The role of noninvasive imaging in the diagnostic workup for pulsatile tinnitus

Objective We sought to assess the diagnostic yield of advanced noninvasive imaging in the evaluation of patients with pulsatile tinnitus. Background Pulsatile tinnitus can be caused by high-risk cerebrovascular pathologies such as arteriovenous fistulae. The role of advanced noninvasive imaging, including magnetic resonance angiography and magnetic resonance venography, in the diagnostic evaluation of pulsatile tinnitus is not well defined. Design and methods We performed a retrospective cohort study of patients presenting for outpatient diagnostic evaluation of pulsatile tinnitus from January 2018 to March 2020 at Weill Cornell Medicine. Patients with non-pulsatile tinnitus and established etiologic diagnoses were excluded. Systematic chart abstraction was summarized using standard descriptive statistics. Univariate logistic regression was used to identify factors associated with nondiagnostic noninvasive imaging. Results A total of 187 patients (139 (74.3%) women) took part in this study, with a mean age of 48.6 years (standard deviation ( SD) = 15.5 years) and a mean body mass index (BMI) of 26.9 kg/m2 ( SD = 6.1 kg/m2). Of the 187 patients, 121 (64.7%) underwent exclusively noninvasive imaging, and 66 (35.3%) patients also had digital subtraction angiography (DSA). In patients who had exclusively noninvasive imaging, 62 (51.2%) patients received a diagnosis. In patients who underwent noninvasive and DSA imaging, 14 (21.2%) patients received a diagnosis based on DSA. Patients who were older at symptom onset (odds ratio (OR) = 1.05; 95% confidence interval (CI) 1.01–1.09) and those with a lower BMI (OR = 0.88, 95% CI 0.77–0.98) were more likely to have nondiagnostic noninvasive imaging. Conclusion Noninvasive cerebrovascular imaging often uncovers the etiology of pulsatile tinnitus. DSA remains useful for additional evaluation for patients with specific associated features.

CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

Impact of radiation on the incidence and management of ureteroenteric strictures: a contemporary single center analysis

Background Ureteroenteric stricture incidence has been reported as high as 20% after urinary diversion. Many patients have undergone prior radiotherapy for prostate, urothelial, colorectal, or gynecologic malignancy. We sought to evaluate the differences between ureteroenteric stricture occurrence between patients who had radiation prior to urinary diversion and those who did not. Methods An IRB-approved cystectomy database was utilized to identify ureteroenteric strictures among 215 patients who underwent urinary diversion at a single academic center between 2016 and 2020. Chart abstraction was conducted to determine the presence of confirmed stricture in these patients, defined as endoscopic diagnosis or definitive imaging findings. Strictures due to malignant ureteral recurrence were excluded (3 patients). Statistical analysis was performed using chi squared test, t-test, and Wilcoxon Rank-Sum Test, logistic regression, and Kaplan–Meier analysis of stricture by cancer type. Results 65 patients had radiation prior to urinary diversion; 150 patients did not have a history of radiation therapy. Benign ureteroenteric stricture rate was 5.3% (8/150) in the non-radiated cohort and 23% (15/65) in the radiated cohort (p = < 0.001). Initial management of stricture was percutaneous nephrostomy (PCN) in 78% (18/23) and the remaining 22% (5/23) were managed with primary retrograde ureteral stent placement. Long term management included ureteral reimplantation in 30.4% (7/23). Conclusions Our study demonstrates a significant increase in rate of ureteroenteric strictures in radiated patients as compared to non-radiated patients. The insult of radiation on the ureteral microvascular supply is likely implicated in the cause of these strictures. Further study is needed to optimize surgical approach such as utilization of fluorescence angiography for open and robotic approaches.

Assessing financial difficulty in patients with multiple myeloma: Preliminary results of ALLIANCE A231602CD.

8031 Background: New orally administered anticancer treatments have launched in recent years, promising gains in survival and quality of life, but with high prices.Financial difficulties encountered over the course of cancer diagnosis and treatment is a growing concern. These difficulties include inability to pay for basic necessities, presence of medical debt, and high out of pocket burdens relative to income. The primary objective of this study was to estimate the proportion of patients with multiple myeloma (MM) who experience financial difficulties in the past 12 months.Methods: Data collection entailed a comprehensive, theoretically grounded telephone survey and companion medical chart abstraction. Subjects included individuals with a current diagnosis of MM whose current or recent treatment included pharmaceutical-based care and who were not enrolled in a treatment-based trial. Practices eligible to recruit respondents included 44 NCORP affiliates of the Alliance. 14 geographically diverse NCORP affiliates participated between 11/2019 and 6/2020. The primary endpoint of the study was the proportion of subjects who reported financial difficulty in the past 12 months, as measured by the EORTC QLQ-C30 item #28. This proportion and 95% Wilson score confidence interval were estimated for all MM patients who responded to the financial difficulty question ((# reported financial difficulty)/(total # in that category who answered the question)). NCI Central IRB approved this study. Results: 393 subjects were recruited. 304 subjects completed the survey (77.4% response rate). Mean age was 67.5 years (SD 9.8), 143 (46.4%) were female, 24 (7.8%) self-reported race as ‘Black or African American’, 82 (26.6%) reported insured by government insurance Medicare only, 116 (38.2%) reported highest education as high school or below, and 94 (30.5%) reported high income. Mean time from diagnosis to survey enrollment was 3.6 years (SD 4.5). 292 (95.1%) were currently receiving treatment and 192 (62.5%) reported currently receiving a pre-defined ‘expensive’ oral pharmaceutical-based cancer treatment. 20.2% (95% CI:16.1%, 25.0%) reported financial difficulties. Conclusions: This is the first national study to systematically assess the prevalence of financial difficulties and its correlates among MM patients. Approximately 1 in 5 surveyed patients reported financial difficulties. Results of this study aim to inform efforts to improve financial navigation and resources for cancer patients.

Prenatal IgE as a Risk Factor for the Development of Childhood Neurodevelopmental Disorders

Background: Few studies have examined if maternal allergic disease is associated with an offspring's neurodevelopment. We hypothesized that Th-2 biased maternal immune function assessed as total serum immunoglobulin (Ig) E is associated with attention deficit hyperactivity disorder (ADHD).Methods: Data are from the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study (WHEALS), a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal total IgE was measured prenatally and at 1-month postpartum. Child total IgE was assessed at birth, 6 months, and 2 years of age. ADHD diagnosis was based on the parental report at the 10–12-year study visits or medical chart abstraction. Total IgE was log2 transformed. Poisson regression models with robust error variance were used to calculate the risk ratios (RR). Inverse probability weighting was used to correct for potential bias due to a loss to follow-up and non-response.Results: Of the 636 maternal-child pairs in the analysis, 513 children were neurotypical and 123 had ADHD. Maternal prenatal total IgE was significantly associated with ADHD even after adjustment for potential confounders (RR = 1.08, 95% CI 1.03–1.13). Maternal and child IgE measures were positively and significantly correlated, but child total IgE was not associated with ADHD at any time point.Conclusions: Maternal prenatal IgE may influence neurodevelopment, but additional studies are needed to confirm and expand these findings.

Anti-tRNA synthetase syndrome interstitial lung disease: A single center experience

BackgroundRecognition of Anti tRNA synthetase (ARS) related interstitial lung disease (ILD) is key to ensuring patients have prompt access to immunosuppressive therapies. The purpose of this retrospective cohort study was to identify factors that may delay recognition of ARS-ILD.MethodsPatients seen at Vanderbilt University Medical Center (VUMC) between 9/17/2017-10/31/2018 were included in this observational cohort. Clinical and laboratory features were obtained via chart abstraction. Kruskal-Wallis ANOVA, Mann-Whitney U, and Fisher’s exact t tests were utilized to determine statistical significance.ResultsPatients with ARS were found to have ILD in 51.9% of cases, which was comparable to the frequency of ILD in systemic sclerosis (59.5%). The severity of FVC reduction in ARS (53.2%) was comparable to diffuse cutaneous systemic sclerosis (56.8%, p=0.48) and greater than dermatomyositis (66.9%, p=0.005) or limited cutaneous systemic sclerosis (lcSSc, 71.8%, p=0.005). Frank honeycombing was seen with ARS antibodies but not other myositis autoantibodies. ARS patients were more likely to first present to a pulmonary provider in a tertiary care setting (53.6%), likely due to fewer extrapulmonary manifestations. Only 33% of ARS-ILD were anti-nuclear antibody, rheumatoid factor, or anti-cyclic citrullinated peptide positive. Patients with ARS-ILD had a two-fold longer median time to diagnosis compared to other myositis-ILD patients (11.0 months, IQR 8.5 to 43 months vs. 5.0 months, IQR 3.0 to 9.0 months, p=0.003).ConclusionsARS patients without prominent extra-pulmonary manifestations are at high risk for not being recognized as having a connective tissue disease related ILD and miscategorized as UIP/IPF without comprehensive serologies.

Abstract P441: Dental Caries a Risk Factor for Intracerebral Hemorrhage

Introduction: Streptococcus mutans is a known cause of dental caries that contains a collagen-binding protein, Cnm, and shows inhibition of platelet aggregation and matrix metalloproteinase-9 activation. This strain has been linked to aggravation of experimental intracerebral hemorrhage (ICH) and may be a risk factor for intracerebral hemorrhage. Methods: Presence of dental caries was assessed in subjects from the Dental Atherosclerosis in Communities Study (DARIC) without prior stroke or intracerebral hemorrhage. This cohort was followed for a period of incident intracerebral hemorrhage, subsequently verified by chart abstraction. Cox regression with time-dependent covariate was used to compute crude and adjusted hazards ratio stratified as <15 years and ≥15 years from the initial dental assessment. Results: Among 6506 subjects, dental caries were recorded in 1227 (19%) subjects. 47 (1%) had ICH over a period of 30 years. Those with dental caries versus those without dental caries had a greater proportion of younger (mean age 61.8±5.6 vs. 62.5±5.6, p<0.001), male (24% vs. 16%, p<0.001), African-American (53% vs 12%, p<0.001) and hypertensive (24% vs. 16%, p<0.001) patients. The association between dental caries and ICH in the first 15 years was not higher (crude HR 1.0, 95% CI 0.4-2.3) and remained so after adjusting for age, gender, race, and hypertension (adj. HR 1.1, 95% CI 0.5-2.9). The association between caries and ICH in the second 15 years was higher (crude HR 3.7, 95% CI 1.1-12.0) and strengthened after adjustment (adjusted OR 4.5, 95% CI 1.3-15.5). This is depicted in the Kaplan-Meier curve below. Conclusion: We report a significant association between dental caries and ICH. Future studies are needed to determine if early treatment of dental caries can reduce the risk of ICH.

Abstract P654: Predicting Afib in Cryptogenic Ischemic Stroke Patients With Implantable Loop Recorders

Paroxysmal atrial fibrillation (Afib) detection in cryptogenic stroke is difficult but essential because it changes management. We describe a scoring system that discriminates between cryptogenic ischemic stroke patients with implantable loop recorder (ILR) that were and were not found to have Afib. Consecutive cryptogenic stroke cases from cardiology’s ILR registry for a 2-year period (7/2017-7/2019) were reviewed. We used standardized case report forms to perform chart abstraction. Cases were excluded if ILR was not placed after the index stroke event, stroke etiology workup was not available, or data was incomplete. Patients found to have Afib on ILR were compared to those without evidence of Afib on ILR. We devised a novel scoring system using variables associated with Afib detection and compared its ability to classify Afib detection against CHA2DS2-VASc and LADS. One hundred fifty-seven patients met inclusion criteria. Afib was detected in 12% of cases (9% at 6 months, 10% at 12 months). The median time from ILR placement to Afib detection was 110 days (IQR 37, 507). Median time from Afib detection to the start of anticoagulation was 3 days (IQR 0, 8). The PAL-CrISP score ranges 0 to 7: age (70=0, ≥70=4), history of antihypertensive medication (no=0, yes=2), PR interval (≤200msec=0, >200msec=1). Of those found to have Afib via ILR, 74% (14/19) had a PAL-CrISP score ≥ 6. PAL-CrISP performed better at predicting Afib detection in cryptogenic ischemic stroke patients with ILR (AUC 0.810, 95% CI 0.706-0.913) than CHA2DS2-VASc (AUC 0.650, 95% CI 0.525-0.774) and LADS (AUC 0.745, 95% CI 0.624-0.866). Using only age, home medication review, and an EKG, the novel PAL-CrISP score performs better at predicting Afib detection than the CHA2DS2-VASc and LADS scores in cryptogenic ischemic stroke patients with an ILR.

Positivity yield of HIV index testing services from selected healthcare facilities in Ondo State, southwest Nigeria

Background: Index testing is a voluntary process whereby HIV seropositive clients are counselled and, after obtaining consent, their sexual and needle sharing partners are offered HIV testing services. Index testing has been associated with high HIV positivity yield. The aim of this study is to determine the positivity yield and identify factors influencing the yield from index testing strategy in selected healthcare facilities in Ondo State, southwest Nigeria. Methodology: Six public hospitals in Ondo State with the highest HIV clients currently on treatment were selected. Records of all clients newly diagnosed to be HIV positive at the selected facilities from June 2018 to September 2019, and who had an outcome for index testing services were reviewed. Data were collected using a chart abstraction template from the index testing registers. Information collected included age and gender of the index clients and their partners, method of referral and notification of partners, HIV test results of partners and linkage status of new HIVpositive partners. Data analyses were done using the Statistical Package for the Social Sciences (SPSS) software version 24.0. Chi-square was used to test association between variables at a significance level of p<0.01. Results: The records of a total of 904 index clients and their partners were reviewed with partner elicitation ratio of 1:1. The mean ages of index clients and their partners were 38.52±10.96 and 38.98±10.79 years respectively, and majority of the index clients (34.6%) and partners (35.5%) were in the 35-44 years age group. A total of 548 index clients were females (60.6%) while 528 of their partners were males (58.4%), indicating predominantly heterosexual (96.4%) and few homosexual (lesbian) relationships (3.6%). One-fifth (20%) of partners tested positive for HIV andwere all (100%) linked to antiretroviral therapy (ART). The HIV positivity rate in partners of male index clients (26.9%) was significantly higher than in partners of female index clients (15.5%) (p<0.01). Partner referral method was mostly through assisted referral (56%) and most (82%) were contacted by the index clients through phone. Conclusion: Due to its high positivity yield, index testing is a veritable strategy to increase HIV case detection and linkage to ART. Hence, proper deployment of index testing will be critical to improving ART coverage and achieving epidemiological control. Keywords: HIV, client; partner; index testing; ART; southwest Nigeria