FACTORS ASSOCIATED WITH DELAYED DIAGNOSIS IN PATIENTS WITH PRIMARY VITREORETINAL LYMPHOMA.

PURPOSE: To identify demographic and clinical factors associated with delayed diagnosis in patients with primary vitreoretinal lymphoma (VRL). METHODS: Retrospective, tertiary referral center-based cohort study of all patients at Mayo Clinic in Rochester, Minnesota, with a biopsy-proven diagnosis of VRL from January 1, 2000, to October 31, 2022. RESULTS: There were 87 patients included during the 22-year study period with 73 patients (83.9%) diagnosed with VRL upon initial evaluation at the tertiary center, with the other 14 patients (16.1%) diagnosed later. The median referral time was 4.8 months (range: 0-113 months). Patients who received an initial diagnosis of inflammatory uveitis or another incorrect diagnosis elsewhere were referred slower than those initially diagnosed with VRL (P = 0.04). The most common incorrect initial diagnosis from an outside institution was inflammatory uveitis (n = 35, 40.2%). When patients were split into four groups based on referral time, prior use of corticosteroids was associated with a significant delay in referral (P = 0.03). CONCLUSION: Diagnosing VRL continues to be challenging, as months-long delays from initial evaluation to expert referral center evaluation are common. Prior use of corticosteroids was associated with delay in diagnosis and referral time, underscoring the need to increase awareness regarding differences between VRL and uveitis.

Population-Based Incidence and Clinical Characteristics of Ocular Adnexal Tumors in Olmsted County, Minnesota.

PURPOSE: To determine the incidence and clinical characteristics of ocular adnexaltumors in Olmsted County, Minnesota. METHODS: Retrospective population-based cohort study of all patients residing in Olmsted County, Minnesota diagnosed with any ocular tumor from January 1, 2006, to December 31, 2015. The medical records of all patients with an incident diagnosis of any ocular adnexal tumor were reviewed using the Rochester Epidemiology Project medical record linkage system for patient demographics, tumor type, and histopathologic confirmation. Incidence rates were calculated per 100,000 person-years. Poisson regression analysis was used to analyze changes in incidence over time. RESULTS: There were 717 patients diagnosed with ocular adnexal tumors during the 10-year study period, yielding an age- and sex-adjusted incidence rate of 59.7 per 100,000 (95% CI 55.4 to 64.0, p < 0.05) per year. In total, 764 tumors were diagnosed. Most tumors were eyelid lesions (N = 756, 99.0%), which were mostly benign (N = 512, 67.8%) with epidermal inclusion cysts (N = 275, 36.0%), hidrocystoma (N = 70, 9.2%), and eyelid sebaceous cysts (N = 46, 6.1%) accounting for the majority. Malignant eyelid lesions (N = 244, 31.9%) were relatively common with basal cell carcinoma (N = 184, 24.1%) and squamous cell carcinoma (N = 49, 6.4%) having the highest frequencies. Orbital tumors (N = 8, 1.0%) were infrequent. Of the orbital tumors, the most common was lacrimal gland adenoidcystic carcinoma (N = 2, 25.0%). CONCLUSIONS: In a population-based setting, most ocular adnexal tumors were benign eyelid lesions. Understanding the epidemiology of ocular adnexal tumors is important to aid providers in diagnosing and facilitating appropriate referrals of potentially vision- and life-threatening malignancies.

Vascular Postoperative Changes After Facial Flap Repairs: An Opportunity for Early Intervention.

BACKGROUND: Flap repair provides unique advantages in facial reconstruction but still carries the potential for undesirable postoperative cosmetic changes. OBJECTIVE: The aims of this study were to describe postoperative vascular outcomes of patients undergoing flap repairs after Mohs micrographic surgery on facial tumors and to assess associations of baseline characteristics with outcomes. MATERIALS AND METHODS: In this study, 7 dermatologists and 1 physician assistant in dermatology assessed preoperative and postoperative photographs of 57 patients who underwent facial Mohs micrographic surgery, evaluating vascular and pigment outcomes and number of telangiectasias. RESULTS: There was a significant difference in number of telangiectasias according to body location (p = .002), where the number of telangiectasias was highest for nose surgery. CONCLUSION: These data suggest that nasal flap repairs are associated with increased postoperative vascular changes. This highlights an opportunity for improved preoperative patient counseling and possible early laser treatment after nasal Mohs micrographic surgery.

Visual acuity and optic nerve size assessed by magnetic resonance imaging in optic nerve hypoplasia.

We investigated the relationship between optic nerve (ON) size and visual acuity in children with optic nerve hypoplasia (ONH). The medical records of patients <19 years with ONH who underwent brain magnetic resonance imaging (MRI) and visual acuity assessment were reviewed. ON diameter at orbital and cisternal segments was assessed independently by two neuroradiologists and compared with visual acuity. ON diameter <1.7 mm represented a cutoff, below which was significantly associated with visual acuity of 20/200 or worse (P = 0.04) and above which was significantly associated with visual acuity of 20/40 or better (P = 0.004). ON diameter measured with MRI may provide an early prognostic indication of visual potential for children with ONH.

Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction.

To uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer's disease, we performed single nucleus RNA sequencing in 24 Alzheimer's disease and control brains and focused on vascular and astrocyte clusters as main cell types of blood-brain-barrier gliovascular-unit. The majority of the vascular transcriptional changes were in pericytes. Of the vascular molecular targets predicted to interact with astrocytic ligands, SMAD3, upregulated in Alzheimer's disease pericytes, has the highest number of ligands including VEGFA, downregulated in Alzheimer's disease astrocytes. We validated these findings with external datasets comprising 4,730 pericyte and 150,664 astrocyte nuclei. Blood SMAD3 levels are associated with Alzheimer's disease-related neuroimaging outcomes. We determined inverse relationships between pericytic SMAD3 and astrocytic VEGFA in human iPSC and zebrafish models. Here, we detect vast transcriptome changes in Alzheimer's disease at the gliovascular-unit, prioritize perturbed pericytic SMAD3-astrocytic VEGFA interactions, and validate these in cross-species models to provide a molecular mechanism of blood-brain-barrier disintegrity in Alzheimer's disease.

Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

County health ranking: untangling social determinants of health and other factors associated with short-term bariatric surgery outcomes.

BACKGROUND: The complex interplay of the social determinants of health, race/ethnicity, and traditional surgical risk factors on outcomes following metabolic surgery is poorly understood. OBJECTIVE: To evaluate the relationship between the social determinants of health as measured by county health ranking (CHR) and short-term metabolic surgery outcomes. SETTING: Five accredited bariatric program sites at a national academic health system. METHODS: Data were collected from 5 sites of a single health system from 2010 to 2021. Current procedural terminology codes identified primary and revisional cases. Patient characteristics, procedural data, and 30-day occurrences were collected. CHRs for health factors were determined by ZIP Code and stratified into best, middle, and worst terciles. The primary outcome was 30-day complications, readmissions, or reinterventions/reoperations. Logistic regression assessed the correlation between CHR tercile and morbidity. RESULTS: We analyzed 4,315 primary and 370 revisional metabolic surgery cases. Overall, 64.0%, 27.4%, and 8.6% of patients lived in the best, middle, and worst CHR terciles, respectively. Patients in the middle and worst CHR terciles were more commonly older; non-Hispanic Black or Hispanic; suffered from preexisting chronic obstructive pulmonary disease or hypertension, were dialysis dependence, were on therapeutic anticoagulation, or had inferior vena cava filters. Middle and worst CHR tercile patients were more likely to undergo index sleeve gastrectomy or robotic-assisted surgery and have surgery performed by a self-designated general surgeon. Thirty-day outcomes were similar across CHR terciles. Racial disparity in multiple short-term outcomes persisted despite adjustment for CHR tercile. CONCLUSION: Higher-risk patients are more likely to be from counties with lower CHRs, but CHR was not independently associated with 30-day outcomes after metabolic surgery.

Dexamethasone, Glycemic Control, and Outcomes in Patients With Type 2 Diabetes Mellitus Undergoing Elective, Primary Total Joint Arthroplasty.

Background: Dexamethasone (DEX) has been shown to reduce pain and postoperative nausea and vomiting for patients undergoing elective total joint arthroplasty (TJA). We investigated the impact of DEX on glycemic control and outcomes in patients with type 2 diabetes mellitus undergoing elective primary TJA. Methods: All patients with type 2 diabetes mellitus undergoing primary elective TJA between January 2016 and December 2021 at 4 sites within 1 hospital system were identified. Propensity scores were calculated to match patients receiving or not receiving DEX. Primary outcomes were perioperative blood glucose levels and the incidence of hyperglycemia. Secondary outcomes were the amount of insulin administered, the occurrence of 30-day postoperative surgical site infections, hospital readmission, and mortality. Results: After matching, we identified 1372 patients. DEX administration was associated with a significant increase in mean blood glucose levels in mg/dL on postoperative days (PODs) 0 to 2: POD 0 (28.4, 95% confidence interval [CI]: 24.6-32.1), POD 1 (14.4, 95% CI: 10.1-18.8), POD 2 (12.4, 95% CI: 7.5-17.2) when comparing patients who did or did not receive DEX. Additionally, patients receiving DEX, compared to patients who did not receive DEX, had increased odds of experiencing hyperglycemia on POD 0 (odds ratio: 4.0, 95% CI: 3.1-5.2). DEX was not associated with a significant difference in insulin administration, surgical site infections, hospital readmission, or mortality. Conclusions: In our review of 1372 patients with propensity-matched type 2 diabetes mellitus undergoing elective, primary TJA, we found that DEX administration was associated with an increased risk of elevated mean glucose on POD 0-2, hyperglycemia on POD 0, but was not associated with an increase in total insulin dose administered nor occurrence of surgical site infections, hospital readmission, or mortality within 30 days of surgery in patients who received DEX compared to patients who did not receive DEX. Level of Evidence: IV.

Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone.

BACKGROUND: Simultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a "safety net" policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss. RESULTS: Sixty-six thousand seventy-nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan-Meier estimates .61 vs. .89 and .90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups. CONCLUSION: KALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK. BRIEF SUMMARY: Patients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

CSF biomarkers of immune activation and Alzheimer's disease for predicting cognitive impairment risk in the elderly.

The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (N = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels. We observed age-related correlations with AD biomarkers such as total tau, phosphorylated tau-181, neurofilament light chain (NfL), and YKL40. APOE4 was associated with lower Aß42 and higher SNAP25 in CSF. We explored baseline variables predicting cognitive decline risk, finding age, CSF Aß42, NfL, and REG4 to be independently correlated. Subjects with older age, lower Aß42, higher NfL, and higher REG4 at baseline had increased cognitive impairment risk during follow-up. This suggests that assessing CSF inflammatory molecules and AD biomarkers could predict cognitive impairment risk in the elderly.

Total Knee Arthroplasty With and Without Schedule II Opioids: A Randomized, Double-Blinded, Placebo-Controlled Trial.

INTRODUCTION: Orthopedic surgeons are the third highest prescribers of narcotics. Previous work demonstrated that surgeons prescribe three times the narcotics required, and most patients do not properly dispose of leftover medication following surgery. This has prompted the creation of multimodal pain regimens to reduce reliance on narcotics. It is unknown if these pathways can effectively eliminate opioids following total knee arthroplasty (TKA). Our purpose was to evaluate a multimodal regimen without schedule II narcotics following TKA, in a randomized, blinded fashion. We hypothesized that there would be no difference in pain scores between groups. METHODS: A total of 43 narcotic-naïve patients participated in a randomized, double-blinded, placebo-controlled trial. Postoperative protocols were identical between cohorts, except for the study medication. The narcotic group received an encapsulated 5 mg oxycodone, whereas the control group received an encapsulated placebo. Perioperative outcomes were compared with routine statistical analysis. RESULTS: Four patients withdrew early secondary to pain: three in the placebo group and one in the narcotic group (p=1.00). We found no difference in hospital length of stay (p=0.09) or pain scores at all time points between cohorts (all p>0.05). There was a higher proportion of patients using a narcotic in the opioid treatment arm at day 30 (40% vs. 21.4%, p=0.29) and day 60 (20% vs. 7.1%, p=0.32), although this was not statistically significant. CONCLUSION: A multimodal regimen without schedule II narcotics demonstrates equivalent pain scores and may reduce the risk of long-term opioid dependence following TKA.

Role of GBA variants in Lewy body disease neuropathology.

Rare and common GBA variants are risk factors for both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the degree to which GBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rare GBA variants. Neuropathological outcomes included LBD subtype, presence of a high likelihood of clinical DLB (per consensus guidelines), LB counts in five cortical regions, tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putamen, ventrolateral substantia nigra neuronal loss, Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, phospho-ubiquitin (pS65-Ub) level, TDP-43 pathology, and vascular disease. Sequencing of GBA exons revealed a total of 42 different variants (4 common [MAF > 0.5%], 38 rare [MAF < 0.5%]) in our series, and 165 cases (17.5%) had a copy of the minor allele for ≥ 1 variant. In analysis of common variants, p.L483P was associated with a lower Braak NFT stage (OR = 0.10, P < 0.001). In gene-burden analysis, presence of the minor allele for any GBA variant was associated with increased odds of a high likelihood of DLB (OR = 2.00, P < 0.001), a lower Braak NFT stage (OR = 0.48, P < 0.001), a lower Thal amyloid phase (OR = 0.55, P < 0.001), and a lower pS65-Ub level (ß: -0.37, P < 0.001). Subgroup analysis revealed that GBA variants were most common in LBD cases with a combination of transitional/diffuse LBD and Braak NFT stage 0-II or Thal amyloid phase 0-1, and correspondingly that the aforementioned associations of GBA gene-burden with a decreased Braak NFT stage and Thal amyloid phase were observed only in transitional or diffuse LBD cases. Our results indicate that in LBD, GBA variants occur most frequently in cases with greater LB pathology and low AD pathology, further informing disease-risk associations of GBA in PD, PD dementia, and DLB.

Erratum: Neurofilament light chain and vaccination status associate with clinical outcomes in severe COVID-19.

[This corrects the article DOI: 10.1016/j.isci.2022.105272.].

The Relationship Between Anti-SSA-52 and Interstitial Lung Disease.

OBJECTIVE: The aims of this study were to assess whether a relationship between anti-SSA-52 and interstitial lung disease (ILD) can be further defined, and to enhance screening, detection, and potentially guide treatment. METHODS: A historical cohort study of 201 patients was conducted at a single tertiary care center between January 1, 2016 and December 31, 2020. All included patients were anti-SSA-52 antibody positive. Chart review was performed for laboratory values, symptoms, pulmonary function tests, treatment, and imaging. Chest computed tomographies were reviewed by chest radiologists. RESULTS: Among anti-SSA-52 antibody-positive patients, ILD was found in 125 (62.2%) compared with 76 (37.8%) with no ILD (p = 0.001). For those with ILD, 78 (62.4%) were diagnosed with connective tissue disease (CTD)-associated ILD, 28 (22.4%) were diagnosed ILD only, and 19 (15.2%) met the criteria for interstitial pneumonia with autoimmune features. In patients with CTD-ILD, 18 (23.0%) had their ILD diagnosis made over 6 months before a CTD diagnosis, and an additional 43 (55.1%) had their ILD and CTD diagnosed within 6 months of each other (p < 0.001). Common computed tomography patterns were nonspecific interstitial pneumonia/organizing pneumonia overlap in 44 (35.2%), 25 (20.0%) nonspecific interstitial pneumonia, and 15 (12%) usual interstitial pneumonia. Twenty-eight (35.9%) had antisynthetase syndrome, followed by 16 (20.5%) with dermatomyositis, 10 (12.8%) with CTD overlap, and 6 (7.7%) with systemic scleroderma. CONCLUSIONS: There was a significant association between anti-SSA-52 antibodies and ILD across a wide spectrum of rheumatological diagnoses. A significant portion of patients were diagnosed with ILD either at the same time or before their CTD diagnosis. Further study will be needed to assess effective treatment and response.

Loneliness, immunological recovery patterns, and health-related quality of life (HRQOL) outcomes in patients receiving hematopoietic stem cell transplantation.

PURPOSE: Loneliness may compromise health-related quality of life (HRQOL) outcomes and the immunological impacts of loneliness via neuroendocrinological mechanisms likely have consequences for patients who have undergone a hematopoietic stem cell transplantation (HSCT). RESEARCH APPROACH AND MEASURES: Loneliness (pre-transplant), immunological recovery (Day 30, Day 100, 1-year post-transplant), and HRQOL (Day 100, 1 year) were measured in a sample of 205 patients completing a HSCT (127 autologous, 78 allogenic). RESULTS: Greater levels of pre-transplant loneliness predicted poorer HRQOL at Day 100 and 1-year follow-up. Loneliness also was associated with higher absolute neutrophil to absolute lymphocyte (ANC/ALC) ratios in the entire sample at Day 30, which in turn was associated with Day 100 HRQOL. CONCLUSIONS: Findings demonstrate that pretransplant loneliness predicts HRQOL outcomes and associates with inflammatory immunological recovery patterns in HSCT patients. The balance of innate neutrophils to adaptive lymphocytes at Day 30 present a distinct profile in lonely individuals, with this immunity recovery profile predicting reduced HRQOL 100 days after the transplant. Addressing perceptions of loneliness before HSCT may be an important factor in improving immunological recovery and HRQOL outcomes.

A prospective study of the relationship between illness perception, depression, anxiety, and quality of life in hematopoietic stem cell transplant patients.

AIM: The aim of study was to investigate whether depression and anxiety symptoms and illness perception prior to hematopoietic stem cell transplantation (HSCT) predict health related quality of life (HRQOL) at Day 100 and 1 year following HSCT. METHODS: A total of 205 patients who underwent HSCT (N = 127 autologous transplants, N = 78 allogeneic transplants) were included in this prospective study. Baseline assessment was assessed prior to transplantation and post HSCT data were collected at Day 100 and 1 year. At baseline we assessed depressive symptoms (Patient Health Questionnaire-9), anxiety symptoms (Generalized Anxiety Disorder-7), illness perception (Brief Illness Perception Questionnaire), and HRQOL (Functional Assessment of Cancer Therapy-BMT). RESULTS: Patients who expressed a greater level of concern about the severity, course, and ability to exert control over one's illness (i.e., illness perception) and who reported a greater level of depression and anxiety symptoms prior to HSCT reported lower HRQOL at both Day 100 and 1 year posttransplant, with a similar degree of association observed at the two follow-up time points. CONCLUSIONS: Our findings suggest that pretransplant perceptions about their illness and negative mood are significant predictors of HRQOL following HSCT. Illness perception, depression, and anxiety are potentially modifiable risk factors for less than optimal outcome after HCSCT and intervention strategies should be explored.

Predictive Value of the International Classification of Diseases, 9th Revision Codes for Identifying Ocular Oncology Diagnoses.

Introduction: The aim of this study was to determine the predictive value of International Classification of Diseases, 9th Revision (ICD-9) billing codes for identifying ocular oncology diagnoses. Methods: Population-based retrospective cohort study of all Olmsted County, Minnesota residents with any ocular neoplasm-related ICD-9 code from January 1, 2006 to October 1, 2015. All medical records were reviewed for confirmation of ocular neoplasm. Diagnoses with ≥5 cases confirmed via a medical record review were compared to corresponding ICD-9 codes. Main outcome measures included positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of ICD-9 codes. Results: Among 3,932 subjects with ≥1 ocular neoplasm-related ICD-9 code, 21 diagnoses met study criteria. The most frequent intraocular, extraocular/orbital, and ocular surface diagnoses were choroidal nevus (n = 824), epidermal inclusion cyst (n = 263), and conjunctival nevus (n = 74), respectively. PPVs ranged from 1.2% to 73.8%, NPVs from 96.9% to 100%, sensitivity from 0% to 100%, and specificity from 85.7% to 100%. Among malignant neoplasms, PPV ranged from 0% to 73.8%: ocular surface squamous neoplasia (PPV: 0%), choroidal melanoma (PPV: 25.0%), eyelid squamous cell carcinoma (PPV: 46.7%), and eyelid basal cell carcinoma (PPV: 73.8%). Among benign neoplasms, PPV ranged from 1.2% (dermoid cyst) to 61.6% (choroidal nevus). Conclusion: There was a wide variation in a predictive value of ocular neoplasm-related ICD-9 billing codes, which suggests that ocular oncology-related claims data alone may overestimate the true number of ocular oncology diagnoses.

Improved outcomes of kidney after liver transplantation after the implementation of the safety net policy.

The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3 mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.

Genome-wide association study identifies APOE and ZMIZ1 variants as mitophagy modifiers in Lewy body disease.

The PINK1-PRKN pathway mediates a critical quality control to maintain mitochondrial health and function. Together the kinase-ligase pair identifies and decorate damaged mitochondria with phosphorylated ubiquitin (p-S65-Ub). This selective label serves as the mitophagy tag and facilitates their degradation via autophagy-lysosome system. While complete loss of PINK1 or PRKN function causes early-onset Parkinson disease, much broader mitophagy impairments are emerging across neurodegenerative disorders. We previously found age- and disease-dependent accumulation of p-S65-Ub signal in the hippocampus of autopsy brains with Lewy body disease (LBD). However, the contribution of genetic variation to mitochondrial damage and p-S65-Ub levels remains unknown in LBD cases. To identify novel regulators of PINK1-PRKN mitophagy in LBD, we performed an unbiased genome-wide association study of hippocampal p-S65-Ub level with 1,012 autopsy confirmed LBD samples. Using an established, mostly automated workflow, hippocampal sections were immunostained for p-S65-Ub, scanned, and quantified with unbiased algorithms. Functional validation of the significant hit was performed in animal model and human induced pluripotent stem cells (hiPSCs). We identified a strong association with p-S65-Ub for APOE4 (rs429358; ß : 0.50, 95% CI: 0.41 to 0.69; p =8.67x10 -25 ) and a genome-wide significant association for ZMIZ1 (rs6480922; ß : -0.33, 95% CI: -0.45 to -0.22; p =1.42x10 -8 ). The increased p-S65-Ub levels in APOE4 -carrier may be mediated by both co-pathology-dependent and -independent mechanisms, which was confirmed in Apoe-targeted replacement mice and hiPSC-derived astrocytes. Intriguingly, ZMIZ1 rs6480922 also significantly associated with increased brain weight and reduced neuropathological burden indicating a potential role as a resilience factor. Our findings nominate novel mitophagy regulators in LBD brain ( ZMIZ1 locus) and highlight a strong association of APOE4 with mitophagy alteration. With APOE4 being the strongest known risk factor for clinical Alzheimer's disease and dementia with Lewy bodies, our findings suggest a common mechanistic link underscoring the importance of mitochondrial quality control.

Choroidal Nevus Features Associated with Subspecialty Referral.

OBJECTIVE: To identify choroidal nevus features associated with referral to a retina or ocular oncology subspecialist. DESIGN: Population-based retrospective cohort study. SUBJECTS: Patients diagnosed with choroidal nevus. METHODS: Population-based retrospective cohort study of residents of Olmsted County, Minnesota, with an incident diagnosis of choroidal nevus from January 1, 2006, to December 31, 2015 using the Rochester Epidemiology Project, a medical record linkage system. Tumor features and patient demographics associated with referral to a retina or ocular oncology subspecialist were assessed. Wilcoxon rank sum test, chi-square test, and Fisher exact test were used for statistical analysis. MAIN OUTCOME MEASURES: Tumor features and patient demographics associated with referral to subspecialty care. RESULTS: There were 826 incident diagnoses of choroidal nevus, of which 88 cases (11%) were referred, with highest level of referral being retina in 29 cases (33%) and ocular oncology in 59 cases (67%). None of the analyzed demographic features were associated with choroidal nevus referral to subspecialty care. Tumor features associated with referral (vs. not referred) included greater mean basal diameter (4.6 mm vs. 2.4 mm, P < 0.001), greater mean tumor thickness (0.7 mm vs. 0.1 mm, P < 0.001), greater distance to optic disc (6.9 mm vs. 3.4 mm, P = 0.02), halo around nevus (5.7% vs. 0.4%, P < 0.001), and drusen on OCT (51% vs. 25%, P = 0.002). Presence of orange pigment (8% vs. 0%, P = 0.14), subretinal fluid (9% vs. 2.5%, P = 0.09), and low internal reflectivity on A-scan (7.7% vs. 0%, P = 1.00) were not found more frequently in the subspecialty referral group. CONCLUSIONS: Greater basal diameter and mean tumor thickness of choroidal nevus were associated with referral to retina or ocular oncology. However, several features associated with increased risk of malignant transformation were not associated with subspecialty referral. These findings highlight the importance of educating eye care providers about high-risk tumor features associated with choroidal nevus transformation to melanoma. In the primary eye care setting where not all multimodal imaging may be available, we encourage color photography and OCT with referral for any features of basal diameter > 5 mm, presence of subretinal fluid, or thickness too large for capture by enhanced-depth imaging OCT. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.