist) and disease progression (31.3%, radiation oncologist). In the multivariable analysis, older age (continuous, OR: 0.96; p < 0.01) and Hispanic ethnicity (OR: 0.39; p < 0.01) were protective against loss of follow-up, while increased number of gestations (continuous, OR: 1.23, p = 0.01) and living farther from the cancer center (continuous, OR: 1.002; p = 0.03) increased the chance of loss of follow-up. Conclusion: Younger, non-Hispanic, multiparous women that live far from the community cancer center have an increased chance of follow-up discontinuity, which are attributed to financial reasons in more than 20% of the cases.

Three-dimensional (3D) anatomic location, extension, and timing of severe osteoradionecrosis of the mandible.

Background: The purpose of this study was to describe the topography, extension (volume), and timing of severe osteoradionecrosis (ORN) that required mandible resection in patients previously treated for head and neck cancer at a high-volume Veterans Affairs Medical Center. Materials and methods: The records from a reference hyperbaric oxygen clinic were retrospectively analyzed (n = 50, 2018-2021). Inclusion criteria were: I) severe ORN defined as progressive ORN that required resection; II) pathologic confirmation of ORN; and III) availability of pre-operative CT-imaging. Using a radiotherapy (RT) imaging software, we performed a detailed volumetric (3D) analysis of the bone involvement by ORN. Time intervals from RT to surgery for ORN and from surgery to the last follow-up were calculated. Results: All patients that met inclusion criteria (n = 10) were male with significant smoking history (median 47.5 pack-years) and a median age of 57 years old at the time of RT. The primary tumors were: oropharynx (n = 6), oral cavity (n = 3) and nasopharynx (n = 1). The median time from RT to ORN surgery was 8 years. The most common ORN location was the posterior lateral body (molar) and six patients had associated fractures. The mean ORN volume was 3.6 cc (range: 0.6-8.3), corresponding to a mean 6.3% (range: 0.7-14) of the total mandibular volume. After a median follow-up of 13.5 months, no recurrence of ORN occurred. Three patients died of non-cancer and non-ORN-recurrence related causes (1 y OS 77.1%). Conclusion: Severe ORN occurred after a median of 8 years from the previous RT and usually affected the posterior lateral body. Surgical resection achieved excellent ORN control.

Endoscopic assessment of radiological stage IVA cervical cancer: A bivariate meta-analysis supporting an evidence-based staging algorithm proposal.

OBJECTIVE: To optimize the use of confirmatory endoscopic exams (cystoscopy/proctoscopy) in the staging of locally advanced cervical cancer (LACC), the present study evaluates the predictive value of radiological exams (CT and MRI) to detect bladder/rectum invasion. METHODS: A systematic search of databases (PubMed and EMBASE) was performed (CRD42021270329). The inclusion criteria were: a) cervix cancer diagnosis; b) staging CT and/or MRI (index test); c) staging cystoscopy and/or proctoscopy (standard test); and d) numbers of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) provided. A random-effects bivariate meta-analysis of positive predictive value (PPV) and negative predictive value (NPV) was performed with moderator analyses by imaging modality (CT and MRI) and prevalence. RESULTS: Nineteen studies met the inclusion criteria, totaling 3480 and 1641 patients for bladder and rectum analyses, respectively. For bladder invasion (prevalence ranged from 0.9% to 34.5%), the overall PPV was 45% (95% confidence interval, 33%-57%, based on 19 studies). Per subgroup, the PPV was 31% for MRI/prevalence ≤6%, 33% for CT/prevalence ≤6%, and 69% for CT/prevalence >6%. For rectal invasion (prevalence ranged from 0.4% to 20.0%), the overall PPV was 30% (95% confidence interval, 17%-47%, based on 8 studies). Per subgroup, the PPV was 36% for MRI/prevalence ≤1%, 17% for MRI/prevalence >1%, and 38% for CT/prevalence >1%. The overall NPV for bladder invasion and rectal invasion were 98% (95% confidence interval, 97%-99%) and 100% (95% confidence interval, 99%-100%), respectively. Considering prevalence and radiological modality, the point estimate of NPV varied from 95% to 100% for bladder invasion and from 99% to 100% for rectum invasion. CONCLUSIONS: Due to low PPV (<50%) of radiological staging, endoscopic exams may be necessary to correctly assess radiological stage IVA LACC. However, they are not necessary after negative radiological exam (NPV ≥95%).

MiR-451a and let-7i-5p loaded extracellular vesicles attenuate heme-induced inflammation in hiPSC-derived endothelial cells.

Hemolysis is associated with many pathologies, including trauma, sepsis, hemorrhagic stroke, malaria, and genetic disorders such as sickle cell disease (SCD). When hemolysis occurs, free-heme drives vascular inflammation, resulting in oxidative tissue damage and cardiometabolic complications. A better understanding of heme clearance and detoxification is essential to preventing sustained tissue damage. Human induced pluripotent stem cell (hiPSC)-derived endothelial cells (hiPSC-ECs) provide a novel source of patient-specific cells and tissues for disease modeling, drug discovery, and regenerative therapeutics. Here we report the use of hiPSC-ECs to elucidate the role of miR-451a and let-7i-5p-loaded extracellular vesicles (EVs, such as exosomes) in the inflammatory response to free-heme as a model for heme-induced inflammation. We provide evidence of a significant correlation between miR-451a and let-7i-5p-loaded circulating exosomes in plasmodium-infected patients with reported clinical benchmarks of malaria-severity (e.g., Hemoglobin (Hb) levels, white blood cell counts). Additionally, we determined that exposure of Plasmodium falciparum (Pf) parasites to EVs, loaded with either miRNA, significantly reduces their counts in vitro. Using hiPSCs derived from individuals with wild-type Hb (HbAA) or homozygous sickle cell mutated Hb (HbSS) genotypes, we demonstrate that heme-treated hiPSC-ECs secreted inflammatory products (cytokines, chemokines and growth factors) into supporting media at concentrations that were similar to that reported in HbAA and HbSS serum. This inflammatory response was attenuated by exposure with miR-451a or let-7i-5p-loaded EVs. We also found a decrease in transcription of ICAM1 and P-Selectin, as well as the secretion of key inflammatory cytokines (e.g., CXCL10, TNF-α, and IFN-γ). Based on these findings, we propose a model in which increased levels of exosomal miR-451a and let-7i-5p in Plasmodium-infected individuals will attenuate inflammatory responses to free-heme and parasite-derived products. As a result, infected erythrocytes will less likely adhere to the endothelium, sequester in brain micro vessels, and reduce vaso-occlusive crises that exacerbate cerebral malaria.

Stage Presentation, Care Patterns, Treatment Outcomes, and Impact of Radiotherapy on Overall Survival for Adrenocortical Carcinoma.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare cancer with few well-powered studies regarding epidemiology or outcomes and even fewer studies to guide an evidence-based management approach. The effect of radiation therapy (RT) is particularly understudied and remains unclear, outside of general oncologic principles. We sought to describe current care patterns in the management of ACC and how these practices affect survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients with ACC who could be staged by the American Joint Committee on Cancer (AJCC) system diagnosed between 1988 and 2015 were included. A classification and regression tree analysis identified subgroups of patients who may have benefitted from RT. Multivariable Cox regression analysis was used to compare overall survival (OS). Propensity score adjustment was used to compare OS for a subset of node-negative, nonmetastatic patients who received adjuvant RT following radical surgery. RESULTS: Among 865 eligible patients included in the analysis, only 10.5% received RT. In stage III node-negative patients, adjuvant RT following radical surgery was associated with a significantly improved OS compared with surgery alone. CONCLUSION: Medically fit persons with stage III, node-negative ACC should receive adjuvant RT after surgical resection.

Acute effect of high glucose on long-term cell growth: a role for transient glucose increase in proximal tubule cell injury.

Although chronic exposure of renal cells to high glucose has been shown to cause cell injury, the effect of acute exposure has not been elucidated. In this study, we demonstrate that acute (10 min) exposure of human proximal tubule epithelial cells (hPTEC) to high glucose (25 mM) induces a time-dependent dual effect consisting of an early proliferation and a late apoptosis. Acute exposure of hPTEC to high glucose induced a twofold increase in DNA synthesis and cell number at 12 h. However, after 36 h, a significant decrease in cell growth is observed, followed by apoptosis. On glucose treatment, both p42/p44 mitogen-activated protein (MAP) kinases and the downstream signaling intermediate NF-kappaB were phosphorylated and translocated to the nucleus. Pretreatment of cells with MAP kinase and NF-kappaB-specific inhibitors abolished glucose-induced proliferation. However, these inhibitors were ineffective in preventing glucose-induced apoptosis. Interestingly, conditioned medium from cells exposed to high-glucose concentrations inhibited proliferation and concomitantly induced apoptosis in normal cells, suggesting that the inhibitory effect of glucose occurs through secretion of a secondary factor(s). In parallel to apoptosis, we observed an increased production of reactive oxygen species (ROS). Pretreatment of cells with the antioxidant N-acetyl cysteine reversed glucose-mediated ROS production and apoptosis, suggesting that ROS is involved in apoptosis. Our study demonstrates for the first time that a single high-glucose exposure for 10 min alone is sufficient to elicit proliferation and apoptosis in hPTEC and suggests that episodes of transient increase in glucose may contribute to cell damage leading to epithelial cell dysfunction.