Valeria Fabre

The First US Domestic Report of Disseminated Mycobacterium avium Complex and Anti-Interferon-γ Autoantibodies

IntroductionAnti-interferon-γ (IFNγ) autoantibodies have been associated with disseminated mycobacterial infections, mostly in patients from Southeast Asia.PurposeWe studied an American-born, Caucasian female with M. avium complex infection of the subglottic mucosa and brain for underlying etiologies of infection.MethodsPlasma 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.ResultsPatient plasma contained high-titer IgG anti-IFNγ autoantibodies, primarily of the IgG1 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.ConclusionsDisseminated 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.

Correlation of ALOX15 expression with eosinophilic or reflux esophagitis in a cohort of pediatric patients with esophageal eosinophilia

The differential diagnosis between eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) is often challenging. We recently showed that the ALOX15 protein is expressed in 95% of esophageal biopsies from patients with a definitive diagnosis of EoE. Here we correlated ALOX15 expression with the clinical classification of EoE or GERD in a cohort of consecutive pediatric patients (n = 62) with at least 1 esophageal biopsy containing at least 15 eosinophils per high-power field (eos/HPF). The patients were categorized into the following groups: (1) at least 15 eos/HPF in the distal esophagus only (n = 24), (2) at least 15 eos/HPF in the proximal esophagus only (n = 5), and (3) at least 15 eos/HPF in the distal and proximal biopsies (n = 33). Control groups included patients with GERD with biopsies containing 6 to 15 eos/HPF (n = 9), patients with GERD with 5 eos/HPF or less (n = 15), patients with candida esophagitis (n = 15), and patients with normal biopsies (n = 15). ALOX15 was positive in 90.5% of patients with EoE (13/16 in group 1, 4/4 in group 2, 31/33 in group 3) versus 44% of patients with GERD (4/8 in group 1, 0/1 in group 2, and 0/0 in group 3), 2 of 9 (22%) of patients with 6 to 15 eos/HPF, and was negative in all patients with GERD with biopsies containing 5 eos/HPF or less, all patients with candida esophagitis, and all normal controls. In conclusion, ALOX15 is a sensitive marker of EoE; however, subpopulations of patients with GERD with >5 eos/HPF also express ALOX15. Positive ALOX15 expression is more prevalent in EoE than in GERD and may prove to be a useful diagnostic marker in patients with discrepant biopsy findings between the proximal and distal esophagus.

Developing an Assessment Framework for Essential Internal Medicine Subspecialty Topics

Background Assessing residents by direct observation is the preferred assessment method for infrequently encountered subspecialty topics, but this is logistically challenging. Objective We developed an assessment framework for internal medicine (IM) residents in subspecialty topics, using tuberculosis diagnosis for proof of concept. Methods We used a 4-step process at 8 academic medical centers that entailed (1) creating a 10-item knowledge assessment tool; (2) pilot testing on a sample of 129 IM residents and infectious disease fellow volunteers to evaluate validity evidence; (3) implementing the final tool among 886 resident volunteers; and (4) assessing outcomes via retrospective chart review. Outcomes included tool score, item performance, and rates of obtaining recommended diagnostics. Results Following tool development, 10 infectious disease experts provided content validity. Pilot testing showed higher mean scores for fellows compared with residents (7 [SD = 1.8] versus 3.8 [SD = 1.7], respectively, P < .001) and a satisfactory Kuder-Richardson Formula 20 (0.72). Implementation of the tool revealed a 14-minute (SD = 2.0) mean completion time, 61% (541 of 886) response rate, 4.4 (SD = 1.6) mean score, and ≤ 57% correct response rate for 9 of 10 items. On chart review (n = 343), the rate of obtaining each recommended test was ≤ 43% (113 of 261), except for chest x-rays (96%, 328 of 343). Conclusions Our assessment framework revealed knowledge and practice gaps in tuberculosis diagnosis in IM residents. Adopting this approach may help ensure assessment is not limited to frequently encountered topics.

Impact of Case-Specific Education and Face-to-Face Feedback to Prescribers and Nurses in the Management of Hospitalized Patients With a Positive Clostridium difficile Test

Abstract Background Approaches to changing providers’ behavior around Clostridium difficile (CD) management are needed. We hypothesized that case-specific teaching points and face-to-face discussions with prescribers and nurses would improve management of patients with a positive CD test. Methods Charts of patients age ≥18 years with positive CD tests hospitalized July 2016 to May 2017 were prospectively reviewed to assess CD practices and generate management recommendations. The study had 4 periods: baseline (pre-intervention), intervention #1, observation, and intervention #2. Both interventions consisted of an in-person, real-time, case-based discussion and education by a CD Action Team (CDAT). Assessment occurred within 24 hours of a positive CD test for all periods; during the intervention periods, management was also assessed within 48 hours after CDAT-delivered recommendations. Outcomes included proportion of patients receiving optimized treatment and incidence rate ratios of practice changes (both CDAT-prompted and CDAT-independent). Results Overall, the CDAT made recommendations to 84 of 96 CD cases during intervention periods, and providers accepted 43% of CDAT recommendations. The implementation of the CDAT led to significant improvement in bowel movement (BM) documentation, use of proton pump inhibitors, and antibiotic selection for non-CD infections. Selection of CD-specific therapy improved only in the first intervention period. Laxative use and treatment of CD colonization cases remained unchanged. Only BM documentation, a nurse-driven task, was sustained independent of CDAT prompting. Conclusions A behavioral approach to changing the management of positive CD tests led to self-sustained practice changes among nurses but not physicians. Better understanding of prescribers’ decision-making is needed to devise enduring interventions.