Disparities In Disease Severity Research Articles

Social Determinants of Health and Health-Related Quality of Life Following Pediatric Septic Shock: Secondary Analysis of the Life After Pediatric Sepsis Evaluation Dataset, 2014-2017.

Social determinants of health (SDOH) are associated with disparities in disease severity and in-hospital outcomes among critically ill children. It is unknown whether SDOH are associated with later outcomes. We evaluated associations between SDOH measures and mortality, new functional morbidity, and health-related quality of life (HRQL) decline among children surviving septic shock. Secondary analysis of the Life After Pediatric Sepsis Evaluation (LAPSE) prospective cohort study was conducted between 2014 and 2017. Twelve academic U.S. PICUs were involved in the study. Children younger than 18 years with community-acquired septic shock were involved in the study. None. We assessed associations between race, ethnicity, income, education, marital status, insurance, language, and home U.S. postal code with day 28 mortality, new functional morbidity at discharge per day 28, and HRQL decline using logistic regression. Of 389 patients, 32% ( n = 98) of families had household income less than $50,000 per year. Median Pediatric Risk of Mortality (PRISM) score was 11 (interquartile range 6, 17). We found that English language and Area Deprivation Index less than 50th percentile were associated with higher PRISM scores. Mortality was 6.7% ( n = 26), new functional morbidity occurred in 21.8% ( n = 78) of patients, and HRQL decline by greater than 10% occurred in 31.0% of patients ( n = 63). We failed to identify any association between SDOH measures and mortality, new functional morbidity, or HRQL decline. We are unable to exclude the possibility that annual household income greater than or equal to $50,000 was associated with up to 81% lesser odds of mortality and, in survivors, more than three-fold greater odds of HRQL decline by greater than 10%. In this secondary analysis of the 2014-2017 LAPSE dataset, we failed to identify any association between SDOH measures and in-hospital or postdischarge outcomes following pediatric septic shock. This finding may be reflective of the high illness severity and single disease (sepsis) of the cohort, with contribution of clinical factors to functional and HRQL outcomes predominating over prehospital and posthospital SDOH factors.

Perioperative Outcomes After Carotid Revascularization in Asian Patients Varies With Asian Procedure Density

The nature of postoperative outcomes following carotid revascularization is understudied in Asian patients. We aimed to determine if there are disparities in disease severity and postoperative outcomes in Asian patients following carotid revascularization and whether this varies with procedure frequency in Asian patients. We analyzed the Society for Vascular Surgery Vascular Quality Initiative Carotid Endarterectomy and Carotid Artery Stenting datasets from 2003 to 2021. We divided regions into tertiles based on Asian procedure density. Propensity scores were used to match White and Asian patients based on age, sex, comorbidities, contralateral carotid occlusion, and procedure type. Logistic and Cox regressions were performed within the matched cohort. The primary outcome variable was in-hospital ipsilateral stroke/death/myocardial infarction and we also examined differences in disease severity, center and surgeon volume, and late outcomes. A total of 159,608 White and 1766 Asian patients underwent carotid revascularization and we identified 2704 patients in the matched cohort. On adjusted analysis, there was no difference in symptomatic disease rate between groups (35%). However, Asian patients more commonly presented with >80% ipsilateral stenosis (63% vs 52%; P < .001) and a moderate/severe preoperative Rankin score (7.6% vs 5.1%; P = .007), which did not vary with Asian procedure density. The rate of in-hospital stroke/death/myocardial infarction was higher in Asian patients (2.6% vs 1.3%; P = .012), and this disparity was more pronounced in the lowest tertile of Asian procedure density (4.3% vs 0.5%; P < .001). Logistic regression within the propensity-matched cohort demonstrated Asian race was associated with a decreased odds of care by highest volume centers and surgeons, which was largely consistent across tertiles of Asian procedure density (Table I). Asian race was associated with twofold greater odds of in-hospital stroke/death/myocardial infarction, which was driven by the lowest tertile regions of Asian procedure density. After clustering at surgeon and center level, the effect of Asian race was mitigated. Cox regression within the matched cohort demonstrated that Asian race was protective against late mortality, with no differences in 1-year stroke or reintervention-free survival (Table II). Asian patients are more likely to present with a greater degree of carotid stenosis, preoperative risk, and experience worse perioperative outcomes. The increased odds of perioperative stroke/death/myocardial infarction is driven by regions with low Asian procedure density and is also mediated by the volume of centers and surgeons with which Asian patients tend to undergo care. These results highlight the need to understand the social and cultural effects on outcomes disparities in Asian patients.Table ILogistical regression of outcomes in propensity-matched cohortAssociation With Asian RaceOR (95% CI; P)ORa (95% CI; P)In-hospital stroke/death/myocardial infarction2.1 (1.2-3.7; P = .014)1.4 (0.7-3.0; P = .354)Operation at highest volume centers0.2 (0.2-0.3; P < .001)--Operation with highest volume surgeons0.3 (0.3-0.4; P < .001)--CI, Confidence interval; OR, odds ratio.aLogistical regression with clustering at surgeon and center level. Open table in a new tab Table IICox regression of late outcomes in propensity-matched cohortAsian RaceHR (95% CI, P)Long-term mortality0.6 (0.4-0.9; P = .011)1-year stroke-free survival1.1 (0.3-3.9; P = .878)1-year reintervention-free survival5.0 (0.8-33.0; P = .091)HR, Hazard ratio; OR, odds ratio. Open table in a new tab

Asian race is associated with peripheral arterial disease severity and postoperative outcomes

ObjectiveThe nature of peripheral arterial disease and postoperative outcomes are understudied in Asian patients. We aimed to determine if there are disparities in disease severity at the time of presentation and postoperative outcomes with regard to Asian race. MethodsWe analyzed the Society for Vascular Surgery Vascular Quality Initiative Peripheral Vascular Intervention dataset from 2017 to 2021, which includes endovascular lower extremity interventions. Propensity scores were used to match White and Asian patients based on age, sex, comorbidities, ambulatory/functional status, and intervention level. Differences were examined with regard to Asian race across all patients in the United States, Canada, and Singapore, and separately in the United States and Canada only. The primary outcome was emergent intervention. We also examined differences in severity of disease and postoperative outcomes. ResultsA total of 80,312 White and 1689 Asian patients underwent peripheral vascular intervention. After propensity score matching, we identified 1669 matched pairs of patients across all centers including Singapore and 1072 matched pairs in the United States and Canada only. Among the matched cohort consisting of all centers, Asian patients had a higher rate of emergent intervention to prevent limb loss (5.6% vs 1.7%, P < .001). The majority of Asian patients presented with chronic limb threatening ischemia at a higher rate than White patients within the cohort including Singapore (71% vs 66%, P = .005). Within both propensity-matched cohorts, the rate of in-hospital death was higher in Asian patients (all centers: 3.1% vs 1.2%, P < .001; United States and Canada only: 2.1% vs 0.8%, P = .010). Logistic regression demonstrated greater odds of emergent intervention in Asian patients from all centers including Singapore (odds ratio [OR], 3.3; 95% confidence interval [CI], 2.2-5.1, P < .001) but not in the United States and Canada only (OR, 1.4; 95% CI, 0.8-2.8, P = .261). In addition, Asian patients had greater odds of in-hospital death in both matched cohorts (all centers: OR, 2.6; 95% CI, 1.5-4.4, P < .001; United States and Canada: OR, 2.5; 95% CI, 1.1-5.8, P = .026). Asian race was associated with a greater risk of loss of primary patency at 18 months (all centers: hazard ratio, 1.5; CI, 1.2-1.8, P = .001; United States and Canada only: hazard ratio, 1.5; CI, 1.2-1.9, P = .002). ConclusionsAsian patients are more likely to present with advanced peripheral arterial disease and undergo emergent intervention to prevent limb loss, in addition to having worse postoperative outcomes and long-term patency. These results highlight the need for improved screening and postoperative follow-up in this understudied population.

The Pathological Activation of Microglia Is Modulated by Sexually Dimorphic Pathways.

Microglia are the primary immunocompetent cells of the central nervous system (CNS). Their ability to survey, assess and respond to perturbations in their local environment is critical in their role of maintaining CNS homeostasis in health and disease. Microglia also have the capability of functioning in a heterogeneous manner depending on the nature of their local cues, as they can become activated on a spectrum from pro-inflammatory neurotoxic responses to anti-inflammatory protective responses. This review seeks to define the developmental and environmental cues that support microglial polarization towards these phenotypes, as well as discuss sexually dimorphic factors that can influence this process. Further, we describe a variety of CNS disorders including autoimmune disease, infection, and cancer that demonstrate disparities in disease severity or diagnosis rates between males and females, and posit that microglial sexual dimorphism underlies these differences. Understanding the mechanism behind differential CNS disease outcomes between men and women is crucial in the development of more effective targeted therapies.

Abstract IA007: Regulation of metastasis efficiency via mitochondrial genetics

Abstract While there has been increasing appreciation for the roles of mitochondria in cancer, most efforts investigating the genetics of cellular functions study only the nuclear genome. To overcome technical complications of studying the specific contributions of mitochondrial genetics, we created mitochondrial nuclear exchange (MNX) mice by transferring an oocyte nucleus from strain-x into an enucleated oocyte from strain-y. Using MNX mice, we made the following discoveries demonstrating the profound role(s) of mtDNA on several complex phenotypes. - Crossing nuclear genome-matched female mice with male transgenic mice bearing oncogenes, tumorigenicity and metastasis were up- or down-regulated depending upon mtDNA. - MNX mice exhibit different autochthonous tumor formation. - When syngeneic (i.e., histocompatible) mammary and melanoma cells were injected into MNX mice, metastasis changed 3-5X, depending on mtDNA SNP. C57BL/6J mtDNA inhibited metastasis while C3H/HeN mtDNA increased metastasis. - MNX mice have selectively altered epigenetic marks (DNA methylation and histone marks) in the nuclear genome. - MNX mice with higher ROS form more metastases. Scavenging ROS reduced metastasis. - Baseline immune profiles differ in MNX mice compared to nDNA-matched counterparts and polarization states of myeloid populations infiltrating lung metastases were also significantly different. - Metabolomic profiling of &amp;gt;5000 metabolites showed minor differences, none of which appear to correlate with the above-referenced phenotypic changes. - MNX mice have distinct gut microbiota than matched wild-type strains, suggesting mitochondrial-bacterial communication. Together, these results demonstrate that mitochondrial genes are among metastatic quantitative trait loci by intrinsic and extrinsic mechanisms. Candidate signals from mitochondria to the nucleus or bacteria will be reported. And since mitochondrial SNP are markers of genetic ancestry, our findings also suggest that mtDNA SNP could serve as prognostic biomarkers and partially explain racial disparities in disease severity. Support: Susan G. Komen for the Cure (SAC11037), METAvivor Research &amp; Support Inc., National Foundation for Cancer Research, National Cancer Institute P30-CA168524. Citation Format: Danny R. Welch. Regulation of metastasis efficiency via mitochondrial genetics [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr IA007.

Asian Race Negatively Impacts Peripheral Vascular Disease Severity and Postoperative Outcomes

The nature of peripheral vascular disease and postoperative outcomes are understudied in Asian American patients. We aimed to determine if there are disparities in disease severity at time of presentation and postoperative outcomes with regard to Asian race.

Abstract 15800: Inter-race and Ethnicity Comparisons in Pulmonary Hypertension From the Pulmonary Vascular Phenomics (PVDOMICS) Program

Intro: Recent World Symposium of Pulmonary Hypertension (WSPH) Group 1 data indicate significant racial and ethnic disparities in disease severity and mortality. It is unclear if these differences extend to other forms of PH and if they are a reflection of comorbidities. The PVDOMICS program incorporates deep phenotyping across all WSPH groups allowing for a first-time side-by-side comparison. The aims of this study are to evaluate inter-racial/ethnic factors of disease severity and comorbidities among patients with PH. Methods/Results: Participants in PVDOMICS prospectively underwent comprehensive testing for echocardiography, PFT, chest imaging, 6-minute walk, cardiac MRI, and hemodynamics with provocation. WSPH group assignment was assessed according to guideline recommendations. Race and ethnicity were self-reported. Statistical testing and sample sizes are described in the Table . In 692 PH participants, Non-Hispanic whites (NHW) were older and more often male than non-Hispanic African American (AA) and Hispanic patients. WSPH Group 1 was less but Groups 4 and 5 more common in AA than NHW. There were no inter-race/ethnicity differences in the percent of PH patients on PH therapy (range 53-63%, p=0.23). Comorbidities such as diabetes and lung disease were more common in AA vs. NHW. Hispanics showed lower left atrial (LA) volume on echo, LA filling pressures with exercise, as well as increased cardiac index relative to NHW. Right ventricular function on cardiac MRI was similar between groups ( Table ). When WSPH Group 1 was analyzed separately, inter-racial/ethnic comparisons were generally similar. Conclusions: Significant inter-racial/ethnic differences are evident across all WSPH groups. Comorbidities appear to drive part of the differences among AA patients while Hispanic patients exhibit factors that may prove beneficial. How these differences contribute to varying disease risk and outcomes across race and ethnicity remain to be seen.

Operational Challenges of a Low-Dose CT Lung Cancer Screening Program During the Coronavirus Disease 2019 Pandemic

Operational Challenges of a Low-Dose CT Lung Cancer Screening Program During the Coronavirus Disease 2019 Pandemic

Racial and Ethnic Disparities in Disease Severity on Admission Chest Radiographs among Patients Admitted with Confirmed Coronavirus Disease 2019: A Retrospective Cohort Study.

BackgroundDisease severity on chest radiographs (CXR) has been associated with higher risk of disease progression and adverse outcomes from COVID-19. Few studies have evaluated COVID-19-related racial/ethnic disparities in radiology.PurposeTo evaluate whether Non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission CXR compared with White/Non-Hispanic patients.MethodsSingle-institution, retrospective cohort study approved by the IRB. Patients hospitalized with confirmed COVID-19 infection (3/27/20-4/10/20) were identified using the electronic medical record (EMR) (n=326, mean age: 59 years (SD: 17 years), M:F (188:138). Primary outcome was severity of lung disease on admission CXR, measured by modified Radiographic Assessment of Lung Edema (mRALE) score. Secondary outcome was a composite adverse clinical outcome of intubation, ICU admission, or death. Primary exposure was racial/ethnic category: White/Non-Hispanic versus Non-White [i.e., Hispanic, Black, Asian, Other]. Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race/ethnicity.ResultsNon-White patients had significantly higher mRALE scores (median 6.1, 95% CI 5.4–6.7) compared with White/Non-Hispanic patients (median 4.2, 95% CI 3.6–4.9) (unadjusted average difference 1.8, 95% CI 0.9–2.8, p<0.01). For both White (Adjusted HR, 1.3, 95%CI 1.2-1.4, p<0.001) and Non-White patients (Adjusted HR 1.2, 95%CI 1.1-1.3, p<0.001), increasing mRALE scores were associated with a higher likelihood of experiencing composite adverse outcome with no evidence of interaction (p = 0.16). Multivariable linear regression analyses demonstrated that Non-White patients presented with higher mRALE scores on admission CXR versus White/Non-Hispanic patients (adjusted average difference 1.6, 95% CI 0.5–2.7, p<0.01). Adjustment for hypothesized mediators revealed that the association between race/ethnicity and mRALE scores was mediated by limited English proficiency (p<0.01).ConclusionNon-White patients hospitalized with COVID-19 infection were more likely to present with higher severity of disease on admission CXR than White/Non-Hispanic patients, and increased severity was associated with worse outcomes for all patients.

African Americans Have More Severe Disease at Presentation Among Adults With Crohnʼs Disease, and Asians Have More Severe Disease at Presentation Among Adults With Ulcerative Colitis

Introduction: Severity of disease at presentation among adults with inflammatory bowel disease (IBD) affects disease progression and treatment options. While IBD is well studied in Caucasians, IBD epidemiology is less well studied among ethnic minorities. Disparities in severity of disease at presentation may reflect delayed diagnoses or barriers in access to specialty care, challenges that may affect underserved safety-net populations to a greater extent. Our study evaluates ethnic disparities in severity of disease at presentation among adults with IBD in a diverse urban community-based healthcare system. Methods: All consecutive adults with IBD seen in the gastroenterology clinics of a community-based safety-net hospital from July 2014 to October 2016 were retrospectively evaluated to compare race/ethnicity-specific disparities in severity of disease at presentation. Disease severity in patients with Crohn's disease (CD) was evaluated with the Crohn's Disease Activity Index (CDAI) and the Harvey-Bradshaw Index (HBI). Disease severity in adults with ulcerative colitis (UC) was evaluated using the Simple Clinical Colitis Activity Index (SCCAI) and the Mayo score. Race/ethnicity-specific comparisons of disease activity scores utilized Student's t-test.Table: Table. Race/Ethnicity Disparities in SCCAI Scores at PresentationTable: Table. Race/Ethnicity Disparities in HBI Scores at PresentationResults: Of 157 IBD patients, 59 had CD (54.2% male, mean age 38.2, 42.3% African American, 22.0% Caucasian, 20.3% Hispanic and 8.5% Asian) and 98 had UC (56.1% male, mean age 40.1, 31.0% African American, 29.8% Hispanic, 17.9% Asian, 19.1% Caucasian). For CD patients, the mean HBI score was 6.4 (SD 4.1) and the mean CDAI score was 118.4 (SD 74.6). HBI scores were higher in African Americans vs Hispanics (7.6 vs. 4.2, p=0.037). There was also a trend toward higher CDAI scores in African Americans. In UC patients the mean Mayo score was 6.6 (SD 3.1) and the mean SCCAI score was 6.49 (SD 4.0). Stratified by race/ethnicity, mean SCCAI scores were higher in non-Caucasians vs Caucasians (7.0 vs. 5.4, p=0.03) and in Asians vs Caucasians (8.0 vs. 4.6, p=0.02), and Hispanics trended toward higher mean SCCAI scores vs Caucasians (6.9 vs. 4.6, p=0.08). Similar trends were observed in the Mayo scores with more severe disease in Asians. Conclusion: In adults with IBD at an ethnically diverse safety-net hospital system, significant race/ethnicity-specific disparities in disease severity at presentation were observed. African Americans with CD presented with the most severe disease and Asians with UC presented with the most severe disease.

Racial and ethnic disparities in lung transplant listing and waitlist outcomes

The United States lung transplant registry data demonstrate differences in adult waitlist mortality by race/ethnicity. It is unknown whether these differences persist after risk adjustment or occur secondary to disparities in disease severity at the time of listing. Adult lung transplant waitlist candidates between May 4, 2005 and March 5, 2015 were identified and compared by non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and Asian race/ethnicity. A competing risk proportional hazards model was used to assess the association of race/ethnicity with the unadjusted and adjusted risk of waitlist death or removal for too sick, transplant, or removal for other reason. Disease illness severity at transplant listing was compared by race/ethnicity. There were 20,684 lung transplant candidates identified (82% NHW, 9% NHB, 6% Hispanic, 2% Asian and 1% other). Non-white candidates had higher unadjusted waitlist mortality, which was fully mitigated by adjusting for other risk factors (NHB: hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.93 to 1.18; Hispanic: HR 1.02, 95% CI 0.99 to 1.18; Asian: HR 0.90, 95% CI 0.70 to 1.16). Adjusted waitlist access to transplant was lower in non-white candidates (NHB: HR 0.88, 95% CI 0.83 to 0.94; Hispanic: HR 0.87, 95% CI 0.81 to 0.94; Asian: HR 0.83, 95% CI 0.73 to 0.96). NHW candidates with obstructive lung disease and pulmonary fibrosis were older with less illness severity at listing than non-white candidates. Within the current lung allocation system, there is no difference in risk-adjusted waitlist mortality by race/ethnicity, but non-white waitlist candidates have lower risk-adjusted access to lung transplant. Non-white candidates are generally younger with greater disease-specific illness severity at the time of lung transplant listing.

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes for children with Cushing disease (CD).Methods129 children with CD, 45 Hispanic/Latino or African American (HI/AA) and 84 non-Hispanic White (non-HW), are included. A 10-point index for rating severity (CD-severity) incorporated degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD-severity.ResultsThe mean CD-severity for the HI/AA group was worse than the non-HW group (4.9 ± 2.0 vs 4.1 ± 1.9, p = 0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (p=0.027) and older age (p=0.014) were the most important predictors of worse CD-severity. When followed up a median of 2.3 years after surgery, the relative risk of persistent CD combined with recurrence was 2.8 times higher in HI/AA compared to non-HW (95% CI: 1.2–6.5).ConclusionsOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, risk of persistent and recurrent CD was higher in minority children.

Impact of Expanded Insurance Coverage on Racial Disparities in Vascular Disease: Insights From Massachusetts.

To evaluate the impact of health insurance expansion on racial disparities in severity of peripheral arterial disease. Lack of insurance and non-white race are associated with increased severity, increased amputation rates, and decreased revascularization rates in patients with peripheral artery disease (PAD). Little is known about how expanded insurance coverage affects disparities in presentation with and management of PAD. The 2006 Massachusetts health reform expanded coverage to 98% of residents and provided the framework for the Affordable Care Act. We conducted a retrospective cohort study of nonelderly, white and non-white patients admitted with PAD in Massachusetts (MA) and 4 control states. Risk-adjusted difference-in-differences models were used to evaluate changes in probability of presenting with severe disease. Multivariable linear regression models were used to evaluate disparities in disease severity before and after the 2006 health insurance expansion. Before the 2006 MA insurance expansion, non-white patients in both MA and control states had a 12 to 13 percentage-point higher probability of presenting with severe disease (P < 0.001) than white patients. After the expansion, measured disparities in disease severity by patient race were no longer statistically significant in Massachusetts (+3.0 percentage-point difference, P = 0.385) whereas disparities persisted in control states (+10.0 percentage-point difference, P < 0.001). Overall, non-white patients in MA had an 11.2 percentage-point decreased probability of severe PAD (P = 0.042) relative to concurrent trends in control states. The 2006 Massachusetts insurance expansion was associated with a decreased probability of patients presenting with severe PAD and resolution of measured racial disparities in severe PAD in MA.

What Metabolic Syndrome Contributes to Brain Outcomes in African American & Caucasian Cohorts.

Metabolic syndrome (MetS), i.e., meeting criteria for any three of the following: hyperglycemia, hypertension, hypertriglyceridemia, low high-density lipoprotein and/or abdominal obesity, is associated with negative health outcomes. For example, MetS negatively impacts cognition; however, less is known about incremental MetS risk, i.e., meeting 1 or 2 as opposed to 3 or more criteria. We hypothesized incremental MetS risk would negatively contribute to cognition and relevant neuroanatomy, e.g., memory and hippocampal volumes, and that this risk extends to affective functioning. 119 non-demented/non-depressed participants (age=60.1+12.9;~50% African American) grouped by incremental MetS risk-no (0 criteria met), low (1-2 criteria met), or high (3+ criteria met)-were compared across cognition, affect and relevant neuroanatomy using multivariable linear regressions. Exploratory analyses, stratified by race, consider the role of health disparities in disease severity of individual MetS component (e.g., actual blood pressure readings) on significant results from primary analyses. Incremental MetS risk contributed to depressive symptomatology (no<low<high), learning and memory performance (no>low=high) after controlling for age, race (n.s.) and IQ. Different indices of disease severity contributed to different aspects of brain structure and function by race providing empirical support for future studies of the impact distinct health disparities in vascular risk have on brain aging. MetS compromised mood, cognition and hippocampal structure with incremental risk applying to some but not all of these outcomes. Care providers may wish to monitor a broader spectrum of risk including components of MetS like blood pressure and cholesterol levels when considering brain-behavior relationships in adults from diverse populations.

Threat to Fixation at Diagnosis and Lifetime Risk of Visual Impairment in Open-Angle Glaucoma

To investigate whether threat to fixation (TTF) at diagnosis increases the risk of central vision loss and glaucoma blindness. Retrospective cohort study. A total of 309 patients (309 eyes) with glaucoma were followed up until death; 203 patients (65.7%) had primary open-angle glaucoma, and 106 patients (34.2%) had exfoliation glaucoma. Study eyes were divided into 2 groups according to TTF in the first glaucomatous visual field: (1) eyes with TTF, defined as visual field loss (VFL) including ≥1 of the 4 innermost points depressed at P < 1% level in 24-2 or 30-2 Humphrey fields; (2) eyes without TTF, defined as VFL only outside the 4 innermost points. Lifetime risk of visual acuity (VA) loss and glaucoma blindness in the 2 groups was compared by logistic regression analysis. A matching technique was used to adjust for differences in disease stage at presentation. The relative influence of TTF on the risk of blindness in the 2 matched groups was analyzed by the Kaplan-Meier method. Visual acuity <0.3 and blindness from glaucoma (World Health Organization criteria) at last visit. Threat to fixation was detected in 58.9% of the eyes at diagnosis. The frequency of TTF increased with stage of glaucomatous loss: 28.3% in eyes with mean deviation (MD) >-6.00 decibels (dB) versus 95.7% with MD <-20.00 dB. Univariate analysis demonstrated that eyes with TTF at presentation compared with eyes without TTF became blind more often (56/182 [30.8%] vs. 22/127 [17.3%]; P = 0.008) and faster (mean time from diagnosis to blindness, 84.6±50.7 vs. 126.7±51.4 months; P < 0.002). However, in multivariate analysis, TTF was not an independent risk factor for VA <0.3 (odds ratio, 1.43; 95% confidence interval, 0.75-2.74) or blindness (odds ratio, 1.03; 95% confidence interval, 0.52-2.01). With regard to patient survival time, there were no differences between eyes with TTF and eyes without TTF after adjusting for disparities in disease severity at presentation (P = 0.934). Including TTF in the assessment of risk for glaucoma blindness did not add any important information when the stage of VFL was taken into account.

Autoimmune liver disease

To review studies that improve the diagnosis and treatment of autoimmune hepatitis and extend the understanding of its pathogenic mechanisms. A simplified diagnostic scoring system has high sensitivity and specificity. Biliary changes detected by MRI are of uncertain nature and significance. New candidate autoantigens have been identified by proteomic analyses. T regulatory cells suppress disease activity; their adoptive transfer is beneficial in animal models. Budesonide in combination with azathioprine is effective frontline therapy. Bone marrow-derived mesenchymal stem cell transplantation may emerge as salvage therapy. Screening for hepatocellular cancer is justified. Racial disparities in disease severity, mortality, and treatment remain unexplained. Diagnosis has been simplified and management strategies have been upgraded. Biliary changes have been recognized but are of uncertain nature and significance. New antigens and antibodies have been described. T-cell populations that modulate disease activity have been characterized, and adoptive transfer of T regulatory cells is possible. Budesonide in combination with azathioprine is effective frontline therapy, and therapeutic interventions that target critical pathogenic mechanisms are feasible.

Development of the Allocation System for Deceased Donor Liver Transplantation

As the number of pre- and post-transplant solid organ recipients continues to grow, it becomes important for all physicians to have an understanding of the process of organ procurement and allocation. In the United States, the current system for allocation and transplantation of human solid organs has been heavily influenced by the experience in deceased donor liver transplantation (DDLT). This review highlights the significant changes that have occurred over the past 10 years in DDLT, with specific attention to the impact of the Model for Endstage Liver Disease (MELD) score on organ allocation and pre- and post-transplant survival. DDLT is managed by the United Network for Organ Sharing (UNOS) which oversees organ procurement and allocation across geographically defined Organ Procurement Organizations (OPOs). For many years, deceased donor livers were allocated to waiting list patients based on subjective parameters of disease severity and accrued waiting time. In addition, organs have traditionally been retained within the OPO where they are procured contributing to geographic disparities in disease severity at the time of transplantation among deceased donor recipients. In response to a perceived unfairness in organ allocation, Congress issued its "Final Rule" in 1998. The Rule called for a more objective ranking of waiting list patients and more parity in disease severity among transplant recipients across OPOs. To date, little progress has been made in eliminating geographic inequities. Patients in the smallest OPOs continue to receive liver transplants at a lower level of disease severity. However, strides have been made to standardize assessments of disease severity and better prioritize waiting list patients. The MELD score has emerged as an excellent predictor of short-term mortality in patients with advanced liver disease, and patients listed for liver transplantation are now ranked based on their respective MELD scores. This has improved organ access to the most severely ill patients without compromising waiting list mortality or post-transplant survival. The current system for DDLT remains imperfect but has improved significantly in the past decade. As the number of patients in need of DDLT grows, the system will continue to evolve to meet this increasing demand.