Maryland Medical Center Research Articles

Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes

African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations. To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes. This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024. Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records. A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included. A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (β = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, β = 0.008; SE, 0.003; P = .01; q value = .21). In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.

Behavioral Assessment With the Coma Recovery Scale-Revised Is Safe and Feasible in Critically Ill Patients With Disorders of Consciousness.

Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans after brain injury. The Coma Recovery Scale-Revised (CRS-R) is a sensitive measure of consciousness validated in the rehabilitation phase of care. We tested the feasibility, safety, and impact of CRS-R-guided rehabilitation in the ICU for patients with DoC after acute hemorrhagic stroke. Retrospective cohort study. This single-center study was conducted in the neurocritical care unit at the University of Maryland Medical Center. We analyzed records from consecutive patients with subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), who underwent serial CRS-R assessments during ICU admission from April 1, 2018, to December 31, 2021, where CRS-R less than 8 is vegetative state/unresponsive wakefulness syndrome (VS/UWS); CRS-R greater than or equal to 8 is a minimally conscious state (MCS). None. Outcomes included adverse events during CRS-R evaluations and associations between CRS-R and discharge disposition, therapy-based function, and mobility. We examined the utility of CRS-R compared with other therapist clinical assessment tools in predicting discharge disposition. Seventy-six patients (22 SAH, 54 ICH, median age = 59, 50% female) underwent 276 CRS-R sessions without adverse events. Discharge to acute rehabilitation occurred in 4.4% versus 41.9% of patients with a final CRS-R less than 8 and CRS-R greater than or equal to 8, respectively (odds ratio [OR] 13.4; 95% CI, 2.7-66.1; p < 0.001). Patients with MCS on final CRS-R completed more therapy sessions during hospitalization and had improved mobility and functional performance. Compared with other therapy assessment tools, the CRS-R had the best performance in predicting discharge disposition (area under the curve: 0.83; 95% CI, 0.72-0.94; p < 0.0001). Early neurorehabilitation guided by CRS-R appears to be feasible and safe in the ICU following hemorrhagic stroke complicated by DoC and may enhance access to inpatient rehabilitation, with the potential for lasting benefit on recovery. Further research is needed to assess generalizability and understand the impact on long-term outcomes.

Abstract 7665: Detection of γ-OHPdG as a hepatocellular carcinoma recurrence biomarker by CTCs and LC-MS/MS

Abstract Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death globally. Recurrence risks following curative resection remain high, ~50% after three years and 75-100% over five years. A biomarker for HCC recurrence is urgently needed to help lead treatment strategies. We previously showed that hepatic γ-hydroxy-1, N2-propano-2′-deoxyguanosine (γ-OHPdG), a DNA adduct derived from lipid peroxidation, increased during hepatocarcinogenesis. Furthermore, in a retrospective study, higher γ-OHPdG levels in post-surgical liver tumor tissues were associated with poorer survival (p&amp;lt;0.0001) and shorter recurrence-free survival (p=0.007), suggesting that it may be a prognostic biomarker for HCC (Hepatology 2018). In this study, we aimed to test γ-OHPdG detected in livers after curative resection as a recurrence biomarker in a prospective study and, in addition, we developed a new non-invasive method for γ-OHPdG in circulating tumor cells (CTCs). This multicenter study seeks to validate γ-OHPdG as a biomarker for HCC recurrence. Methods: A total of 28 HCC patients undergoing hepatectomy at MedStar/Georgetown University Hospital, Johns Hopkins University Hospital, and the University of Maryland Medical Center were enrolled. γ-OHPdG was detected in DNA isolated from hepatic tumors and non-tumors by a previous liquid chromatograph-tandem mass spectrometry (LC-MS/MS) method and in HCC CTCs isolated from blood samples. CTCs were isolated using hepatocyte-specific rabbit anti-asialoglycoprotein-1 (ASGPR-1), followed by staining with mouse anti-γ-OHPdG antibodies. Clinical outcomes were correlated with γ-OHPdG in liver tissues and CTCs. Results: In our current cohort of 28 patients (mean age: 64.7 years; 82% male), five patients experienced HCC recurrence, with an estimated progression-free survival (PFS) rate of 85% over 8 months. γ-OHPdG levels (adducts/109 nucleotides) detected by LC-MS/MS varied widely in tumor tissues (5-56, mean: 11.8) and non-tumor tissue (7-71, mean: 20.6). Preliminary analysis showed shorter PFS associated with γ-OHPdG in non-tumors (cutoff: 16, p=0.0271). γ-OHPdG (arbitrary units x107) in CTCs also varied widely in the nucleus (0.95-18.84, mean: 2.85) and in the whole cell (0.16- 52.18, mean: 9.72). Total CTC γ-OHPdG intensity in both the nucleus (p=0.006) and in the whole cell (p=0.005) was associated with its levels in non-tumor tissue. Furthermore, a shorter PFS was associated with CTC count (cutoff: 270 cells, p=0.01), and total CTC whole cell γ-OHPdG intensity (cutoff: 21.17 × 107 arbitrary units, p=0.002). Conclusion: Preliminary results suggest that γ-OHPdG, measured in tissues by LC-MS/MS and in blood by CTC, predicts HCC recurrence. Once evaluated in all enrolled subjects, multiple variant analyses will be carried out to include stage, AFP, grade of differentiation, vascular invasion on surgical samples, and status of viral hepatitis infection. Citation Format: Mark Kuo, Merve Ozge Aktop, Elie Ghabi, Mahmoud A. Ouf, Margaret Carder, Vinona Muralidaran, Jhalen Ascue, Marketa Hlouskova, Pengfei Wu, Guang Cheng, Stephen S. Hecht, Hong-Bin Fang, Nader Hanna, Jin He, Alexander H. Kroemer, Monika Aggarwal, Aiwu R. He, Fung-Lung Chung. Detection of γ-OHPdG as a hepatocellular carcinoma recurrence biomarker by CTCs and LC-MS/MS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7665.

Comparison of three rapid diagnostic tests for bloodstream infections using Benefit-risk Evaluation Framework (BED-FRAME).

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 positive blood cultures were collected from the University of Maryland Medical Center. The RDTs were compared by their sensitivities, time-to-results, hands-on time, and BED-FRAME analysis. The overall sensitivity of all platforms compared to culture results from monomicrobial-positive blood cultures was 88.3%. However, the three RDTs differed in their accuracy for identifying Gram-positive bacteria, Gram-negative bacteria, and yeast. Time-to-results for FLAT MS, Sepsityper, and BioFire BCID2 were all approximately one hour. Hands-on times for FLAT MS, Sepsityper, and BioFire BCID2 were 10 (±1.3), 40 (±2.8), and 5 (±0.25) minutes, respectively. BED-FRAME demonstrated that each RDT had utility at different pathogen prevalence and relative importance. BED-FRAME is a useful tool that can used to determine which RDT is best for a healthcare center.

Abstract PR007: Neighborhood socioeconomic deprivation, racial segregation, and prostate tumor RNA expression of stress-related genes among African American and European American men

Abstract INTRODUCTION: African American (AA) men experience greater prostate cancer incidence and mortality compared to European American (EA) men. Growing literature supports associations of neighborhood social factors (NSF) including neighborhood socioeconomic deprivation and residential segregation with advanced or aggressive prostate cancer, and AA men may experience these factors to a greater extent than EA men. Here we tested associations of NSF with prostate tumor RNA expression of stress-related genes, hypothesizing that these factors would be related and contribute to prostate tumor aggressiveness. METHODS: We leveraged available transcriptomic data from prostate tumor tissue for AA and EA men with prostate cancer who received radical prostatectomy surgery at the University of Maryland Medical Center. We geocoded each participant’s address at diagnosis, determined the corresponding census tract, and assigned tract-based Area Deprivation Index (ADI) and Racial Isolation Index (RI) scores to each participant. Based on data availability, ADI analyses included men diagnosed in 2005 or later (118 AA men and 43 EA men), and RI analyses included those diagnosed in 2009 or later (110 AA men and 37 EA men). We evaluated 105 stress-related genes, including those in the Conserved Transcriptional Response to Adversity, among others. We fit separate linear regression models for expression of each gene in relation to ADI or RI, respectively. Models were adjusted for race and age and year at surgery. We obtained q-values (p-values adjusted for multiple comparisons) using the Benjamini-Hochberg method. RESULTS: Median (interquartile range) ADI scores were 116 (101-131) for AA men and 91 (83-103) for EA men, and RI scores were 0.68 (0.38-0.87) for AA men and 0.10 (0.05-0.14) for EA men, indicating greater neighborhood deprivation and Black residential segregation among AA participants. The greatest values for these scores were concentrated in central and west Baltimore. ADI scores were positively and significantly (p&amp;lt;0.05) associated with expression for 11 genes. One gene, HTR6 (serotonin pathway), remained significant after multiple comparison adjustment (beta=0.0029, 95% confidence interval: 0.0014-0.0043; p&amp;lt;0.001; q=0.02). RI scores were positively and significantly associated with expression for 7 genes (p&amp;lt;0.05), but findings did not remain significant after multiple comparison adjustment. Four genes, including HTR6, IFIT2 and MX2 (roles in Type I IFN response), and IGLL1 (antibody synthesis) were significantly associated with both ADI and RI (p&amp;lt;0.05). Top findings among AA men only were similar to the overall results (AA and EA men combined). CONCLUSIONS: We identified several genes in stress-related pathways whose expression in prostate tumor tissue was higher among men with higher neighborhood deprivation or higher racial segregation. Additional analyses will consider other neighborhood measures, including historical redlining, to further investigate the role of NSF in prostate tumor RNA expression, tumor aggressiveness, and prostate cancer disparities. Citation Format: Joseph Boyle, Jessica Yau, Jimmie L. Slade, Derrick Butts, Yuji Zhang, Teklu B. Legesse, Ashley Cellini, Kimberly Clark, Jessica Wimbush, Nicholas Ambulos Jr., Jing Yin, Arif Hussain, Eberechukwu Onukwugha, Cheryl L. Knott, David C. Wheeler, Kathryn Hughes Barry. Neighborhood socioeconomic deprivation, racial segregation, and prostate tumor RNA expression of stress-related genes among African American and European American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR007.

HIV-Associated Lymphoma in an Urban Clinic Population: Epidemiology and Outcomes during the Antiretroviral Therapy Era

Introduction- People living with human immunodeficiency virus (HIV) infection (PLWH) are at increased risk for Hodgkin and non-Hodgkin lymphoma. Incidence of HIV-associated lymphoma fell dramatically after the introduction of combined antiretroviral therapy (cART) in the mid-1990s, and the distribution of lymphoma subtypes shifted away from those associated with severe immunosuppression. This study examines trends in the incidence and outcomes of HIV-associated lymphomas diagnosed and treated at an urban, minority-serving cancer center in the United States since 2000. Methods- A retrospective cohort of patients diagnosed with or treated for HIV-associated lymphoma at University of Maryland Medical Center in Baltimore from 2000-2021 was identified and analyzed. Data from patients diagnosed with lymphoma from 2000-2013 was previously published. Data on patients diagnosed or treated for lymphoma at UMMC from 2014-2021 was abstracted from patients' electronic medical records. Data was summarized using simple descriptive statistics. Categorical variables were compared using Chi-squared tests. Results- The previously published study noted 160 patients with HIV-associated lymphoma during 2000-2013 (P1), of whom 131 had sufficient data for analysis. We identified 51 PLWH diagnosed with or treated for lymphoma at UMMC from 2014-2021 (P2), of whom 50 had sufficient data for analysis. The majority were male (73% during P1, 60% during P2) and African American (80% in P1, 76% in P2). Median age at diagnosis was 45 years in P1 and 42 years in P2. Median CD4 count at diagnosis was 104 cells/ul during P1 and 103 cells/ul (IQ range 35-194.5) during P2. PLWH not diagnosed with HIV prior to their lymphoma diagnosis remained similar (23% P1, 26% P2). The proportion of PLWH on cART at the time of lymphoma diagnosis increased over the course of the study period, from 28/131 (21%) to 30/50 (60%) during P2 (p&amp;lt;0.0001). Median Log 10 viral load (HIV-1 RNA copies/mL) was 4.7 during P1 and 2.7 during P2. Diffuse large B-cell lymphoma (DLBCL) was the most common type of lymphoma throughout the study period, representing 54 of 131 (41%) cases during P1 and 29 of 50 (58%) of cases during P2. Hodgkin lymphoma (HL) was the 2 nd-most common lymphoma, comprising 18% of cases during P1 and 16% during P2 (Table 1). The proportion of patients receiving some lymphoma treatment was 85% during P1 and 96% during P2, including 92% who received chemotherapy and/or monoclonal antibodies. Fourteen patients during P2 died prior to, during, or within eight weeks of completing 1st-line lymphoma treatment, including four deaths due to progressive lymphoma and six deaths due to infection. 54% of evaluable patients during P2 achieved a complete response (CR) to first-line treatment. 12-month overall survival (OS) was 49% during P1 and 61% during P2 (p=0.31). 24-month OS was 41% during P1 and 50% during P2 (p=0.44). Progression free survival (PFS) in P2 was 51% at 12 months and 42% at 24 months. For PLWH with DLBCL during P2, 56% achieved a CR to 1 st-line therapy; PFS was 49% at 12 months and 46% at 24 months. OS for this group was 62% at 12 months and 53% at 24 months. For all patients with DLBCL (with and without HIV) treated at our center from 2015-2019, 77% achieved CR to 1 st-line therapy, PFS was &amp;gt;61% at 24 months, and OS was &amp;gt;69% at 24 months. Three PLWH had perinatal acquisition of HIV and a mean age of 27 years at lymphoma diagnosis. 24-month OS for this group was 33%, compared to 51% for PLWH with other routes of transmission (p=0.78). Conclusions- Patients with HIV-associated lymphoma during P2 were more likely to be on cART and had lower viral loads at time of lymphoma diagnosis than during P1, but had similarly low CD4 counts. Distribution of lymphoma subtypes was similar during the two periods, with DLBCL and HL most common. Outcomes remain poor, especially among those patients with low CD4 counts and detectable viremia at the time of diagnosis. Prolonged duration of HIV viremia or immune suppression, related to early acquisition of infection or intermittent or partial adherence to cART, may increase the risk of adverse lymphoma outcomes. Engaging and retaining patients in HIV care is essential to reducing mortality from HIV-associated lymphoma. HIV therapies that more quickly suppress viremia and promote rapid immune reconstitution might also improve lymphoma outcomes.

A 10-Year Retrospective Review on the Use of Prophylactic Spinal Reconstruction in Spinal Surgery Involving High-Risk Patients.

Spinal surgeries are being offered to a broader patient population who are both medically and surgically complex. History of prior spinal surgery, advanced age, and presence of comorbidities, such as obesity, malnutrition, steroid use, and tobacco use, are risk factors for postoperative complications. Prophylactic spinal reconstruction at the time of spinal surgery has been shown to have improved outcomes and decreased wound complications; however, outcomes focusing specifically on complex patients with a history of previous spinal surgery (or surgeries) have not been well described. This is a retrospective study performed at the University of Maryland Medical Center (Baltimore, MD) of high-risk patients who underwent complex spinal surgery with prophylactic spinal reconstruction from 2011 to 2022. One hundred forty-three consecutive surgeries from 136 patients were included in the study. Patients younger than 17 years or who had an incomplete medical record were excluded. Most patients were female (63.6%) versus male (31.5%). The average American Society of Anesthesiologists score was 3. All but 6 patients (11%) had a history of at least 1 spinal surgery, with nearly half of patients having had between 2 and 5 spinal surgeries. Reconstruction was performed with paraspinous flaps in most cases (n = 133 [93%]). The overall complication rate was 10.5%, with surgical site infection being the most common complication. Seventeen patients (12.5%) underwent reoperation within 90 days of initial surgery. Average length of follow-up was 4.18 months (range, 0.03-40.53 months). In appropriately selected patients, prophylactic spinal reconstruction offers improved outcomes with decreased wound complications compared with salvage. For large defects, paraspinous flaps are recommended over other reconstructive options. Prolonged drain placement is felt to be protective against complications.

Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors

The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood. To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer. This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003. Participants were recruited through the University of Maryland Medical Center, with additional collection sites at Baltimore-area hospitals. Data analysis was performed from March 1 through December 1, 2022. Year 2000 census tract-level socioeconomic deprivation measured via neighborhood deprivation index (NDI) as a standardized score, with Black and White race being ascertained through self-report. The primary outcome was tissue DNA methylation using genome-wide measurements. The secondary outcome was tissue gene expression. Participants included 185 women with breast cancer (110 Black [59.5%], 75 White [40.5%]). Mean (SD) age at surgery was 56.0 (14.1) years. Neighborhood deprivation was higher for Black women than for White women (Mean [SD] NDI, 2.96 [3.03] for Black women and -0.54 [1.91] for White women; difference, -3.50; 95% CI, -4.22 to -2.79; P < .001). In unstratified analysis, 8 hypomethylated CpG sites were identified as associated with the NDI, including sites in 2 tumor suppressor genes, LRIG1 and WWOX. Moreover, expression of the 2 genes inversely correlated with neighborhood deprivation. In the race-stratified analysis, the negative correlation between the LRIG1 gene body CpG site cg26131019 and the NDI remained significant in Black women. A neighborhood deprivation-associated decrease in gene expression was also observed for LRIG1 and WWOX in tumors from Black women. In this study, high neighborhood deprivation was associated with differences in tissue DNA methylation and gene expression among Black women. These findings suggest that continued investment in public health interventions and policy changes at the neighborhood level may help to remedy biological alterations that could make minoritized populations more susceptible to chronic diseases.

The Impact of COVID-19 and Policy Changes on Immediate Postpartum Contraception and Permanent Contraception at an Urban Hospital: A Retrospective Cohort Study.

Objective: At the onset of the COVID-19 pandemic, in addition to increased use of telemedicine visits and a temporary suspension of interval tubal ligations, providers at the University of Maryland Medical Center were encouraged to counsel patients interested in long-acting reversible contraception (LARC) about immediate postpartum placement. We assessed immediate postpartum contraception uptake following these policy changes. Materials and Methods: In this retrospective cohort study, we compared patients who delivered a live born infant(s) before the pandemic ("pre-COVID cohort," December 16, 2019-March 1, 2020) and at the beginning of the pandemic ("during-COVID cohort," March 16-May 31, 2020). We collected electronic medical record data, including sociodemographic characteristics and contraception choices antenatally and through 1 year postpartum for 631 patients (321 pre-COVID, 310 during-COVID). Results: Odds of immediate postpartum LARC use in the during-COVID cohort were 33% higher than in the pre-COVID cohort, but this was not statistically significant (adjusted odds ratio 1.33, 95% confidence interval: 0.81-2.19). We found no difference in numbers of patients who received immediate postpartum tubal ligation (10% pre-COVID vs. 11% during-COVID). No patients in the during-COVID cohort obtained interval tubal ligations within 6 months of delivery. Contraceptive choices differed at postpartum visits (p = 0.03), with a decrease in delayed postpartum LARC placement in the during-COVID cohort (15% pre-COVID vs. 8% during-COVID). Conclusions: When COVID-19-related hospital policies prompted increased counseling on immediate postpartum LARC and suspension of interval tubal ligations, patients tended to be more likely to choose immediate postpartum LARC. Situational resource restrictions and targeted counseling may influence patient choices and access to desired contraceptive methods.

Low-dose Induction of Buprenorphine in Pregnancy: A Case Series.

Because of a risk of precipitated withdrawal occurring from buprenorphine induction in people who use fentanyl, low-dose inductions are becoming increasingly common. However, little evidence exists on the use of this method in pregnant people. We conducted a case series of all pregnant people treated for opioid use disorder with low-dose buprenorphine induction at the University of Maryland Medical Center between January 1, 2021, and August 22, 2022. Primary outcome was completion of induction regimen. Secondary outcomes were self-report of withdrawal, continuation of buprenorphine until delivery, and return to or continuation of illicit opioid use. Six pregnant people were prescribed a total of 10 buprenorphine inductions. Five of the 6 pregnant people (83.3%) completed at least 1 induction, none of whom experienced precipitated withdrawal. Two of 6 (33.3%) continued buprenorphine until the time of delivery, and 1 of 6 (16.7%) abstained from illicit opioid use. The low-dose buprenorphine induction regimen described was successful in 5 of 6 pregnant individuals. Further research, particularly regarding continuation rates, is needed.

THU669 Time To Achieve Euthyroidism In Graves Disease Using Methimazole In An Urban Population

Abstract Disclosure: S.S. Habbsa: None. E. Yunasan: None. A. Krishnan: None. K.M. Munir: None. Context: Previous studies of treatment response in Graves disease have shown that that the mean time to reach euthyroidism with methimazole (MMI) was several weeks to months. In 1987 Okamura et al. concluded that the average period was 6-7 weeks with MMI 30mg daily. Nakamura et al. showed similar data in 2007 (5.8 +/- 4 weeks). These studies were performed in Japanese hospitals over 15 years ago. Limited data exists regarding treatment response times with different doses in a diverse urban population, which may vary with regards to typical dietary patterns, thyroid hormone metabolism and thionamide pharmacokinetics. Objective: The objective of this retrospective chart review was to determine the mean time to achieve euthyroidism with MMI in patients with newly diagnosed Graves disease in Baltimore City. Methods: Patients with Graves hyperthyroidism newly diagnosed in the last 5 years were identified from outpatient endocrine and primary care clinics within the University of Maryland Medical Center healthcare system. Time to achieve euthyroidism (from the start of thionamide therapy to date of euthyroid labs, defined as normal free T4 level) was assessed. Results: 128 patients with recently diagnosed Graves hyperthyroidism were identified (126 patients treated with MMI only and 2 with PTU only). 78% of subjects were female and the mean age at diagnosis was 47 years. The average daily dose of MMI ranged from 2.5mg to 60mg. On average, Free T4 decreased by 0.47 ng/dL per week. The mean time to achieve euthyroidism was 10.1 weeks (8.6, 11.6) overall, similar in males and females. On sub analysis, time to achieve euthyroidism was lower in younger males (age &amp;lt; 40 years) [6.6 weeks (3.9, 9.3)] and older females (age &amp;gt; 40 years) [8.3 (6.9, 9.7)]. Conclusion: The above data may inform expectations for treatment response for newly diagnosed Graves disease, specifically in an urban population on a Westernized diet. Patient forums have shown increasing interest in therapeutic alternatives to thionamides, including specialized diets. This data may help to determine whether other proposed therapies for initial treatment of Graves hyperthyroidism are more or less efficacious. Presentation: Thursday, June 15, 2023

Court rules against employee

Case name: Marshall v. University of Maryland Medical Center, No. 20‐2067 (4th Cir. 06/27/23).

Court rules against employee

Case name: Marshall v. University of Maryland Medical Center, No. 20‐2067 (4th Cir. 06/27/23).

The UTH-UMB Global Health Education Collaboration: Building a Bidirectional Exchange Based on Equity and Reciprocity.

The global health exchange program between the University Teaching Hospitals (UTH) of Lusaka, Zambia and the University of Maryland, Baltimore (UMB) has been operating since 2015. As trainees and facilitators of this exchange program, we describe our experiences working in Lusaka and Baltimore, and strengths and challenges of the partnership. Since 2015, we have facilitated rotations for 71 UMB trainees, who spent four weeks on the Infectious Disease (ID) team at UTH. Since 2019 with funding from UMB, nine UTH ID trainee physicians spent up to six weeks each rotating on various ID consult services at University of Maryland Medical Center (UMMC). Challenges in global health rotations can include inadequate preparation or inappropriate expectations among high-income country trainees, low-value experiences for low- and middle-income country trainees, lack of appropriate mentorship at sites, and power imbalances in research collaborations. We try to mitigate these issues by ensuring pre-departure and on-site orientation for UMB trainees, cross-cultural mentored experiences for all trainees, and intentional sharing of authorship and credit on scientific collaborations. We present a description of our medical education collaboration as a successful model for building equitable and reciprocal collaborations between low- and middle-income countries and high-income countries, and offer suggestions for future program initiatives to enhance global health education equity among participants and organizations.

Examining Predictors of Early Admission and Transfer to the Critical Care Resuscitation Unit.

Previous studies have demonstrated that rapid transfer to definitive care improves the outcomes for many time-sensitive conditions. The critical care resuscitation unit (CCRU) improves the operations of the University of Maryland Medical Center (UMMC) by expediting the transfers and resuscitations for critically ill patients who exceed the resources at other facilities. In this study we investigated CCRU transfer patterns to determine patient characteristics and logistical factors that influence bed assignments and transfer to the CCRU. We hypothesized that CCRU physicians prioritize transfer for critically ill patients. Therefore, those patients would be transferred faster. We performed a retrospective review of all non-traumatic adult patients transferred to the CCRU from other hospitals between January 1-December 31, 2018. The primary outcome was the interval from transfer request to CCRU bed assignment. The secondary outcome was the interval from transfer request to CCRU arrival. We used multivariate logistic regressions to determine associations with the outcomes of interest. A total of 1,741 patients were admitted to the CCRU during the 2018 calendar year. Of those patients, 1,422 were transferred from other facilities and were included in the final analysis. Patients' mean age was 57 ± 17 years with a median Sequential Organ Failure Assessment (SOFA) score of 3 [interquartile range 1-6]. Median time from transfer request to CCRU bed assignment was 8 (0-70) minutes. A total of 776 (55%) patients underwent surgical intervention after arrival. Using the median transfer request to bed assignment time, we found that patients requiring stroke neurology (odds ratio [OR] 5.49, 95% confidence interval [CI] 2.85-10.86), having higher SOFA score (OR 1.04, 95% CI 1.001-1.07), and needing an immediate operation (OR 2.85, 95% CI 1.98-4.13) were associated with immediate bed assignment time (≤8 minutes). Patients who were operated on (OR 0.74, 95% CI 0.55-0.99) were significantly less likely to have an immediate bed assignment time. The CCRU expedited the transfer of critically ill patients who needed urgent interventions from outside facilities. Higher SOFA scores and the need for urgent neurological or surgical intervention were associated with near-immediate CCRU bed assignment. Other institutions with similar models to the CCRU should perform studies to confirm our observations.

Neighborhood socioeconomic status and length of stay after congenital heart disease surgery.

Socioeconomic factors are associated with health outcomes and can affect postoperative length of stay after congenital heart disease (CHD) surgery. The hypothesis of this study is that patients from neighborhoods with a disadvantaged socioeconomic status (SES) have a prolonged length of hospital stay after CHD surgery. Pre- and postoperative data were collected on patients who underwent CHD surgery at the University of Maryland Medical Center between 2011 and 2019. A neighborhood SES score was calculated for each patient using data from the United States Census Bureau and patients were grouped by high vs. low SES neighborhoods. The difference of patient length of stay (LOS) from the Society for Thoracic Surgeons median LOS for that surgery was the primary outcome measure. Linear regression was performed to examine the association between the difference from the median LOS and SES, as well as other third variables. The difference from the median LOS was -4.8 vs. -2.2 days in high vs. low SES groups (p = 0.003). SES category was a significant predictor of LOS in unadjusted and adjusted regression analyses. There was a significant interaction between Norwood operation and SES-patients with a low neighborhood SES who underwent Norwood operation had a longer LOS, but there was no difference in LOS by SES in patients who underwent other operations. Neighborhood SES is a significant predictor of the LOS after congenital heart disease surgery. This effect was seen primarily in patients undergoing Norwood operation.

Comparison of 3 diagnostic platforms for identification of bacteria and yeast from positive blood culture bottles

Managing bloodstream infections requires fast and accurate diagnostics. Culture-based diagnostic methods for identification from positive blood culture require 24-hour subculture, potentially delaying time to appropriate therapy. Positive blood cultures were collected (n = 301) from September 2021 to August 2022 at the University of Maryland Medical Center. Platforms compared were BioFire® BCID2, Sepsityper®, and short-term culture. For monomicrobial cultures, FilmArray® BCID2 identified 88.3% (241/273) of pathogens. Rapid Sepsityper® identified 76.9% (210/273) of pathogens. Sepsityper® extraction identified 82.4% (225/273) of pathogens. Short-term culture identified 83.5% (228/273) of pathogens. For polymicrobial cultures, Sepsityper®, short-term culture, and BioFire® BCID2 had complete identifications at 10.7% (3/28), 0%, and 92.9% (26/28), respectively. Time-to-results for Rapid Sepsityper®, Sepsityper® extraction, BioFire® BCID2, and Short-term culture were 35, 52, 65, and 306 minutes, respectively. Performance of these platforms can reduce time-to-results and may help effectively treat bloodstream infections faster. Accuracy, time-to-result, and hands-on time are important factors when evaluation diagnostic platforms.

Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report

A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome. Physiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit. To ascertain the cause of xenograft dysfunction, we did extensive immunological and histopathological studies, including electron microscopy and quantification of porcine cytomegalovirus or porcine roseolovirus (PCMV/PRV) in the xenograft, recipient cells, and tissue by DNA PCR and RNA transcription. We performed intravenous immunoglobulin (IVIG) binding to donor cells and single-cell RNA sequencing of peripheral blood mononuclear cells. After successful xenotransplantation, the graft functioned well on echocardiography and sustained cardiovascular and other organ systems functions until postoperative day 47 when diastolic heart failure occurred. At postoperative day 50, the endomyocardial biopsy revealed damaged capillaries with interstitial oedema, red cell extravasation, rare thrombotic microangiopathy, and complement deposition. Increased anti-pig xenoantibodies, mainly IgG, were detected after IVIG administration for hypogammaglobulinaemia and during the first plasma exchange. Endomyocardial biopsy on postoperative day 56 showed fibrotic changes consistent with progressive myocardial stiffness. Microbial cell-free DNA testing indicated increasing titres of PCMV/PRV cell-free DNA. Post-mortem single-cell RNA sequencing showed overlapping causes. Hyperacute rejection was avoided. We identified potential mediators of the observed endothelial injury. First, widespread endothelial injury indicates antibody-mediated rejection. Second, IVIG bound strongly to donor endothelium, possibly causing immune activation. Finally, reactivation and replication of latent PCMV/PRV in the xenograft possibly initiated a damaging inflammatory response. The findings point to specific measures to improve xenotransplant outcomes in the future. The University of Maryland School of Medicine, and the University of Maryland Medical Center.

Cardiac Xenotransplantation: Barriers, Future Directions, and Ethical Considerations.

Since data collection began in 1995, 12,713 people have died while waiting for a heart transplant. Combined with a significant number of individuals with end-stage organ disease-eligible and waiting to receive a transplant offer-is a critical shortage of registered organ donors and acceptable organs. Strategies to overcome this organ shortage include efforts to increase the number of individuals registered as donors as well as new therapeutic approaches to managing organs that would have been otherwise deemed unacceptable for donation. One emerging technology that has the potential to further alleviate the demand for organs is xenotransplantation, where genetically engineered animal tissue or organ is transplanted into a human patient. While still in its elementary phases, this method shows great promise in reducing transplant wait-time and ultimately improving the quality of life and survival rate of transplant recipient patients. In 2021-2022, researchers at the University of Maryland Medical Center performed the first pig-to-human cardiac xenotransplantation on a live recipient. This review analyzes the case and discusses barriers, future directions, and ethical considerations to implementing cardiac xenotransplantation as a standard of care.

Hypertension, smoking, and preexistence of multiple cardiac risk factors correlate with carfilzomib-induced cardiovascular adverse events in a racially diverse population.

Use of the proteasome inhibitor carfilzomib has become a standard of care in patients with relapsed/refractory multiple myeloma. An association between carfilzomib and cardiovascular adverse events has been well documented, but this had not been investigated in a racially diverse population. Black patients in particular are underrepresented in the reported outcomes of treatment with carfilzomib. The purpose of this study was to identify risk factors for carfilzomib-associated cardiovascular events in a diverse, single-center population. We conducted a retrospective review of 161 patients with multiple myeloma treated with carfilzomib between 2011 and 2020 at the University of Maryland Medical Center. Over half (86) were Black patients, with the remainder (75) being White patients. We did a multivariate analysis to determine risk factors for developing cardiovascular events during treatment with carfilzomib. There was no statistically significant association with cardiotoxicity and race, gender, or age at first dose of carfilzomib. In multivariable analysis, patients with history of hypertension had a higher risk of cardiotoxicity [adjusted odds ratio (OR): 2.5; 95% CI: 1.1-5.9; P = 0.03] as did those with a history of smoking [OR: 2.8; 95% CI: 1.3-6.4; P = 0.01]. Here we report the largest cohort of Black patients treated with carfilzomib as yet reported. The results of this single center retrospective study show history of hypertension and smoking are associated with carfilzomib associated cardiotoxicity in a diverse patient population. There is a need for well-designed prospective studies enrolling a diverse population to investigate potential interventions to prevent carfilzomib-associated cardiotoxicity.