Recent Publications by CFE Educators

Importance

Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.

Objective

To present a case series of patients with diagnostically challenging subacute or chronic meningitis using metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) supported by a statistical framework generated from mNGS of control samples from the environment and from patients who were noninfectious.

Design, Setting, and Participants

In this case series, mNGS data obtained from the CSF of 94 patients with noninfectious neuroinflammatory disorders and from 24 water and reagent control samples were used to develop and implement a weighted scoring metric based on z scores at the species and genus levels for both nucleotide and protein alignments to prioritize and rank the mNGS results. Total RNA was extracted for mNGS from the CSF of 7 participants with subacute or chronic meningitis who were recruited between September 2013 and March 2017 as part of a multicenter study of mNGS pathogen discovery among patients with suspected neuroinflammatory conditions. The neurologic infections identified by mNGS in these 7 participants represented a diverse array of pathogens. The patients were referred from the University of California, San Francisco Medical Center (n = 2), Zuckerberg San Francisco General Hospital and Trauma Center (n = 2), Cleveland Clinic (n = 1), University of Washington (n = 1), and Kaiser Permanente (n = 1). A weighted z score was used to filter out environmental contaminants and facilitate efficient data triage and analysis.

Main Outcomes and Measures

Pathogens identified by mNGS and the ability of a statistical model to prioritize, rank, and simplify mNGS results.

Results

The 7 participants ranged in age from 10 to 55 years, and 3 (43%) were female. A parasitic worm (Taenia solium, in 2 participants), a virus (HIV-1), and 4 fungi (Cryptococcus neoformans, Aspergillus oryzae, Histoplasma capsulatum, and Candida dubliniensis) were identified among the 7 participants by using mNGS. Evaluating mNGS data with a weighted z score-based scoring algorithm reduced the reported microbial taxa by a mean of 87% (range, 41%-99%) when taxa with a combined score of 0 or less were removed, effectively separating bona fide pathogen sequences from spurious environmental sequences so that, in each case, the causative pathogen was found within the top 2 scoring microbes identified using the algorithm.

Conclusions and Relevance

Diverse microbial pathogens were identified by mNGS in the CSF of patients with diagnostically challenging subacute or chronic meningitis, including a case of subarachnoid neurocysticercosis that defied diagnosis for 1 year, the first reported case of CNS vasculitis caused by Aspergillus oryzae, and the fourth reported case of C dubliniensis meningitis. Prioritizing metagenomic data with a scoring algorithm greatly clarified data interpretation and highlighted the problem of attributing biological significance to organisms present in control samples used for metagenomic sequencing studies.

We present cases of localized alopecia on the vertex scalp of two girls after elaborate professional hairstyling marketed as the "Princess Package" at a major U.S. theme park. Localized alopecia followed pain, erythema, and delayed crusting due to necrosis of the scalp. The majority of the affected alopecic areas had evidence of regrowth at interval follow-up, but small areas of scarring alopecia remained. We propose that these cases represent a type of alopecia caused by a combination of pressure ischemia and acute traction alopecia.

OBJECTIVE

To describe a framework for leveraging big data for research and quality improvement purposes and demonstrate implementation of the framework for design of the Department of Veterans Affairs (VA) Colonoscopy Collaborative.

METHODS

We propose that research utilizing large-scale electronic health records (EHRs) can be approached in a 4 step framework: 1) Identify data sources required to answer research question; 2) Determine whether variables are available as structured or free-text data; 3) Utilize a rigorous approach to refine variables and assess data quality; 4) Create the analytic dataset and perform analyses. We describe implementation of the framework as part of the VA Colonoscopy Collaborative, which aims to leverage big data to 1) prospectively measure and report colonoscopy quality and 2) develop and validate a risk prediction model for colorectal cancer (CRC) and high-risk polyps.

RESULTS

Examples of implementation of the 4 step framework are provided. To date, we have identified 2,337,171 Veterans who have undergone colonoscopy between 1999 and 2014. Median age was 62 years, and 4.6 percent (n = 106,860) were female. We estimated that 2.6 percent (n = 60,517) had CRC diagnosed at baseline. An additional 1 percent (n = 24,483) had a new ICD-9 code-based diagnosis of CRC on follow up.

CONCLUSION

We hope our framework may contribute to the dialogue on best practices to ensure high quality epidemiologic and quality improvement work. As a result of implementation of the framework, the VA Colonoscopy Collaborative holds great promise for 1) quantifying and providing novel understandings of colonoscopy outcomes, and 2) building a robust approach for nationwide VA colonoscopy quality reporting.

BACKGROUND & AIMS

The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients.

METHODS

We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained.

RESULTS

Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01).

CONCLUSIONS

In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.

PURPOSE

To identify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM).

METHODS AND MATERIALS

A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed.

RESULTS

The median survival for the prior/present cohorts was 9.6/12 months, respectively (P  .01). Four prognostic factors (Karnofsky performance status, extracranial metastases, number of BM, and hemoglobin b) were significant for survival after the diagnosis of BM. Of the 6 drug types studied, only cytokine use after BM was associated with improved survival. The use of whole-brain radiation therapy declined from 50% to 22%, and the use of stereotactic radiosurgery alone increased from 46% to 58%. Nonneurologic causes of death were twice as common as neurologic causes.

CONCLUSIONS

Additional prognostic factors refine prognostication in this larger contemporary cohort. Patterns of care have changed, and survival of RCC patients with BM has improved over time. The reasons for this improvement in survival remain unknown but may relate to more aggressive use of local brain metastasis therapy and a wider array of systemic treatment options for those patients with progressive extracranial tumor.

PURPOSE

In this study we aimed to define the prevalence of preoperative and postoperative post-micturition incontinence or post-void dribbling after anterior urethroplasty for urethral stricture disease. We also sought to determine risk factors for its presence.

MATERIALS AND METHODS

We retrospectively reviewed a prospectively maintained, multi-institutional urethral stricture database to evaluate post-micturition incontinence using a single question from a validated questionnaire, "How often have you had a slight wetting of your pants a few minutes after you had finished urinating and had dressed yourself?" Possible answers were never-0 to all the time-3. The presence of post-micturition incontinence was defined as any answer greater than 0. Comparisons were made to stricture type and location, repair type and patient medical comorbidities.

RESULTS

Preoperative and postoperative post-micturition incontinence questionnaires were completed by 614 and 331 patients, respectively. Patients without complete data available were excluded from study. Preoperative post-micturition incontinence was present in 73% of patients, of whom 44% stated that this symptom was present most of the time. Overall postoperative post-micturition incontinence was present in 40% of patients and again it was not predicted by stricture location or urethroplasty type. Of the 331 patients with followup questionnaires 60% reported improvement, 32% reported no change and 8% reported worsening symptoms. The overall rate of de novo post-micturition incontinence was low at 6.3%.

CONCLUSIONS

The prevalence of preoperative post-micturition incontinence is high and likely under reported. In most patients post-micturition incontinence improves after urethroplasty and the prevalence of de novo post-micturition incontinence is low. The presence of post-micturition incontinence was not predicted by stricture length or location, or urethroplasty repair type.

OBJECTIVE

To understand the prevalence of chronic perineal pain, activity limitations, and patient satisfaction after urethroplasty.

METHODS

From 2014 to 2016, we prospectively enrolled men undergoing urethroplasty for bulbar urethral strictures. Patients, before and after surgery, completed questions from the Core Lower Urinary Tract Symptom Score assessing pain frequency in the bladder and penis or urethra, as well as nonvalidated questions assessing perineal pain. Overall satisfaction with their current urinary condition and pain-related activity limitations at home, work, or during exercise were also measured. Patients with 3 months of follow-up were excluded. Pre-and postoperative scores were compared using the Wilcoxon signed-rank test.

RESULTS

Thirty-five men were included in the study. Mean age and body mass index were 44.6 years and 30.9 kg/m, respectively. Urethroplasties were anastomotic in 24 (69%) and were single-stage buccal graft substitution in 11 (31%). Median follow-up after surgery was 483 days (range: 90-810 days). A total of 10 patients (29%) reported worsening perineal pain intensity after surgery, whereas 8 (23%) reported improvement and 17 (48%) reported no change. Overall, pain frequency in the bladder, penis or urethra, and perineum improved. Home and exercise pain-related activity restrictions improved significantly after surgery. Satisfaction with current urinary condition also improved with 91% reporting feeling "delighted," "pleased," or "mostly satisfied" with their current condition.

CONCLUSION

Patients are highly satisfied with their urinary condition after urethroplasty. Pain frequency in the bladder and the urethra significantly improves after urethroplasty; however, perineal pain intensity can worsen and become chronic after surgery in some patients.

OBJECTIVE

Several cross-sectional studies have reported an association between visual contrast sensitivity (a functional measure of low contrast vision) and poor cognitive performance or dementia, but no studies have investigated this association prospectively in a population-based cohort with final adjudication of mild cognitive impairment (MCI)/dementia.

METHODS

In a prospective, community-based study of aging women (Study of Osteoporotic Fractures), we analyzed whether visual contrast sensitivity was associated with increased risk of MCI or dementia and/or worse performance on various cognitive tests assessed 10 years later. Contrast sensitivity was assessed at baseline in each eye using a VISTECH VCTS 6500 wall chart. MCI/dementia was adjudicated by an expert panel. Multivariate logistic and linear regression models were analyzed.

RESULTS

Of 1,352 white (88.2%) and African American (11.8%) women with a mean age of 77.7 years (standard deviation = 3.3), 536 (39.6%) went on to develop MCI/dementia over 10 years. MCI/dementia risk was more than doubled (odds ratio = 2.16, 95% confidence interval = 1.58-2.96) in women with the lowest quartile of contrast sensitivity compared to the highest (p  0.0001 for the linear trend). Reduced baseline contrast sensitivity was also associated with lower performance on several cognitive measures assessed 10 years later.

INTERPRETATION

Among older women, reduced contrast sensitivity is associated with a greater risk of MCI/dementia. These findings suggest that visual system neurodegeneration or dysfunction may parallel or precede dementia-related cortical or subcortical degeneration, and that contrast sensitivity testing may be useful in identifying aging adults at high risk for dementia. Ann Neurol 2018;83:730-738.