A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

Combining donor derived cell free DNA and gene expression profiling for non-invasive surveillance after heart transplantation.

BACKGROUND: Donor-derived cell free DNA (dd-cfDNA) and gene expression profiling (GEP) offer noninvasive alternatives to rejection surveillance after heart transplantation; however, there is little evidence on the paired use of GEP and dd-cfDNA for rejection surveillance. METHODS: A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd-cfDNA and GEP. The primary outcomes were survival and rejection-free survival at 1 year post-transplant. RESULTS: In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), P < .01. At 1-year, there were no differences between the paired testing and GEP groups in survival (98.4% vs. 94.7%, P = .23) or rejection-free survival (81.3% vs. 73.7% P = .28). CONCLUSIONS: Compared to post-transplant rejection surveillance with GEP alone, pairing dd-cfDNA and GEP testing was associated with similar survival and rejection-free survival at 1 year while requiring significantly fewer biopsies.

Conviction Narrative Theory and the Theory of Narrative Thought.

Conviction Narrative Theory bears a close resemblance to the Theory of Narrative Thought, although the two were designed to address different questions. In this commentary, we detail some of the more pronounced similarities and differences and suggest that resolving the latter could produce a third theory of narrative cognition that is superior to either of these two.

Impact of diabetes mellitus on clinical outcomes after heart transplantation.

PURPOSE: Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center. METHODS: We performed a retrospective study (range 01/2008 - 07/2018), n = 244. The primary outcome was survival; secondary outcomes included acute rejection, cardiac allograft vasculopathy, infection requiring hospitalization, macrovascular events, and dialysis initiation post-transplant. Comparisons were performed using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Pretransplant DM was present in 75 (30.7%) patients and was associated with a higher risk for infection requiring hospitalization (p < 0.05), but not with survival or other outcomes. Among the 144 patients without pretransplant DM surviving to 1 year, 29 (20.1%) were diagnosed with PTDM at the 1-year follow-up. After multivariable adjustment, PTDM diagnosis at 1-year remained associated with worse subsequent survival (hazard ratio 2.72, 95% confidence interval 1.03-7.16). Predictors of PTDM at 1-year included cytomegalovirus seropositivity and higher prednisone dose (> 5 mg/day) at 1-year follow-up. CONCLUSIONS: Compared to HTx recipients without baseline DM, those with baseline DM have a higher risk for infections requiring hospitalization, and those who develop DM after HTx have worse survival.

Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada.

PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT3 antagonists are recommended over dexamethasone.

Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically summarize the risk relationship between different levels of alcohol consumption and incidence of liver cirrhosis. METHODS: MEDLINE and Embase were searched up to March 6, 2019, to identify case-control and cohort studies with sex-specific results and more than 2 categories of drinking in relation to the incidence of liver cirrhosis. Study characteristics were extracted and random-effects meta-analyses and meta-regressions were conducted. RESULTS: A total of 7 cohort studies and 2 case-control studies met the inclusion criteria, providing data from 2,629,272 participants with 5,505 cases of liver cirrhosis. There was no increased risk for occasional drinkers. Consumption of one drink per day in comparison to long-term abstainers showed an increased risk for liver cirrhosis in women, but not in men. The risk for women was consistently higher compared to men. Drinking ≥5 drinks per day was associated with a substantially increased risk in both women (relative risk [RR] = 12.44, 95% confidence interval [CI]: 6.65-23.27 for 5-6 drinks, and RR = 24.58, 95% CI: 14.77-40.90 for ≥7 drinks) and men (RR = 3.80, 95% CI: 0.85-17.02, and RR = 6.93, 95% CI: 1.07-44.99, respectively). Heterogeneity across studies indicated an additional impact of other risk factors. DISCUSSION: Alcohol is a major risk factor for liver cirrhosis with risk increasing exponentially. Women may be at higher risk compared to men even with little alcohol consumption. More high-quality research is necessary to elucidate the role of other risk factors, such as genetic vulnerability, body weight, metabolic risk factors, and drinking patterns over the life course. High alcohol consumption should be avoided, and people drinking at high levels should receive interventions to reduce their intake.

Parvovirus B19-induced severe anemia in heart transplant recipients: Case report and review of the literature.

We report a case of a 64-year-old woman who developed transfusion-dependent anemia after cardiac transplantation, the etiology of which was unknown after initial comprehensive evaluation. At the suggestion of the Transplant Infectious Diseases consultant, microbial agents with red blood cell tropism pertinent to this patient such as Parvovirus B 19 (B19V) were investigated. The B19V viral load by PCR in peripheral blood was >100 000 000 copies/ml and after treatment with intravenous immunoglobulin (IVIG), her anemia resolved. Here, we summarize the clinical and virologic characteristics, treatment, and outcome of fifteen cases of B19V-induced anemia in heart transplant recipients. Spontaneous recovery from anemia secondary to B19V has also been reported in some heart transplant recipients, possibly due to an absence of their B19V P-antigen receptor and/or reduction in their immunosuppression. Therefore, in heart transplant patients, B19V should be suspected early as a cause of severe anemia of unknown etiology. The extent that B19V-induced anemia is underdiagnosed in heart transplant recipients is unknown.

Outcomes of patients with infection related to a ventricular assist device after heart transplantation.

BACKGROUND: Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short-term survival and infectious incidence rates in the post-transplantation period and assess risk factors for infectious episodes after transplantation. METHODS: Retrospective single-center study of all consecutive adult heart transplant patients from 2008 to 2017. Survival data were estimated and summarized using the Kaplan-Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine-Gray model. The outcome of interest is the time to first infection diagnosis with post-transplant death as the competing event. RESULTS: Among 278 heart transplant patients, 74 (26.5%) underwent LVAD implantation. Twenty-one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs 27.8 kg/m2 , P = .03). Median follow-up post-transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11-3.39, P = .020) and recipient COPD (HR 2.14, [95% CI] 1.39-3.32, P = .001) when adjusted for recipient age, gender, hypertension, diabetes mellitus, and body mass index. CONCLUSIONS: Patients with LVAD-related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted.

A case-control study analyzing mannitol dosing for prevention of cisplatin-induced acute nephrotoxicity.

BACKGROUND: Mannitol is an osmotic diuretic given routinely as part of cisplatin regimens to prevent nephrotoxicity, but there are limited data on the ideal dosage. At our center, three different doses of mannitol are used: 12, 20, and 40 g per cycle for cisplatin doses of ≥50 mg/m2. The primary objective was to determine if variations in mannitol dosing significantly influence the incidence of cisplatin-induced acute nephrotoxicity. METHODS: A case-control study was performed. Electronic records of 1462 consecutive outpatients who received cisplatin at ≥ 50 mg/m2 per cycle between January 2010 and December 2014 were reviewed. Patients experiencing nephrotoxicity of any grade within 30 days of last cisplatin dose, as defined by NCI CTCAE 4.0, were matched to a minimum of two and maximum of five controls based on the following criteria: age ± 5 years, baseline estimated glomerular filtration rate ± 10 ml/min/1.73 m2, cisplatin dose per cycle, and presence of diabetes. Conditional logistic regression was used to identify baseline predictors of cisplatin-induced acute nephrotoxicity. RESULTS: Of the 1245 included patients, 237 had nephrotoxicity and 1008 were matched controls. Median baseline estimated glomerular filtration rate for cases and controls were 83 and 80 ml/min/1.73 m2, respectively. A total of 3.8% of cases experienced ≥ grade 3 nephrotoxicity. Univariable analysis showed that diabetes, lymphoma, low baseline estimated glomerular filtration rate, and low baseline magnesium level were significantly associated with nephrotoxicity, whereas mannitol dosing did not show any association (odds ratio 1.08; p = 0.29). In multivariable analysis, diabetes and lymphoma retained statistical significance, but baseline estimated glomerular filtration rate and baseline magnesium level showed nonsignificant associations with nephrotoxicity. CONCLUSIONS: Cisplatin-induced acute nephrotoxicity remains common in patients with good baseline renal function despite preventive measures. Diabetes and lymphoma are predictors of nephrotoxicity, whereas mannitol dosing has no significant influence, suggesting that doses may be standardized across cisplatin regimens.

Delirium after lung transplantation: Association with recipient characteristics, hospital resource utilization, and mortality.

BACKGROUND: Delirium is associated with increased morbidity and mortality. The factors associated with post-lung transplant delirium and its impact on outcomes are under characterized. METHODS: The medical records of 163 consecutive adult lung transplant recipients were reviewed for delirium within 5 days (early-onset) and 30 hospital days (ever-onset) post-transplantation. A multivariable logistic regression model assessed factors associated with delirium. Multivariable negative binomial regression and Cox proportional hazards models assessed the association of delirium with ventilator duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, and one-year mortality. RESULTS: Thirty-six percent of patients developed early-onset, and 44% developed ever-onset delirium. Obesity (OR 6.35, 95% CI 1.61-24.98) and bolused benzodiazepines within the first postoperative day (OR 2.28, 95% CI 1.07-4.89) were associated with early-onset delirium. Early-onset delirium was associated with longer adjusted mechanical ventilation duration (P=.001), ICU LOS (P<.001), and hospital LOS (P=.005). Ever-onset delirium was associated with longer ICU (P<.001) and hospital LOS (P<.001). After adjusting for clinical variables, delirium was not significantly associated with one-year mortality (early-onset HR 1.65, 95% CI 0.67-4.03; ever-onset HR 1.70, 95% CI 0.63-4.55). CONCLUSIONS: Delirium is common after lung transplant surgery and associated with increased hospital resources.

Cost and yield considerations when expanding recruitment for genetic studies: the primary open-angle African American glaucoma genetics study.

BACKGROUND: African Americans have been historically under-represented in genetic studies. More research is needed on effective recruitment strategies for this population, especially on approaches that supplement traditional clinic enrollment. This study evaluates the cost and efficacy of four supplemental recruitment methods employed by the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. METHODS: After enrolling 2304 patients from University of Pennsylvania ophthalmology clinics, the POAAGG study implemented four new recruitment methods to supplement clinic enrollment. These methods included: 1) outreach in the local community, 2) in-house screening of community members ("in-reach"), 3) expansion to two external sites, and 4) sampling of the Penn Medicine Biobank. The cost per subject was calculated for each method and enrollment among cases, controls, and suspects was reported. RESULTS: The biobank offered the lowest cost ($5/subject) and highest enrollment yield (n = 2073) of the four methods, but provided very few glaucoma cases (n = 31). External sites provided 88% of cases recruited from the four methods (n = 388; $85/subject), but case enrollment at these sites declined over the next 9 months as the pool of eligible subjects was depleted. Outreach and in-reach screenings of community members were very high cost for low return on enrollment ($569/subject for 102 subjects and $606/subject for 45 subjects, respectively). CONCLUSIONS: The biobank offered the most cost-effective method for control enrollment, while expansion to external sites was necessary to recruit richly phenotyped cases. These recruitment methods helped the POAAGG study to exceed enrollment of the discovery cohort (n = 5500) 6 months in advance of the predicated deadline and could be adopted by other large genetic studies seeking to supplement clinic enrollment.

The effect of Ai Chi aquatic therapy on individuals with knee osteoarthritis: a pilot study.

[Purpose] To examine the efficacy of Ai Chi in relieving the pain and stiffness of knee osteoarthritis and improving, physical functioning, proprioception and quality of life. [Subjects and Methods] Twenty-five persons with knee osteoarthritis completed 5 weeks Ai Chi practice (60 minutes per session, twice per week, 10 sessions in total). Knee pain and stiffness were measured before and after the intervention program. [Results] Significant improvements in pain, self-perceived physical functioning and self-perceived stiffness were observed after the Ai-Chi intervention. On average, no significant change in knee range of motion, 6-minute walk test distances or proprioception was observed. [Conclusion] A five-week Ai Chi intervention can improve the pain and stiffness of knee osteoarthritis and self-perceived physical functions and quality of life improvement. Ai Chi may be another treatment choice for people with knee OA to practice in the community.

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

The Association Between Limited English Proficiency and Unplanned Emergency Department Revisit Within 72 Hours.

STUDY OBJECTIVE: Language barriers are known to negatively affect many health outcomes among limited English proficiency patient populations, but little is known about the quality of care such patients receive in the emergency department (ED). This study seeks to determine whether limited English proficiency patients experience different quality of care than English-speaking patients in the ED, using unplanned revisit within 72 hours as a surrogate quality indicator. METHODS: We conducted a retrospective cohort study in an urban adult ED in 2012, with a total of 41,772 patients and 56,821 ED visits. We compared 2,943 limited English proficiency patients with 38,829 English-speaking patients presenting to the ED after excluding patients with psychiatric complaints, altered mental status, and nonverbal states, and those with more than 4 ED visits in 12 months. Two main outcomes-the risk of inpatient admission from the ED and risk of unplanned ED revisit within 72 hours-were measured with odds ratios from generalized estimating equation multivariate models. RESULTS: Limited English proficiency patients were more likely than English speakers to be admitted (32.0% versus 27.2%; odds ratio [OR]=1.20; 95% confidence interval [CI] 1.11 to 1.30). This association became nonsignificant after adjustments (OR=1.04; 95% CI 0.95 to 1.15). Included in the analysis of ED revisit within 72 hours were 32,857 patients with 45,546 ED visits; 4.2% of all patients (n=1,380) had at least 1 unplanned revisit. Limited English proficiency patients were more likely than English speakers to have an unplanned revisit (5.0% versus 4.1%; OR=1.19; 95% CI 1.02 to 1.45). This association persisted (OR=1.24; 95% CI 1.02 to 1.53) after adjustment for potential confounders, including insurance status. CONCLUSION: We found no difference in hospital admission rates between limited English proficiency patients and English-speaking patients. Yet limited English proficiency patients were 24% more likely to have an unplanned ED revisit within 72 hours, with an absolute difference of 0.9%, suggesting challenges in ED quality of care.

Tolerability of Vidaza (azacitidine) subcutaneous administration using a maximum volume of 3 ml per injection.

The azacitidine (Vidaza®) product monograph indicates that doses greater than 4 ml should be divided equally into two syringes and injected into different sites. Although 2 ml is a more commonly used maximum volume for subcutaneous injections, there is a lack of evidence to support the use of any given maximum volume with azacitidine. Applying the status quo of 2 ml to azacitidine results in patients receiving 3-4 injections per visit. This prospective study evaluated the frequency and type of injection site reactions when the maximum subcutaneous injection volume was increased from 2 to 3 ml per injection site. Among 30 patients, 309 doses were administered, and injection site reactions were noted in 92.9% of all doses, with the majority (82.2%) being grade 1; only 10.7% of doses resulted in grade 2 reactions, and there were no grade 3 or 4 reactions. There was no increase in frequency or severity of injection site reactions when the maximum volume was increased to 3 ml. The median number of injections that patients received per visit decreased from 3 to 2 after the volume was increased, and there was a statistically significant reduction in the incidence of pain. Decreasing the number of injections also facilitates ease of rotation of injection sites and decreases pharmacy preparation time. This is the first time that injection site reaction data relating to injection volume have been reported for azacitidine.

Tolerability of Velcade (Bortezomib) subcutaneous administration using a maximum volume of 3 mL per injection site.

Subcutaneous injection is now commonly used as a standard for bortezomib administration. The bortezomib (Velcade(®)) product monograph recommends that intravenous injections be prepared at a concentration of 1 mg/mL, while subcutaneous injections may be prepared at a concentration of 2.5 mg/mL. Many institutions and subcutaneous administration guidelines use 2 mL as the maximum volume for subcutaneous injection. Using 2 mL as the maximum volume for injection would mean that many patients receiving bortezomib will receive two injections during each visit with common dosing parameters. In this prospective study evaluating a change to subcutaneous administration, bortezomib 1 mg/mL was administered subcutaneously at a higher maximum of 3 mL per injection site. For 57 individual patients, 339 doses were administered. Skin reactions were noted in 42% with all reactions being Grade 1 or 2. Patients tolerated subcutaneous injections well and only four patients were switched back to intravenous route. This is the first time that subcutaneous bortezomib of a volume up to a maximum of 3 mL (bortezomib 3 mg) per injection site has been reported. This higher single dose is well tolerated with limited skin reactions, no significant hypotension and facilitates ease of administration with only 5 patients needing two injections per visit. If the maximum volume for injection was kept at 2 mL, a total of 46 patients would have received two injections per visit.

Reconsidering a science of psychology built on laws.

At one time, psychologists aspired to build a science composed of interrelated descriptive laws and the theories that explain them--a nomothetic science. For various reasons this goal was abandoned. In its place, we have a collection of theories that, for the most part, are organized by topic and subdiscipline or by themes and shared language (e.g., characterization of cognition in terms of information processing, which is neither a law nor a rigorous theory but a viewpoint or approach). As things stand, although our theories and research are scientific, we have failed to create a coherent science. In this article the nomothetic goal is reconsidered, and an example of how we might begin to achieve it is described.

Misogynistic Extremism: A Scoping Review.

In recent years, the concept of "misogynistic extremism" has emerged as a subject of interest among scholars, governments, law enforcement personnel, and the media. Yet a consistent understanding of how misogynistic extremism is defined and conceptualized has not yet emerged. Varying epistemological orientations may contribute to the current conceptual muddle of this topic, reflecting long-standing and on-going challenges with the conceptualization of its individual components. To address the potential impact of misogynistic extremism (i.e., violent attacks), a more precise understanding of what this phenomenon entails is needed. To summarize the existing knowledge base on the nature of misogynistic extremism, this scoping review analyzed publications within English-language peer-reviewed and gray literature sources. Seven electronic databases and citation indexes were systematically searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist and charted using the 2020 PRISMA flow diagram. Inclusion criteria included English peer-reviewed articles and relevant gray literature publications, which contained the term "misogynistic extremism" and other closely related terms. No date restrictions were imposed. The search strategy initially yielded 475 publications. After exclusion of ineligible articles, 40 publications remained for synthesis. We found that misogynistic extremism is most frequently conceptualized in the context of misogynistic incels, male supremacism, far-right extremism, terrorism, and the black pill ideology. Policy recommendations include increased education among law enforcement and Countering and Preventing Violent Extremism experts on male supremacist violence and encouraging legal and educational mechanisms to bolster gender equality. Violence stemming from misogynistic worldviews must be addressed by directly acknowledging and challenging socially embedded systems of oppression such as white supremacy and cisheteropatriarchy.

Primary Open-Angle Glaucoma Is Associated with Short-Term Memory Decline and Dementia in Individuals of African Ancestry.

Background: Over the last decade, studies have suggested that primary open-angle glaucoma (POAG) may be associated with cognitive impairment and dementia, as both pathologies are age-related neurodegenerative processes. It remains unclear to what extent neurodegeneration in POAG extends to other neurological functions beyond vision, such as cognition. This follow-up study examined the potential association between POAG and cognitive decline in an African ancestry population. Methods: The Telephone-Montreal Cognitive Assessment (T-MoCA) was administered to POAG cases and controls previously enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Cases were assessed for retinal nerve fiber layer (RNFL) thickness and for the presence of dementia via chart review. Comparisons between POAG cases and controls were performed using two-sample t-tests for the T-MoCA total score and five subsection scores, and using chi-squared tests for incidence of dementia. Current scores were compared to scores from this same cohort from 7 years prior. Results: The T-MoCA was administered to 13 cases and 20 controls. The mean ± standard deviation (SD) T-MoCA total score was 15.5 ± 4.0 in cases and 16.7 ± 3.5 in controls (p = 0.36). However, there was a borderline significant difference in the delayed recall sub-score (2.3 ± 1.6 for cases vs. 3.4 ± 1.5 for controls, p = 0.052) and a significant difference in its sub-domain, the memory index score (MIS, 9.1 ± 4.3 for cases vs. 12.1 ± 3.0 for controls, p = 0.02). There were no significant differences between cases and controls for the remaining subsections. During 7 years of follow-up, a higher incidence of dementia was noted in POAG cases (7.1% for cases vs. 0% for controls, p = 0.058). Over 7 years, there was no significant deterioration in the cognitive performance of cases versus controls, and no association was seen between RNFL thinning and cognitive impairment. Conclusions: In this small-sample follow-up study of African ancestry individuals, POAG cases demonstrated worse short-term memory and higher incidence of dementia compared to controls. Future larger studies are needed to further investigate the presence and impact of neurodegeneration in POAG.

HLA sensitization is associated with an increased risk of primary graft dysfunction after heart transplantation.

Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). We sought to determine the association between pretransplant human leukocyte antigen (HLA) sensitization, as measured using the calculated panel reactive antibody (cPRA) value, and the risk of PGD. METHODS: Consecutive adult HT recipients (n = 596) from 1/2015 to 12/2019 at 2 US centers were included. Severity of PGD was based on the 2014 International Society for Heart and Lung Transplantation consensus statement. For each recipient, unacceptable HLA antigens were obtained and locus-specific cPRA (cPRA-LS) and pre-HT donor-specific antibodies (DSA) were assessed. RESULTS: Univariable logistic modeling showed that peak cPRA-LS for all loci and HLA-A was associated with increased severity of PGD as an ordinal variable (all loci: OR 1.78, 95% CI: 1.01-1.14, p = 0.025, HLA-A: OR 1.14, 95% CI: 1.03-1.26, p = 0.011). Multivariable analysis showed peak cPRA-LS for HLA-A, recipient beta-blocker use, total ischemic time, donor age, prior cardiac surgery, and United Network for Organ Sharing status 1 or 2 were associated with increased severity of PGD. The presence of DSA to HLA-B was associated with trend toward increased risk of mild-to-moderate PGD (OR 2.56, 95% CI: 0.99-6.63, p = 0.053), but DSA to other HLA loci was not associated with PGD. CONCLUSIONS: Sensitization for all HLA loci, and specifically HLA-A, is associated with an increased severity of PGD. These factors should be included in pre-HT risk stratification to minimize the risk of PGD.