Persistence of Contact Lens-Induced Corneal Parainflammation Following Lens Removal.

Purpose: Contact lens wear induces corneal parainflammation involving increased immune cell numbers after 24 hours' (CD11c+, Lyz2+, γδ-T cells) and six days' (Ly6G+ cells) wear. We investigated the time course of onset and resolution of these responses. Methods: LysMcre or C57BL/6J mice were fitted with a contact lens (four to 48 hours). Contralateral eyes did not wear lenses. After lens removal, Lyz2+, MHC-II+ or Ly6G+ cells were examined by quantitative imaging. RT-qPCR determined cytokine gene expression. Results: Lens wear for 24 hours increased corneal Lyz2+ cells versus contralateral eyes approximately two-fold. Corneas remained free of visible pathology. The Lyz2+ response was not observed after four or 12 hours' wear, nor after 12 hours' wear plus 12 hours' no wear. Lens removal after 24 hours' wear further increased Lyz2+ cells (∼48% after one day), which persisted for four days, returning to baseline by seven days. Lyz2+ cells in contralateral eyes remained at baseline. MHC-II+ cells showed a similar response but without increasing after lens removal. Lens wear for 48 hours showed reduced Lyz2+ cells versus 24 hours' wear with one day discontinuation, correlating with reduced IL-1ß and IL-18 gene expression. Lens wear for 24 hours did not induce Ly6G+ responses six days after removal. Conclusions: Lens-induced corneal parainflammation involving Lyz2+ cells requires 24 hours' wear but persists after lens discontinuation, requiring seven days for reversal. Lens wear for 48 hours may suppress initial Lyz2+ cell and cytokine responses. The significance of parainflammation during and after lens wear remains to be determined.

Immunogenicity of Cemiplimab: Low Incidence of Antidrug Antibodies and Cut-Point Suitability Across Tumor Types.

The immunogenicity of cemiplimab, a fully human immunoglobulin G4 monoclonal antibody directed against programmed cell death 1, was assessed in patients across multiple tumor types. The development of antidrug antibodies (ADAs) against cemiplimab was monitored using a validated bridging immunoassay. To identify ADA-positive samples in the assay, statistically determined cut points were established by analyzing baseline clinical study samples from a mixed population of different tumor types, and this validation cut point was used to assess immunogenicity in all subsequent studies. Regulatory guidance requires that ADA assay cut points be verified for appropriateness in different patient populations. Thus, for the cemiplimab ADA assay, we evaluated whether each new oncology population was comparable with the validation population used to set the cut point. Assay responses from 2393 individual serum samples from 8 different tumor types were compared with the validation population, using established statistical methods for cut-point determination and comparison, with no significant differences observed. Across tumor types, the immunogenicity of cemiplimab was low, with an overall treatment-emergent ADA incidence rate of 1.9% and 2.5% at intravenous dose regimens of 3 mg/kg every 2 weeks and 350 mg every 3 weeks, respectively. Moreover, no neutralizing antibodies to cemiplimab were detected in patients with ADA-positive samples, and there was no observed impact of cemiplimab ADAs on pharmacokinetics. Study-specific cut points may be required in some diseases, such as immune and inflammatory diseases; however, based on this analysis, in-study cut points are not required for each new oncology disease indication for cemiplimab.

Rapid surveillance of New York City healthcare center egress behaviors during the 2020 COVID-19 lockdown.

This rapid response surveillance project was funded by the National Science Foundation (NSF) to collect "perishable" data on egress behaviors and neighborhood conditions surrounding healthcare centers (HCCs) in New York City (NYC) during the initial NYC COVID-19 PAUSE ordinance from March 22nd to May 19th, 2020. Anonymized data on NYC HCC egress behaviors were collected by observational field workers using phone-based mapping applications. Each egress trip record includes the day of week, time of day, destination category type, along with an array of behavioral outcome categories, ambient weather conditions and socio-economic factors. Egress trajectories with precise estimates of distance traveled and the spatial dispersion or "spread" around each HCC were added via post-processing. The data collection and cleaning process resulted in 5,030 individual egress records from 18 facilities over a 9-week period.

Contact lens-induced corneal parainflammation involving Ly6G+ cell infiltration requires IL-17A and γδ T cells.

PURPOSE: Previously, using a murine model, we reported that contact lens (CL) wear induced corneal parainflammation involving CD11c+ cells after 24 h and Ly6G+ cells (neutrophils) after 5-6 days. Here, we investigated the role of IL-17 and γδ T cells in the CL-induced neutrophil response. METHODS: CL-wearing C57BL/6 wild-type (WT) mice were compared to lens-wearing IL-17A/F single or double gene knock-out mice, or mice treated with UC7-13D5 monoclonal antibody to functionally deplete γδ T cells. Contralateral eyes served as no lens wear controls. Corneal Ly6G+ and γδ T cell responses were quantified as was expression of genes encoding pro-inflammatory cytokines IL-17A/F, IL-ß, IL-18 and expression of IL-17A/F protein. RESULTS: After 6 days lens wear, WT corneas showed Ly6G+ cell infiltration while remaining free of visible pathology. In contrast, lens-wearing corneas of IL-17AF (-/-), IL-17A (-/-) mice and γδ T cell-depleted mice showed little or no Ly6G+ cell infiltration. No Ly6G+ cell infiltration was detected in contralateral eye controls. Lens-wearing WT corneas also showed a significant increase in γδ T cells after 24 h that was maintained after 6 days of wear, and significantly increased cytokine gene expression after 6 days versus contralateral controls: IL-18 & IL-17A (∼3.9 fold) and IL-23 (∼6.5-fold). Increased IL-17A protein (∼4-fold) was detected after 6 days lens wear. γδ T cell-depletion abrogated these lens-induced changes in cytokine gene and protein expression. CONCLUSION: Together, these data show that IL-17A and γδ T cells are required for Ly6G+ cell (neutrophil) infiltration of the cornea during contact lens-induced parainflammation.

Relations Between Adolescent Sensation Seeking and Risky Sexual Behaviors Across Sex, Race, and Age: A Meta-Analysis.

Sensation seeking (SS)-the seeking of novel and intense sensations or experiences and the willingness to take risks for the sake of such experiences-has been shown to be related to various risky sexual behaviors (RSBs) in areas such as multiple sexual partners, condom use, and sexual initiation. The aims of the current meta-analysis were to examine (1) how SS relates to specific RSBs in adolescents and (2) how the overall relationship between SS and RSB differs across sex, race, and age. Overall, a total of 40 studies met the inclusion criteria for our meta-analysis examining the relationship between SS and RSB, contributing 102 effect sizes. RSB variables included unprotected sex; multiple sexual partners; hazardous sexual activity; sexual initiation; virginity status; and history of sexually transmitted disease (STD) diagnosis. Moderating effects of sex, race, and age were also examined. The overall mean effect size of the correlational relationship between adolescent SS and RSB was statistically significant, as were the mean effect sizes of the relationships between SS and RSB subgroups, except for history of STD diagnosis. Race and age did not significantly moderate the overall relationship between SS and RSB; however, results indicated that SS and RSB relations were stronger in females compared to males. Our findings suggest that adolescents with elevations in SS tendencies tend to engage in more RSBs compared to their peers with lower levels of SS, increasing their risk of unplanned pregnancy and STD acquisition.

Structural variant analysis of a cancer reference cell line sample using multiple sequencing technologies.

BACKGROUND: The cancer genome is commonly altered with thousands of structural rearrangements including insertions, deletions, translocation, inversions, duplications, and copy number variations. Thus, structural variant (SV) characterization plays a paramount role in cancer target identification, oncology diagnostics, and personalized medicine. As part of the SEQC2 Consortium effort, the present study established and evaluated a consensus SV call set using a breast cancer reference cell line and matched normal control derived from the same donor, which were used in our companion benchmarking studies as reference samples. RESULTS: We systematically investigated somatic SVs in the reference cancer cell line by comparing to a matched normal cell line using multiple NGS platforms including Illumina short-read, 10X Genomics linked reads, PacBio long reads, Oxford Nanopore long reads, and high-throughput chromosome conformation capture (Hi-C). We established a consensus SV call set of a total of 1788 SVs including 717 deletions, 230 duplications, 551 insertions, 133 inversions, 146 translocations, and 11 breakends for the reference cancer cell line. To independently evaluate and cross-validate the accuracy of our consensus SV call set, we used orthogonal methods including PCR-based validation, Affymetrix arrays, Bionano optical mapping, and identification of fusion genes detected from RNA-seq. We evaluated the strengths and weaknesses of each NGS technology for SV determination, and our findings provide an actionable guide to improve cancer genome SV detection sensitivity and accuracy. CONCLUSIONS: A high-confidence consensus SV call set was established for the reference cancer cell line. A large subset of the variants identified was validated by multiple orthogonal methods.

Ultra-deep sequencing validates safety of CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells.

As CRISPR-based therapies enter the clinic, evaluation of safety remains a critical and active area of study. Here, we employ a clinical next generation sequencing (NGS) workflow to achieve high sequencing depth and detect ultra-low frequency variants across exons of genes associated with cancer, all exons, and genome wide. In three separate primary human hematopoietic stem and progenitor cell (HSPC) donors assessed in technical triplicates, we electroporated high-fidelity Cas9 protein targeted to three loci (AAVS1, HBB, and ZFPM2) and harvested genomic DNA at days 4 and 10. Our results demonstrate that clinically relevant delivery of high-fidelity Cas9 to primary HSPCs and ex vivo culture up to 10 days does not introduce or enrich for tumorigenic variants and that even a single SNP in a gRNA spacer sequence is sufficient to eliminate Cas9 off-target activity in primary, repair-competent human HSPCs.

Topical antibiotics reduce CD11c+ cell numbers in the healthy murine cornea and modulate their response to contact lens wear.

Previously we reported contact lens-induced CD11c+ cell responses in healthy mouse corneas, a phenomenon that also occurs in humans. To test involvement of ocular-associated bacteria, the impact of topical antibiotics on corneal CD11c+ cell populations during 24 h of lens wear was examined. Corneas were treated with gentamicin and ofloxacin (0.3%) or gentamicin alone, some also treated prior to lens wear (24 h). Contralateral PBS-treated eyes served as controls. CD11c-YFP (Yellow Fluorescent Protein) mice allowed CD11c+ cell visualization. Viable bacteria, on the ocular surface or contact lens, were labeled using FISH (16S rRNA-targeted probe) or click-chemistry (alkDala). Antibiotic treatment reduced baseline CD11c+ cell numbers without lens wear and suppressed CD11c+ cell responses to lens wear if corneas were both pretreated and treated during wear. Few bacteria colonized corneas or lenses under any circumstances. Conjunctival commensals were significantly reduced by antibiotics with or without lens wear, but minimally impacted by lens wear alone. Deliberate inoculation with conjunctival commensals triggered CD11c+ cell responses irrespective of antibiotic pretreatment. These results suggest that while lens wear does not necessarily increase quantifiable numbers of conjunctival commensals, those neutralized by antibiotics play a role in lens-associated CD11c+ cell responses and maintaining baseline CD11c+ cell populations.

Bioanalytical Challenges due to Prior Checkpoint Inhibitor Exposure: Interference and Mitigation in Drug Concentration and Immunogenicity Assays.

Monoclonal antibodies (mAbs) are a leading class of biotherapeutics. In oncology, patients often fail on early lines of biologic therapy to a specific target. Some patients may then enroll in a new clinical trial with a mAb specific for the same target. Therefore, immunoassays designed to quantify the current mAb therapy or assess immunogenicity to the drug may be susceptible to cross-reactivity or interference with residual prior biologics. The impact of two approved anti-PD-1 mAbs, pembrolizumab and nivolumab, was tested in several immunoassays for cemiplimab, another approved anti-PD-1 mAb. The methods included a target-capture drug concentration assay, a bridging anti-drug antibody (ADA) assay and a competitive ligand-binding neutralizing antibody (NAb) assay. We also tested bioanalytical strategies to mitigate cross-reactivity or interference in these assays from other anti-PD-1 biologics. Both pembrolizumab and nivolumab cross-reacted in the cemiplimab drug concentration assay. This was mitigated by addition of antibodies specific to pembrolizumab or nivolumab. ADA specific for pembrolizumab and nivolumab did not interfere in the cemiplimab ADA assay. However, pembrolizumab and nivolumab generated a false-positive response in a target-capture NAb assay. Our results demonstrate that similar exogenous pre-existing anti-PD-1 mAbs (biotherapeutics) such as pembrolizumab and nivolumab are detected and accurately quantified in the cemiplimab drug concentration assay. However, once steady state is achieved for the new therapy, prior biologics would likely not be detected. Cross-reactivity and interference in immunoassays from previous treatment with class-specific biotherapeutic(s) pose significant bioanalytical challenges, especially in immuno-oncology.

Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing.

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.

SENTI-101, a Preparation of Mesenchymal Stromal Cells Engineered to Express IL12 and IL21, Induces Localized and Durable Antitumor Immunity in Preclinical Models of Peritoneal Solid Tumors.

Advanced peritoneal carcinomatosis including high-grade ovarian cancer has poor prognoses and a poor response rate to current checkpoint inhibitor immunotherapies; thus, there is an unmet need for effective therapeutics that would provide benefit to these patients. Here we present the preclinical development of SENTI-101, a cell preparation of bone marrow-derived mesenchymal stromal (also known as stem) cells (MSC), which are engineered to express two potent immune-modulatory cytokines, IL12 and IL21. Intraperitoneal administration of SENTI-101 results in selective tumor-homing and localized and sustained cytokine production in murine models of peritoneal cancer. SENTI-101 has extended half-life, reduced systemic distribution, and improved antitumor activity when compared with recombinant cytokines, suggesting that it is more effective and has lower risk of systemic immunotoxicities. Treatment of tumor-bearing immune-competent mice with a murine surrogate of SENTI-101 (mSENTI-101) results in a potent and localized immune response consistent with increased number and activation of antigen presenting cells, T cells and B cells, which leads to antitumor response and memory-induced long-term immunity. Consistent with this mechanism of action, co-administration of mSENTI-101 with checkpoint inhibitors leads to synergistic improvement in antitumor response. Collectively, these data warrant potential clinical development of SENTI-101 for patients with peritoneal carcinomatosis and high-grade ovarian cancer.Graphical abstract: SENTI-101 schematic and mechanism of actionSENTI-101 is a novel cell-based immunotherapeutic consisting of bone marrow-derived mesenchymal stromal cells (BM-MSC) engineered to express IL12 and IL21 intended for the treatment of peritoneal carcinomatosis including high-grade serous ovarian cancer. Upon intraperitoneal administration, SENTI-101 homes to peritoneal solid tumors and secretes IL12 and IL21 in a localized and sustained fashion. The expression of these two potent cytokines drives tumor infiltration and engagement of multiple components of the immune system: antigen-presenting cells, T cells, and B cells, resulting in durable antitumor immunity in preclinical models of cancer.

Case of hypoactive delirium precipitated by thiamine deficiency.

Thiamine is an essential cofactor in the process of nucleic acid synthesis. Neuronal tissues are especially sensitive to thiamine deficiency, manifesting as Wernicke's encephalopathy (WE). The typical triad of WE, encephalopathy, oculomotor dysfunction and gait ataxia, is only present in less than one-third of the cases. We present the case of a middle-aged man with hypoactive delirium due to presumed thiamine deficiency, who had a prolonged hospital course and a delayed diagnosis of the cause of altered mental status. The presentation of this disorder solely as a decreased level of consciousness is uncommon but has been reported in the literature. It is essential to recognise WE as a treatable condition that may manifest only as a hypoactive delirium. The delay in the diagnosis and treatment may lead to coma and death.

Policy and Pandemic: The Changing Practice of Nephrology During the Coronavirus Disease-2019 Outbreak.

The coronavirus (coronavirus disease-2019) pandemic has changed care delivery for patients with end-stage kidney disease. We explore the US healthcare system as it pertains to dialysis care, including existing policies, modifications implemented in response to the coronavirus disease-2019 crisis, and possible next steps for policy makers and nephrologists. This includes policies related to resource management, use of telemedicine, prioritization of dialysis access procedures, expansion of home dialysis modalities, administrative duties, and quality assessment. The government has already established policies that have instated some flexibilities to help providers focus their response to the crisis. However, future policy during and after the coronavirus disease-2019 pandemic can bolster our ability to optimize care for patients with end-stage kidney disease. Key themes in this perspective are the importance of policy flexibility, clear strategies for emergency preparedness, and robust health systems that maximize accessibility and patient autonomy.

Skeletal tissue regulation by catalase overexpression in mitochondria.

Accumulation of oxidative damage from excess reactive oxygen species (ROS) may contribute to skeletal aging and mediate adverse responses to physiological challenges. Wild-type (WT) mice and transgenic mice (male, 16 wk of age) with human catalase targeted to the mitochondria (mCAT) were analyzed for skeletal responses to the remodeling stimuli of combined hind-limb unloading and exposure to ionizing radiation (137Cs, 2 Gy). Treatment for 2 wk caused lipid peroxidation in the bones WT but not mCAT mice, showing that transgene expression mitigated oxidative stress. Ex vivo osteoblast colony growth rate was 95% greater in mCAT than WT mice and correlated with catalase activity levels (P < 0.005, r = 0.67), although terminal osteoblast and osteoclast differentiation were unaffected. mCAT mice had lower cancellous bone volume and cortical size than WT mice. Ambulatory control mCAT animals also displayed reduced cancellous and cortical structural properties compared with control WT mice. In mCAT but not WT mice, treatment caused an unexpectedly rapid radial expansion (+8% cortical area, +22% moment of inertia), reminiscent of compensatory bone growth during advancing age. In contrast, treatment caused similar structural deficits in cancellous tissue of mCAT and WT mice. In sum, mitochondrial ROS signaling via H2O2 was important for the acquisition of adult bone structure and catalase overexpression failed to protect cancellous tissue from treatment. In contrast, catabolic stimuli caused radial expansion in mCAT not WT mice, suggesting that mitochondrial ROS in skeletal cells act to suppress tissue turnover in response to remodeling challenges.

COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care.

Coronavirus disease-2019 (COVID-19) has caused a pandemic that has affected millions of people worldwide. COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is spread by close contact and by respiratory droplets. It has also impacted different aspects of caring for people with kidney disease, including those with acute kidney injury (AKI), chronic kidney disease (CKD), those requiring kidney replacement therapy (KRT), and those with a kidney transplant. All of these patients are considered high risk. The lessons learned from the COVID-19 pandemic will hopefully serve to protect patients with kidney disease in a similar situation in the future.

Correlating computed tomography pulmonary angiography signs of right ventricular strain in pulmonary embolisms to clinical outcomes.

INTRODUCTION: Right ventricular strain (RVS) in pulmonary embolism (PE) can be used to stratify risk and direct intervention. The clinical significance of computed tomography pulmonary angiogram (CTPA)-derived radiologic signs of RVS, however, remains incompletely characterized. We retrospectively analyzed a cohort of persons with acute PE to determine which, if any, findings of RVS on CTPA correlate with clinical outcomes. METHODS: All patients with PE diagnosed on CTPA from March 2013 through February 2015 at Lyndon B. Johnson Hospital were identified. Their records were retrospectively reviewed to identify length of stay, intensive care unit (ICU) placement, hemodynamic failure, use of thrombolytics, vasopressor requirement, mechanical ventilation, and attributable mortality. Three radiologists, blinded to clinical outcomes, separately reviewed the cohort's CTPAs to identify signs of RVS - pulmonary trunk size, internal size of the right and left ventricles, paradoxical interventricular septal bowing, inferior vena cava (IVC) contrast reflux, and hepatic vein contrast reflux. RESULTS: In our cohort of 102 persons, 12 demonstrated hemodynamic failure, 13 required ICU placement, 3 received thrombolysis, and 5 had death attributable to PE. The greatest interobserver agreement among radiologists existed for the presence of increased pulmonary trunk size (0.76 kappa by %agreement) and hepatic vein contrast reflux (0.92 kappa by %agreement). A multiple regression analysis found that when 100% radiologist agreement existed, presence of paradoxical intravenous septal bowing predicted thrombolytic usage (P = 0.02), and the presence of IVC reflux predicted attributable mortality (P = 0.03). CONCLUSION: Only IVC contrast reflux was associated with increased mortality, and no other sign of RVS on CTPA correlated with clinical outcomes. This suggests that most signs of RVS on CTPA do not reliably predict PE severity. Therefore, RVS seen by CTPA should be used cautiously in weighing the decision to initiate thrombolytics.

A luminescence-based assay for monitoring changes in alpha-synuclein aggregation in living cells.

Parkinson's disease is characterized by the accumulation of protein aggregates in the brain, termed Lewy bodies. Lewy bodies are predominantly composed of α-synuclein and mutations that increase the aggregation potential of α-synuclein have been associated with early on-set disease. Assays capable of reporting on the solubility of α-synuclein in living cells could provide a means to interrogate the influence of mutations on aggregation as well as identify small molecules capable of modulating the aggregation of α-synuclein. Herein, we repurpose our previously reported self-assembling NanoLuc luciferase fragments to engineer a platform for detecting α-synuclein solubility in living cells. This new assay is capable of reporting on changes in α-synuclein solubility caused by disease-relevant mutations as well as inhibitors of aggregation. In the long term, this new assay platform provides a means to investigate the influence of mutations on α-synuclein solubility as well as identify potential tool compounds capable of modulating α-synuclein aggregation.

Classification accuracy of the rare symptoms and symptom combinations scales of the Structured Inventory of Malingered Symptomatology in three archival samples.

OBJECTIVE: The Structured Inventory of Malingered Symptomatology (SIMS; Widows & Smith, 2005) is a 75-item self-report measure intended to screen for potentially feigned symptoms of mental illness and/or cognitive impairment. We investigated the classification accuracy of 2 new detection scales (Rare Symptoms [RS] and Symptom Combinations [SC]) developed by Rogers, Robinson, and Gillard (2014) that appeared useful in identifying simulated mental disorder in their derivation sample of psychiatric inpatients. HYPOTHESIS: We hypothesized that the rates of classification accuracy Rogers et al. reported for these 2 scales would generalize to other samples in which the utility of the SIMS previously has been investigated. METHOD: We computed RS and SC scores from archival SIMS data collected as part of 3 research projects investigating malingering detection methods: (a) general population prison inmates and inmates in a prison psychiatric unit receiving treatment for mental disorder (N = 115), (b) college students (N = 196), and (3) community-dwelling adults (N = 48). RESULTS: Results supported the global classification accuracy of RS and SC but the suggested cut-score for both scales (>6) produced poor sensitivity. Lower potential cut-offs did, however, improve sensitivity to feigning somewhat while not excessively diminishing specificity. CONCLUSION: These results emphasize the importance of generalizability research when investigating the clinical utility of forensic mental health assessment methods, particularly specific decision rules used to classify individuals into discrete categories. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

HIV and pericardial fat are associated with abnormal cardiac structure and function among Ugandans.

OBJECTIVES: To examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown. METHODS: One hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes. RESULTS: Median age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3 g/m2 higher LV mass index (LVMI) (95% CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95% CI -1.66 to -0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95% CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all p<0.05). CONCLUSIONS: In Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.