Impact of HIV on CD8+ T Cell CD57 Expression Is Distinct from That of CMV and Aging

Background: Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase ‘‘immunosenesence’’ of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear. Methods: We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection. Results: Compared to HIV-uninfected adults without CMV (n = 12), those with asymptomatic CMV infection (n = 31) had a higher proportion of CD28-CD8+ T cells expressing CD57 (P = 0.005). Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P = 0.007). In contrast, untreated HIV-infected CMV+ participants (n = 55) had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P,0.0001) and were enriched for less well-differentiated CD28- transitional memory (TTR) CD8+ T cells (P,0.0001). Chronically HIV-infected adults maintaining ART-mediated viral suppression (n = 96) had higher proportions of CD28-CD8+ T cells expressing CD57 than untreated patients (P,0.0001), but continued to have significantly lower levels than HIV-uninfected controls (P = 0.001). Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P,0.0001), which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts. Conclusions: Unlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well-differentiated CD28- CD8+ T cells and decreasing the proportion of CD28- CD8+ T cells that express CD57

CD56negCD16+NK cells are activated mature NK cells with impaired effector function during HIV-1 infection

BACKGROUND: A subset of CD3(neg)CD56(neg)CD16(+) Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations. RESULTS: Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16(+) cells are a heterogeneous population comprised of CD7(+) NK cells and CD7(neg) non-classical myeloid cells. CD7(+)CD56(neg)CD16(+) NK cells are significantly expanded in HIV-1 infection. CD7(+)CD56(neg)CD16(+) NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7(+)CD56(+)CD16(+) NK cells. CD7(+)CD56(neg) NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7(+)CD56(+) NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7(+)CD56(neg)CD16(+) NK cells may have recently engaged target cells. Furthermore, CD7(+)CD56(neg)CD16(+) NK cells have significantly increased expression of CD95, a marker of NK cell activation. CONCLUSIONS: Taken together, CD7(+)CD56(neg)CD16(+) NK cells are activated, mature NK cells that may have recently engaged target cells

Does Educator Training or Experience Affect the Quality of Multiple-Choice Questions?

© 2015 AUR. Rationale and Objectives: Physicians receive little training on proper multiple-choice question (MCQ) writing methods. Well-constructed MCQs follow rules, which ensure that a question tests what it is intended to test. Questions that break these are described as "flawed." We examined whether the prevalence of flawed questions differed significantly between those with or without prior training in question writing and between those with different levels of educator experience. Materials and Methods: We assessed 200 unedited MCQs from a question bank for our senior medical student radiology elective: an equal number of questions (50) were written by faculty with previous training in MCQ writing, other faculty, residents, and medical students. Questions were scored independently by two readers for the presence of 11 distinct flaws described in the literature. Results: Questions written by faculty with MCQ writing training had significantly fewer errors: mean 0.4 errors per question compared to a mean of 1.5-1.7 errors per question for the other groups (P < .001). There were no significant differences in the total number of errors between the untrained faculty, residents, and students (P values .35-.91). Among trained faculty 17/50 questions (34%) were flawed, whereas other faculty wrote 38/50 (76%) flawed questions, residents 37/50 (74%), and students 44/50 (88%). Trained question writers' higher performance was mainly manifest in the reduced frequency of five specific errors. Conclusions: Faculty with training in effective MCQ writing made fewer errors in MCQ construction. Educator experience alone had no effect on the frequency of flaws; faculty without dedicated training, residents, and students performed similarly

Does Educator Training or Experience Affect the Quality of Multiple-Choice Questions?

© 2015 AUR. Rationale and Objectives: Physicians receive little training on proper multiple-choice question (MCQ) writing methods. Well-constructed MCQs follow rules, which ensure that a question tests what it is intended to test. Questions that break these are described as "flawed." We examined whether the prevalence of flawed questions differed significantly between those with or without prior training in question writing and between those with different levels of educator experience. Materials and Methods: We assessed 200 unedited MCQs from a question bank for our senior medical student radiology elective: an equal number of questions (50) were written by faculty with previous training in MCQ writing, other faculty, residents, and medical students. Questions were scored independently by two readers for the presence of 11 distinct flaws described in the literature. Results: Questions written by faculty with MCQ writing training had significantly fewer errors: mean 0.4 errors per question compared to a mean of 1.5-1.7 errors per question for the other groups (P < .001). There were no significant differences in the total number of errors between the untrained faculty, residents, and students (P values .35-.91). Among trained faculty 17/50 questions (34%) were flawed, whereas other faculty wrote 38/50 (76%) flawed questions, residents 37/50 (74%), and students 44/50 (88%). Trained question writers' higher performance was mainly manifest in the reduced frequency of five specific errors. Conclusions: Faculty with training in effective MCQ writing made fewer errors in MCQ construction. Educator experience alone had no effect on the frequency of flaws; faculty without dedicated training, residents, and students performed similarly

Risk stratification and radiologic evaluation of central venous port malfunction

Background Appropriate indications for radiologic evaluation of central venous ports are not fully understood. We aimed to quantitatively assess the utility of clinical history and imaging in the evaluation of malfunctioning central venous ports. Methods Clinical history, plain radiographs, and line injections intended to evaluate central venous port malfunction in 153 consecutive cases over a nearly 4-year period were retrospectively reviewed by 2 radiologists. Radiographs and line injections were separately categorized as normal or abnormal, and a consensus was reached on the final imaging diagnosis. The likelihood of a port-related abnormality necessitating immediate intervention was determined for all represented combinations of clinical history, radiographic findings, and line injection results. Results A radiologic diagnosis was made in 96.1% of cases; 19.7% of these diagnoses were classified as critical, requiring prompt intervention. Very low risk histories had a 0.0% incidence of critical port abnormalities in our cohort, regardless of imaging findings. Low risk histories had a 10.5% incidence of a critical abnormality and were best evaluated either by line injection, either directly or following an abnormal chest radiograph. Intermediate and high risk histories were associated with a 30.5% and 61.1% incidence of critical port abnormalities, respectively, and were best evaluated by line injection without preceding chest radiograph. Conclusions There are several scenarios in which imaging does not meaningfully affect management of malfunctioning central venous ports. Recognizing these inefficiencies may allow for more appropriate and cost-effective use of radiographs and line injections to evaluate the cause of port malfunction. © 2014, ASSOCIATION FOR VASCULAR ACCESS. Published by Elsevier Inc. All rights reserved

Patients prefer results from the ordering provider and access to their radiology reports

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 = 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