Summary Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.

BackgroundIn healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging (“immunosenesence”) in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.Methodology/Principal FindingsWe measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.Conclusions/SignificanceLong-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.

The ACR Task Force on Medical Student Education in Radiology, in partnership with the Alliance of Medical Student Educators in Radiology, investigated the current status of how and to what extent medical imaging was being taught in medical schools. The task force executed a 3-part survey of medical school deans, radiology department chairs, and intern physicians. The results provided an updated understanding of the status of radiology education in medical schools in the United States. This summary includes recommendations about how individual radiology departments and ACR members can assist in advancing the specialty of diagnostic radiology through medical student education.

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Clinically oriented material is being incorporated increasingly early into medical school curricula. Traditional models of incorporating radiology early on, mainly as an adjunct to pathology or anatomy instruction, are not focused on learning important aspects of clinical radiology. Medical students can be better served by an integrated curriculum that focuses on appropriate ordering of radiology studies, an intuitive understanding of imaging modalities, and understanding the patient experience.

Purpose: Imaging results are generally communicated to patients by referring providers. Directly communicating results has been suggested as a way for radiologists to add value, though few studies have investigated patients' preferences in this regard. The aim of this study was to determine patients' preferences for receiving their imaging results. Methods:In this institutional review board-approved study, adult outpatients undergoing CT or MRI at an academic medical center and an affiliated county hospital over a 4-week period (n ¼ 2,483) were surveyed. The survey assessed patients' preferred delivery method for radiology results and their understanding of radiologists' education and role.Results: A total of 617 surveys (25% response rate) were completed, 475 (77%) and 142 (23%) by academic medical center and county hospital patients, respectively. Among all respondents, the majority of patients (387 of 617 [63%]) preferred models of results delivery centered on the referring physician as opposed to the radiologist. Regardless of who verbally relayed the results, 64% of all respondents (398 of 617) wanted the option to receive a copy of the report, and 522 of 614 (85%) wanted to see their images. Among patients wanting copies of their reports, academic medical center patients expressed equal interest in mail, e-mail, and online portal options (33%, 31%, and 36%, respectively), and county hospital patients preferred mail (55%, 28%, and 17%, respectively) (P < .001).Conclusions: Patients prefer receiving their imaging results through their referring providers. Many patients would also like to view their images and receive copies of their reports, potential avenues through which radiologists could add value.

Purpose: To compare the rates of hepatotoxicity after transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS) who were stratified into comparable risk groups. Materials and Methods:A retrospective review of patients with HCC who were treated with transarterial chemoembolization between January 2005 and December 2009 was performed. Of 158 patients with comparable model for end-stage liver disease (MELD) scores, 10 had a patent TIPS. Hepatobiliary severe adverse events (SAEs) occurring after transarterial chemoembolization were documented. In addition, 1-year survival and liver transplantation rate after transarterial chemoembolization were calculated in each group. Results:The incidence of hepatobiliary SAEs after transarterial chemoembolization was nearly two times higher in patients with a TIPS (70%) than in patients without a TIPS (36%; P ¼ .046). The liver transplantation rate 1 year after transarterial chemoembolization was 2.5 times higher in patients with a TIPS (80%) than in patients without a TIPS (32%; P ¼ .004). There was no significant difference in 1-year survival between the two groups after transarterial chemoembolization. Conclusions:Patients with HCC and a patent TIPS are more likely to develop significant hepatotoxicity after transarterial chemoembolization than comparable patients without a TIPS in place.

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