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Background Many infectious diseases present with rashes. Despite this, limited data have been published regarding dermatology training in infectious disease (ID) fellowships. We aimed to understand the perceived importance, current effectiveness, and existence of dermatology curricula for ID fellows in the United States (US). Methods Over four weeks in March-April 2022, we emailed US ID fellowship program directors (PDs) individualized links to a Qualtrics survey. Up to two reminder emails were sent. Using NRMP Match Results and Data, we identified 151 PDs. Email addresses were found for 147 PDs. Descriptive data analysis was performed. This study was IRB exempt. Results Response rate was 91/147 (62%). Most PDs (79/91, 87%) felt like it was very-to-extremely important for ID fellows to know basic dermatologic manifestations of infections (Image 1), though 91% (82/90) felt that they were only slightly-to-moderately effective at preparing fellows for this (Image 2). Most (55/90; 61%) programs do not have a formal dermatology curriculum for their fellows. Lack of faculty capacity, lack of reliable resources, and other topics taking priority were most commonly selected as significant barriers to implementing a dermatology curriculum (Image 3). Of the programs that do not have a dermatology curriculum, 76% (41/54) of PDs were interested in incorporating an externally produced dermatology curriculum with synchronous lectures (81%), asynchronous content (78%), and flipped classroom guides (72%) being the most favored educational strategies. For programs that currently have a dermatology curriculum (35/90, 39%), 67% (22/33) of PDs felt their fellows found their current dermatology curriculum very-to-extremely valuable. Conclusion These data indicate that current ID training often does not include formal dermatology-ID training. This data, along with a planned focus group of fellows, will help inform the development of a dermatology-ID curriculum to help address this content gap and improve ID fellowship education. Disclosures All Authors: No reported disclosures.

Background Many abstracts are submitted to scientific meetings each year. Scholarly work benefits from peer review, yet specific feedback from abstract reviewers is rarely given to authors. Here reviewers provided feedback to all authors who submitted Medical Education abstracts to IDWeek 2021. Methods All IDWeek 2021 abstract reviewers for the Medical Education category were invited to an abstract review instructional webinar and were asked to provide feedback on each assigned abstract in a free text box on the review website. Each submitting author was sent this feedback when informed of their abstract disposition. In October 2021, these authors were sent an email containing a link to a survey soliciting their perspectives on the feedback; the survey included demographic questions and Likert scale questions. Descriptive data analysis was performed. All 10 reviewers participated in one of two virtual, semi-structured focus groups about their experience. Two authors conducted thematic analysis on transcripts. Results Among abstract authors, 18/26 (69%) responded to the survey. All respondents found the feedback helpful. Twelve (67%) incorporated the feedback into their IDWeek presentations. All 14 submitters who plan to write a manuscript intend to incorporate the feedback into that work. Most (94%) would want to receive feedback on future abstract submissions (Figure); all wish other scientific meetings would provide feedback on abstracts. Among reviewers, common themes included that they (1) provided more attentive reviews due to a sense of responsibility to provide thoughtful feedback, (2) found the work rewarding, (3) improved their abstract-reviewing skills, (4) planned to use this experience to help trainees write better abstracts, and (5) felt this activity built community within IDSA. While providing feedback required more time than past reviews, all would volunteer to provide feedback in the future. Conclusion Authors who submitted Medical Education abstracts to IDWeek valued abstract feedback and used it to strengthen their presentations; reviewers found it to be a positive experience and would do it again. IDSA and other societies should consider providing feedback for all abstract categories. Disclosures All Authors: No reported disclosures.

In 2014, trained health care provider capacity was insufficient to deliver care to an estimated 70,000 persons in Maryland with chronic hepatitis C virus (HCV) infection. The goal of Maryland Community Based Programs to Test and Cure Hepatitis C, a public health implementation project, was to improve HCV treatment access by expanding the workforce. Sharing the Cure (STC) was a package of services deployed 10/1/14 to 9/30/18 that included enhanced information technology and public health infrastructure, primary care provider training, and practice transformation. Nine primary care sites enrolled. HCV clinical outcomes were documented among individuals who presented for care at sites and met criteria for HCV testing including risk factor or birth cohort (born between 1945 and 1965) based testing. Fifty-three providers completed the STC training. STC providers identified 3,237 HCV antibody positive patients of which 2,624 (81%) were RNA+. Of those HCV RNA+, 1,739 (66%) were staged, 932 (36%) were prescribed treatment, 838 (32%) started treatment, 721 (28%) completed treatment, and 543 (21%) achieved cure. Among 1,739 patients staged, 693 (40%) patients had a liver fibrosis assessment score < F2, rendering them ineligible for treatment under Maryland Medicaid guidelines. HCV RNA testing among HCV antibody positive people increased from 40% (baseline) to 95% amongst STC providers. Of 554 patients with virologic data reported, 543 (98%) achieved cure. Primary care practices can effectively serve as HCV treatment centers to expand treatment access. However, criteria by insurance providers in Maryland was a major barrier to treatment.

Infectious diseases fellows’ futures have been uniquely imperiled by the pandemic. In this article, we issue a call to action to sustain their careers as the future leaders of infectious diseases inquiry.

BackgroundGraduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Few data have been published regarding the consequences of this transition. We desired to understand (1) infectious diseases (ID) fellowship programs’ recruitment efforts and the effect of virtual recruitment on application and interview numbers, and (2) the number of programs to which matched applicants applied and interviewed, and their perspectives on virtual recruitment.MethodsIn 2020-21 we surveyed all United States ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach.ResultsPD response rate was 68/158 (43%); applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed. Applicants especially valued online program structure information, PD program overview videos, fellow testimonials, didactic and curriculum content, and current fellow profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want at least an option for virtual recruitment moving forward.ConclusionsVirtual recruitment enabled programs to accommodate more applicants and highlighted applicants’ preferences for programs’ augmented online presences and time-limited interview days. Most programs and applicants want the option for virtual interviews.Main PointsVirtual recruitment enables programs to accommodate more applicants. Applicants value programs’ augmented online presences and favor time-limited interview days. Most programs and applicants prefer in-person interviews and want at least an option for virtual interviews.

Background Graduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Limited data have been published regarding the consequences of this transition. We aimed to understand (1) infectious diseases (ID) fellowship programs’ recruitment efforts and the effect of virtual recruitment on application and interview numbers and (2) the number of programs to which matched applicants applied and interviewed and applicants’ perspectives on virtual recruitment. Methods In 2020–2021, we surveyed all US ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach. Results The PD response rate was 68/158 (43%); the applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed compared with the previous year. Applicants especially valued the online program structure information, PD program overview videos, didactic and curriculum content, and fellow testimonials and profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want an option for virtual recruitment. Conclusions Virtual recruitment enabled programs to accommodate more applicants and highlighted applicants’ preferences for programs’ augmented online presences and time-limited interview days. Most programs and applicants want an option for virtual interviews., Virtual recruitment enables programs to accommodate more applicants. Applicants value programs’ augmented online presence and favor time-limited interview days. While most programs and applicants prefer in-person interviews, most also want an option for virtual interviews.

BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1–2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, −53%; 95% CI, −255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, −66%; 95% CI, −250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10(3) IU per milliliter and 1804.93×10(3) IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.)

The coronavirus disease 2019 (COVID-19) pandemic has affected many providers, but its impact on Infectious Diseases (ID) fellows in the United States is largely undescribed. In this study, we discuss key issues that emerged from the first national ID Fellows Call with respect to the ID fellow’s role during the COVID-19 pandemic, teaching/learning, and research., In this brief report, we discuss the impact of the COVID-19 pandemic on Infectious Diseases (ID) fellows in the United States, specifically with respect to the ID fellow’s role during the COVID-19 pandemic, teaching/learning, and research during fellowship.

One of the many challenges that has befallen the Infectious Diseases and Graduate Medical Education communities during the coronavirus disease 2019 (COVID-19) pandemic is the maintenance of continued effective education and training of the future leaders of our field. With the remarkable speed and innovation that has characterized the responses to this pandemic, educators everywhere have adapted existing robust and safe learning environments to meet the needs of our learners. This paper will review distinct aspects of education and training of the Infectious Diseases fellows we believe the COVID-19 pandemic has impacted most, including mentoring, didactics, and wellness. We anticipate that several strategies developed in this context and described herein will help to inform training and best practices during the pandemic and beyond.

Background There is currently no single treatment that mitigates all harms caused by severe acute respiratory syndrome coronavirus 2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as an adjunctive immune-modulating therapy. Methods This was an observational retrospective study of hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19). The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. A time-dependent propensity score–matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections. Results This analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (adjusted hazard ratio [aHR], 0.38; 95% CI, 0.21 to 0.70) and no change in time to clinical improvement (aHR, 1.13; 95% CI, 0.68 to 1.87). The 1:1 matched data set also showed a lower mortality rate (27.8% vs 34.4%) and reduced hazards of death (aHR, 0.47; 95% CI, 0.25 to 0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared with controls. Secondary infection rates were similar between the 2 groups. Conclusions Tocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection., In this retrospective study of adult patients hospitalized with COVID-19, tocilizumab was associated with a 62% reduction in hazard of death. Tocilizumab may have a role as adjunctive therapy for COVID-19 among patients with hyperinflammation including elevated IL-6.

Key Clinical Message The true danger of the spider bite stems from misdiagnosis and resultant delay in proper treatment of entities that, unlike spider bites, are not self‐limited. Obtaining a complete exposure and travel history is central to the development of an accurate and appropriate differential diagnosis.

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors’ Committee focused the 2018 National Fellowship Program Directors’ Meeting at IDWeek on “Remediation of the Struggling Fellow.” Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges., Helping to remediate struggling learners is a common challenge for educators. Here ID fellowship training program directors provide tangible, actionable resources to assist with these efforts, which demand clear and objective data, thoughtful review and reflection, and collaboration among stakeholders.

Background Although Lyme disease is the most common vector-borne infection in the United States, diagnostic accuracy within community settings is not well characterized. Methods A retrospective observational cohort study of patients referred to an academic center with a presumed diagnosis or concern for Lyme disease between 2000 and 2013 was performed to analyze diagnoses and treatments. Characteristics of those with Lyme disease and those misdiagnosed as having Lyme disease were compared. Results Of 1261 patients, 911 (72.2%) did not have Lyme disease, 184 (14.6%) had active or recent Lyme disease, 150 (11.9%) had a remote history of Lyme disease, and 16 (1.3%) were identified as having possible Lyme disease. Patients without current Lyme disease were more likely to be female (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.08–2.45), to have had symptoms for >3 months (OR, 8.78; 95% CI, 5.87–13.1), to have higher symptom counts (OR per additional symptom, 1.08; 95% CI, 1.02–1.13), to have had more Lyme-related laboratory testing (OR per additional laboratory test, 1.17; 95% CI, 1.03–1.32), and to have been diagnosed with what were regarded as coinfections (OR, 3.13; 95% CI, 1.14–8.57). Of the 911 patients without Lyme disease, 764 (83.9%) had received antimicrobials to treat Lyme disease or their coinfections. The percentage of patients established to have Lyme disease was lower than in earlier studies of referred populations. Conclusions Among patients referred to an academic Infectious Diseases practice for Lyme disease, incorrect diagnoses and unnecessary antibiotic treatment were common, both for Lyme disease and for coinfections., Of 1261 patients referred for evaluation of presumptive Lyme disease, only 26.5% were diagnosedaccurately. Those without current Lyme disease were more likely to be female, have a longer duration of symptoms, and be inaccurately diagnosed with co-infections.

Background Effective career mentorship enhances well-being, productivity, and advancement in academic medicine. The pathway to success for clinician educators (CE) is often ill-defined. Career development resources and support for this pathway vary across institutions. To address this need, we created a mentoring program pairing junior faculty pursuing careers as CEs with more experienced CEs from other institutions during IDWeek 2018 and 2019. Methods Prior to IDWeek 2018 and 2019, a survey was sent through the IDSA listserv to identify members pursuing CE careers interested in extra-institutional career mentorship. These faculty were paired with mentors who were established career CEs identified via the IDSA Medical Education Workgroup. Mentees completed a brief individual development plan (IDP) and identified 3 discussion topics. Mentors received the mentee’s IDP and CV prior to IDWeek and were given brief guidance on successful mentoring. One hour advising sessions were held during IDWeek and ended with the creation of a mentee action plan and a scheduled follow-up call. Post-participation surveys were sent to mentees and mentors. Results 31 different mentees and 15 mentors participated in the program over two years. 26 (84%) mentees completed the post-session survey. 25 (96%) mentees and 14 (93%) mentors reported being very satisfied with their meetings at IDWeek. All mentees created an action plan with their mentor. 16 (62%) strongly agreed and 10 (38%) somewhat agreed that they planned to make changes based on the meeting. 21 (81%) mentees strongly agreed they received advice they were unable to get at their own institution. After the session, 18 (69%) strongly agreed they felt connected to a supportive CE community at IDSA; none strongly agreed in the pre-survey. All mentors and mentees agreed that this program was a resource that IDSA should consider expanding. Qualitative response themes from mentees emphasized the usefulness of an external perspective. Conclusion A mentoring program for junior faculty during IDWeek was feasible and effective for CEs. Through these interactions, mentees planned changes to enhance their careers and felt newly supported by the IDSA community. This model could be used for other ID career paths at future meetings. Disclosures All Authors: No reported disclosures

BackgroundInternal medicine physicians are often the first providers to encounter patients with a new diagnosis of tuberculosis. Given the public health risks of missed tuberculosis cases, assessing internal medicine residents’ ability to diagnose tuberculosis is important.MethodsInternal medicine resident knowledge and practice patterns in pulmonary tuberculosis diagnosis at 7 academic hospitals were assessed utilizing (a) a 10-item validated pulmonary tuberculosis diagnosis assessment tool and (b) a retrospective chart review of 343 patients who underwent a pulmonary tuberculosis evaluation while admitted to a resident-staffed internal medicine or infectious disease service. Our primary outcomes were the mean score and percentage of correct responses per assessment tool question, and the percentage of patients who had Centers for Disease Control and Prevention–recommended tuberculosis diagnostic tests obtained.ResultsOf the 886 residents who received the assessment, 541 responded, yielding a response rate of 61%. The mean score on the assessment tool (SD) was 4.4 (1.6), and the correct response rate was 57% (311/541) or less on 9 of 10 questions. On chart review, each recommended test was obtained for ≤43% (148/343) of patients, other than chest x-ray (328/343; 96%). A nucleic acid amplification test was obtained for 18% (62/343) of patients, whereas 24% (83/343) had only 1 respiratory sample obtained. Twenty patients were diagnosed with tuberculosis.ConclusionsSignificant knowledge and practice gaps exist in internal medicine residents’ abilities to diagnose tuberculosis. As residents represent the future providers who will be evaluating patients with possible tuberculosis, such deficiencies must be addressed.

Lyme disease is a common disease that uncommonly affects the heart. Because of the rarity of this diagnosis and the frequent absence of other concurrent clinical manifestations of early Lyme disease, consideration of Lyme carditis demands a high level of suspicion when patients in endemic areas come to attention with cardiovascular symptoms and evidence of higher-order heart block. A majority of cases manifest as atrioventricular block. A minority of Lyme carditis cases are associated with myopericarditis. Like other manifestations of Lyme disease, carditis can readily be managed with antibiotic therapy and supportive care measures, such that affected patients almost always completely recover.

Feedback is one of the core components of teaching in the clinical setting. Traditionally, this activity has emphasized observations made by senior physicians and delivered to medical trainees. However, the optimal approach to feedback remains uncertain, and the literature abounds with trainee-perceived inadequacies in feedback content, quality, and impact. Moreover, given the multiplicity of demands on trainees and their physician mentors, we propose that medical trainees themselves-specifically, medical residents-are poised to serve as unique adjunct effectors of feedback. We propose a model of "clinical coaching" for residents as teachers, with emphasis on the active roles of both the feedback "giver" and "recipient". We define "clinical coaching" as "a helping longitudinal relationship between coach and apprentice that provides continuing feedback on and assistance with improving performance." Here, "coach" is the more experienced trainee (e.g. supervising resident), and "apprentice" is the less experienced trainee (e.g. intern or medical student). By working to better recognize and prepare residents for this vital role, we propose to encourage efforts to optimize the structure, execution, and impact of feedback in the contemporary climate of medical education.

Introduction Senior trainees (residents) are poised to be unique effectors of clinical feedback. While several curricula are available to teach residents to give or elicit feedback, our curriculum is unique in that it teaches both the giving and elicitation of feedback and focuses on the longitudinal coaching relationship as opposed to onetime feedback interactions. This curriculum provides a framework, called clinical coaching, for streamlining and enhancing feedback interactions between senior and junior trainees. Methods This curriculum consists of: (1) a video module, (2) an interactive workshop, and (3) role-plays. Participants view the module, which simulates traditional feedback contrasted with the suggested approach. Next, an interactive workshop stimulates reflection on feedback, then defines and demonstrates clinical coaching. Finally, participants practice coaching with prewritten scenarios that illustrate critical steps in clinical coaching. Results This workshop was initially conducted in September 2014 with 50 participants. Thirty-nine house staff completed the postcurricular survey (13 had attended the workshop, 26 had not). Recognition of interns soliciting feedback one or more times per week was greater amongst workshop attendees (83% of residents, 78% of interns), as compared to nonattendees (53% of residents, 67% of interns). Preparation to give feedback differed amongst resident attendees versus nonattendees (0% vs. 19%, respectively, reported no preparation). Discussion These results highlight a need to increase awareness of and preparedness for the vital role that trainees can play in coaching. Training house staff in coaching has the potential to transform feedback for teachers and learners alike.

INTRODUCTION: Anti-interferon-γ (IFNγ) autoantibodies have been associated with disseminated mycobacterial infections, mostly in patients from Southeast Asia. PURPOSE: We studied an American-born, Caucasian female with M. avium complex infection of the subglottic mucosa and brain for underlying etiologies of infection. METHODS: Plasma was screened for anticytokine autoantibodies using a Luminex-based approach. The ability of patient plasma to block IFNγ-induced STAT1 phosphorylation in normal blood cells was evaluated by flow cytometry with intracellular staining. Plasma inhibition of IFNγ production and IFNγ-induced cytokines in normal and patient blood cells washed of autologous plasma was also evaluated. RESULTS: Patient plasma contained high-titer IgG anti-IFNγ autoantibodies, primarily of the IgG(1) subclass. Patient but not control plasma prevented IFNγ-induced STAT1 phosphorylation and expression of the IFNγ-inducible cytokines tumor necrosis factor (TNF) α and interleukin (IL)-12 in normal blood cells. Patient blood cells washed free of autologous plasma demonstrated normal IFNγ production and response. CONCLUSIONS: Disseminated nontuberculous mycobacterial infections should always prompt immune evaluation. This first case of disseminated nontuberculous mycobacterial infection and anti-IFNγ autoantibodies in an American-born Caucasian suggests that anti-cytokine autoantibodies are not racially or regionally restricted.

Background The development of a safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of elimination efforts, providing the rationale for the first HCV vaccine efficacy trial. Methods In a randomized, multicenter, double-blind, placebo-controlled efficacy trial (NCT01436357), we evaluated a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara boost, both encoding nonstructural proteins of HCV. HCV-uninfected adults 18–45 years old at-risk for HCV infection due to injection drug use were randomized to receive the prime-boost regimen or placebo at Days 0 and 56. Trial participants were monitored for vaccine reactogenicity, adverse events, and HCV viremia. Vaccine safety, immunogenicity, and efficacy against progression to chronic HCV infection were assessed. Results A total of 455 subjects received the prime-boost regimen or two doses of placebo, with 202 and 199 in the respective groups included in the according-to-protocol efficacy cohort. Overall incidence of infection was 14.1 infections per 100 person-years. There were no differences in development of chronic infection between vaccine and placebo arms, with 14 chronically infected subjects in each group. Specifically, the vaccine efficacy in preventing chronic infection was −0.53 (95% confidence interval [CI], −2.5 to 0.34). Of vaccinated subjects, 78% generated T-cell responses to ≥1 vaccine-encoded HCV antigens. The vaccine was generally safe and well tolerated with no serious vaccine-related adverse events. There were more solicited reports of adverse events after either injection in the vaccine group (81%) than in the placebo group (59%), with the difference mainly due to injection-site reactions. Serious adverse events and deaths occurred with similar frequencies in the two groups. Conclusion A randomized, placebo controlled, Phase I/II trial of a prime-boost vaccine to prevent chronic HCV infection was completed in an at-risk population, demonstrating the feasibility of conducting rigorous vaccine research in people who inject drugs. The regimen elicited robust immune responses without evident safety concerns, but did not provide protection against chronic HCV infection. Disclosures Ventzislav Vassilev, PhD, GlaxoSmithKlein Vaccines (Employee), Lan Lin, MD, GlaxoSmithKlein Vaccines (Employee), Alfredo Nicosia, PhD, ReiThera (Employee, Shareholder), Antonella Folgori, PhD, ReiThera (Employee), ReiThera (Employee, Shareholder. Other Authors: No reported disclosures.

Interferon alfa has been used to treat chronic hepatitis C virus (HCV) infection since the early 1990s and remains the backbone of many treatment regimens involving HCV protease inhibitors [1–3]. Interferon alfa, however, has many side effects, including cytopenias [1]. When patients are treated with one of the long-acting, pegylated formulations of interferon, pegylated interferon (peg-IFN) alfa-2a, or peg-IFN alfa-2b, in combination with ribavirin (RBV) for up to 48 weeks, the incidence of severe neutropenia, defined as an absolute neutrophil count (ANC) of 3000) and the breadth of data collected, the Individualized Dosing Efficacy vs Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) study provides a unique opportunity to evaluate the incidence of and risk factors associated with acute infections among patients receiving HCV treatment with peg-IFN/RBV, with an emphasis on understanding the relationship between treatment-induced cytopenias and infection [15].

Background The Infectious Diseases Society of America guidelines recommend either 14 days of trimethoprim-sulfamethoxazole (TMP-SMX) or 7 days of ciprofloxacin for the treatment of pyelonephritis. Antibiotic courses of 7 days of TMP-SMX vs 7 days of ciprofloxacin for pyelonephritis have not been previously compared. We evaluated the odds of a subsequent, symptomatic urinary tract infection (UTI) for women with Escherichia coli pyelonephritis receiving a 7-day course of TMP-SMX vs a 7-day course of ciprofloxacin. Methods Women ages 16 years and older with E. coli pyelonephritis presenting to 5 health care facilities in the greater Maryland area between 2010 and 2016 receiving either TMP-SMX or ciprofloxacin were included. Patients were excluded if they met any of the following criteria: (a) pregnancy, (b) dialysis dependency, (c) E. coli not susceptible to the treatment prescribed, (d) polymicrobial urine culture, or (e) >48 hours of antibiotic therapy other than TMP-SMX or ciprofloxacin. Results Of 272 women meeting eligibility criteria, 81 (30%) and 191 (70%) received 7 days of TMP-SMX and 7 days of ciprofloxacin, respectively. In an adjusted model, the likelihood of a recurrent UTI within 30 days for the TMP-SMX and ciprofloxacin groups was similar (adjusted odds ratio 2.30; 95% confidence interval, 0.72-7.42). Conclusions Our findings suggest that 7 days of TMP-SMX therapy may result in similar clinical outcomes compared with 7 days of ciprofloxacin for the treatment of pyelonephritis. Considering the frequency of pyelonephritis and risks of antibiotic resistance and associated toxicities, decreasing the duration of antibiotic therapy for pyelonephritis may impact a large number of women.

Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs.

The condition of most patients with Lyme disease improves after initial antibiotic therapy; however, 10 to 20% of treated patients may have lingering symptoms of fatigue, musculoskeletal pains, disrupted sleep, and lack of customary mental functions. The plausible idea that additional antimicrobial therapy for potentially persistent bacterial infection would foster improvement has been a touchstone of hope in the 40 years since discovery of the disease in the mid-1970s. Patients with long-standing symptoms and well-documented, previously treated Lyme disease have been the focus of a number of randomized, placebo-controlled studies in North America that assessed whether additional antibiotic therapy offers . . .

Objective.To describe the method used to develop a flexible, computerized database for recording and reporting rates of influenza vaccination among healthcare personnel who were classified by their individual levels (hereafter, “tiers”) of direct patient contact.Design.Three-year descriptive summary.Setting.Large, academic, tertiary care medical center in the United States.Participants.All of the medical center's healthcare personnel.Methods.The need to develop a computer-based system to record direct patient care tiers and vaccination data for healthcare personnel was identified. A plan that was to be implemented in stages over several seasons was developed.Results.Direct patient care tiers were defined by consensus opinion on the basis of the extent, frequency, and intensity of direct contact with patients. The definitions of these tiers evolved over 3 seasons. Direct patient care classifications were assigned and recorded in a computerized database, and data regarding the receipt of vaccination were tracked by using the same database. Data were extracted to generate reports of individual, departmental, and institutional vaccination rates, both overall and according to direct patient care tiers.Conclusions.Development of a computerized database to record direct patient care tiers for individual healthcare workers is a daunting but manageable task. Widespread use of these direct patient care definitions will facilitate uniform comparisons of vaccination rates between institutions. This computerized database can easily be used by infection control personnel to accomplish several other key tasks, including vaccination triage in the context of shortage or delay, prioritization of personnel to receive interventions in times of crisis, and monitoring the status of other employee health or occupational health measures.

Allergic bronchopulmonary aspergillosis (ABPA) results from a hypersensitivity response to airways colonization with Aspergillus fumigatus, and it occurs most often in individuals with asthma or cystic fibrosis. Allergic bronchopulmonary aspergillosis is an indolent, but potentially progressive, disease in patients. In patients infected with human immunodeficiency virus (HIV), ABPA is rare, and its description in the literature is limited to case reports. We describe the occurrence of ABPA in a 37-year-old woman with well controlled HIV infection. This represents the first documented case of ABPA in an HIV-infected patient whose only pulmonary comorbidity included the ramifications of prior acute respiratory distress syndrome due to Pneumocystis jirovecii pneumonia. We also review prior case reports of ABPA in HIV-infected patients and consider risk factors for its development.

Excellence in clinical care should be recognized and rewarded. A recent paradigm defined clinical excellence through seven key domains. This work examines ID clinical excellence in these domains, and in doing so highlights the important skill sets of ID physicians., Clinical excellence should be recognized, particularly in the current climate that appropriately prioritizes relationship-centered care. In order to develop a recognition model, a definition of clinical excellence must be created and agreed upon. A paradigm recently suggested by C. Christmas describes clinical excellence through the following domains: diagnostic acumen, professionalism and humanism, communication and interpersonal skills, skillful negotiation of the healthcare system, knowledge, taking a scholarly approach to clinical practice, and having passion for clinical medicine. This work references examples of infectious disease (ID) clinical excellence across Christmas' domains and, in doing so, both examines how the definition of clinical excellence applies to ID practice and highlights the importance of ID physicians. Emphasizing such aspirational standards may not only inspire trainees and practicing physicians to pursue their own fulfilling clinical ID careers, it may also encourage health systems to fully value outstanding ID physicians who labor tirelessly to provide patients with exceptional care.

P. acnes shoulder prosthetic joint infections were predominantly characterized by pain and functional loss. Inflammatory marker elevation occurred in just under 50% of cases. Isolates were broadly susceptible to guideline concordant antimicrobials. Antibiotic-only and combined antibiotic-surgical intervention outcomes were similar., Background. Prosthetic joint infections (PJIs) significantly complicate joint arthroplasties. Propionibacterium acnes is an increasingly recognized PJI pathogen, yet limited clinical and therapeutic data exist. We sought to examine characteristics of P. acnes shoulder PJIs and compare surgical and nonsurgical management outcomes. Methods. A retrospective analysis of P. acnes shoulder PJIs was conducted at an academic center in Baltimore, Maryland from 2000 to 2013. Results. Of 24 cases of P. acnes shoulder PJIs, 92% were diagnosed after extended culture implementation; 42% in the delayed and 46% in the late postsurgical period. Joint pain and diminished function were the predominant presenting clinical signs. Erythrocyte sedimentation rate and C-reactive protein elevations occurred in 47% and 44%, respectively. All tested isolates were susceptible to β-lactams, moxifloxacin, vancomycin, and rifampin. Clindamycin resistance was identified in 6%. Of the antibiotic-only treated cases, 67% had a favorable clinical outcome compared with 71% (P = 1.0) of cases with a combined antibiotic-surgical approach. Favorable outcome with and without rifampin therapy was 73% and 60% (P = .61), respectively. Conclusions. Propionibacterium acnes PJI diagnoses increased with extended culture. Inflammatory markers were elevated in a minority of cases. Isolates maintained broad antimicrobial susceptibility. Compared to combined antibiotic-surgical approaches, antibiotic-only approaches were similarly successful in selected cases.

The spirochete Borrelia burgdorferi may afflict skin, heart, joints, and the central or peripheral nervous system. This agent of Lyme disease, perhaps because of its varied presentations, is often raised as the cause of headache, fatigue, and subjective neurocognitive dysfunction. For clinicians who trained in the 20th century when the spirochete Treponema pallidum was invoked as the “Great Imitator,” testing for Lyme disease now seems as or more common than it had been for syphilis. With a narrower disease spectrum than syphilis, is such frequent testing for Lyme disease justified, and how should results be interpreted? If contemplating Lyme neuroborreliosis, understanding the epidemiologic likelihood of acquiring this tick-borne infection, its potential manifestations, and proper interpretation of serologic testing are all essential. For patients from Lyme-endemic areas, Lyme disease is among the most common causes of facial nerve palsy, aseptic meningitis, and neuroradiculitis. While such manifestations of early disseminated Lyme disease arise in up to 10% to 15% of patients not treated at an earlier stage, late neurologic complications such as encephalitis and diffuse polyneuropathy are exceptionally rare. Despite the rarity of late Lyme neuroborreliosis, many physicians include Lyme disease in their differential diagnosis for a variety of chronic neurologic syndromes. This approach may be partly because of brain imaging reports that commonly reference Lyme disease among the possible explanations for nonspecific white matter changes, despite the fact that B burgdorferi infection essentially never causes such findings.1 B burgdorferi infection is well known to affect the seventh and less commonly sixth cranial nerves. An often-posed question, therefore, is whether B burgdorferi infection can produce other isolated cranial neuropathies, such as sensorineural hearing loss and optic neuritis. A recent review advocated against screening patients with sudden-onset sensorineural hearing loss for Lyme disease because of an unproven causative relationship.2 While children with Lyme meningitis can have papilledema, and adults with B burgdorferi–driven optic neuritis manifesting as papillitis have been described, this latter phenomenon appears uncommon. A case series of 440 patients with optic neuritis from a Lyme-endemic region found 25 seropositive but only 1 with evidence of active B burgdorferi infection.3 The rarity of this association was reinforced in the accompanying literature review. Lyme disease is often investigated during the initial evaluation of conditions such as multiple sclerosis, amyotrophic lateral sclerosis, dementia, or parkinsonism. Many patients facing these devastating diseases maintain hope for a curable diagnosis, such as Lyme disease; this optimism is bolstered by Internet resources supporting such notions. A critical point, however, is the highly focal geographic distribution of Lyme disease—none of the aforementioned neurologic diseases are unique to areas with high Lyme disease transmission. Furthermore, Lyme disease is readily distinguished from these conditions on clinical grounds. Patients with Lyme disease do not exhibit the white matter plaques seen on imaging of patients with multiple sclerosis, for example, and when patients with Lyme disease have oligoclonal bands in their cerebrospinal fluid, they are actually reactive against B burgdorferi. Lyme disease does not produce the upper motor neuron signs seen in amyotrophic lateral sclerosis.4 While sometimes considered as an explanation for objective neuropathology, more often asked is if Lyme disease explains subjective neurocognitive dysfunction. Such inquiries likely stem from early reports of neurocognitive symptoms accompanying objective, inflammatory manifestations of Lyme disease, including Lyme arthritis.1 While such symptoms can be seen with Lyme disease, this association should not be taken to mean that all patients with subjective neurocognitive dysfunction have Lyme disease; such symptoms can also be found not only among patients with other infectious and non-infectious inflammatory conditions, but also among otherwise healthy persons.1 Even among patients with Lyme disease, the presence of subjective neurocognitive symptoms is more likely to reflect systemic inflammation than genuine central nervous system infection. This point was highlighted in a study of patients with erythema migrans, among whom the presence of symptoms such as headache, vertigo, paresthesias, and memory, concentration, or sleep disturbance did not predict the presence of cerebrospinal fluid (CSF) pleocytosis indicative of authentic central nervous system infection.5 If after careful consideration, neuroborreliosis is entertained as a diagnostic possibility, can laboratory testing help confirm or exclude the diagnosis? For patients with syndromes compatible with Lyme neuroborreliosis, such as seventh nerve palsy or aseptic meningitis, the positive predictive value of serologic testing is high, as is the negative predictive value of acute followed by convalescent testing. IgG immunoblots are particularly important, especially when considering the high prevalence of false-positive IgM immunoblots—perhaps the most common pitfall of Lyme diagnostics. In one representative series, more than 50% of patients with headaches and nearly 25% with neurocognitive symptoms thought potentially attributable to Lyme disease were due to something else, as a false-positive IgM immunoblot was the only test result suggesting B burgdorferi infection.6 The high (27.5%) prevalence of false-positive IgM immunoblots in this series is one of the primary reasons screening for Lyme disease is discouraged when the diagnosis is improbable. The IgM immunoblot is only useful for patients with illnesses of less than 4 weeks’ duration that are compatible with early Lyme disease. After 4 weeks of illness, Lyme IgM immunoblots should be disregarded irrespective of their reported result. The attribution of IgG immunoblot seropositivity to a patient’s illness still requires clinical judgment; a positive IgG immunoblot is nondiagnostic without a compatible clinical syndrome. Low probability testing often lands patients in consultants’ offices, creating challenges explaining results and countermanding the often patient-driven inclination to “just try antibiotics” that may lead to harmful drug adverse effects without chance of benefit. This approach may also delay arrival at the correct diagnosis and treatment. In the event that the diagnosis of neuroborreliosis remains plausible but uncertainty remains, assessing the ratio of B burgdorferi antibodies between CSF and blood can be useful. Isolated CSF antibody testing is discouraged, as correcting for blood antibody levels is essential to distinguish intrathecal antibody production from spillage into the CSF. A ratio of 1.3 or more is usually considered positive, but as with all antibody-based Lyme diagnostics, considering the clinical context is essential. Furthermore, elevated CSF antibody levels can persist even after adequate antibiotic therapy. Patients with persistently positive serologic test results and ongoing symptoms can present a challenge, especially when a compelling alternative diagnosis has not been discovered. Unlike syphilis, where the rapid plasma reagin titer declines with adequate treatment, there is no test of cure for Lyme disease. Patients without new symptoms or findings should not be retested or retreated because seropositivity, including IgM, can persist for decades. For patients with a history of Lyme disease and persistent symptoms, the ineffectiveness of additional courses of antibiotic therapy in those previously treated should stay further antibiotics.7 While B burgdorferi infection can cause neurologic disease, familiar presentations far outnumber atypical manifestations. Consultants should base neuroborreliosis diagnoses on epidemiology, objective findings, and sound laboratory testing. When Lyme disease is deemed unlikely, educating patients and referring physicians alike will help avoid unnecessary antibiotic therapy and direct consideration of alternative diagnoses. While Lyme disease is no imposter, syphilis’ title as the Great Imitator remains secure for now.

Background The nervous system is known to be the third most commonly (12–15%) affected site in Lyme disease (LD) in the U.S. Though previous studies reported peripheral neuropathy, encephalopathy, and encephalitis with some frequency in later stage LD, limited contemporary data exist on the frequency, presentation, and outcomes of these entities. Methods Retrospective review of 1261 patients referred (2000–2013, single center) for presumptive LD was performed for neuroborreliosis. Symptoms less than 3 months were designated early LD. Patients with remote history of treated neuroborreliosis (> 2 years) were excluded. The diagnosis of LD followed CDC criteria. Response to antibiotics was assessed at the last clinical visit. Results Of 185 diagnosed with LD, 19% (35/185) had neuroborreliosis, including 29 early LD (ELD) and 6 late LD (LLD). The mean age was 44 yrs (±20) in ELD and 61(±11) in LLD. The median symptom duration was 14d (1–69) in ELD and 182d (140–2570) in LLD. Facial nerve palsy was most common, 54% (19/29 in ELD vs. 0/6 in LLD), followed by meningitis 20% (4/29 vs. 3/6), radiculopathy 20% (6/29 vs. 1/6), encephalopathy 3% (0/29 vs. 1/6), and peripheral neuropathy 3% (0/29 vs. 1/6) (P = 0.001). No encephalitis was identified. The median treatment duration (days) was 30 (10–135) in ELD and 56 (28–230) in LLD. All 35 patients were treated with doxycycline and/or ceftriaxone (16, 46% IV). Of the 32 followed patients, 28/32 (88%) responded to antibiotics, whereas 4/32 (12%) remained symptomatic with median follow-up duration of 72 days. Four non-responsive cases included 1 ELD (radiculopathy) and 3 LLDs (meningitis, encephalopathy, and peripheral neuropathy). The rate of non-response to antibiotics was higher in late LD (4% of ELD vs. 60% of LLD; P = 0.008). There was no statistically significant difference between outcome groups when comparing age, treatment duration, history of anxiety/depression, and route of treatment (p > 0.05, respectively). Conclusion Encephalopathy, encephalitis, and peripheral neuropathy ascribed to LD were uncommon in this population and poorly responsive to antibiotics. This raises the question whether LD truly was causal or if irreversible damage occurs by late stage LD. Future studies are needed in this regard. Disclosures All authors: No reported disclosures.

Although Lyme disease responds to short courses of antibiotics, tick-borne Borrelia burgdorferi has been advanced by some as a frequent explanation for medically unexplained symptoms such as continual fatigue, musculoskeletal pains, and subjective neurocognitive dysfunction. Often called “chronic Lyme disease” by adherents of this philosophy, it is loosely defined, and practitioners liberally prescribe nostrums, including prolonged antimicrobial therapies, in a belief that this eradicates suspected infection. Perhaps due to the lack of supportive data, proponents of this theory have developed their own meetings, literature, activist groups, and substantial internet activities to advance their views. Forces motivating this movement are explored, as are tactics used to advance non-scientific ideas that have included legal action and garnering legislative endorsement. While neither logical nor evidence-based, “chronic Lyme disease” harnesses corrosive energies that taint modern medicine and society.

Objective: To determine the feasibility of next-generation sequencing (NGS) microbiome approaches in the diagnosis of infectious disorders in brain or spinal cord biopsies in patients with suspected CNS infections. Methods: In a prospective pilot study, we applied NGS in combination with a new computational analysis pipeline to detect the presence of pathogenic microbes in brain or spinal cord biopsies from 10 patients with neurologic problems indicating possible infection but for whom conventional clinical and microbiology studies yielded negative or inconclusive results. Results: Direct DNA and RNA sequencing of brain tissue biopsies generated 8.3 million to 29.1 million sequence reads per sample, which successfully identified with high confidence the infectious agent in 3 patients for whom validation techniques confirmed the pathogens identified by NGS. Although NGS was unable to identify with precision infectious agents in the remaining cases, it contributed to the understanding of neuropathologic processes in 5 others, demonstrating the power of large-scale unbiased sequencing as a novel diagnostic tool. Clinical outcomes were consistent with the findings yielded by NGS on the presence or absence of an infectious pathogenic process in 8 of 10 cases, and were noncontributory in the remaining 2. Conclusions: NGS-guided metagenomic studies of brain, spinal cord, or meningeal biopsies offer the possibility for dramatic improvements in our ability to detect (or rule out) a wide range of CNS pathogens, with potential benefits in speed, sensitivity, and cost. NGS-based microbiome approaches present a major new opportunity to investigate the potential role of infectious pathogens in the pathogenesis of neuroinflammatory disorders.

The primary objective of this study was to determine whether patients with putative late-onset Lyme arthritis based upon synovial fluidBorrelia burgdorferiIgM and IgG immunoblot testing offered by commercial laboratories satisfied conventional criteria for the diagnosis of Lyme arthritis. Secondary objectives included assessing the prior duration and responsiveness of associated antibiotic therapy. We conducted a retrospective analysis of 11 patients referred to an academic medical center infectious disease clinic during the years 2007 to 2009 with a diagnosis of Lyme disease based upon previously obtained synovial fluidB. burgdorferiimmunoblot testing. Ten of the 11 (91%) patients with a diagnosis of late-onset Lyme arthritis based upon interpretation of synovial fluidB. burgdorferiimmunoblot testing were seronegative and did not satisfy published criteria for the diagnosis of late-onset Lyme arthritis. None of the 10 patients had a clinical response to previously received antibiotics despite an average course of 72 days. Diagnosis of Lyme arthritis should not be based on synovial fluidB. burgdorferiimmunoblot testing. This unvalidated test does not appear useful for the diagnosis of Lyme disease, and this study reinforces the longstanding recommendation to useB. burgdorferiimmunoblot testing only on serum samples and not other body fluids. Erroneous interpretations of “positive” synovial fluid immunoblots may lead to inappropriate antibiotic courses and delays in diagnosis of other joint diseases.

Black Americans are disproportionally infected with hepatitis C virus (HCV) and are less likely than whites to respond to treatment with peginterferon (PEG-IFN) plus ribavirin (RBV). The impact of race on HCV treatment eligibility is unknown. We therefore performed a retrospective analysis of a phase 3B multicenter clinical trial conducted at 118 United States community and academic medical centers to evaluate the rates of and reasons for HCV treatment ineligibility according to self-reported race. In all, 4,469 patients were screened, of whom 1,038 (23.2%) were treatment ineligible. Although blacks represented 19% of treated patients, they were more likely not to be treated due to ineligibility and/or failure to complete required evaluations (40.2%) than were nonblack patients (28.5%; P0.001). After the exclusion of persons not treated due to undetectable HCV RNA or nongenotype 1 infection, blacks were 65% less likely than nonblacks to be eligible for treatment (28.1%17.0%; relative risk, 1.65; 95% confidence interval, 1.46-1.87; P0.001). Blacks were more likely to be ineligible due to neutropenia (14% versus 3%, P0.001), anemia (7% versus 4%, P = 0.02), elevated glucose (8% versus 3%, P0.001), and elevated creatinine (5% versus 1%, P0.001).Largely due to a higher prevalence of neutropenia and uncontrolled medical conditions, blacks were significantly less likely to be eligible for HCV treatment. Increased access to treatment may be facilitated by less conservative neutrophil requirements and more effective care for chronic diseases, namely, diabetes and renal insufficiency.

In Reply We agree with Lautner and colleagues that, in addition to the ratio of Borrelia burgdorferi antibodies between cerebrospinal fluid (CSF) and serum, tests, such as CSF white blood cell count, can be useful in the assessment of neuroborreliosis. Indeed, CSF analysis is a pivotal tool in making a diagnosis of meningitis. However, whether liberal use of CSF testing to assess for possible neuroborreliosis among patients not suspected to have meningitis would be practiced (given barriers to obtaining samples) or aid in enhancing diagnosis is uncertain. Early neuroborreliosis—with its most common manifestations of facial nerve palsy, aseptic meningitis, and neuroradiculitis—should only be entertained when patients at epidemiologic risk come to attention with compelling clinical findings. Among such patients, peripheral blood serologic testing for B burgdorferi is highly sensitive; for persons initially seronegative, convalescent serologies help confirm the diagnosis.1 Lyme C6 peptide antibody testing can also be very valuable in this setting and has been shown to be more sensitive than standard 2-tier antibody testing in persons with early neuroborreliosis.2 However, antibodies to B burgdorferi in CSF may be negative during early infection.3 Furthermore, while patients with facial nerve palsy attributable to Lyme disease often have a lymphocytic CSF pleocytosis, CSF analysis is not needed for patients without signs or symptoms of meningitis who are suspected to have this diagnosis owing to its excellent response to treatment with oral doxycycline.4 Late Lyme encephalomyelitis—meaning genuine infection of the brain parenchyma and/or spinal cord by B burgdorferi—is exceptionally uncommon.5 This rare diagnosis should only be considered for patients at appropriate risk for infection who have objective neurologic deficits with corresponding imaging study abnormalities. While CSF study results for such patients are abnormal, given the rarity of this entity, initial Lyme disease–related testing should include only peripheral blood serologic testing, as such patients will be B burgdorferi seropositive. While nonspecific markers of CSF inflammation are typically elevated among persons with neuroborreliosis, these elevations have not been sufficiently studied to truly distinguish neuroborreliosis from other inflammatory neurologic diseases, as discussed by Lautner and colleagues. Because the oligoclonal bands present in the CSF of patients with neuroborreliosis are anti-Borrelial antibodies, CSF oligoclonal band testing provides little additional diagnostic value from a Lyme disease perspective. We view measurement of CSF CXCL13 levels as similarly nonspecific. Several studies have described elevated CSF CXCL13 in persons with neuroborreliosis, with decline identified following appropriate antimicrobial therapy. This test may be valuable in distinguishing active neuroborreliosis from subjective neurocognitive symptoms thought potentially attributable to B burgdorferi infection. However, a number of other conditions, including tick-borne encephalitis and neurosyphilis, are associated with elevated CSF CXCL13 levels.3,6 At present, CSF CXCL13 levels do not adequately discriminate neuroborreliosis from other neuroinflammatory conditions to justify diagnostic CSF testing for assessment of this parameter alone.3

Primary endpoint was SVR 24 weeks post-therapy (Roche TaqMan LLD = 9.3 IU/mL). Relapse was the proportion of patients with undetectable HCV-RNA at end of treatment and detectable posttreatment. Results: In treatment-naive patients, anemia and EPO use occurred in: BOC 49.4% (363/734) and 43.3% (318/734), respectively; PR control, 29.7% (108/363) and 24.0% (87/363), respectively. In both placebo and BOC groups, SVR was more frequent in patients who developed anemia compared to those who did not (P < 0.001, Table). In previous-treatment-failure patients, anemia and EPO use occurred in: BOC 48.6% (157/323) and 43.3% (140/323), respectively; PR control, 25% (20/80) and 21.2% (17/80), respectively. In the BOC group, SVR was more frequent in patients who developed anemia compared to those who did not (P< 0.001, Table). In both patient groups, EPO was prescribed in 78.5% of anemic patients treated with BOC (408/520) and 68.0% (87/128) of those in the PR control group. Conclusions: Higher SVR rates were observed among previously untreated and previous-treatment-failure patients who developed anemia during BOC or control PR therapy. Since ~80% of anemic patients took EPO, additional research is needed to understand the relationship of SVR, R dose reduction, and EPO use.

A previously healthy 34-year-old man was evaluated for two years of progressive digital clubbing. He denied fevers, night sweats, cardiopulmonary symptoms, travel, or unusual exposures. Physical examination demonstrated no pathologic lymphadenopathy, genital lesions or penile discharge. The patient had dramatic clubbing of all digits and erythematous nail beds (Figs. 1 and ​and22). Figure 1 Digital clubbing. Figure 2 Digital clubbing. There are many different diseases associated with clubbing. Pulmonary diseases are most commonly associated, but cardiac conditions, gastrointestinal diseases, and various infections are also found with clubbing. The patient’s evaluation included unremarkable labs for systemic diseases such as malignancy, liver disease, and inflammatory bowel disease. His cardiopulmonary evaluation included echocardiography, pulmonary function testing, polysomnography and chest computed tomography. These were also unrevealing. The patient’s PPD test and RPR were nonreactive. His HIV antibody test (with Western blot) returned positive. CD4+ lymphocyte count was 401/μL and viral load was 205,000 copies/mL.1 Digital clubbing is associated with HIV. Among one convenience sample of 76 HIV-infected patients, 28 (36 %) had objectively confirmed clubbing—thus, HIV testing is recommended as part of a diagnostic algorithm.1,2 While HIV screening is now recommended for all patients aged 15–65 years, this case highlights the need for HIV diagnostic testing in patients with digital clubbing.3

A human recombinant L-type Ca2+ channel (alpha1C,77) was coexpressed with the rat angiotensin AT1A receptor in Xenopus laevis oocytes. In oocytes expressing only alpha1C,77 channels, application of human angiotensin II (1-10 microM) did not affect the amplitude or kinetics of Ba2+ currents (IBa). In sharp contrast, in oocytes coexpressing alpha1C,77 channels and AT1A receptors, application of 1 nM to 1 microM angiotensin gradually and reversibly inhibited IBa, without significantly changing its kinetics. The inhibitory effect of angiotensin on IBa was abolished in oocytes that had been preincubated with losartan (an AT1A receptor antagonist) or thapsigargin or injected with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate, pertussis toxin, guanosine-5'-O-(2-thio)diphosphate, or heparin, suggesting that the recombinant alpha1C channels were regulated by angiotensin through G protein-coupled AT1A receptors via activation of the inositol trisphosphate-dependent intracellular Ca2+ release pathway. Consistent with this hypothesis, no cross-signaling occurred between the AT1A receptor and a splice variant of alpha1C lacking Ca2+ sensors (alpha1C,86). The data suggest that the regulation of recombinant L-type Ca2+ channels by angiotensin is mediated by inositol trisphosphate-induced intracellular Ca2+ release and occurs at the molecular motif responsible for the Ca2+-induced inactivation of the channels.

A live, attenuated form of Mycobacterium bovis, bacillus Calmette–Guérin (BCG), is commonly used as intravesical immunotherapy for non-invasive urothelial bladder carcinoma. While complications are rare, dissemination can occur. A case of mycotic aortic aneurysm following BCG administration with recovery of Mycobacterium bovis in culture is reported. A review of the published experience with this problem is also presented.

Background: Whipple’s disease is a rare, multisystemic, chronic infectious disease which classically presents as a wasting illness characterized by polyarthralgia, diarrhea, fever, and lymphadenopathy. Pleuropericardial involvement is a common pathologic finding in patients with Whipple’s disease, but rarely causes clinical symptoms. We report the first case of severe fibrosing pleuropericarditis necessitating pleural decortication in a patient with Whipple’s disease. Case presentation: Our patient, an elderly gentleman, had a chronic inflammatory illness dominated by constrictive pericarditis and later severe fibrosing pleuritis associated with a mildly elevated serum IgG4 level. A pericardial biopsy showed dense fibrosis without IgG4 plasmacytic infiltration. The patient received immunosuppressive therapy for possible IgG4-related disease. His poor response to this therapy prompted a re-examination of the diagnosis, including a request for the pericardial biopsy tissue to be stained for Tropheryma whipplei. Conclusions: Despite a high prevalence of pleuropericardial involvement in Whipple’s disease, constrictive pleuropericarditis is rare, particularly as the dominant disease manifestation. The diagnosis of Whipple’s disease is often delayed in such atypical presentations since the etiologic agent, Tropheryma whipplei, is not routinely sought in histopathology specimens of pleura or pericardium. A diagnosis of Whipple’s disease should be considered in middle-aged or elderly men with polyarthralgia and constrictive pericarditis, even in the absence of gastrointestinal symptoms. Although Tropheryma whipplei PCR has limited sensitivity and specificity, especially in the analysis of peripheral blood samples, it may have diagnostic value in inflammatory disorders of uncertain etiology, including cases of polyserositis. The optimal approach to managing constrictive pericarditis in patients with Whipple’ sd isease is uncertain, but limited clinical experience suggests that a combination of pericardiectomy and antibiotic therapy is of benefit.