A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk.

BackgroundTumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway.ResultTo develop a deeper understanding of the interactions between cells within human lung tumors, we perform RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We map the cell-specific differential expression of prognostically associated secreted factors and cell surface genes, and computationally reconstruct cross-talk between these cell types to generate a novel resource called the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identify and validate a prognostically unfavorable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also find a prognostically favorable association between infiltration of mast cells and less aggressive tumor cell behavior.ConclusionThese results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance

Partial Reversal of Anosmia Following Platinum-Based Chemotherapy in a Patient With Colorectal Adenocarcinoma

Platinum-based chemotherapy is known to cause taste and smell changes (TSCs) via a host of mechanisms, including altered receptor activity, saliva/mucus production, and induction of receptor destruction via mitotic inhibition. In the literature to date, these changes have primarily resulted in worsening of taste and smell. In this case report, we document the first instance of an individual regaining their sense of olfactory detection following treatment with oxaliplatin for colorectal adenocarcinoma. We theorize that the improvement in his sense of smell may have resulted from oxaliplatin-induced destruction of his nasal polyps through the caspase-9/procaspase-9 apoptotic pathway, a pathway shared with other mechanisms of nasal polyp destruction. These findings were supported by nasal endoscopy and sphenoid sinusoscopy, which demonstrated no clinical persistence of nasal polyps, in contrast to nasal endoscopy prior to chemotherapy which demonstrated persistent nasal polyposis. Objective smell testing post-treatment revealed a diminished ability to discriminate odors. Chemotherapy-induced TSCs play a key role in poor weight gain, food aversion, emotional distress, and an overall decrease in quality of life, and patients should be informed of these potential consequences prior to starting treatment. However, in patients with anosmia secondary to nasal polyposis, treatment with platinum-based chemotherapy may provide an additional therapeutic benefit. Further studies may help elucidate the potential therapeutic benefits of these agents in managing steroid-resistant polyposis for patients suffering from olfactory dysfunction

Characterization of patients requiring inpatient hospital ethics consults- A single center study.

INTRODUCTION: Ethics consultations are often needed at difficult junctures of medical care. However, data on the nature of how patient characteristics, including race/ethnicity, language, and diagnosis, affect ethics consult outcomes are lacking. METHODS: We performed a retrospective cohort study of all patients who were seen by the Ethics Consult Service between 2017 and 2021 at a large tertiary academic center with the aim of determining whether patient demographic and clinical factors were associated with the timing of ethics consult requests and recommendations of the ethics team. RESULTS: We found that patients admitted for COVID-19 had significantly longer median times to consult from admission compared with other primary diagnoses (19 vs 8 days respectively, p = 0.015). Spanish-speaking patients had longer median times to consult from admission compared to English speaking patients (20 vs 7 days respectively, p = 0.008), indicating that language barriers may play a role in the timing of ethics consultation. CONCLUSIONS: This study demonstrates the need to consider clinical and demographic features when planning and prioritizing ethics consultations at large institutions to enhance consult efficiency, resource utilization, and patient experience and autonomy

Characterization of Patients Requiring Inpatient Hospital Ethics Consults- A Single Center Study

Ethics consultations are often needed at difficult junctures of medical care. However, data on the nature of how patient characteristics, including race/ethnicity, language, and diagnosis, affect ethics consult outcomes are lacking. We performed a retrospective cohort study of all patients who were seen by the Ethics Consult Service between 2017 and 2021 at a large tertiary academic center with the aim of determining whether patient demographic and clinical factors were associated with the timing of ethics consult requests and recommendations of the ethics team. We found that patients admitted for COVID-19 had significantly longer median times to consult from admission compared with other primary diagnoses (19 vs. 8 days respectively, p=0.015). Spanish-speaking patients had longer median times to consult from admission compared to English speaking patients (20 vs 7 days respectively, p=0.008), indicating that language barriers may play a role in the timing of ethics consultation. This study demonstrates the need to consider clinical and demographic features when planning and prioritizing ethics consultations at large institutions to enhance consult efficiency, resource utilization, and patient experience and autonomy