University Of Pittsburgh Medical Center Research Articles

Endoscopic Endonasal Approach for Residual and Recurrent Craniopharyngioma after Transcranial Approach: A Multi-institutional Experience

Abstract Objectives While the endoscopic endonasal approach (EEA) has become a well-established surgery for resection of craniopharyngiomas (CP), the utility of this procedure following subtotal resection from open transcranial approach (TCA) surgery has yet to be explored. Here we present a multi-institutional case series of patients who underwent EEA for treatment of recurrent CP originally treated by TCA, demonstrating the viability of this approach as salvage surgery. Design Retrospective cohort. Setting Loyola University Medical Center and University of Pittsburgh Medical Center. Participants Patients who underwent EEA for recurrent CP following an initial TCA between 2003 and 2018. Main Outcome Measures Gross total resection (GTR) rate, surgical complications, visual outcomes, and endocrine outcomes Results Patients who underwent EEA for recurrent CP following a prior TCA had a GTR rate of 77%. EEA reoperation was not associated with worsening of visual outcomes as compared with the primary TCA (0% visual worsening after EEA reoperation vs. 40% after primary TCA, p = 0.055). While primary TCA resulted in worsening endocrinopathies in 100% of patients (including seven patients with permanent diabetes insipidus), subsequent EEA for re-resection of CP resulted in stable (30.8%) or improved (69.2%) endocrine function in all patients (p < 0.001). Conclusions EEA achieves reasonable GTR rates and is an effective, safe surgical option for recurrent CP postinitial TCA. This approach demonstrated stable or improved visual and endocrinologic outcomes in all patients within our two-institution series. Thus, EEA should be considered as an efficacious form of retreatment in cases of progressive and recurrent CP.

Abstract PO1-07-09: Benefit of Adherence to Annual Mammography Screening: Results from 8,305 Cancers in an Institutional Database

Abstract Purpose: There is much debate on the starting age and frequency for asymptomatic mammographic breast cancer screening. We analyzed data from our medical center to determine the effect of the frequency of screening on the likelihood of a woman being diagnosed with a late-stage cancer and on the all-cause mortality. Method: For this study, we used our institutional breast cancer care data mart, which contains data for all patients who had breast imaging or were treated for breast cancer at a University of Pittsburgh Medical Center (UPMC) facility between 2004 and 2019 inclusive. Including only women 40 years and older, 8,145 had at least one screening mammogram prior to their diagnosis of breast cancer. Screening exams less than 260 days apart were considered to be from the same screening episode. For the 8,145 women, we determined the interval between their two most recent screening mammograms and grouped them into: (i) Baseline (only 1 prior screening episode prior to diagnosis); (ii) Compliant (less than or equal to 15 months between the two most recent screening episodes); (iii) Delayed (more than 15 months but less than 27 months between the two most recent screening episodes); and (iv) Missed (more than 27 months between the two most recent screening episodes. Late-stage cancer was defined as TNM stage 2b or worst. In cancers arising in those with at least two prior screening examinations, we estimated and tested significance of effects of adherence category on risk of late-stage cancer using logistic regression. We estimated the corresponding effects on survival to death from any cause using proportional hazards model. The effect of compliance was evaluated univariately followed by the multivariable analysis accounting for demographic and clinical characteristics including age, race, and menopausal status. Analysis within practically relevant subgroups was performed for additional illustration. Results: For all-cause death 5-year mortality rate post-diagnosis was 4.2% for the Compliant group (n=3369, median follow-up 5.13 years), 5.9% for the Delayed group (n=1340, median follow-up 4.64 years), and 12.2% for the Missed group (n=1129, median follow-up 3.36 years). The overall 5-year mortality rate was 6.1% (n=8145, median follow 5.12 years). Both unadjusted and adjusted for age, menopausal status, and ethnicity, the poorer survival with lesser compliance was highly significant (with the adjusted hazard ratios relative to the baseline group of 0.5, 0.8, and 1.3 for the three compliance groups respectively, p< 0.001). In the population overall, there was a significant trend of increasing risk of stage 2B or worse with lesser adherence to annual screening, the proportions being 9%, 14%, and 19% for the compliant, delayed, and missed groups respectively (p< 0.001). This remained significant when adjusted for age, menopausal status, or ethnicity (p< 0.001). The trend was significant within major demographic subgroups, except for a relatively small subpopulation of women with unknown menopausal status. Conclusions: Annual mammographic screening resulted in lower all-cause mortality and lower risk of late-stage cancers, for both white and black women and pre- and post-menopausal women. Our study clearly shows a benefit to screening all women over the age of 40 annually over longer periods between screens. Table of Late-Stage Cancers by Screening Adherence and Demographic Factors Diagnosis of breast cancer at stage 2B or higher by screening adherence group and demographic factors Citation Format: Robert Nishikawa, Andriy Bandos, Stephen Duffy, Durwin Logue, Margarita Zuley. Benefit of Adherence to Annual Mammography Screening: Results from 8,305 Cancers in an Institutional Database [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-09.

Exploring the Patient Experience and Perspective in Virtual-First Primary Care: A Cross-Sectional Study from an Integrated Health System.

Background: Little is known about the implication of launching virtual-first primary care (VPC) in a health system. Our experience and survey can guide others to establish their virtual-first programs. This study examines implementation, patient perspectives, and satisfaction with VPC at University of Pittsburgh Medical Center (UPMC). Methods: We conducted a Web-based survey to examine factors associated with the likelihood of early adoption and continued use of VPC. We used bivariate comparisons and cluster analysis to evaluate the results. The survey was sent to 1,420 patients seen between August 2022 and January 2023. Responses related to demographics, doctor-patient relations, savings, experience, and future preferences of use were aggregated. To evaluate the relationship between demographics and survey responses, we conducted univariate analysis. Results: Females and patients between 40 and 50 years of age were the primary users and indicated the most interest in continued use. Health insurance status seems not to be a significant predictor in the selection and use of VPC. Most (78%) felt that the physician-patient relationship was unimpaired. The survey showed that 90% of patients saved time by using VPC, and 66% reported saving money on tolls, childcare, or gasoline. Only 13% reported not wanting to continue VPC. Discussion: A majority of surveyed patients felt the doctor-patient relationship was not negatively affected in VPC. VPC programs can be implemented with high patient satisfaction in an integrated health system. VPC is acceptable to most patients, and further expansion of the model is warranted.

Mortality, Hospitalization, and Cardiac Interventions in Patients With Atrial Fibrillation Aged

The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear. Adult (n=67 221; mean age, 72.4±12.3 years; and 45% female) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073). Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% female) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (P=0.007 and P=0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (males aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; females aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]). Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.

Gamma knife radiosurgery for clival metastasis: case series and systematic review.

Clival metastatic cancer is rare and has limited literature to guide management. We describe management of clival metastasis with Gamma Knife radiosurgery (GKRS). We augment our findings with a systematic review of all forms of radiation therapy for clival metastasis. Records of 14 patients with clival metastasis who underwent GKRS at the University of Pittsburgh Medical Center from 2002 to 2023 were reviewed. Treatment parameters and clinical outcomes were assessed. A systematic review was conducted using evidence-based guidelines. The average age was 61 years with male predominance (n = 10) and average follow-up of 12.4 months. The most common primary cancers were prostate (n = 3) and lung (n = 3). The average time from cancer diagnosis to clival metastasis was 34 months. The most common presenting symptoms were headache (n = 9) and diplopia (n = 7). Five patients presented with abducens nerve palsies, and two presented with oculomotor nerve palsies. The median tumor volume was 9.3cc, and the median margin dose was 15Gy. Eleven patients achieved tumor control after one procedure, and three with progression obtained tumor control after repeat GKRS. One patient recovered abducens nerve function. The median survival from cancer diagnosis and GKRS were 49.7 and 15.3 months, respectively. The cause of death was progression of systemic cancer in six patients, clival metastasis in one, and unknown in four. The systematic review included 31 studies with heterogeneous descriptions of treatment and outcomes. Clival metastasis is rare and associated with poor prognosis. GKRS is a safe, effective treatment for clival metastasis.

Navigating the challenges of establishing a new residency program in anatomic pathology based on the Accreditation Council for Graduate Medical Education International standards in the post–Soviet era Kazakhstan: strategies and successes

In 1991, after the dissolution of the Soviet Union, newly independent Kazakhstan faced challenges of a healthcare system in transition. Anatomic pathology practice remains one of the least developed medical specialties in Kazakhstan. Acute shortage of pathologists is a universal phenomenon. There is no subspecialty pathology practice as yet. Residency programs in anatomic pathology are found only in a few tertiary health institutions in the big cities. Nazarbayev University School of Medicine was established in 2015 to reform medical education in Kazakhstan. Prior to this time, in 2010, Nazarbayev University was established to lead higher education reforms in the country. Each school in Nazarbayev University was paired with an international partner to jump-start its trajectory to excellence. Establishing a new residency program in anatomic pathology based on a western pedagogy was a new innovation that needed multi-level stakeholder consultation and support. In partnership with the University of Pittsburgh School of Medicine and its hospital system, the University of Pittsburgh Medical Center, we established the first residency program in anatomic pathology based on the Accreditation Council for Graduate Medical Education International standards in Central Asia. We have identified 5 strategic approaches that led to our rapid success, including targeted strategic partnership; robust engagement with the local stakeholders; adoption and contextualizing of an existing pedagogy; ensuring adequate and fit-for-purpose infrastructure; and organizational restructuring and optimization. We hope that these suggestions will be translatable to help those facing the arduous but exciting task of establishing a new residency program from scratch.

Is LDL cholesterol associated with long-term mortality among primary prevention adults? A retrospective cohort study from a large healthcare system

ObjectivesAmong primary prevention-type adults not on lipid-lowering therapy, conflicting results exist on the relationship between low-density lipoprotein cholesterol (LDL-C) and long-term mortality. We evaluated this relationship in a real-world evidence...

Towards Reproducible, Automated, and Scalable Anomaly Detection

Anomaly detection (AD), often termed outlier detection, is a key machine learning (ML) task, aiming to identify uncommon yet crucial patterns in data. With the increasing complexity of the modern world, the applications of AD span wide—from NASA's spacecraft monitoring to early patient prioritization at University of Pittsburgh Medical Center. Technology giants like Google and Amazon also leverage AD for service disruption identification. Here, I will traverse my AD works with promising new directions, particularly emphasizing reproducible benchmarks (Part 1), automated algorithms (Part 2), and scalable systems (Part 3).

Copy-number variants in the ACMG secondary finding genes: A reporting framework for clinical cytogeneticists

PurposeTo determine the pathogenicity and frequency of copy-number variants (CNV) in the 81 secondary finding (SFv3.2) genes recommended by the American College of Medical Genetics and Genomics (ACMG). MethodsReview of published evidence on pathogenicity of partial or complete copy-number losses or gains in ACMG SFv3.2 was performed. Frequency of reportable CNVs in the ACMG SFv3.2 genes was investigated among 10,959 patients tested by chromosomal microarray analysis in a single academic testing laboratory at the University of Pittsburgh Medical Center during 2011 to 2023. ResultsWe identified 57 ACMG SFv3.2 genes for which sufficient evidence supports reporting of partial or complete copy-number losses as secondary findings. On the contrary, reporting of copy-number gains was not supported by evidence in any of the ACMG SFv3.2 genes. Overall, CNVs in SFv3.2 genes were detected in 32 of 10,959 (0.29% or 1 in 343) patients in our cohort. ConclusionThis study provides a framework for consistent reporting of CNVs, detected by chromosomal microarray analysis, exome, or genome sequencing, in any of the ACMG SFv3.2 genes. To our knowledge, this is the largest cohort of patients studied for estimation of frequency of reportable CNVs in the ACMG SFv3.2 genes.

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey.

Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue? Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding. For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility. As such, standards for quality assurance and clinical care in preserving immature testicular tissue should be established. A detailed survey was sent to 17 centres within the recently established ORCHID-NET consortium, which offer testicular tissue cryopreservation to patients under the age of 18 years. The study encompassed 60 questions and remained open from 1 July to 1 November 2022. Of the 17 invited centres, 16 completed the survey, with representation from Europe, Australia, and the USA. Collectively, these centres have cryopreserved testicular tissue from patients under the age of 18 years. Data are presented using descriptive analysis. Since the establishment of the first formal fertility preservation programme for pre-pubertal males in 2002, these 16 centres have cryopreserved tissue from 3118 patients under the age of 18 years, with both malignant (60.4%) and non-malignant (39.6%) diagnoses. All centres perform unilateral biopsies, while 6/16 sometimes perform bilateral biopsies. When cryopreserving tissue, 9/16 centres preserve fragments sized ≤5 mm3 with the remainder preserving fragments sized 6-20 mm3. Dimethylsulphoxide is commonly used as a cryoprotectant, with medium supplements varying across centres. There are variations in funding source, storage duration, and follow-up practice. Research, with consent, is conducted on stored tissue in 13/16 centres. While this is a multi-national study, it will not encompass every centre worldwide that is cryopreserving testicular tissue from males under 18 years of age. As such, it is likely that the actual number of patients is even higher than we report. Whilst the study is likely to reflect global practice overall, it will not provide a complete picture of practices in every centre. Given the research advances, it is reasonable to suggest that cryopreserved immature testicular tissue will in the future be used clinically to restore fertility. The growing number of patients undergoing this procedure necessitates collaboration between centres to better harmonize clinical and research protocols evaluating tissue function and clinical outcomes in these patients. K.D. is supported by a CRUK grant (C157/A25193). R.T.M. is supported by an UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health at the University of Edinburgh is supported by MRC (MR/N022556/1). C.L.M. is funded by Kika86 and ZonMW TAS 116003002. A.M.M.v.P. is supported by ZonMW TAS 116003002. E.G. was supported by the Research Program of the Research Foundation-Flanders (G.0109.18N), Kom op tegen Kanker, the Strategic Research Program (VUB_SRP89), and the Scientific Fund Willy Gepts. J.-B.S. is supported by the Swedish Childhood Cancer Foundation (TJ2020-0026). The work of NORDFERTIL is supported by the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115), the Swedish Research Council (2018-03094; 2021-02107), and the Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2021-00073; 2022-00317; 2023-00353). C.E is supported by the Health Department of the Basque Government (Grants 2019111068 and 2022111067) and Inocente Inocente Foundation (FII22/001). M.P.R. is funded by a Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. A.F. and N.R. received support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. K.E.O. is funded by the University of Pittsburgh Medical Center and the US National Institutes of Health HD100197. V.B-L is supported by the French National Institute of Cancer (Grant Seq21-026). Y.J. is supported by the Royal Children's Hospital Foundation and a Medical Research Future Fund MRFAR000308. E.G., N.N., S.S., C.L.M., A.M.M.v.P., C.E., R.T.M., K.D., M.P.R. are members of COST Action CA20119 (ANDRONET) supported by COST (European Cooperation in Science and Technology). The Danish Child Cancer Foundation is also thanked for financial support (C.Y.A.). The authors declare no competing interests. N/A.

Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates.

To investigate the genomic diversity and β-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.

INFLAMMATORY BOWEL DISEASE AND RHEUMATOID ARTHRITIS

Abstract Inflammatory bowel disease has been associated with arthritis since the late 20th century, but it was not until a few decades ago that IBD-associated arthritis was recognized as a distinct pathology independent from rheumatoid arthritis (RA). There is evidence that RA and other autoimmune conditions exist in higher rates in patients with IBD compared to the general population. This is an important distinction because of the different pathophysiology, clinical manifestations, management, complications, and prognosis of both diseases. METHODS: This study was reviewed and approved by the University of Pittsburgh Medical Center of Central Pennsylvania Review Board. Using Epic’s SlicerDicer function, patients with Inflammatory Bowel disease were identified using ICD-10 codes (K50 and K51). Those with incomplete information or duplicated were excluded obtaining a total of 3613 patients. Data collected included basic demographic information, surgical history, and the presence of Rheumatoid arthritis. We reported continuous variables as mean (range) and categorical variables as number (percent). We used Student’s t-test to analyze between group differences for the continuous variables. When it was determined that variances for the comparisons of continuous data were unequal, Welch-Satterthwaite t test statistics were used. We used chi-square test to analyze between group differences for the categorical variables. The Fisher exact test was employed when any of the expected frequencies was five or less. All tests were 2-sided with criterion for statistical significance at a p-value less than 0.05. All the analyses were done by SAS 9.4 (SAS Institute, Cary NC). RESULTS: Of the approximately 2.7 million adults in SlicerDicer, there were 3613 patients (0.13%) identified with Inflammatory Bowel disease. Patients with Ulcerative Colitis accounted for 37% of the total group (n= 1343) and 2270 patients (62.8%) had Crohn’s Disease. From the total, 2084 were women (57.68%) and 1529 (42.32%) were men. The mean age was 53.3 +- 18.5. 848 (23.47%) had documented Rheumatoid arthritis. Mortality was higher in patients with IBD and RA than those with IBD alone (7.31% vs 3.98%, p value= &amp;lt;0.0001). More than 90% of the patients were white (n=3321). CONCLUSION: IBD patients with RA have higher mortality than patients with IBD alone.

Outcomes after Perioperative Transient Ischemic Attack Following Cardiac Surgery.

Perioperative transient ischemic attacks (PTIAs) are associated with significantly increased rates of postoperative complications such as low cardiac output, atrial fibrillation, and significantly higher mortality in cardiac procedures. The current literature on PTIAs is sparse and understudied. Therefore, we aim to understand the effects of PTIA on hospital utilization, readmission, and morbidity. Using data on all the cardiac procedures at the University of Pittsburgh Medical Center from 2011 to 2019, fine and gray analysis was performed to identify whether PTIAs and covariables correlate with increased hospital utilization, stroke, all-cause readmission, Major Adverse Cardiac and Cerebrovascular Events (MACCE), MI, and all-cause mortality. Logistic regression for longer hospitalization showed that PTIA (HR: 2.199 [95% CI: 1.416-3.416] increased utilization rates. Fine and gray modeling indicated that PTIA (HR: 1.444 [95% CI: 1.096-1.902], p < 0.01) increased the rates of follow-up all-cause readmission. However, PTIA (HR: 1.643 [95% CI: 0.913-2.956] was not statistically significant for stroke readmission modeling. Multivariate modeling for MACCE events within 30 days of surgery (HR: 0.524 [95% CI: 0.171-1.605], p > 0.25) and anytime during the follow-up period (HR: 1.116 [95% CI: 0.825-1.509], p > 0.45) showed no significant correlation with PTIA. As a result of PTIA's significant burden on the healthcare system due to increased utilization, it is critical to better define and recognize PTIA for timely management to improve perioperative outcomes.

DeepBiomarker2: Prediction of Alcohol and Substance Use Disorder Risk in Post-Traumatic Stress Disorder Patients Using Electronic Medical Records and Multiple Social Determinants of Health.

Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. We developed DeepBiomarker2 by leveraging deep learning and natural language processing to analyze lab tests, medication use, diagnosis, social determinants of health (SDoH) parameters, and psychotherapy for outcome prediction. To increase the model's interpretability, we further refined our contribution analysis to identify key features by scaling with a factor from a reference feature. We applied DeepBiomarker2 to analyze the EMR data of 38,807 patients from the University of Pittsburgh Medical Center diagnosed with post-traumatic stress disorder (PTSD) to determine their risk of developing alcohol and substance use disorder (ASUD). DeepBiomarker2 predicted whether a PTSD patient would have a diagnosis of ASUD within the following 3 months with an average c-statistic (receiver operating characteristic AUC) of 0.93 and average F1 score, precision, and recall of 0.880, 0.895, and 0.866 in the test sets, respectively. Our study found that the medications clindamycin, enalapril, penicillin, valacyclovir, Xarelto/rivaroxaban, moxifloxacin, and atropine and the SDoH parameters access to psychotherapy, living in zip codes with a high normalized vegetative index, Gini index, and low-income segregation may have potential to reduce the risk of ASUDs in PTSD. In conclusion, the integration of SDoH information, coupled with the refined feature contribution analysis, empowers DeepBiomarker2 to accurately predict ASUD risk. Moreover, the model can further identify potential indicators of increased risk along with medications with beneficial effects.

Prediction of adverse events risk in patients with comorbid post-traumatic stress disorder and alcohol use disorder using electronic medical records by deep learning models

BackgroundIdentifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-risk population. MethodsWe analyzed electronic medical records of 5565 patients from University of Pittsburgh Medical Center to predict adverse events (opioid use disorder, suicide related events, depression, and death) within 3 months at any encounter after the diagnosis of PTSD+AUD by using DeepBiomarker2. We integrated multimodal information including: lab tests, medications, co-morbidities, individual and neighborhood level social determinants of health (SDoH), psychotherapy and veteran data. ResultsDeepBiomarker2 achieved an area under the receiver operator curve (AUROC) of 0.94 on the prediction of adverse events among those PTSD+AUD patients. Medications such as vilazodone, dronabinol, tenofovir, suvorexant, modafinil, and lamivudine showed potential for risk reduction. SDoH parameters such as cognitive behavioral therapy and trauma focused psychotherapy lowered risk while active veteran status, income segregation, limited access to parks and greenery, low Gini index, limited English-speaking capacity, and younger patients increased risk. ConclusionsOur improved version of DeepBiomarker2 demonstrated its capability of predicting multiple adverse event risk with high accuracy and identifying potential risk and beneficial factors.

Going Going Gonad: Assessing Iron Staining Impact on Fertility for Patients with Sickle Cell Disease

Introduction: Medical advances in the care of patients with sickle cell disease (SCD) and other hemoglobinopathies have allowed for the focus of care to shift and incorporate long-term quality of life metrics, such as fertility. Concerns for reproductive health in patients with SCD stem from the underlying disease itself as well as from medical therapies that are offered such as hydroxyurea, chronic red blood cell transfusions, and stem cell transplant (SCT). Iron deposition from chronic transfusions in other tissues is known to result in end organ damage and lifelong consequences. While little is known about iron overload and fertility, one study noted testicular iron deposition on MRI in pubertal males with transfusion-dependent beta-thalassemia; results were notable for lower sperm concentrations and a lower percentage of sperm with normal morphology, indicating that iron overload likely has an impact on fertility for patients. Iron deposition has not been studied in the pre-pubertal hemoglobinopathy population. Fertility counseling in this patient population does not often occur until patients are considering SCT as a curative therapy option, as the conditioning regimens for SCT are gonadotoxic. Without a good understanding of the impact of chronic transfusions on fertility for patients with hemoglobinopathies, it is difficult to determine the optimal time to offer fertility preservation to families. We aim to assess iron overload on testicular tissue to gain a better understanding of the impact that medical management and chronic transfusions can have on fertility for a patient with SCD. Methods: Our study is a cross-sectional evaluation of patients with SCD who underwent testicular tissue cryopreservation (TTC) as a part of a multicenter research protocol through the University of Pittsburgh Medical Center (UPMC) prior to SCT. As part of the TTC protocol, each patient provided a small piece of tissue for research, with the remaining cryopreserved for patient use. All samples were evaluated for the presence of germ cells. For this study, demographics, treatment data, imaging results, and labs pertinent to hormonal profile and iron status were obtained. All samples from patients with SCD and thalassemia will undergo additional pathology review to evaluate for the presence of germ cells and iron. At the time of this abstract, the tissue for two patients had been analyzed. Results: Banked research tissue from UPMC includes 77 patients with SCD and 21 patients with beta thalassemia major. Of the 77 SCD patient samples, 42 were found to have germ cells, 34 have not yet been analyzed and 1 had no germ cells present. Of the 21 samples from patients with beta thalassemia major, 17 were found to have germ cells, 3 were not yet analyzed and 1 had no germ cells present. To date, we have obtained pathology review on two patients, both with Hb SS genotype and were on the maximum tolerated dose of hydroxyurea prior to TTC. Patient 1 had been on hydroxyurea for 7 years and had 13 units of blood transfusions, and Patient 2 on hydroxyurea for 4 years and 6units of blood transfusions prior to TTC. Both patients were found to have normal testicular tissue histopathology with presence of germ cells and without evidence of iron on staining (Table 1). Conclusions: Based on our preliminary data it can be noted that patients without significant iron burden, based on low ferritin and a limited transfusion history may not have a significant impact on their testicular histopathology with their iron staining being negative. We will expand our patient cohort to include patients who have a severe disease course requiring more blood transfusions to determine whether this is associated with increased iron deposition in their testicular tissue and/or reduced germ cell numbers. This information will allow teams to optimize the timing of fertility discussions and possible preservation in this patient population, even outside of curative treatment.

Incidence of postoperative hyponatremia after endoscopic endonasal pituitary transposition for skull base pathologies.

Pituitary transposition is a novel surgical approach to access the retroinfundibular space and interpeduncular cistern. Few studies have evaluated post-surgical outcomes, including incidence of hyponatremia, following pituitary transposition. This is a retrospective study including 72 patients who underwent endoscopic endonasal surgery involving pituitary transposition for non-pituitary derived tumors over a decade at the University of Pittsburgh Medical Center. Anterior pituitary deficiencies and replacement therapy, tumor pathology and pre-operative serum sodium (Na) were recorded. Na was assessed at postoperative day 1, 3, 5, 7, and 10. Anatomical/surgical parameters included sellar height, sellar access angle to approach the tumor, and cranial extension of the tumor above the sellar floor (B) compared to the height of the gland (A) (B/A). T-test (normally distributed variables) and Wilcoxon rank-sum test (not-normally distributed) were applied for mean comparison. Logistic regression analyzed correlations between anatomical/surgical parameters and postoperative hyponatremia. 55.6% of patients developed post-operative transient hyponatremia. Two patients (5%) developed severe hyponatremia (sodium level < 120 mmol/L). Eleven (15.3%) patients required desmopressin replacement immediately post-operatively, and 2 other patients needed desmopressin after discharge and after sodium nadir developed. Hyponatremia was inversely associated with sellar access angle (p = 0.02) and the tumor cranial extension above the sellar floor showing a trend towards significance (p = 0.09). More than half of patients who had pituitary transposition developed transient hyponatremia. Hyponatremia was more common in those with narrower sellar access angle and smaller cranial extension of the tumor above the sellar floor. Anatomical/surgical parameters may allow risk-stratification for post-operative hyponatremia following pituitary transposition.

Abstract 15930: Using Charlson Comorbidity Index to Predict 1-Year All-Cause Mortality in ICD Recipients

Introduction: Primary prevention implantable cardioverter-defibrillators (PP-ICD) are indicated in patients with left ventricular ejection fraction (LVEF) ≤ 35% despite 3 months of maximally tolerated guideline directed medical therapy (GDMT), who are expected to survive at least 1 year. The Seattle Heart Failure Score, commonly used for evaluation of 1 year survival, only addresses heart failure mortality. The Charlson Comorbidity Index (CCI) is a validated model of comorbid conditions used to predict 1-year all-cause mortality. Objectives: We aimed to create a predictive model using the CCI to guide eligibility for PP-ICD based on predicted 1-year all-cause mortality in patients with severe cardiomyopathy. Methods: We analyzed clinical data from the University of Pittsburgh Medical Center, a large multi-hospital system, between January 2010 and July 2021. Patients receiving PP-ICD were included. We used a logistical regression model based on patients’ CCI, age, race, mean number of GDMT medications, the presence of coronary artery disease (CAD), and baseline LVEF. Results: Of the total cohort of 2,864 patients (mean age 67±12 years; Male 69%; White 85%; LVEF 24±7%; CAD 62%), 235 (8.2%) patients died within 1 year. Patients were on average prescribed 2.0±0.8 GDMT agents and had a mean CCI of 1.4± 1.6. CCI was significantly associated with adjusted 1-year mortality (OR 1.41 per standard deviation of CCI, 95% CI 1.35-1.71, p&lt; 0.001). A receiver operator curve was generated (Figure 1) and a CCI cutoff of 1.54, yielded a sensitivity of 71% and a specificity of 59% (AUC 0.70). Conclusions: Our data demonstrate that a model incorporating the CCI can predict 1-year all-cause mortality in PP-ICD recipients with modest accuracy and could therefore assist in shared-decision making around PP-ICD therapy. Future work should focus on refining the model for higher predictive accuracy.

Abstract 17646: Maternal and Neonatal Outcomes in Pregnant Women With Congenital Heart Disease: The Magee Obstetric Maternal and Infant (MOMI) ACHD Substudy

Introduction: Adult patients with congenital heart disease (ACHD) have a life-long burden of cardiovascular morbidity that contributes to increased maternal and neonatal risk during pregnancy and the peripartum period. Hypothesis: Women with ACHD and their neonates have a higher risk of adverse pregnancy and peripartum outcomes as compared to women without ACHD. Methods: We matched 565 deliveries from women with ACHD and 1130 deliveries from women without cardiac disease (1:2 matching), for a delivery year, race and maternal age as a substudy of the Magee Obstetric Maternal and Infant (MOMI) study, of women who received perinatal care at the Magee-Womens Hospital at the University of Pittsburgh Medical Center between 1995-2020. We evaluated for in-hospital maternal and neonatal outcomes. Results: Of the 565 women with ACHD, 24.0% had aortic outflow and mitral valve abnormalities, 19.5% had pulmonary outflow and tricuspid valve abnormalities, 28.1% had isolated atrial or ventricular septal defects, 0.3% had single ventricle physiology, and 1.4% had outflow vessel abnormalities. Maternal and neonatal outcomes are summarized in Table 1. Women with ACHD had a higher rate of pregnancy loss (32.4% vs 26.2% p&lt;0.001), induction of labor, and cesarean section. Neonates from ACHD women were delivered at an earlier gestational age, with a lower birth weight, and had a higher incidence of respiratory distress syndrome. ACHD women had a higher incidence of cardiovascular events (predominantly arrhythmias and pulmonary edema) and required intensive care more frequently (10.5% vs 1.2%, p&lt;0.001) and for longer periods (2.1±1.8 vs. 1.1±0.3 days; P=0.027) after delivery. Conclusion: Women with ACHD are at higher risk for adverse clinical outcomes during pregnancy and delivery. Neonates of ACHD women are delivered slightly earlier by induction of labor and have consequent sequelae after birth.

Abstract 19180: Early Rhythm Control is Associated With Improved Outcomes in Hypertrophic Cardiomyopathy Patients With Atrial Fibrillation

Background: Atrial fibrillation in hypertrophic cardiomyopathy (HCM) patients is associated with worse outcomes with regards to stroke, heart failure hospitalization and death. Contemporary data on Rhythm control (RyC) strategies and outcomes in HCM patients is limited. Objectives: We aimed to assess the clinical characteristics of HCM patients with AF receiving RyC (antiarrhythmic drug and/or catheter ablation) vs no rhythm control (NRC) and compare clinical outcomes between the two groups. Methods: We analyzed the electronic health records of the University of Pittsburgh Medical Center, a large multi-hospital system, between 2010 and 2022. Differences between baseline demographics, cardiovascular risk factors, and comorbidity burden were evaluated with t tests. Adjusted Cox proportional hazards and Kaplan-Meier analyses were performed to evaluate associations between use of rhythm control and all-cause age-adjusted mortality. Results: A total of 552 patients with HCM and AF were analyzed, of which 118 received RyC and 434 NRC. The RyC group was relatively younger (age 64 vs 70), received initial evaluation by a cardiologist (70% vs 57%), had lower CHA2DS2VASC scores (mean 2.5 vs 3.1) and fewer comorbidities (mean Elixhauser scores 3.0 vs 4.7). There were no significant differences in either ejection fraction or left atrial diameter between the groups. Among RyC patients, 38 received catheter ablation and 80 received antiarrhythmic drug as the initial RyC strategy. Over a median follow up of 2.9 years (IQR 0.96-6.0), use of RyC was associated with decreased mortality after adjustment for age, Elixhauser score, and CHA2DS2VASC score (HR 0.54, 95% CI 0.30-0.95, p&lt;0.05, figure 1). Conclusion: Rhythm control in HCM and AF patients is associated with better outcomes as suggested by decreased overall mortality. Prospective studies are needed to establish the best RyC strategy in this cohort.