6-Thioguanine nucleotide levels are associated with infliximab but not adalimumab levels in inflammatory bowel disease patients on combination therapy.

BACKGROUND: Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). AIMS: We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy. METHODS: We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels. RESULTS: The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. CONCLUSION: 6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.

Noninvasive multi-cancer detection using blood-based cell-free microRNAs.

Patients diagnosed with early-stage cancers have a substantially higher chance of survival than those with late-stage diseases. However, the option for early cancer screening is limited, with most cancer types lacking an effective screening tool. Here we report a miRNA-based blood test for multi-cancer early detection based on examination of serum microRNA microarray data from cancer patients and controls. First, a large multi-cancer training set that included 1,408 patients across 7 cancer types and 1,408 age- and gender-matched non-cancer controls was used to develop a 4-microRNA diagnostic model using 10-fold cross-validation. In three independent validation sets comprising a total of 4,875 cancer patients across 13 cancer types and 3,722 non-cancer participants, the 4-microRNA model achieved greater than 90% sensitivity for 9 cancer types (lung, biliary tract, bladder, colorectal, esophageal, gastric, glioma, pancreatic, and prostate cancers) and 75-84% sensitivity for 3 cancer types (sarcoma, liver, and ovarian cancer), while maintaining greater than 99% specificity. The sensitivity remained to be > 99% for patients with stage 1 lung cancer. Our study provided novel evidence to support the development of an inexpensive and accurate miRNA-based blood test for multi-cancer early detection.

Designed endocytosis-inducing proteins degrade targets and amplify signals.

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras1,2 (LYTACs) and cytokine receptor-targeting chimeras3 (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor. Here we describe computational design approaches for endocytosis-triggering binding proteins (EndoTags) that overcome these challenges. We present EndoTags for insulin-like growth factor 2 receptor (IGF2R) and asialoglycoprotein receptor (ASGPR), sortilin and transferrin receptors, and show that fusing these tags to soluble or transmembrane target protein binders leads to lysosomal trafficking and target degradation. As these receptors have different tissue distributions, the different EndoTags could enable targeting of degradation to different tissues. EndoTag fusion to a PD-L1 antibody considerably increases efficacy in a mouse tumour model compared to antibody alone. The modularity and genetic encodability of EndoTags enables AND gate control for higher-specificity targeted degradation, and the localized secretion of degraders from engineered cells. By promoting endocytosis, EndoTag fusion increases signalling through an engineered ligand-receptor system by nearly 100-fold. EndoTags have considerable therapeutic potential as targeted degradation inducers, signalling activators for endocytosis-dependent pathways, and cellular uptake inducers for targeted antibody-drug and antibody-RNA conjugates.

Single-cell sensor analyses reveal signaling programs enabling Ras-G12C drug resistance.

Clinical resistance to rat sarcoma virus (Ras)-G12C inhibitors is a challenge. A subpopulation of cancer cells has been shown to undergo genomic and transcriptional alterations to facilitate drug resistance but the immediate adaptive effects on Ras signaling in response to these drugs at the single-cell level is not well understood. Here, we used Ras biosensors to profile the activity and signaling environment of endogenous Ras at the single-cell level. We found that a subpopulation of KRas-G12C cells treated with Ras-G12C-guanosine-diphosphate inhibitors underwent adaptive signaling and metabolic changes driven by wild-type Ras at the Golgi and mutant KRas at the mitochondria, respectively. Our Ras biosensors identified major vault protein as a mediator of Ras activation through its scaffolding of Ras signaling pathway components and metabolite channels. Overall, methods including ours that facilitate direct analysis on the single-cell level can report the adaptations that subpopulations of cells adopt in response to cancer therapies, thus providing insight into drug resistance.

The impact of high-order features on performance of radiomics studies in CT non-small cell lung cancer.

High-order radiomic features have been shown to produce high performance models in a variety of scenarios. However, models trained without high-order features have shown similar performance, raising the question of whether high-order features are worth including given their increased computational burden. This comparative study investigates the impact of high-order features on model performance in CT-based Non-Small Cell Lung Cancer (NSCLC) and the potential uncertainty regarding their application in machine learning. Three categories of features were retrospectively retrieved from CT images of 347 NSCLC patients: first- and second-order statistical features, morphological features and transform (high-order) features. From these, three datasets were constructed: a "low-order" dataset (Lo) which included the first-order, second-order, and morphological features, a high-order dataset (Hi), and a combined dataset (Combo). A diverse selection of datasets, feature selection methods, and predictive models were included for the uncertainty analysis, with two-year survival as the study endpoint. AUC values were calculated for comparisons and Kruskal-Wallis testing was performed to determine significant differences. The Hi (AUC: 0.41-0.62) and Combo (AUC: 0.41-0.62) datasets generate significantly (P < 0.01) higher model performance than the Lo dataset (AUC: 0.42-0.58). High-order features are selected more often than low-order features for model training, comprising 87 % of selected features in the Combo dataset. High-order features are a source of data that can improve machine learning model performance. However, its impact strongly depends on various factors that may lead to inconsistent results. A clear approach to incorporate high-order features in radiomic studies requires further investigation.

A Screening Strategy to Mitigate Vision Impairment by Engaging Adults Who Underuse Eye Care Services.

Importance: Underuse of eye care services leads to underdiagnosed and undertreated eye disease. Objective: To assess the reasons for underuse of eye care and whether a novel, free eye disease screening program is engaging adults who are both at high risk of eye disease and were underusing eye care services. Design, Setting, and Participants: In a population-based cross-sectional study, adult participants from the first year of the Michigan Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (MI-SIGHT) Program were included. The participants were recruited from primary care clinics serving 2 low-income communities. Recruitment occurred between June 28, 2020 and June 27, 2021 at the free clinic, and between January 27, 2021 and January 26, 2022 at a federally qualified health clinic. Data were analyzed from December 7, 2022, to May 29, 2024. Participants received comprehensive eye disease screening and completed surveys assessing health and prior eye care use. Risk factors for eye disease included age 65 years and older, diabetes, personal or family history of eye disease, and self-identifying as Black or African American individuals who were aged 50 years or older. Underuse of eye care was defined as no eye examination in 2 or more years. Main Outcomes and Measures: Percentage of participants who were at high risk of eye disease and underused eye care services before accessing this program. Results: A total of 1171 MI-SIGHT participants were a mean (SD) age of 55 (14.5) years; 437 (38%) identified as male; 591 (54%) self-identified as Black or African American, 101 (10%) as Hispanic or Latino, and 371 (34%) as White; 492 (43%) had high school education or less, and 696 (70%) reported an annual household income of less than $30 000. Characteristics of participants reporting not having had an eye examination in 2 years or more included 23% (n = 151) of participants 65 years and over, 33% (n = 214) of participants who self-reported diabetes, 25% (n = 130) of participants reporting a family history of glaucoma, 3% (n = 14) of those with self-reported glaucoma; and 33% (n = 202) of Black or African-American participants aged 50 years and older. In participants who reported not having had an eye examination in 2 or more years, 21% (n = 137) screened positive for glaucoma, 20% (n = 129) for cataract, 6% (n = 38) for diabetic retinopathy, and 1% (n = 9) for age-related macular degeneration. Reported reasons for why participants had not had an eye examination included no insurance (175 of 627 [28%]), no reason to go (no problem) (135 of 627 [22%]), and cost of eye examination (101 of 627 [16%]). Conclusions and Relevance: The findings of this study suggest that placing eye disease detection programs in primary care clinics in underserved areas may improve eye disease detection and treatment, possibly mitigating needless vision loss in the US.

Thoracic Intervertebral Disc Herniation Associated With Chronic Anabolic Androgenic Steroid Use: A Case Report.

Anabolic androgenic steroids (AAS) are relatively cheap and accessible medications, commonly used by athletes and bodybuilders for performance enhancement and muscle growth stimulation. AAS usage has been associated with musculoskeletal injuries, such as tendon and ligament ruptures, and numerous other detrimental health effects. Despite these risks, individuals continue to self-administer these drugs in supraphysiologic doses. Here, we present a case of a male bodybuilder with chronic AAS use who developed a spinal thoracic intervertebral disc herniation requiring decompression and fusion. We use this case to highlight a severe potential risk associated with chronic AAS abuse and review the current literature on the biochemical, physical, and physiologic mechanisms linking chronic AAS use, weight-bearing exercise, and the risk of musculoskeletal injuries such as intervertebral disc herniations.

The impact of a multidisciplinary intervention to reduce severe retinopathy of prematurity in Kampala, Uganda.

BACKGROUND: To address the threat of retinopathy of prematurity (ROP) in Sub-Saharan Africa (SSA), the Stop Infant Blindness in Africa (SIBA) project introduced a comprehensive program, including subspecialty training and oxygen management equipment. METHODS: A before-and-after retrospective cohort study compared preterm infants < 1750 g or < 34 weeks' gestation before (2022) and after (2023) program implementation. Outcomes included: the proportion with severe ROP, the proportion with Zone III vascularization on first examination, and factors associated with severe ROP. RESULTS: Overall, 140 infants were screened before and 122 after program implementation. The proportion with Zone III vascularization increased from 16.1% (N = 11) pre-intervention to 44.9% (N = 32) post-intervention (p = 0.001). The proportion with severe ROP decreased from 27.8% (N = 19) to 12.8% (N = 9, p = 0.03). Factors predicting severe ROP on adjusted analyses were gestational age and blood transfusion. CONCLUSION: In SSA, introduction of a comprehensive program to prevent and treat ROP can decrease the risk of severe ROP.

A 5' UTR Language Model for Decoding Untranslated Regions of mRNA and Function Predictions.

The 5' UTR, a regulatory region at the beginning of an mRNA molecule, plays a crucial role in regulating the translation process and impacts the protein expression level. Language models have showcased their effectiveness in decoding the functions of protein and genome sequences. Here, we introduced a language model for 5' UTR, which we refer to as the UTR-LM. The UTR-LM is pre-trained on endogenous 5' UTRs from multiple species and is further augmented with supervised information including secondary structure and minimum free energy. We fine-tuned the UTR-LM in a variety of downstream tasks. The model outperformed the best known benchmark by up to 5% for predicting the Mean Ribosome Loading, and by up to 8% for predicting the Translation Efficiency and the mRNA Expression Level. The model also applies to identifying unannotated Internal Ribosome Entry Sites within the untranslated region and improves the AUPR from 0.37 to 0.52 compared to the best baseline. Further, we designed a library of 211 novel 5' UTRs with high predicted values of translation efficiency and evaluated them via a wet-lab assay. Experiment results confirmed that our top designs achieved a 32.5% increase in protein production level relative to well-established 5' UTR optimized for therapeutics.

Computational design of non-porous pH-responsive antibody nanoparticles.

Programming protein nanomaterials to respond to changes in environmental conditions is a current challenge for protein design and is important for targeted delivery of biologics. Here we describe the design of octahedral non-porous nanoparticles with a targeting antibody on the two-fold symmetry axis, a designed trimer programmed to disassemble below a tunable pH transition point on the three-fold axis, and a designed tetramer on the four-fold symmetry axis. Designed non-covalent interfaces guide cooperative nanoparticle assembly from independently purified components, and a cryo-EM density map closely matches the computational design model. The designed nanoparticles can package protein and nucleic acid payloads, are endocytosed following antibody-mediated targeting of cell surface receptors, and undergo tunable pH-dependent disassembly at pH values ranging between 5.9 and 6.7. The ability to incorporate almost any antibody into a non-porous pH-dependent nanoparticle opens up new routes to antibody-directed targeted delivery.

The substantial burden of iatrogenic vascular injury on the vascular surgery workforce at an academic medical center.

OBJECTIVE: Vascular surgeons are often called upon to provide emergent surgical assistance to other specialties for iatrogenic complications, both intraoperatively and in the inpatient setting. The management of iatrogenic vascular injury remains a critical role of the vascular surgeon, especially in the context of the increasing adoption of percutaneous procedures by other specialties. This study aims to characterize consultation timing, management, and outcomes for iatrogenic vascular injuries. METHODS: This study identified patients for whom vascular surgery was consulted for iatrogenic vascular complications from February 1, 2022, to May 12, 2023. Patient information, including demographic information, injury details, and details of any operative intervention, was retrospectively collected from February 1, 2022, to October 13, 2022, and prospectively collected for the remainder of the study period. Analyses were performed with R (version 2022.02.03). RESULTS: There were 87 patients with consultations related to iatrogenic vascular injury. Of these, 42 (46%) were female and the mean age was 59 years (±18 years). The most common consulting services were cardiology (32%), cardiothoracic surgery (26%), general surgery (8%), and neurointerventional radiology (10%). Reasons for consultation included hemorrhage (36%), limb ischemia (36%), and treatment of pseudoaneurysm (23%). A total of 24% of consults were intraoperative, 20% of consults related to extracorporeal membrane oxygenation cannulation, and 16% of consults related to ventricular assist devices including left ventricular assist device and intra-aortic balloon pump. The majority of these consult requests (60%) occurred during evening and night hours (5 PM to 7 AM). Emergent intervention was required in 62% of cases and consisted of primary open surgical repair of arterial injury (54%), endovascular intervention (21%), and open thromboembolectomy (15%). Overall, in-hospital mortality for the patient cohort was 20% and the reintervention rate was 23%, reflecting the underlying complexity of the illness and nature of the vascular injury in this patient group. CONCLUSIONS: Vascular surgeons play an essential role in managing emergent life-threatening hemorrhagic and ischemic iatrogenic vascular complications in the hospitalized setting. The complications require immediate bedside or intraoperative consult and often emergent open surgical or endovascular intervention. Furthermore, many of these require urgent management in the evening or overnight hours, and therefore the high frequency of these events represents a potential significant resource utilization and workforce issue to the vascular surgery workforce.

Strategies for improving the performance of prediction models for response to immune checkpoint blockade therapy in cancer.

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valuable to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning methods to predict a patient's response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is challenging to develop well-performed gene expression signatures. In this study, we used several published melanoma datasets and investigated approaches that can improve the construction of gene expression-based prediction models. We found that merging datasets from multiple studies and incorporating prior biological knowledge yielded prediction models with higher predictive accuracies. Our finding suggests that these two strategies are of high value to identify ICB response biomarkers in future studies.

The natural history of celiac artery aneurysms.

OBJECTIVES: The goal of this study was to document the natural history of celiac artery aneurysms (CAAs). BACKGROUND: Celiac artery aneurysms are rare. Existing literature is skewed towards outcomes after intervention of large, symptomatic aneurysms but the behavior of untreated CAAs is poorly understood. METHODS: This is a single institution, retrospective analysis of patients with CAA diagnosed by CT imaging (2015-2019) identified through an institutional radiology database. Radiologic, demographic, and follow-up data were analyzed. The primary endpoint was the mean growth rate of CAAs. RESULTS: Of the 76 patients included, 86.8% were men with a mean age at presentation of 69.8 years. The mean CAA diameter on index imaging was 15.4 +/- 3.8 mm (range, 7-30 mm). All were classified as true aneurysms and 76.3% were saccular. All patients had clinical follow-up with mean follow-up 31.2 months +/- 21.6 months. No patient developed symptoms or rupture. The mean radiological follow-up among 45 patients was 25.2 +/- 16.8 months. Over this period, 16 CAAs (35.6%) enlarged, while 29 (64.4%) remained stable. One patient (1.3%) underwent intervention for increasing size in the setting of a chronic dissection. On multivariate analysis, age <70 was significantly associated with increased risk of aneurysm growth. CONCLUSIONS: In this institutional review of patients with CAAs, the majority of aneurysms remained stable in size, with no patients developing symptoms or rupture over clinical follow-up. Given the observed benign behavior of these aneurysms, guidelines that suggest conservative management of CAAs less than 2 cm seems appropriate.

Antidepressant Dispensing to US Adolescents and Young Adults: 2016-2022.

BACKGROUND: Mental health worsened in adolescents and young adults after the coronavirus disease 2019 (COVID-19) outbreak in March 2020, but whether antidepressant dispensing to this population changed is unknown. METHODS: We identified antidepressant prescriptions dispensed to US individuals aged 12 to 25 years from 2016 to 2022 using the IQVIA Longitudinal Prescription Database, an all-payer national database. The outcome was the monthly antidepressant dispensing rate, defined as the monthly number of individuals with ≥1 dispensed antidepressant prescription per 100 000 people. We fitted linear segmented regression models assessing for level or slope changes during March 2020 and conducted subgroup analyses by sex and age group. RESULTS: Between January 2016 and December 2022, the monthly antidepressant dispensing rate increased 66.3%, from 2575.9 to 4284.8. Before March 2020, this rate increased by 17.0 per month (95% confidence interval: 15.2 to 18.8). The COVID-19 outbreak was not associated with a level change but was associated with a slope increase of 10.8 per month (95% confidence interval: 4.9 to 16.7). The monthly antidepressant dispensing rate increased 63.5% faster from March 2020 onwards compared with beforehand. In subgroup analyses, this rate increased 129.6% and 56.5% faster from March 2020 onwards compared with beforehand among females aged 12 to 17 years and 18 to 25 years, respectively. In contrast, the outbreak was associated with a level decrease among males aged 12 to 17 years and was not associated with a level or slope change among males aged 18 to 25 years. CONCLUSIONS: Antidepressant dispensing to adolescents and young adults was rising before the COVID-19 outbreak and rose 63.5% faster afterward. This change was driven by increased antidepressant dispensing to females and occurred despite decreased dispensing to male adolescents.

ASSOCIATION OF METFORMIN USE WITH RISK OF NEWLY ONSET NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEVELOPMENT.

PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD). METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed. RESULTS: Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g. CONCLUSION: Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.

Association of Contrast Sensitivity With Eye Disease and Vision-Related Quality of Life.

PURPOSE: To investigate contrast sensitivity (CS) as a screening tool to detect eye disease and assess its association with both eye disease and vision-related quality of life. DESIGN: Cross-sectional study. METHODS: Setting and population: Adults receiving care from a free clinic and a Federally Qualified Health Center in Michigan. MAIN OUTCOME MEASURES: Screening positive for eye disease and Visual Function Questionnaire (VFQ) score. OBSERVATION: Participants received a vision exam reviewed via telemedicine for disease, completed a demographic survey, and the 9-item VFQ. The ability of CS to predict eye disease was explored and area under the curve (AUC) is reported. Logistic and linear regression were used to investigate the continuous effect of CS on the probability of screening positive for eye disease and VFQ score, respectively, adjusting for age and visual acuity. RESULTS: 1159 included participants were, on average, 54.9 ± 14.5 years old, 62% identified as female, 34% as White, 54% as Black, 10% as Hispanic/Latino, and reported mean VFQ score of 79.7 ± 15.3. CS ranged from 0.00 to 1.95 log units (mean = 1.54 ± 0.24), 21% of eyes had glaucoma, 19% cataract, 6% DR, and 2% AMD. AUCs were 0.53 to 0.73. A 0.3 log unit decrease in better eye CS was associated with increased odds of glaucoma (odds ratio [OR] = 1.35, confidence interval [CI] = 1.09-1.67), cataract (OR = 1.35, CI = 1.05-1.72), DR (OR = 2.05, CI = 1.51-2.77), and AMD (OR = 2.08, CI = 1.10-3.91). A 0.3 log unit increase in better eye CS was associated with a 5.9 unit increase in VFQ. CONCLUSION: While CS alone is not sufficient to identify people with eye disease, it is an important measure of visual function that can add value to comprehensive eye screening.

Computationally designed sensors detect endogenous Ras activity and signaling effectors at subcellular resolution.

The utility of genetically encoded biosensors for sensing the activity of signaling proteins has been hampered by a lack of strategies for matching sensor sensitivity to the physiological concentration range of the target. Here we used computational protein design to generate intracellular sensors of Ras activity (LOCKR-based Sensor for Ras activity (Ras-LOCKR-S)) and proximity labelers of the Ras signaling environment (LOCKR-based, Ras activity-dependent Proximity Labeler (Ras-LOCKR-PL)). These tools allow the detection of endogenous Ras activity and labeling of the surrounding environment at subcellular resolution. Using these sensors in human cancer cell lines, we identified Ras-interacting proteins in oncogenic EML4-Alk granules and found that Src-Associated in Mitosis 68-kDa (SAM68) protein specifically enhances Ras activity in the granules. The ability to subcellularly localize endogenous Ras activity should deepen our understanding of Ras function in health and disease and may suggest potential therapeutic strategies.

A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization.

Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin & eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes. A Kidney Donor Quality Score (KDQS) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. The performance on wedge biopsies was additionally evaluated. Our model identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis; 90% of tubules. Whole-slide features of Sclerotic Glomeruli (GS)%, Arterial Intimal Fibrosis (AIF)%, and Interstitial Space Abnormality (ISA)% demonstrated strong correlations with corresponding pathologists' scores of all 2431 kidneys, but had superior associations with post-transplant estimated glomerular filtration rates in 2033 and graft loss in 1560 kidneys. The combination of KDQS and other factors predicted one- and four-year graft loss in a discovery set of 520 kidneys and a validation set of 1040 kidneys. By using the composite KDQS of 398 discarded kidneys due to "biopsy findings", we suggest that if transplanted, 110 discarded kidneys could have had similar survival to that of other transplanted kidneys. Thus, our composite KDQS and survival prediction models may facilitate risk stratification and organ utilization while potentially reducing unnecessary organ discard.

Visual Impairment from Uncorrected Refractive Error among Participants in a Novel Program to Improve Eye Care Access among Low-Income Adults in Michigan.

PURPOSE: To assess the rate of visual impairment (VI) from uncorrected refractive error (URE) and associations with demographic and socioeconomic factors among low-income patients presenting to the Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT) program. DESIGN: Cross-sectional study. PARTICIPANTS: Adults ≥ 18 years without acute ocular symptoms. METHODS: MI-SIGHT program participants received a telemedicine-based eye disease screening and ordered glasses through an online optical store. Participants were categorized based on refractive error (RE) status: VI from URE (presenting visual acuity [PVA], ≤ 20/50; best-corrected visual acuity [BCVA], ≥ 20/40), URE without VI (PVA, ≥ 20/40; ≥ 2-line improvement to BCVA), and no or adequately corrected RE (PVA, ≥ 20/40; < 2-line improvement to BCVA). Patient demographics, self-reported visual function, and satisfaction with glasses obtained through the program were compared among groups using analysis of variance, Kruskal-Wallis, chi-square, and Fisher exact testing. MAIN OUTCOME MEASURES: PVA, BCVA, and presence of VI (defined as PVA ≤ 20/50). RESULTS: Of 1171 participants enrolled in the MI-SIGHT program during the first year, average age was 55.1 years (SD = 14.5), 37.7% were male, 54.1% identified as Black, and 1166 (99.6%) had both PVA and BCVA measured. VI was observed in 120 participants (10.3%); 96 had VI from URE (8.2%), 168 participants (14.4%) had URE without VI, and 878 (75.3%) had no or adequately corrected RE. A smaller percentage of participants with VI resulting from URE reported having a college degree, and a larger percentage reported income < $10 000 compared with participants with no or adequately corrected RE (3.2% vs. 14.2% [P = 0.02]; 45.5% vs. 21.6% [P < 0.0001], respectively). Visual function was lowest among participants with VI from URE, followed by those with URE without VI, and then those with no or adequately corrected RE (9-item National Eye Institute Visual Function Questionnaire composite score, 67.3 ± 19.6 vs. 77.0 ± 14.4 vs. 82.2 ± 13.3, respectively; P < 0.0001). In total, 71.2% (n = 830) ordered glasses for an average cost of $36.80 ± $32.60; 97.7% were satisfied with their glasses. CONCLUSIONS: URE was the main cause of VI at 2 clinics serving low-income communities and was associated with reduced vision-related quality of life. An online optical store with lower prices made eyeglasses accessible to low-income patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Techniques and Preferences for Nonvalved Aqueous Shunts: A Survey of American Glaucoma Society Members.

PURPOSE: To assess practice patterns and opinions of glaucoma specialists regarding indications, surgical technique, and postoperative management for nonvalved aqueous shunts. DESIGN: Anonymous online survey study. PARTICIPANTS: American Glaucoma Society (AGS) members. METHODS: An anonymous online survey was distributed to glaucoma specialists via the AGS forum from June to August 2022. MAIN OUTCOME MEASURES: Survey questions and responses were assessed in 4 sections: (1) general demographics and practice patterns; (2) nonvalved tubes vs. trabeculectomy; (3) nonvalved tubes vs. valved tubes; and (4) nonvalved tube techniques. RESULTS: There were 132 respondents; nonvalved tubes were reported to be performed more often than trabeculectomy by 61% of respondents within 5 years of completing training and 23% of respondents with more than 15 years since completing training. The most frequently preferred types of nonvalved tubes were Baerveldt-350 (41%), Baerveldt-250 (27%), and ClearPath-250 (18%). In patients with lower target intraocular pressure (IOP), 92% of respondents preferred trabeculectomy over nonvalved tube; 33% cited a cutoff of < 12 mmHg, and 31% cited a cutoff of < 15 mmHg. In patients with higher preoperative IOP, 50% of respondents preferred valved over nonvalved tubes; 29% cited a cutoff of > 40 mmHg, and 38% cited a cutoff of > 30 mmHg. The most frequently used ligature was 7-0 Vicryl (69%). The most frequently used strategies for early IOP lowering were fenestrations without wicks (70%) and with wicks (22%), with one 10-0 Nylon being the most used wick technique (22%). Overall, 37% of respondents use a ripcord; among ripcord users, 55% use it for hypotony prevention (3-0 Prolene most common for this purpose at 35%), and 40% use it for optional early IOP lowering (4-0 Nylon most common for this purpose at 21%). If IOP is too high at postoperative week 4, 38% of respondents do not open the tube early. CONCLUSIONS: We demonstrate significant heterogeneity regarding specific indications, surgical technique, and postoperative management for nonvalved tubes. Future work is needed to identify and develop standardized guidelines alongside best practices. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.