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.

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.

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.

Continuous Glucose Monitoring for Patients with COVID-19 Pneumonia: Initial Experience at a Tertiary Care Center.

OBJECTIVE: Patients hospitalized with COVID-19 and hyperglycemia require frequent glucose monitoring, usually performed with glucometers. Continuous glucose monitors (CGMs) are common in the outpatient setting but not yet approved for hospital use. We evaluated CGM accuracy, safety for insulin dosing, and CGM clinical reliability in 20 adult patients hospitalized with COVID-19 and hyperglycemia. METHODS: Study patients were fitted with a remotely monitored CGM. CGM values were evaluated against glucometer readings. The CGM sensor calibration was performed if necessary. CGM values were used to dose insulin, without glucometer confirmation. RESULTS: CGM accuracy against glucometer, expressed as mean absolute relative difference (MARD), was calculated using 812 paired glucometer-CGM values. The aggregate MARD was 10.4%. For time in range and grades 1 and 2 hyperglycemia, MARD was 11.4%, 9.4%, and 9.1%, respectively, with a small variation between medical floors and intensive care units. There was no MARD correlation with mean arterial blood pressure levels, oxygen saturation, daily hemoglobin levels, and glomerular filtration rates. CGM clinical reliability was high, with 99.7% of the CGM values falling within the "safe" zones of Clarke error grid. After CGM placement, the frequency of glucometer measurements decreased from 5 to 3 and then 2 per day, reducing nurse presence in patient rooms and limiting viral exposure. CONCLUSION: With twice daily, on-demand calibration, the inpatient CGM use was safe for insulin dosing, decreasing the frequency of glucometer fingersticks. For glucose levels >70 mg/dL, CGMs showed adequate accuracy, without interference from vital and laboratory values.

Towards defining morphologic parameters of normal parous and nulliparous breast tissues by artificial intelligence.

BACKGROUND: Breast terminal duct lobular units (TDLUs), the source of most breast cancer (BC) precursors, are shaped by age-related involution, a gradual process, and postpartum involution (PPI), a dramatic inflammatory process that restores baseline microanatomy after weaning. Dysregulated PPI is implicated in the pathogenesis of postpartum BCs. We propose that assessment of TDLUs in the postpartum period may have value in risk estimation, but characteristics of these tissues in relation to epidemiological factors are incompletely described. METHODS: Using validated Artificial Intelligence and morphometric methods, we analyzed digitized images of tissue sections of normal breast tissues stained with hematoxylin and eosin from donors ≤ 45 years from the Komen Tissue Bank (180 parous and 545 nulliparous). Metrics assessed by AI, included: TDLU count; adipose tissue fraction; mean acini count/TDLU; mean dilated acini; mean average acini area; mean "capillary" area; mean epithelial area; mean ratio of epithelial area versus intralobular stroma; mean mononuclear cell count (surrogate of immune cells); mean fat area proximate to TDLUs and TDLU area. We compared epidemiologic characteristics collected via questionnaire by parity status and race, using a Wilcoxon rank sum test or Fisher's exact test. Histologic features were compared between nulliparous and parous women (overall and by time between last birth and donation [recent birth: ≤ 5 years versus remote birth: > 5 years]) using multivariable regression models. RESULTS: Normal breast tissues of parous women contained significantly higher TDLU counts and acini counts, more frequent dilated acini, higher mononuclear cell counts in TDLUs and smaller acini area per TDLU than nulliparas (all multivariable analyses p < 0.001). Differences in TDLU counts and average acini size persisted for > 5 years postpartum, whereas increases in immune cells were most marked ≤ 5 years of a birth. Relationships were suggestively modified by several other factors, including demographic and reproductive characteristics, ethanol consumption and breastfeeding duration. CONCLUSIONS: Our study identified sustained expansion of TDLU numbers and reduced average acini area among parous versus nulliparous women and notable increases in immune responses within five years following childbirth. Further, we show that quantitative characteristics of normal breast samples vary with demographic features and BC risk factors.

Serum hormone levels and normal breast histology among premenopausal women.

PURPOSE: Breast terminal duct lobular units (TDLUs) are the main source of breast cancer (BC) precursors. Higher serum concentrations of hormones and growth factors have been linked to increased TDLU numbers and to elevated BC risk, with variable effects by menopausal status. We assessed associations of circulating factors with breast histology among premenopausal women using artificial intelligence (AI) and preliminarily tested whether parity modifies associations. METHODS: Pathology AI analysis was performed on 316 digital images of H&E-stained sections of normal breast tissues from Komen Tissue Bank donors ages ≤ 45 years to assess 11 quantitative metrics. Associations of circulating factors with AI metrics were assessed using regression analyses, with inclusion of interaction terms to assess effect modification. RESULTS: Higher prolactin levels were related to larger TDLU area (p < 0.001) and increased presence of adipose tissue proximate to TDLUs (p < 0.001), with less significant positive associations for acini counts (p = 0.012), dilated acini (p = 0.043), capillary area (p = 0.014), epithelial area (p = 0.007), and mononuclear cell counts (p = 0.017). Testosterone levels were associated with increased TDLU counts (p < 0.001), irrespective of parity, but associations differed by adipose tissue content. AI data for TDLU counts generally agreed with prior visual assessments. CONCLUSION: Among premenopausal women, serum hormone levels linked to BC risk were also associated with quantitative features of normal breast tissue. These relationships were suggestively modified by parity status and tissue composition. We conclude that the microanatomic features of normal breast tissue may represent a marker of BC risk.

Evaluating atrial fibrillation artificial intelligence for the ED: statistical and clinical implications.

OBJECTIVE: An artificial intelligence (AI) algorithm has been developed to detect the electrocardiographic signature of atrial fibrillation (AF) present on an electrocardiogram (ECG) obtained during normal sinus rhythm. We evaluated the ability of this algorithm to predict incident AF in an emergency department (ED) cohort of patients presenting with palpitations without concurrent AF. METHODS: This retrospective study included patients 18 years and older who presented with palpitations to one of 15 ED sites and had a 12­lead ECG performed. Patients with prior AF or newly diagnosed AF during the ED visit were excluded. Of the remaining patients, those with a follow up ECG or Holter monitor in the subsequent year were included. We evaluated the performance of the AI-ECG output to predict incident AF within one year of the index ECG by estimating an area under the receiver operating characteristics curve (AUC). Sensitivity, specificity, and positive and negative predictive values were determined at the optimum threshold (maximizing sensitivity and specificity), and thresholds by output decile for the sample. RESULTS: A total of 1403 patients were included. Forty-three (3.1%) patients were diagnosed with new AF during the following year. The AI-ECG algorithm predicted AF with an AUC of 0.74 (95% CI 0.68-0.80), and an optimum threshold with sensitivity 79.1% (95% Confidence Interval (CI) 66.9%-91.2%), and specificity 66.1% (95% CI 63.6%-68.6%). CONCLUSIONS: We found this AI-ECG AF algorithm to maintain statistical significance in predicting incident AF, with clinical utility for screening purposes limited in this ED population with a low incidence of AF.

Post-Liver Transplant Early Allograft Dysfunction Modifies the Effect of Pre-Liver Transplant Renal Dysfunction on Post-Liver Transplant Survival.

Pre-liver transplantation (LT) renal dysfunction is associated with poor post-LT survival. We studied whether early allograft dysfunction (EAD) modifies this association. Data on 2,856 primary LT recipients who received a transplant between 1998 and 2018 were retrospectively reviewed. Patients who died within the first post-LT week or received multiorgan transplants and previous LT recipients were excluded. EAD was defined as (1) total bilirubin ≥ 10 mg/dL on postoperative day (POD) 7, (2) international normalized ratio ≥1.6 on POD 7, and/or (3) alanine aminotransferase or aspartate aminotransferase ≥2000 IU/mL in the first postoperative week. Pre-LT renal dysfunction was defined as serum creatinine >1.5 mg/dL or on renal replacement therapy at LT. Patients were divided into 4 groups according to pre-LT renal dysfunction and post-LT EAD development. Recipients who had both pre-LT renal dysfunction and post-LT EAD had the worst unadjusted 1-year, 3-year, and 5-year post-LT patient and graft survival, whereas patients who had neither renal dysfunction nor EAD had the best survival (P < 0.001). After adjusting for multiple factors, the risk of death was significantly higher only in those with both pre-LT renal dysfunction and post-LT EAD (adjusted hazard ratio [aHR], 2.19; 95% confidence interval [CI], 1.58-3.03; P < 0.001), whereas those with renal dysfunction and no EAD had a comparable risk of death to those with normal kidney function at LT (aHR, 1.12; 95% CI, 0.86-1.45; P = 0.41). Results remained unchanged when pre-LT renal dysfunction was redefined using different glomerular filtration rate cutoffs. Pre-LT renal dysfunction negatively impacts post-LT survival only in patients who develop EAD. Livers at higher risk of post-LT EAD should be used with caution in recipients with pre-LT renal dysfunction.

The changing impact of pre-liver transplant renal dysfunction on post-transplant survival: results of 2 decades from a single center.

INTRODUCTION AND OBJECTIVES: Renal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. MATERIALS AND METHODS: We retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver-kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998-2002, n = 488), era-2 (2003-2007, n = 889), era-3 (2008-2012, n = 703) and era-4 (2013-2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. RESULTS: Pre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. CONCLUSIONS: Pre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.

Opioid Use in Fibromyalgia Continues Despite Guidelines That Do Not Support Its Efficacy or Risk.

BACKGROUND/OBJECTIVE: The aim of this cross-sectional study is to determine the prevalence of opioid use in a large sample of fibromyalgia (FM) patients and examine the factors associated with opioid prescription/use despite multiple clinical guidelines that do not recommend opioid use in this population. METHODS: Data were collected from a convenience sample of 698 patients admitted from August 2017 to May 2019 into an intensive 2-day Fibromyalgia Treatment Program at a tertiary medical center in the United States after FM diagnosis. Patients were administered the Fibromyalgia Impact Questionnaire-Revised, the Center for Epidemiologic Study of Depression Scale, and the Pain Catastrophizing Scale upon admission to the program. Demographic information and opioid use were self-reported. Logistic regression analysis was utilized to determine associations between patient-related variables and opioid use in this prospective study. RESULTS: Of 698 patients, 27.1% (n = 189) were taking opioids at intake. Extended duration of symptoms (>3 years), increased age, higher degree of functional impairment, and increased pain catastrophizing were significantly associated with opioid use. CONCLUSIONS: Opioids are not recommended for the treatment of FM under current guidelines. Greater burden of illness appeared to be associated with the prescription and use of opioids in this population. These findings suggest that some providers may not be aware of current recommendations that have been found to be effective in the management of FM that are contained in guidelines. Alternative approaches to the management of FM that do not involve opioids are reviewed in an effort to improve care.

Tranexamic Acid Administration Is Not Associated With an Increase in Complications in High-Risk Patients Undergoing Primary Total Knee or Total Hip Arthroplasty: A Retrospective Case-Control Study of 38,220 Patients.

BACKGROUND: Tranexamic acid (TXA) administration to reduce postoperative blood loss and transfusion is a well-established practice for total knee arthroplasty (TKA) and total hip arthroplasty (THA). However, clinical concerns remain about the safety of TXA in patients with a history of a prothrombotic condition. We sought to determine the risk of complications between high-risk and low-risk TKA and THA patients receiving TXA. METHODS: We retrospectively reviewed 38,220 patients (8877 high-risk cases) who underwent primary TKA and THA between 2011 and 2017 at our institution. Intravenous TXA was administered in 20,501 (54%) of cases. The rates of thrombotic complications (deep vein thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], and cerebrovascular accident [CVA]) as well as mortality and readmission were assessed at 90 days postoperatively. Additionally, we evaluated 90-day postoperative occurrence of DVT and PE separate from occurrence of MI and CVA. Patients were categorized as high risk if they had a past medical history of a prothrombotic condition prior to surgery. RESULTS: There was no significant difference in the odds of these adverse outcomes between high-risk patients who received TXA and high-risk patients who did not receive TXA (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.18). There were also no differences when evaluating the odds of 90-day postoperative DVT and PE (OR 0.84, 95% CI 0.59-1.19) nor MI and CVA (OR 0.91, 95% CI 0.56-1.49) for high-risk patients receiving TXA vs high-risk patients who did not receive TXA. CONCLUSION: TXA administration to high-risk TKA and THA patients is not associated with a statistically significant difference in adverse outcomes. We present incremental evidence in support of TXA administration for high-risk patients undergoing primary arthroplasties.

PROACTIVE PROTOCOL-BASED MANAGEMENT OF HYPERGLYCEMIA AND DIABETES IN COLORECTAL SURGERY PATIENTS.

OBJECTIVE: The management of diabetic patients undergoing elective abdominal surgery continues to be unsystematic, despite evidence that standardized perioperative glycemic control is associated with fewer postoperative surgical complications. We examined the efficacy of a pre-operative diabetes optimization protocol implemented at a single institution in improving perioperative glycemic control with a target blood glucose of 80 to 180 mg/dL. METHODS: Patients with established and newly diagnosed diabetes who underwent elective colorectal surgery were included. The control group comprised 103 patients from January 1, 2011, through December 31, 2013, before protocol implementation. The glycemic-optimized group included 96 patients following protocol implementation from January 1, 2014, through July 31, 2016. Data included demographic information, blood glucose levels, insulin doses, hypoglycemic events, and clinical outcomes (length of stay, re-admissions, complications, and mortality). RESULTS: Patients enrolled in the glycemic optimization protocol had significantly lower glucose levels intra-operatively (145.0 mg/dL vs. 158.1 mg/dL; P = .03) and postoperatively (135.6 mg/dL vs. 145.2 mg/dL; P = .005). A higher proportion of patients enrolled in the protocol received insulin than patients in the control group (0.63 vs. 0.48; P = .01), but the insulin was administered less frequently (median [interquartile range] number of times, 6.0 [2.0 to 11.0] vs. 7.0 [5.0 to 11.0]; P = .04). Two episodes of symptomatic hypoglycemia occurred in the control group. There was no difference in clinical outcomes. CONCLUSION: Improved peri-operative glycemic control was observed following implementation of a standardized institutional protocol for managing diabetic patients undergoing elective colorectal surgery. ABBREVIATIONS: HbA1c = glycated hemoglobin A1c; IQR = interquartile range.

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.

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.

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.

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.

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.].

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.

Incidence and clinical characteristics of pediatric ocular tumors in a Midwestern US population.

PURPOSE: To investigate the incidence and clinical characteristics of pediatric ocular tumors in a US Midwestern county population. METHODS: Retrospective population-based cohort study of all Olmsted County, Minnesota, pediatric patients (<18 years old) diagnosed with any ocular neoplasm from January 1, 2006, to December 31, 2015. Subjects were identified via the Rochester Epidemiology Project, a record-linkage system that captures virtually all medical care provided in this county. Medical records were reviewed to confirm diagnoses. Age- and sex-adjusted incidence rates were calculated and adjusted to the 2010 Olmsted County, Minnesota, pediatric population. RESULTS: There were 87 incident pediatric ocular tumor diagnoses, yielding an overall age- and sex-adjusted incidence rate of 24.0 per 100,000 per year (95% CI, 19.0-29.1). Females accounted for 46 cases (53%) cases, and 62 (85%) were White. Incidence rate for ocular tumors overall did not differ by patient age (P = 0.08) or sex (P = 0.47). All tumors were benign lesions. The most frequent adnexal/orbital, ocular surface, and intraocular tumors were epidermal inclusion cyst in 18 (21%) cases, conjunctival nevus in 10 (12%), and choroidal nevus in 18 (21%), respectively. The mean follow-up duration was 25.5 months (range, 7 days to 138.6 months), and benign tumor growth occurred in one conjunctival nevus. There were no cases of malignant transformation. CONCLUSIONS: Pediatric ocular tumors were rare with an estimated incidence of approximately 1 in 4,200 pediatric patients in Olmsted County, Minnesota. All lesions were benign, with benign growth in only 1% of cases, and no tumors underwent malignant transformation.