Parental Notification Via Text Messaging for Infant Sickle Screening Programs: Exploration of Feasibility and Acceptability in Uganda.

Sickle cell disease (SCD) in Africa has high prevalence, morbidity, and early mortality. Difficulties in reaching parents following infant SCD screening dampen program effectiveness. Text messaging may support initial postscreening parental notification. We explored SCD awareness, and feasibility and acceptability of text messaging about screening follow-up among convenience samples of caretakers with children under 5 years (n=115) at 3 sites: a SCD family conference or 2 general pediatric clinics in urban or rural Uganda. Two thirds of the conference-based participants and 8% at clinic sites had affected children. At the clinics, 64% of caretakers were aware of SCD. In all, 87% claimed current possession of mobile phones; 89% previously had received messages. A sample text on the availability of screening results and need to bring their child to SCD clinic was at least partially understood by 82%. Overall, 52% preferred communication for initial follow-up by telephone over text message. Concerns about texting included phone access, privacy or cost, and readability of messages. Caretakers identified concerns about distance, cost, or preference for another clinic as additional barriers to SCD follow-up. Findings suggest that text messaging to caretakers may be feasible, but less acceptable compared with a telephone call about initial follow-up from newborn SCD screening.

Genetic rescue models refute nonautonomous rod cell death in retinitis pigmentosa.

Retinitis pigmentosa (RP) is an inherited neurodegenerative disease, in which the death of mutant rod photoreceptors leads secondarily to the non-cell autonomous death of cone photoreceptors. Gene therapy is a promising treatment strategy. Unfortunately, current methods of gene delivery treat only a fraction of diseased cells, yielding retinas that are a mosaic of treated and untreated rods, as well as cones. In this study, we created two RP mouse models to test whether dying, untreated rods negatively impact treated, rescued rods. In one model, treated and untreated rods were segregated. In the second model, treated and untreated rods were diffusely intermixed, and their ratio was controlled to achieve low-, medium-, or high-efficiency rescue. Analysis of these mosaic retinas demonstrated that rescued rods (and cones) survive, even when they are greatly outnumbered by dying photoreceptors. On the other hand, the rescued photoreceptors did exhibit long-term defects in their outer segments (OSs), which were less severe when more photoreceptors were treated. In summary, our study suggests that even low-efficiency gene therapy may achieve stable survival of rescued photoreceptors in RP patients, albeit with OS dysgenesis.

Evaluation of self-calibrated non-linear phase-contrast correction in pediatric and congenital cardiovascular magnetic resonance imaging.

BACKGROUND: The need for background error correction in phase-contrast flow analysis has historically posed a challenge in cardiac magnetic resonance (MR) imaging. While previous studies have shown that phantom correction improves flow measurements, it impedes scanner workflow. OBJECTIVE: To evaluate the efficacy of self-calibrated non-linear phase-contrast correction on flows in pediatric and congenital cardiac MR compared to phantom correction as the standard. MATERIALS AND METHODS: We retrospectively identified children who had great-vessel phase-contrast and static phantom sequences acquired between January 2015 and June 2015. We applied a novel correction method to each phase-contrast sequence post hoc. Uncorrected, non-linear, and phantom-corrected flows were compared using intraclass correlation. We used paired t-tests to compare how closely non-linear and uncorrected flows approximated phantom-corrected flows. In children without intra- or extracardiac shunts or significant semilunar valvular regurgitation, we used paired t-tests to compare how closely the uncorrected pulmonary-to-systemic flow ratio (Qp:Qs) and non-linear Qp:Qs approximated phantom-corrected Qp:Qs. RESULTS: We included 211 diagnostic-quality phase-contrast sequences (93 aorta, 74 main pulmonary artery [MPA], 21 left pulmonary artery [LPA], 23 right pulmonary artery [RPA]) from 108 children (median age 15 years, interquartile range 11-18 years). Intraclass correlation showed strong agreement between non-linear and phantom-corrected flow measurements but also between uncorrected and phantom-corrected flow measurements. Non-linear flow measurements did not more closely approximate phantom-corrected measurements than did uncorrected measurements for any vessel. In 39 children without significant shunting or regurgitation, mean non-linear Qp:Qs (1.07; 95% confidence interval [CI] = 1.01, 1.13) was no closer than mean uncorrected Qp:Qs (1.06; 95% CI = 1.00, 1.13) to mean phantom-corrected Qp:Qs (1.02; 95% CI = 0.98, 1.06). CONCLUSION: Despite strong agreement between self-calibrated non-linear and phantom correction, cardiac flows and shunt calculations with non-linear correction were no closer to phantom-corrected measurements than those without background correction. However, phantom-corrected flows also demonstrated minimal differences from uncorrected flows. These findings suggest that in the current era, more accurate phase-contrast flow measurements might limit the need for background correction. Further investigation of the clinical impact and optimal methods of background correction in the pediatric and congenital cardiac population is needed.

Comparative Analysis of Functional and Structural Decline in Retinitis Pigmentosas.

Retinitis pigmentosa (RP) is a category of inherited retinal dystrophies that is best prognosticated using electroretinography (ERG). In this retrospective cohort study of 25 patients with RP, we evaluated the correlation between 30 Hz flicker ERG and structural parameters in the retina. Internationally standardized 30 Hz flicker ERG recordings, short-wavelength autofluorescence (SW-AF), and spectral domain-optical coherence tomography (SD-OCT) were acquired at two visits at least one year apart. Vertical and horizontal hyperautofluorescent ring diameter measurements with SW-AF, as well as ellipsoid zone (EZ) line width measurements with SD-OCT, were used as structural parameters of disease progression. The 30 Hz flicker ERG amplitude decreased by 2.2 ± 0.8 µV/year (p = 0.011), while implicit times remained unchanged. For SD-OCT, the EZ line decreased by 204.1 ± 34.7 µm/year (p < 0.001). Horizontal and vertical hyperautofluorescent ring diameters decreased by 161.9 ± 25.6 µm/year and 146.9 ± 34.6 µm/year, respectively (p = 0.001), with SW-AF. A correlation was found between the progression rates of the 30 Hz flicker amplitude recorded with Burian-Allen electrodes and both the horizontal ring diameter (p = 0.020) and EZ line (p = 0.044). SW-AF and SD-OCT, two readily available imaging techniques, may be used to prognosticate disease progression because of the reliability of their measurements and correlation with functional outcome.

Antibody-based methods for the measurement of α-synuclein concentration in human cerebrospinal fluid - method comparison and round robin study.

α-Synuclein is the major component of Lewy bodies and a candidate biomarker for neurodegenerative diseases in which Lewy bodies are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterized by reduced concentrations of α-synuclein in cerebrospinal fluid (CSF), with overlapping concentrations compared to healthy controls and variability across studies. Several reasons can account for this variability, including technical ones, such as inter-assay and inter-laboratory variation (reproducibility). We compared four immunochemical methods for the quantification of α-synuclein concentration in 50 unique CSF samples. All methods were designed to capture most of the existing α-synuclein forms in CSF ('total' α-synuclein). Each of the four methods showed high analytical precision, excellent correlation between laboratories (R2 0.83-0.99), and good correlation with each other (R2 0.64-0.93), although the slopes of the regression lines were different between the four immunoassays. The use of common reference CSF samples decreased the differences in α-synuclein concentration between detection methods and technologies. Pilot data on an immunoprecipitation mass spectrometry (IP-MS) method is also presented. Our results suggest that the four immunochemical methods and the IP-MS method measure similar forms of α-synuclein and that a common reference material would allow harmonization of results between immunoassays.

Genetic Rescue Reverses Microglial Activation in Preclinical Models of Retinitis Pigmentosa.

Microglia cells (MGCs) play a key role in scavenging pathogens and phagocytosing cellular debris in the central nervous system and retina. Their activation, however, contributes to the progression of multiple degenerative diseases. Given the potential damage created by MGCs, it is important to better understand their mechanism of activation. Here, we explored the role of MGCs in the context of retinitis pigmentosa (RP) by using four independent preclinical mouse models. For therapeutic modeling, tamoxifen-inducible CreER was introduced to explore changes in MGCs when RP progression halted. The phenotypes of the MGCs were observed using live optical coherence tomography, live autofluorescence, and immunohistochemistry. We found that, regardless of genetic background, MGCs were activated in neurodegenerative conditions and migrated beyond the layers where they are typically found to the inner and outer segments, where degeneration was ongoing. Genetic rescue not only halted degeneration but also deactivated MGCs, regardless of whether the intervention occurred at the early, middle, or late stage of the disease. These findings suggest that halting long-term disease progression may be more successful by downregulating MGC activity while co-administering the therapeutic intervention.

Correlation between B-scan optical coherence tomography, en face thickness map ring and hyperautofluorescent ring in retinitis pigmentosa patients.

OBJECTIVE: To evaluate and compare the B-scan OCT loss of ellipsoid zone, OCT en face thickness map constriction, and hyperautofluorescent ring constriction in RP patients. METHODS: Retrospective case series study. Forty-eight eyes of 24 RP patients with a parafoveal hyperautofluorescent ring were studied. The diagnosis of RP was established by the presence of rod response impairment and a prevalent decrease of scotopic over photopic responses on electroretinography. The FAF and spectral-domain optical coherence tomography (SD-OCT) images were obtained from 24 patients with RP. The measurements of the EZ line width on B-scan OCT, hyperautofluorescent ring area on FAF, and hyperautofluorescent ring area on en face thickness map were performed by two independent graders. The measurements of these three parameters were correlated. RESULTS: The mean age of study patients was 46 years old (sd = 19). The external and internal FAF rings involving the fovea were identified in all study eyes. The area of the thickness ring decreased at an average rate of 0.5 (sd 0.4) mm2 per year (P < 0.001). The average rate of EZ-line constriction was estimated to be 123 (sd 63) µm per year (P < 0.001). The hyperautofluorescent ring area decreased at an average rate of 0.9 (sd 0.98) mm2 per year (P < 0.001). The strongest correlation was observed between hyperautofluorescent ring area and EZ-line width (r = 0.78). CONCLUSIONS: We observed that the hyperautofluorescent ring area exhibits a faster progression rate than the area of the thickness ring. In addition, we found that the EZ-line width had a high positive correlation with the hyperautofluorescent ring area and a moderate positive correlation with area of the thickness ring.

Fundus autofluorescence and ellipsoid zone (EZ) line width can be an outcome measurement in RHO-associated autosomal dominant retinitis pigmentosa.

PURPOSE: To evaluate the progression of retinitis pigmentosa (RP) due to mutations in rhodopsin (RHO) by measuring the short-wavelength autofluorescence (SW-AF) increased autofluorescence ring and ellipsoid zone (EZ)-line width. METHODS: Fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) images were obtained from 10 patients with autosomal dominant RP due to mutations in the RHO gene. Measurements of ring area on FAF images, as well as the EZ line width on SD-OCT images and horizontal, vertical diameter, were performed by two independent masked graders. RESULTS: The ring area decreased by a rate of 0.6 ± 0.2 mm2 per year. We observed that the EZ line width decreased by an average of 152 ± 37 µm per year, while the horizontal and vertical diameters decreased by 106 ± 35 µm and 125 ± 29 µm per year, respectively. Progression rates were similar between eyes. CONCLUSIONS: We observed SW-AF ring constriction and a progressive loss of EZ line width over time.

Reprogramming towards anabolism impedes degeneration in a preclinical model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is an incurable neurodegenerative condition featuring photoreceptor death that leads to blindness. Currently, there is no approved therapeutic for photoreceptor degenerative conditions like RP and atrophic age-related macular degeneration (AMD). Although there are promising results in human gene therapy, RP is a genetically diverse disorder, such that gene-specific therapies would be practical in a small fraction of patients with RP. Here, we explore a non-gene-specific strategy that entails reprogramming photoreceptors towards anabolism by upregulating the mechanistic target of rapamycin (mTOR) pathway. We conditionally ablated the tuberous sclerosis complex 1 (Tsc1) gene, an mTOR inhibitor, in the rods of the Pde6bH620Q/H620Q preclinical RP mouse model and observed, functionally and morphologically, an improvement in the survival of rods and cones at early and late disease stages. These results elucidate the ability of reprogramming the metabolome to slow photoreceptor degeneration. This strategy may also be applicable to a wider range of neurodegenerative diseases, as enhancement of nutrient uptake is not gene-specific and is implicated in multiple pathologies. Enhancing anabolism promoted neuronal survival and function and could potentially benefit a number of photoreceptor and other degenerative conditions.

Examining the Psychosocial Impact of Genetic Testing for Cardiomyopathies.

Inherited cardiomyopathies, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), are the most common monogenic cause of cardiac disease and can rarely lead to sudden cardiac death (SCD). They are characterized by incomplete and age-dependent penetrance and are usually initially symptomatic in adulthood yet can present in childhood as well. Over 20 genes have been identified to cause HCM, and more than 40 genes are known to cause DCM. Genetic testing for these genes has been integrated into medical care; however, the psychological impact of genetic testing and the impact of the uncertainty that comes with receiving these results have not been well studied. This study surveyed 90 adult probands and relatives with a personal or family history of cardiomyopathy from a single hospital-based cardiac genetic program to determine the psychosocial impact of genetic testing for cardiomyopathies. Standardized psychological instruments including an adapted Multidimensional Impact of Cancer Risk Assessment (aMICRA), Impact of Event Scale (IES), and Satisfaction with Decision (SWD) scales were utilized. Patients with positive genetic test results had higher scores for intrusive thoughts, avoidance, and distress when compared to those with negative genetic test results and were also more likely to make or plan to make life changes because of the results of their genetic testing. Satisfaction with the decision to undergo genetic testing was similar regardless of genetic test results. The results of this study provide insight into the patient experience of genetic testing for cardiomyopathies and how these experiences are associated with genetic test results and cardiac history.

Impact of Receiving Secondary Results from Genomic Research: A 12-Month Longitudinal Study.

The impact of returning secondary results from exome sequencing (ES) on patients/participants is important to understand as ES is increasingly utilized in clinical care and research. Participants were recruited from studies using ES and were separated into two arms: 107 who had ES and were offered the choice to learn secondary results (ES group) and 85 who had not yet had ES (No ES group). Questionnaires were administered at baseline and 1 and 12 months, following results disclosure (ES group) or enrollment (No ES group). While the majority (65%) elected to learn all results following pre-test counseling, it was reduced from the 76% who indicated a desire for all results at baseline. Thirty-seven percent received results associated with an increased personal disease risk. There were no differences in changes in any of the psychological and social measures from baseline to post-results disclosure between the ES and No ES groups. Receiving a wide range of secondary findings appeared to have little measurable impact on most participants. The experience of learning secondary results may be related to participants' previous experiences with genetics, as well as the genetic counseling provided. Future research with a more diverse, genetically naïve group, as well as scalable methods of delivery, is needed.

Dose-finding designs for trials of molecularly targeted agents and immunotherapies.

Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, the adoption of these designs continues to remain low.

Research Participants' Preferences for Hypothetical Secondary Results from Genomic Research.

Secondary or incidental results can be identified in genomic research that increasingly uses whole exome/genome sequencing. Understanding research participants' preferences for secondary results and what influences these decisions is important for patient education, counseling, and consent, and for the development of policies regarding return of secondary results. Two hundred nineteen research participants enrolled in genomic studies were surveyed regarding hypothetical preferences for specific types of secondary results, and these preferences were correlated with demographic information and psychosocial data. The majority of research participants (73%) indicated a preference to learn about all results offered, with no clear pattern regarding which results were not desired by the remaining participants. Participants who reported greater interest in genetic privacy were less likely to indicate a preference to learn all results, as were individuals who self-identified as Jewish. Although most research participants preferred to receive all secondary results offered, a significant subset preferred to exclude some results, suggesting that an all-or-none policy would not be ideal for all participants. The correlations between preferences to receive secondary results, religious identification, and privacy concerns demonstrate the need for culturally sensitive counseling and educational materials accessible to all education levels to allow participants to make the best choices for themselves.

A comparison of prevaginal and postvaginal manipulation fetal fibronectin.

BACKGROUND: Fetal fibronectin (fFN) is used as a biomarker for preterm delivery. Currently, its use is discouraged if there has been vaginal manipulation in the previous 24 hours. OBJECTIVE: Our objective is to determine if there are differences between fFN results before and after vaginal manipulation in the form of sterile vaginal exam or transvaginal ultrasound. STUDY DESIGN: This was a prospective observational cohort study at a single center of women between 22-33 6/7 weeks at risk for preterm delivery due to: (1) a history of preterm delivery, short cervix, or multifetal gestation; or (2) symptoms of preterm labor. We excluded women with vaginal bleeding or infection, placenta previa, ruptured membranes, cervical dilation >3 cm, or any form of vaginal manipulation in the previous 24 hours. Specimen A was collected prior to planned vaginal exam or transvaginal ultrasound and specimen B was collected within 4 hours. The agreement between specimens A and B was assessed using descriptive statistics. Test characteristics of specimens A and B using the outcome of preterm delivery (<37 weeks) were calculated. RESULTS: In all, 310 specimen pairs from 237 women were collected. Specimen A was positive in 37 (12%) instances and negative in 273 (88%) while specimen B was positive in 39 (13%) and negative in 271 (87%). There were discordant results in 26 specimen pairs. Of these, 14 (5%) negative specimen A results subsequently became positive for specimen B, and 12 (32%) positive specimen A results became negative for specimen B. Overall, there was a 92% agreement between specimens A and B (confidence interval, 88-94%). The specificity of specimens A and B for preterm birth was 90% vs 89%, respectively, with a negative predictive value of 87% for both. The false-negative rate was 12.8% for specimen A and 13.3% for specimen B. CONCLUSION: There is a moderately high degree of agreement between prevaginal and postvaginal manipulation fFN results. Their test characteristics for evaluating preterm birth are similar with strong specificity and negative predictive values, and their false-negative rates are not clinically different. Consideration should be made to the utilization of postvaginal manipulation fFN when a prevaginal manipulation specimen is not available.

Sample size considerations for clinical research studies in nuclear cardiology.

Sample size calculation is an important element of research design that investigators need to consider in the planning stage of the study. Funding agencies and research review panels request a power analysis, for example, to determine the minimum number of subjects needed for an experiment to be informative. Calculating the right sample size is crucial to gaining accurate information and ensures that research resources are used efficiently and ethically. The simple question "How many subjects do I need?" does not always have a simple answer. Before calculating the sample size requirements, a researcher must address several aspects, such as purpose of the research (descriptive or comparative), type of samples (one or more groups), and data being collected (continuous or categorical). In this article, we describe some of the most frequent methods for calculating the sample size with examples from nuclear cardiology research, including for t tests, analysis of variance (ANOVA), non-parametric tests, correlation, Chi-squared tests, and survival analysis. For the ease of implementation, several examples are also illustrated via user-friendly free statistical software.

Association of Researcher Characteristics with Views on Return of Incidental Findings from Genomic Research.

Whole exome/ genome sequencing (WES/WGS) is now commonly used in research and is increasingly used in clinical care to identify the genetic basis of rare and unknown diseases. The management of incidental findings (IFs) generated through these analyses is debated within the research community. To examine how views regarding genomic research IFs are associated with researcher characteristics and experiences, we surveyed genetic professionals and assessed the effect of professional background and experience on their opinions. Researchers who did not have clinical training, provide clinical care to research participants, or have prior experience returning research results were in general more inclined to offer return of IFs than their colleagues with these characteristics. Understanding this will be important to fully appreciate the impact that policies on return of genetic IFs could have on participants, researchers, and genomic research.

Outcomes of congenital diaphragmatic hernia in the modern era of management.

OBJECTIVE: To identify clinical factors associated with pulmonary hypertension (PH) and mortality in patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: A prospective cohort of neonates with a diaphragm defect identified at 1 of 7 collaborating medical centers was studied. Echocardiograms were performed at 1 month and 3 months of age and analyzed at a central core by 2 cardiologists independently. Degree of PH and survival were tested for association with clinical variables using Fischer exact test, χ(2), and regression analysis. RESULTS: Two hundred twenty patients met inclusion criteria. Worse PH measured at 1 month of life was associated with higher mortality. Other factors associated with mortality were need for extracorporeal membrane oxygenation, patients inborn at the treating center, and patients with a prenatal diagnosis of CDH. Interestingly, patients with right sided CDH did not have worse outcomes. CONCLUSIONS: Severity of PH is associated with mortality in CDH. Other factors associated with mortality were birth weight, gestational age at birth, inborn status, and need for extracorporeal membrane oxygenation.

Vibration Controlled Transient Elastography to Evaluate Steatosis in Candidate Living Donors for Liver Transplantation.

BACKGROUND: The ability of vibration controlled transient elastography (VCTE) to reliably exclude significant steatosis in living donor candidates could obviate the need for invasive liver biopsies, expedite the donor approval process, and reduce recipient wait time. We therefore aimed to determine whether VCTE controlled attenuation parameter (CAP) could be used to detect steatosis in potential living donors. METHODS: Living donor candidates who presented for evaluation between 2016 and 2019 underwent standard donor workup, VCTE, and liver biopsy if indicated. CAP scores were compared with MRI-Fat Fraction and, when available, histologic fat fraction from liver biopsy. Receiver operating characteristic curves were used to identify cutoffs with appropriate sensitivity and specificity for screening. Statistical analysis was conducted using R (version 3.6.0). RESULTS: Seventy-nine candidate living donors presented during the study period, of whom 71 were included in the final analysis and of whom 20 underwent liver biopsy. There was a positive correlation between MRI-Fat Fraction and CAP scores with an observed Spearman correlation coefficient of 0.424 ( P < 0.01). A CAP score of 271.5 dB/m or less was determined to have 89.8% sensitivity and 75% specificity for detecting <5% steatosis on MRI. The correlation between CAP and steatosis of available histologic samples had a Pearson correlation coefficient of 0.603 ( P = 0.005). A CAP cutoff of 276.0 dB/m demonstrated 66.7% sensitivity and 85.7% specificity for detecting <15% histopathologic steatosis and positive and negative predictive values of 71.5% and 82.7%, respectively. CONCLUSIONS: VCTE can be integrated into living donor evaluation to accurately screen for hepatic steatosis.

Urinary tract infections in children: Testing a novel, noninvasive, point-of-care diagnostic marker.

OBJECTIVES: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) appears highly accurate to identify urinary tract infections (UTIs) when obtained via catheterization. Our primary aim was to determine the agreement in uNGAL levels between paired catheter and bag urine specimens. Our secondary aim was to compare the diagnostic test characteristics of quantitative uNGAL, dipstick uNGAL (a potential point-of-care test), and urinalysis (UA). METHODS: This was a prospective study of febrile children < 24 months evaluated for UTIs. We evaluated quantitative uNGAL at a previously identified threshold of 39.1 ng/mL, dipstick uNGAL at its built-in threshold of >50 ng/mL, and UA at standard thresholds for leukocyte esterase (LE). A positive urine culture was defined as >100,000 CFUs/mL of a pathogen. RESULTS: A total of 211 patients were included (10% with positive urine cultures); 116 had paired catheterized and bagged samples. The agreement between catheterized and bagged samples at a quantitative uNGAL cutoff of ≥39.1 ng/mL was 0.76 (95% confidence interval [CI] = 0.67 to 0.83) and 0.77 (95% CI = 0.68 to 0.84) at a uNGAL dipstick threshold of >50 ng/mL. The area under the receiver operating characteristic curve for uNGAL from a catheterized sample was 0.96 (95% CI = 0.89 to 1.00) compared to 0.93 (95% CI = 0.87 to -0.99) from a bagged sample. The sensitivities of catheterized sample quantitative and dipstick uNGAL (90.5%) were higher than UA at a LE threshold of ≥1+ (57.1%). Bagged-sample uNGAL had lower quantitative and dipstick specificities (both 73.8%) than from catheterized samples (94.3% and 95.3% respectively), similar to UA. CONCLUSIONS: uNGAL from bagged and catheterized samples showed insufficient agreement to be used interchangeably. The low specificity of uNGAL from bagged samples suggests that sampling technique affects uNGAL levels.

Foveolar thickness as potential standardized structural outcome measurement in studies of Bietti crystalline dystrophy.

Bietti crystalline dystrophy (BCD) is an ultra-rare orphan disorder that can lead to blindness. Because of the variable rates of progression of the disease, it is necessary to identify suitable outcome measurements for tracking progression in BCD. A retrospective analysis of patients with a clinical and genetic diagnosis of BCD was conducted. Four measurements of spectral domain-optical coherence tomography were compared to patients' best corrected visual acuity. We observed that patients with higher measurements of foveolar thickness, choroidal thickness in the foveolar region, ellipsoid zone band length and the outer nuclear layer + area, had on average better visual acuity. Future studies are needed to validate the structural-functional correlations we observed in BCD and to propose a sensitive and clinically meaningful outcome measurement for tracking this rare, variable disease.