Effective low-cost pediatric vision screening by naive nonophthalmic examiners using the 'Arclight' device.

PURPOSE: To explore whether a low-cost ophthalmoscope (Arclight) can be used by naive nonophthalmic examiners to effectively screen for pediatric eye disease. METHODS: Fifty-four children (108 eyes) were examined by five medical students using an Arclight. Gold standard examination was performed by an ophthalmologist using a slit lamp and indirect ophthalmoscope. Examinations performed included ophthalmoscopy of the optic disc, estimation of the cup-to-disc ratio (CDR), corneal light reflex test (CRT), Bruckner's reflex test (BRT), and evaluation of refractive error. We determined the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the nonophthalmologist's Arclight exam compared to the gold standard findings of comprehensive evaluation by pediatric ophthalmologists. RESULTS: Using the Arclight, the optic nerve exam was successfully completed in 65% of patients. CDRs above and below 0.5 could be determined with 66.7% sensitivity and 84.4% specificity. Arclight CRT measurements were significant (P < .00001) predictors of strabismus, with 80% sensitivity, 95.1%, specificity, 80% PPV, and 95.1% NPV. BRT was not a significant predictor of amblyopia, with a 34.6% sensitivity, 85.7% specificity, 69.2% PPV, and 58.5% NPV. Refractive error was estimated with a success rate of 81% for emmetropia, 38% for myopia, and 21% for hyperopia. The Arclight ease-of-use was rated on average as 4.4 (SD = 0.9) on a scale of 1 to 5, with 1 being the hardest and 5 being the easiest. CONCLUSIONS: Our study shows the Arclight as an affordable and effective alternative to the traditional ophthalmoscope for assessing eye disease in children. This device can improve eye health services in under-resourced regions.

Microbial- and host immune cell-derived extracellular vesicles in the pathogenesis and therapy of periodontitis: A narrative review.

Periodontitis is a chronic inflammatory disease caused by dysbiotic biofilms and destructive host immune responses. Extracellular vesicles (EVs) are circulating nanoparticles released by microbes and host cells involved in cell-to-cell communication, found in body biofluids, such as saliva and gingival crevicular fluid (GCF). EVs are mainly involved in cell-to-cell communication, and may hold promise for diagnostic and therapeutic purposes. Periodontal research has examined the potential involvement of bacterial- and host-cell-derived EVs in disease pathogenesis, diagnosis, and therapy, but data remains scarce on immune cell- or microbial-derived EVs. In this narrative review, we first provide an overview of the role of microbial and host-derived EVs on disease pathogenesis. Recent studies reveal that Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans-derived outer membrane vesicles (OMVs) can activate inflammatory cytokine release in host cells, while M1 macrophage EVs may contribute to bone loss. Additionally, we summarised current in vitro and pre-clinical research on the utilisation of immune cell and microbial-derived EVs as potential therapeutic tools in the context of periodontal treatment. Studies indicate that EVs from M2 macrophages and dendritic cells promote bone regeneration in animal models. While bacterial EVs remain underexplored for periodontal therapy, preliminary research suggests that P. gingivalis OMVs hold promise as vaccine candidates. Finally, we acknowledge the current limitations present in the field of translating immune cell derived EVs and microbial derived EVs in periodontology. It is concluded that microbial and host immune cell-derived EVs have a role in periodontitis pathogenesis and hence may be useful for studying disease pathophysiology, and as diagnostic and treatment monitoring biomarkers.

Holistic Review in Family Medicine Residency Programs: A CERA Study.

BACKGROUND AND OBJECTIVES: Interest in using holistic review for residency recruitment as a strategy to improve the diversity of the physician workforce has increased. However, no data are published on the prevalence of holistic review in the selection process for family medicine residency programs. We designed this study to assess programs' knowledge, skills, and attitudes; prevalence; barriers to implementation; and program characteristics associated with the use of holistic review. METHODS: Data for this study were elicited as part of a 2023 survey conducted by the Council of Academic Family Medicine Educational Research Alliance. The nationwide, web-based survey was sent to 739 family medicine residency program directors. RESULTS: A total of 309 program directors completed the holistic review portion of the survey. Programs that understood and agreed with holistic review used it more in their selection process. Holistic review was more common in programs with higher rates of residents, faculty, and patients that are underrepresented in medicine. Barriers to holistic review utilization were increased number of applicants, increased resources associated with holistic review, and lack of consensus on the holistic review approach. CONCLUSIONS: The holistic review process is an area of growing interest to diversify the physician workforce, especially among residencies caring for underresourced communities. Further discussions on the specific scoring rubrics of family medicine residency programs that use holistic review are needed and could help programs that are facing barriers. Widespread use of holistic review to diversify the physician workforce has the potential to improve patient care access and health.

Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML.

ABSTRACT: The overall prognosis of acute myeloid leukemia (AML) remains dismal, largely because of the inability of current therapies to kill leukemia stem cells (LSCs) with intrinsic resistance. Loss of the stress sensor growth arrest and DNA damage-inducible 45 alpha (GADD45A) is implicated in poor clinical outcomes, but its role in LSCs and AML pathogenesis is unknown. Here, we define GADD45A as a key downstream target of G protein-coupled receptor (LGR)4 pathway and discover a regulatory role for GADD45A loss in promoting leukemia-initiating activity and oxidative resistance in LGR4/HOXA9-dependent AML, a poor prognosis subset of leukemia. Knockout of GADD45A enhances AML progression in murine and patient-derived xenograft (PDX) mouse models. Deletion of GADD45A induces substantial mutations, increases LSC self-renewal and stemness in vivo, and reduces levels of reactive oxygen species (ROS), accompanied by a decreased response to ROS-associated genotoxic agents (eg, ferroptosis inducer RSL3) and acquisition of an increasingly aggressive phenotype on serial transplantation in mice. Our single-cell cellular indexing of transcriptomes and epitopes by sequencing analysis on patient-derived LSCs in PDX mice and subsequent functional studies in murine LSCs and primary AML patient cells show that loss of GADD45A is associated with resistance to ferroptosis (an iron-dependent oxidative cell death caused by ROS accumulation) through aberrant activation of antioxidant pathways related to iron and ROS detoxification, such as FTH1 and PRDX1, upregulation of which correlates with unfavorable outcomes in patients with AML. These results reveal a therapy resistance mechanism contributing to poor prognosis and support a role for GADD45A loss as a critical step for leukemia-initiating activity and as a target to overcome resistance in aggressive leukemia.

Duration of biophysical profile in periviable and very preterm low-risk pregnancies.

BACKGROUND: In recent years, perinatal viability has shifted from 24 to 22 weeks of gestation at many institutions after improvements in survival in neonates delivered at the limit of viability. Monitoring these fetuses is essential because antenatal interventions with resuscitation efforts are available for patients at risk of delivery at the limit of viability. However, fetal monitoring using biophysical profiles has not been extensively studied in very preterm pregnancies, particularly in the periviable period (20 weeks 0 days to 23 weeks 6 days). OBJECTIVE: This study aimed to (1) investigate whether the completion of biophysical profiles within 30 minutes is feasible in very preterm pregnancies, and (2) determine the average observation time required to achieve a score of 8 out of 8 in very preterm pregnancies from 20 weeks 0 days to 31 weeks 6 days. STUDY DESIGN: This study prospectively evaluated biophysical scores in singleton pregnancies undergoing routine ultrasonography at or near viability from 20 weeks 0 days to 23 weeks 6 days (periviable or group I), 24 weeks 0 days to 27 weeks 6 days (group II), and 28 weeks 0 days to 31 weeks 6 days (group III). The results and duration of biophysical profiles were compared with those of a control group (32 weeks 0 days to 35 weeks 6 days) undergoing indicated fetal surveillance. Biophysical profiles were performed for all studied pregnancies until a score of 8 out of 8 was obtained. When >1 biophysical profile was obtained during pregnancy, each was analyzed individually. Pregnancies with fetal anomalies or obstetrical/medical indications for fetal well-being surveillance were excluded. Analysis of variance and post hoc Tukey tests were used for comparisons. RESULTS: Data were collected for 123 participants, yielding 79, 75, and 72 studies for groups I, II, and III, respectively. The control group included 42 patients, yielding 140 studies. At 30 minutes, 80% (63/79) of the studies in the periviable group had a score of 8 out of 8, as opposed to 100% (140/140) in the control group (P<.001). The mean±standard deviation time in minutes to achieve a biophysical score of 8 out of 8 was 23.3±10.1 in the periviable group, as opposed to 9.4±6.5 in controls (P<.001). Extending the study to +2 standard deviations (43.6 minutes) in the periviable group resulted in 97% (77/79) of the scans scoring 8 out of 8 in the absence of adverse outcomes. In the other groups, a biophysical score of 8 out of 8 within 30 minutes was obtained in 97% (73/75) and 100% (72/72) in groups II and III, respectively; the mean±standard deviation times were 17.1±8.4 minutes (group II) and 13.1±7.3 minutes (group III). No adverse outcomes developed during the study participation in groups I to III. CONCLUSION: Biophysical scores of 8 out of 8 can be successfully achieved in low-risk periviable pregnancies (20 weeks 0 days to 23 weeks 6 days) within an observation time longer than the standard 30-minute duration. The time required to reach a score of 8 out of 8 decreases as gestation progresses. We suggest adjusting the observation time for biophysical profile completion according to the gestational age.

An industry perspective approach and control strategy for implementation of ready-to-use cells in bioassays: survey outcome and recommendations.

The BioPhorum Development Group is an industry collaboration enabling the sharing of common practices for the development of biopharmaceuticals. Bioassays are an important part of an analytical control system. Utilization of ready-to-use cells can increase operational flexibility and improve efficiency by providing frozen cell banks uniform stock while removing challenges associated with maintaining cultured cells. The BioPhorum Development Group-Bioassay workstream conducted an intercompany benchmarking survey and group discussions around the use of ready-to-use cells for bioassays. The results of the collaboration provide alignment on nomenclature, production, qualification and implementation of ready-to-use cells to support the assay life cycle.

SHARPening Residency Selection: Implementing a Systematic Holistic Application Review Process.

PROBLEM: Traditional metrics used in residency application review processes are systematically biased against applicants from minoritized communities that are underrepresented in medicine (URiM). These biases harm not just URiM applicants but also residency programs and patients. Although several residency programs have implemented holistic reviews to mitigate these biases, few tested tools exist that can be adapted and implemented in a wide variety of settings within academic medicine. APPROACH: This article describes advances made in the third year of a longitudinal, ongoing quality improvement project that used the A3 framework to improve recruitment of URiM residents to a family medicine residency program. The authors devised a systematic holistic application review process (SHARP) to determine which applicants to invite to interview with the program. SHARP's development began in August 2019, and after significant discussion with program leadership and iterations of rubric refinement, the program adopted SHARP in September 2020 to review applications for the 2021 application cycle. OUTCOMES: Compared with the 2016 to 2020 period before SHARP implementation, data from the 2021 and 2022 residency application cycles after SHARP implementation showed a significant increase in the proportion of interviewed candidates who identify as URiM (from 23% to 38%, P < .001) and matched candidates who identify as URiM (from 27% to 62%, P = .004). There was also a notable increase in the number and diversity of reviewers who evaluated applicants to the program. NEXT STEPS: SHARP is a promising tool to mitigate the effects of racism and other biases against URiM applicants to residency programs. Residency programs across specialties may benefit from adopting SHARP and adapting it based on their own goals and priorities.

Factor XI Inhibition for the Prevention of Catheter-Associated Thrombosis in Patients With Cancer Undergoing Central Line Placement: A Phase 2 Clinical Trial.

BACKGROUND: Despite the ubiquitous utilization of central venous catheters in clinical practice, their use commonly provokes thromboembolism. No prophylactic strategy has shown sufficient efficacy to justify routine use. Coagulation factors FXI (factor XI) and FXII (factor XII) represent novel targets for device-associated thrombosis, which may mitigate bleeding risk. Our objective was to evaluate the safety and efficacy of an anti-FXI mAb (monoclonal antibody), gruticibart (AB023), in a prospective, single-arm study of patients with cancer receiving central line placement. METHODS: We enrolled ambulatory cancer patients undergoing central line placement to receive a single dose of gruticibart (2 mg/kg) administered through the venous catheter within 24 hours of placement and a follow-up surveillance ultrasound at day 14 for evaluation of catheter thrombosis. A parallel, noninterventional study was used as a comparator. RESULTS: In total, 22 subjects (n=11 per study) were enrolled. The overall incidence of catheter-associated thrombosis was 12.5% in the interventional study and 40.0% in the control study. The anti-FXI mAb, gruticibart, significantly prolonged the activated partial thromboplastin time in all subjects on day 14 compared with baseline (P<0.001). Gruticibart was well tolerated and without infusion reactions, drug-related adverse events, or clinically relevant bleeding. Platelet flow cytometry demonstrated no difference in platelet activation following administration of gruticibart. T (thrombin)-AT (antithrombin) and activated FXI-AT complexes increased following central line placement in the control study, which was not demonstrated in our intervention study. CRP (C-reactive protein) did not significantly increase on day 14 in those who received gruticibart, but it did significantly increase in the noninterventional study. CONCLUSIONS: FXI inhibition with gruticibart was well tolerated without any significant adverse or bleeding-related events and resulted in a lower incidence of catheter-associated thrombosis on surveillance ultrasound compared with the published literature and our internal control study. These findings suggest that targeting FXI could represent a safe intervention to prevent catheter thrombosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465760.

Cranberry, but not D-mannose and ibuprofen, prevents against uropathogenic Escherichia coli-induced cell damage and cell death in MDCK cells.

Introduction: The main function of the urinary tract is to form an impermeable barrier against urinary solutes and bacteria. However, this barrier can be compromised by urinary tract infections, most commonly caused by uropathogenic Escherichia coli (UPEC). This can result in damage to the epithelial barrier, leading to decreased epithelial thickness, loss of tight junctions, loss of epithelial integrity, and apoptosis. Due to the rise in antimicrobial resistance, there is worldwide interest in exploring non-antibiotic agents as alternative therapy. Methods: Using the Madin-Darby canine kidney (MDCK) cell line, a widely accepted epithelial cell model for the urinary tract, and the UPEC strain UTI89, this paper aimed to investigate the impact of UPEC on cell integrity, permeability, and barrier functions, and determine whether cranberry, D-mannose and ibuprofen could counteract the effects induced by UPEC. Furthermore, the study examined the protective potential of these agents against UPEC-induced increase in reactive oxygen species (ROS) production and programmed death-ligand 1 (PD-L1) expression. Results: The results demonstrated that UTI89 caused a marked reduction in cell viability and monolayer integrity. Cranberry (3 mg/mL) was protective against these changes. In addition, cranberry exhibited protective effects against UPEC-induced damage to cell barrier integrity, escalation of oxidative stress, and UPEC/TNFα-triggered PD-L1 expression. However, no effect was observed for D-mannose and ibuprofen in alleviating UPEC-induced cell damage and changes in ROS and PD-L1 levels. Conclusion: Overall, cranberry, but not D-mannose or ibuprofen, has a protective influence against UPEC associated damage in urinary epithelial cells.

Immunogenicity of COVID-19 vaccines and their effect on HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. Our study on 68 PWH and 23 HIV-negative participants aged 55 and older post-three vaccine doses showed equally strong anti-spike IgG responses in serum and saliva through week 48 from baseline, while PWH salivary IgA responses were low. PWH had diminished live-virus neutralization responses after two vaccine doses, which were 'rescued' post-booster. Spike-specific T cell immunity was enhanced in PWH with normal CD4+ T cell count, suggesting Th1 imprinting. The frequency of detectable HIV viremia increased post-vaccination, but vaccines did not affect the size of the HIV reservoir in most PWH, except those with low-level viremia. Thus, older PWH require three doses of COVID-19 vaccine for maximum protection, while individuals with unsuppressed viremia should be monitored for adverse reactions from HIV reservoirs.

Characterization of synthetic guide ribonucleic acids through hydrophilic interaction chromatography coupled with mass spectrometry.

In this study, we aimed to develop a hydrophilic interaction liquid chromatography (HILIC) method for the analysis of single guide ribonucleic acid (sgRNA), a critical reagent used in CRISPR genome editing. Our results showed that effective profiling of sgRNA can be achieved by suppressing the surface charge of the stationary phase in HILIC. We identified hydrogen bonding as the primary retention mechanism with potential weak partitioning in HILIC separation of large oligonucleotides like 100-mer sgRNA. Moreover, we demonstrated that direct coupling of HILIC with mass spectrometry (MS) allows the intact mass analysis of sgRNA and its impurities with minimal adduct present. Finally, we characterized the post peak shown in the low temperature HILIC and identified it as sgRNA aggregates. Our findings provide valuable insight into the characterization of sgRNA and highlight the potential of HILIC-MS as a powerful analytical tool for relatively large oligonucleotide analysis.

Characterization of antisense oligonucleotide and guide ribonucleic acid diastereomers by hydrophilic interaction liquid chromatography coupled to mass spectrometry.

Oligonucleotides have become an essential modality for a variety of therapeutic approaches, including cell and gene therapies. Rapid progress in the field has attracted significant research in designing novel oligonucleotide chemistries and structures. Beyond their polar nature, the length of large RNAs and presence of numerous diastereomers for phosphorothioate (PS)-modified RNAs pose heightened challenges for their characterization. In this study, the stereochemistry of a fully-modified antisense oligonucleotide (ASO) and partially-modified guide RNAs (gRNAs) was investigated using HILIC and orthogonal techniques. The profiles of three lots of a fully-modified ASO with PS linkages were compared using ion-pairing RPLC (IPRP) and HILIC. Interestingly, three isomer peaks were partially resolved by HILIC for two lots while only one peak was observed on the IPRP profile. Model oligonucleotides having the same sequence of the five nucleotides incorporated to the 3'-end of the gRNA but differing in their number and position of PS linkages were investigated by HILIC, IPRP, ion mobility spectrometry-mass spectrometry (IM-MS) and nuclear magnetic resonance (NMR). An strategy was ultimately designed to aid in the characterization of gRNA stereochemistry. Ribonuclease (RNase) T1 digestion enabled the characterization of gRNA diastereomers by reducing their number from 32 at the gRNA intact level to 4 or 8 at the fragment level. To our knowledge, this is the first time that HILIC has successfully been utilized for the profiling of diastereomers for various oligonucleotide formats and chemical modifications.

Melasma treatment with a 1064 nm, picosecond-domain laser with a fractionated multibeam lens array.

BACKGROUND AND OBJECTIVES: Picosecond-domain lasers have been fitted with fractionated optics for dermal remodeling. This study evaluates the safety and efficacy of a multiwavelength picosecond-domain laser, using a 1064 nm multibeam lens array, for improving the appearance of melasma. STUDY DESIGN/MATERIALS AND METHODS: Twenty adults with a clinical diagnosis of melasma were enrolled and received 4 monthly 1064-nm, 450 ps laser treatments delivered with a 10 × 10 fractional array of 150 µm microbeams. Cosmetic units with melasma were treated with fluences ranging from 1.7 to 2.9 mJ/microbeam with a repetition rate of 6 Hz. Treatment effect was evaluation of digital images by dermatologists blinded as to the treatment conditions, comparing baseline and 3- and 8-month post-treatment images. Modified melasma area and severity index (mMASI) scores were determined by the study investigator based on clinical photography. Subject self-assessment of treatment effects was also recorded. RESULTS: Blinded reviewers correctly identified the post-treatment image in 16 of the 20 image sets (80%). Ratings demonstrated statistically significant (p < 0.001) improvement on an 11-point scale at both the 3- and 8-month timepoints for a mean improvement of 3.7 point (range -8 to 10) or 37% improvement at the 3-month follow-up, and 2.7 (range -8 to 9) or 27% at the 8-month follow-up for all subjects. The average mMASI score showed highly significant reduction at both the 3- and 8-month follow-ups compared to baseline (p < 0.01). Most subjects (90%) were satisfied with the treatment outcome in melasma at both follow-ups, which is consistent with the treatment outcome and mMASI scores. CONCLUSION: The fractionated, picosecond-domain, 1064 nm laser is safe and effective for improving melasma and should be considered as an adjunct to topical treatment regimens and sun-protection for management of melasma.

TraumaICDBERT, A Natural Language Processing Algorithm to Extract Injury ICD-10 Diagnosis Code from Free Text.

OBJECTIVE: To develop and validate TraumaICDBERT, a natural language processing algorithm to predict injury ICD-10 diagnosis codes from trauma tertiary survey notes. SUMMARY BACKGROUND DATA: The adoption of ICD-10 diagnosis codes in clinical settings for injury prediction is hindered by the lack of real-time availability. Existing natural language processing algorithms have limitations in accurately predicting injury ICD-10 diagnosis codes. METHODS: Trauma tertiary survey notes from hospital encounters of adults between January 2016 and June 2021 were used to develop and validate TraumaICDBERT, an algorithm based on BioLinkBERT. The performance of TraumaICDBERT was compared to Amazon Web Services Comprehend Medical, an existing natural language processing tool. RESULTS: A dataset of 3,478 tertiary survey notes with 15,762 4-character injury ICD-10 diagnosis codes was analyzed. TraumaICDBERT outperformed Amazon Web Services Comprehend Medical across all evaluated metrics. On average, each tertiary survey note was associated with 3.8 (standard deviation: 2.9) trauma registrar-extracted 4-character injury ICD-10 diagnosis codes. CONCLUSIONS: TraumaICDBERT demonstrates promising initial performance in predicting injury ICD-10 diagnosis codes from trauma tertiary survey notes, potentially facilitating the adoption of downstream prediction tools in clinical settings.

Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4 + T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV - participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were 'rescued' after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV - participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral 'blips' in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4 + T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.

Estrogen-based hormonal therapy and the risk of thrombosis in COVID-19 patients.

OBJECTIVE: Estrogen-containing contraceptives and hormone replacement therapy are used commonly, however, the risks of venous and arterial thrombosis imparted by such medications during COVID-19 infection or other similar viral infections remain undescribed. METHODS: To assess the risk of venous and arterial thrombosis in patients receiving oral estrogen-containing therapy (ECT) with COVID-19 as compared to those receiving non-estrogen-based hormonal therapy, we conducted a multicenter cohort study of 991 patients with confirmed COVID-19 infection, 466 receiving estrogen-containing hormonal therapy, and 525 receiving progestin-only or topical therapy. RESULTS: The use of estrogen-containing therapy was found to significantly increase the risk of venous thromboembolism (VTE) following COVID-19 diagnosis after controlling for age (HR 5.46 [95% CI 1.12-26.7, p = .036]). This risk was highest in patients over age 50, with 8.6% of patients receiving estrogen-containing therapy diagnosed with VTE compared to 0.9% of those receiving non-estrogen-based therapies (p = .026). The risk of arterial thrombosis was not significantly associated with oral estrogen use. CONCLUSIONS: These results suggest that estrogen-containing therapy is associated with a significantly increased risk of VTE in COVID-19 patients, especially in older individuals. These findings may guide provider counseling and management of patients with COVID-19 on estrogen-containing therapy.