Citations

AbstractDual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien‐Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1‐year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1‐ (P = .004) and 2‐years post‐transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5‐3.3, P = .58) or graft (HR 1.1, 95% CI .5‐2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard.

Purpose:Voice disorders are best assessed by examining vocal fold dynamics in connected speech. This can be achieved using flexible laryngeal high-speed videoendoscopy (HSV), which enables us to study vocal fold mechanics with high temporal details. Analysis of vocal fold vibration using HSV requires accurate segmentation of the vocal fold edges. This article presents an automated deep-learning scheme to segment the glottal area in HSV from which the glottal edges are derived during connected speech.Method:Using a custom-built HSV system, data were obtained from a vocally healthy participant reciting the “Rainbow Passage.” A deep neural network was designed for glottal area segmentation in the HSV data. A recently introduced hybrid approach by the authors was utilized as an automated labeling tool to train the network on a set of HSV frames, where the glottis region was automatically annotated during vocal fold vibrations. The network was then tested against manually segmented frames using different metrics, intersection over union (IoU), and Boundary F1 (BF) score, and its performance was assessed on various phonatory events on the HSV sequence.Results:The designed network was successfully trained using the hybrid approach, without the need for manual labeling, and tested on the manually labeled data. The performance metrics showed a mean IoU of 0.82 and a mean BF score of 0.96. In addition, the evaluation assessment of the network's performance demonstrated an accurate segmentation of the glottal edges/area even during complex nonstationary phonatory events and when vocal folds were not vibrating, thus overcoming the limitations of the previous hybrid approach that could only be applied to the vibrating vocal folds.Conclusions:The introduced automated scheme guarantees accurate glottis representation in challenging color HSV data with lower image quality and excessive laryngeal maneuvers during all instances of connected speech. This facilitates the future development of HSV-based measures to assess the running vibratory characteristics of the vocal folds in speakers with and without voice disorder.Supplemental Material:https://doi.org/10.23641/asha.19798864

Abstract Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi‐institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty‐two patients were identified with median age of 11 years. Thirty‐three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety‐one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty‐six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow‐up time was 36 months. Overall 5‐year survival was 95% and 5‐year event‐free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

Abstract Introduction End‐of‐life care differs by serious illness diagnosis. Cancer and dementia are serious illnesses that have been associated with less intensive end‐of‐life health care use. It is not known how health care utilization varies in the presence of >1 serious illness. Methods We used the Rochester Epidemiology Project to identify persons living in a midwestern area who died on July 1, 2017–June 30, 2018 at age ≥65 years, and were seriously ill. We examined the number of emergency department (ED), hospital, and intensive care unit (ICU) stays in the last 6 months and the last 30 days of life. We used Poisson regression to determine the incidence rate ratio for ED, hospital, and ICU stay in the last 6 months and 30 days of life by number of serious illness diagnoses. For cancer and dementia, we examined the effect of an additional serious illness. Results We included a population of 1372 adults who were, on average, 84 years, 52% female, and 96% white. Approximately 41% had multiple serious illnesses. Compared to older adults with 1 serious illness diagnosis, rates of hospitalization, and ICU stay for adults with 2 or ≥3 serious illness diagnoses were at least 1.5 times higher in the last 6 months and the last 30 days of life. Rates of ED visits were significantly higher for older adults with 2 or ≥3 serious illness diagnoses in the last 6 months of life, but only higher for those with ≥3 versus 1 serious illness diagnosis in the last 30 days of life. For both cancer and dementia, rates of ED visits, hospitalization and ICU stay were lower for the condition alone than when an additional serious illness diagnosis was present. Conclusion Having multiple serious illnesses increases the risk of health care utilization at the end of life.

Abstract The pre‐mRNA‐processing factor 8, encoded by PRPF8, is a scaffolding component of a spliceosome complex involved in the removal of introns from mRNA precursors. Previously, heterozygous pathogenic variants in PRPF8 have been associated with autosomal dominant retinitis pigmentosa. More recently, PRPF8 was suggested as a candidate gene for autism spectrum disorder due to the enrichment of sequence variants in this gene in individuals with neurodevelopmental disorders. We report 14 individuals with various forms of neurodevelopmental conditions, found to have heterozygous, predominantly de novo, missense, and loss‐of‐function variants in PRPF8 . These individuals have clinical features that may represent a new neurodevelopmental syndrome.

Adductor spasmodic dysphonia (AdSD) is a neurological voice disorder, which affects the control of intrinsic muscles of the larynx during speech. Our previous research has shown that high-speed videoendoscopy (HSV) can be used to measure the glottal attack time for patients with AdSD during connected speech. This study builds upon that to analyze the acoustic signal during the phonation onset and prephonatory adjustments. The phonation onset events are quantified using the HSV data that were obtained simultaneously with the acoustic data. We analyze the power and energy waveform of the acoustic signal during vocal folds’ first contact, first oscillation, and transitory behaviors, extracted from high-temporal resolution HSV data. The data were obtained from five patients with AdSD and five vocally normal participants. The data were recorded while the participant produced: 2 productions of vowel /i/ at habitual pitch and loudness, 2 with a soft glottal attack and 2 with a hard glottal attack, six CAPE-V sentences, and the “Rainbow Passage.” The HSV system included a monochrome high-speed camera coupled with a flexible nasolaryngoscope. The results of this study could assist for more accurate clinical management of adductor spasmodic dysphonia.

Abstract Background The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2– or 3–degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. Results The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2–degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P &lt; 1.2 × 10−4). Conclusion Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

ABSTRACT Introduction Covid-19 has helped drive all forms of medicine away from traditional brick and mortar medical interactions. Given the availability of online services to obtain treatments for ED, we developed a website to facilitate patient education, triage and men's health appointment scheduling. Objective We sought to assess characteristics of men who utilized a novel website to treat their ED. Methods We report on 50 patients who ultimately booked and attended appointments (video or in person) for erectile dysfunction. Patients found our website through our institution's main informational ED pages or through youtube links from our men's health video playlist library. Patients create an institutional account and are then asked a series of MD created questions designed to streamline patient triage and complete the majority of chart documentation ahead of the appointment. Patients are then sent videos relevant to their condition and future appointment options. Results 2300 users investigated the ED portion of the website with 1.8% of patients ultimately following through with an appointment. 13% of patients who explored the ED portion of the site created a user account that allows a questionnaire to be taken. 90% of men who began the ED questionnaire completed with a mean time of 11 minutes. 52% of men offered an appointment based on their responses completed the patient scheduling form. 71% of traffic was on mobile devices with 29% on desktop/tablet. Site use by time of day is shown in figure 1. Mean age of patients was 53. 92% of patients had ED that occurred &gt; 6 months. Mean SHIM score was 8.2 (IQR 4-12). 80% of participants had both desire and opportunity for sexual activity, 20% did not meet both criteria and thus SHIM scores were less valid for these men. Of the users 28% had never tried pde5s, 32% had partial success with pde5s, 24% could not tolerate or afford pde5s and 42% had unsatisfactory results with pde5s. PDE5 naïve patients were seen by an internal medicine MD specializing in men's health, 10 were seen by surgeons as they requested IPPs and the rest were seen by a combination of men's health APPS and urology attendings for second line treatments and penile doppler. Interestingly, 66% of men were interested in undergoing penile doppler to better understand the etiology of their ED. Hypertension (40%) and diabetes (22%) were the most common medical comorbidities. 36% of the cohort had a strong family history of cardiac disease. Conclusions Men with ED can be effectively triaged through a website application. Most men with pde5 refractory ED wish to pursue penile doppler. The majority of patients seen had watched educational video material ahead of time, facilitating a more sophisticated and streamlined patient interaction. Disclosure No

Abstract Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (&gt;28 g/day) with light-to-moderate drinkers (1–28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 &gt; 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose–response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06–1.17; OR for AA genotype = 1.22; 95% CI, 1.14–1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.