University Of Pittsburgh Medical Center Research Articles

A-330 Implementation of a Point of Care Emergency Preparedness policy: Are you ready for a disaster?

Abstract Background CAP Gen.73800 requires laboratories to have an Emergency Preparedness and Response policy. Hospital standards for Joint Commission Accreditation, EM.09.01.01, EM.12.02.09, and EM.16.01.01 require hospitals to have a comprehensive emergency management program including an ability to manage resources and assets during an emergency and conduct exercises to evaluate its plan. According to a survey of 27 POCT departments, only 35% have a POCT policy separate from the main lab and 50% of POCT programs are involved with emergency preparedness drills. With the continuing growth of POC testing, the University of Pittsburgh Medical Center (UPMC) POCT team recognized a need for a collaborative effort between main laboratories, the emergency management team, and POCT to develop a POCT emergency preparedness policy. Methods UPMC POCT team collaborated with emergency management to decide what details regarding POC tests and devices would be needed if the main laboratory was rendered not functional. Additionally, a hazard vulnerability review identified potential internal and external events that could impact patient care. POC coordinators from across the system supplied feedback as to what situations within POC could impact patient safety. Results An evaluation of hazards considered debilitating to the main laboratory included external events, such as weather emergencies or evacuation of the hospital due to safety concerns. Potential internal events including a loss of water or impeded functionality of an instrument platform were identified. Available POC tests may offer solutions to deficits in main lab testing. The POCT program is not immune to potential emergency situations. Connectivity/IT issues can require extensive troubleshooting. Supply chain disruptions that affect the availability of consumables may lead to a reverse scenario where emergency management may assist. On-line training modules are a consideration when labor strikes or staffing shortages require POCT programs to quickly onboard replacement workers as new operators. During pandemics, Coordinators may need to rapidly implement new testing. The UPMC Emergency Preparedness policy was developed as a guide to the POCT team to ensure the continuation of testing ability in these emergent situations and addresses the need for communication with Incident Command. The UPMC POCT Emergency Preparedness policy is linked to a Microsoft Form that can be quickly completed by POC coordinators throughout the system. Responses to the form can be exported to an Excel spreadsheet and will supply emergency management with POC device-specific information, listing devices as battery operated, wireless capable, tabletop or hand-held and provides test menus. This spreadsheet allows coordinators to decide the number of devices and consumables that could be pooled from all facilities within the system. Conclusions Ninety-three percent of survey respondents acknowledged that they could potentially benefit from a POCT emergency preparedness policy. Increasing the number of POCT programs involved in emergency preparedness drills would improve response to emergency management challenges. The UPMC POCT Emergency Management Policy guides POC coordinators through situations, allowing them to pool resources to allow for the continuity of testing necessary for quality patient care.

B-274 Determining Novel Biomarker Candidates Associated With Heroin and Cocaine Exposure Using Urine Metabolomics

Abstract Background Substance abuse poses an escalating health risk in the United States. While acute drug exposure can be tracked using drugs and their metabolites as biomarkers in clinical settings, there is a notable absence of biomarkers for chronic drug exposure or addiction. The development and availability of such biomarkers could significantly enhance clinicians’ ability to identify patients at high risk of addiction, and more accurately predict disease progression and treatment responses. Methods Our study aimed to discover novel biomarkers associated with substance abuse by analyzing raw mass spectrometry (MS) data from urine comprehensive drug screening (UCDS) conducted at the University of Pittsburgh Medical Center (UPMC). The MS data, acquired through untargeted data collection using LC-qToF-MS at the UPMC Clinical Toxicology Laboratory, was initially preprocessed (including peak identification, alignment, and putative annotation) using MS-DIAL to generate a data matrix. This matrix, consisting of objects (cases) and features (m/z and retention time), was further normalized and analyzed using MetaboAnalyst. A combination of statistical methods, including point biserial correlation analysis, volcano plot, significance analysis of microarrays and metabolites (SAM), empirical Bayesian analysis of microarrays and metabolites (EBAM), partial least squares discriminant analysis (PLS-DA), and random forest (RF), were employed to select features significantly associated with the EIA-results. These features were subsequently evaluated for analyte identification using MS-FINDER. Results Our analysis identified nine significant features associated with 6MAM-EIA for heroin abuse, including 6-monoacetylmorphine itself and norfentanyl. For features associated with cocaine metabolite-EIA, 37 significant features were selected, including multiple cocaine metabolites, nicotine metabolites, and norfentanyl. Some of these selected features are likely products of in-source fragmentation or endogenous metabolites. Conclusions Our study has identified a set of potential biomarker candidates for illicit drug exposure. Notably, norfentanyl was found to be significantly associated with both 6MAM-EIA and cocaine metabolite-EIA, reflecting current trends in illicit drug use. Further chemical identification of these biomarkers is planned for future work.

A quality initiative in BRCA testing and timing of BRCA test prior to surgery in HER2- early stage breast cancer.

287 Background: The University of Pittsburgh Medical Center (UPMC) collaborated with Integra Connect PrecisionQ (IC) on a quality initiative to improve BRCA 1/2 (BRCA) testing in patients (pts) with early-stage (I-III) human epidermal growth factor receptor negative (HER2-) breast cancer (BC). The project involved developing a baseline of BRCA testing, reviewing the results with leadership, conducting a focus group with physicians to identify improvements, and then monitoring the results of BRCA testing thereafter during a post-baseline period. The project sought to improve the identification of pts who may be eligible for olaparib given the updated approval on March 11, 2022, for early-stage high-risk germline BRCA mutated pts. We aim to show the improvement in BRCA testing and timing of test in relation to surgery among HER2- BC pts at UPMC. Methods: Using the de-identified IC PrecisionQ database, 202 UPMC pts with early-stage HER2- BC were selected for medical chart curation as baseline group. Pts in the baseline group received surgery between 7/1/2021 to 6/30/2022. The baseline data was reviewed with UPMC clinical leadership and findings were discussed among a focus group of 8 physicians on 7/17/2023. Following the meeting, UPMC practices performed genetic testing at the office as opposed to sending pts to directly to genetic counseling. Post-baseline, we evaluated 70 pts who underwent surgery between 8/1/2023 to 1/31/2024 to assess BRCA rates and timing of BRCA testing in relation to surgery. Descriptive analyses were performed and proportions were compared using a chi-squared test. Results: Among the baseline cohort of 202 pts, 72% were hormone receptor positive (HR+) and 28% were hormone receptor negative (HR-). Among the post-baseline cohort of 70 pts, 77% were HR+ and 23% were HR-. The rate of BRCA testing at baseline was 44% compared to 56% post-baseline (p 0.05). Among HR+ pts, BRCA testing increased from 38% to 50% and among HR- pts, BRCA testing increased from 67% to 81%. The rate of BRCA testing prior to surgery at baseline was 58% (N= 88) compared to 80% (N=40) post-baseline (p <0.01). Among HR+ pts age <65, BRCA testing at baseline was 46% (N=54) compared to 51% (N=35) post-baseline. Among HR- pts age <65 BRCA testing at baseline was 84% (N=25) compared to 100% (N=9) post-baseline. Conclusions: The quality initiative at UPMC that focused on BRCA testing among HER2- BC pts led to an improvement from 44% to 56% of pts being tested. Among those who were tested, there was an increase from 58% to 80% tested prior to surgery. Given the recent updates on January 4 th , 2024 by ASCO and SSO recommending BRCA1/2 testing to all women younger than age 65 with breast cancer, such QIs can be a useful tool to align a practice’s approach to new standards of care.

Hearing Loss in the Unoperated Ear After High-Speed Drilling in Otologic and Skull Base Surgery.

To evaluate if permanent hearing loss occurred in the unoperated ear of patients undergoing otologic and skull base surgery with high-speed otologic drilling. We retrospectively studied 250 patients (mean age 57.8 yr; 120 males, and 130 females) undergoing otologic or skull base surgery with high-speed drilling between 2013 and 2019. The University of Pittsburgh Medical Center. We evaluated preoperative and postoperative audiograms for patients undergoing surgery for cochlear implantation (95 patients, 38.0%), cholesteatoma or chronic ear disease (88 patients, 35.2%), repair of lateral skull base encephalocele (26 patients, 10.4%), resection of vestibular schwannoma or meningioma of the cerebellopontine angle (23 patients, 9.2%), lateral temporal bone resection (8 patients, 3.2%), microvascular decompression (7 patients, 2.8%), or other operations involving a high-speed otologic drill (3 patients, 1.2%). Hearing threshold shift, measured as the difference between postoperative threshold and preoperative threshold for each frequency. The association of age, gender, tested frequency, and surgery type with hearing threshold shift was investigated with analysis of covariance. A total of 102 patients (40.8%) had a 10-dB or greater worsening of their hearing in at least one frequency on their postoperative audiogram in the contralateral, unoperated ear. One hundred six subjects (42.4%) had no change in hearing of 10 dB or greater at any frequency. Among patients with longitudinal postoperative audiograms, accelerated age-related hearing loss was observed in low frequencies. A significant number of patients demonstrated poorer hearing thresholds in the contralateral, unoperated ear after otologic and skull base surgery.

Stereotactic radiosurgery for patients with spinal metastases from prostate cancer.

Spinal metastases may result in intractable pain, neurological deficit, and vertebral body collapse. There are only a few studies describing outcomes following spine stereotactic radiosurgery (SRS) specifically for prostate cancer metastases. A prospectively collected database of patients with prostate cancer spinal metastases treated at the University of Pittsburgh Medical Center from 2003 to 2023 was analyzed. The primary outcome was local control (LC). Secondary outcomes were overall survival (OS), pain resolution, and adverse radiation effects (AREs). Thirty-seven patients and 51 lesions were identified. Fifteen lesions (29%) were previously resected and 34 lesions (67%) were previously irradiated. The median tumor volume was 37.0cc (range: 2.9-263.3). A majority of lesions (71%) were treated in a single fraction (median 20Gy, range: 14-22.5); multi-fractionated treatment consisted of 21-30Gy in 2-5 fractions. Median follow-up was 12 months (range: 1-146). The 6-month, 1-year, and 2-year LC rates were 97%, 91%, and 91%, respectively. No tested prognostic factors were associated with LC, including hormone sensitivity. The 6-month, 1-year, and 2-year OS rates were 71%, 56%, and 32%; age > 70 years (p = 0.048) and tumor volume > 30cc (p = 0.03) were associated with inferior rates of OS. Complete or partial pain response was observed in 58% of patients. There were 8 instances (16%) of AREs, 2 of which were vertebral compression fractures (4%). Radiosurgery as a primary or adjuvant treatment modality for prostate cancer spinal metastases confers durable LC and moderate pain relief with minimal toxicity. Further studies are warranted to optimize management in this patient population.

Evolution of extended-spectrum β-lactamase-producing ST131 Escherichia coli at a single hospital over 15 years

Escherichia coli multi-locus sequence type ST131 is a globally distributed pandemic lineage that causes multidrug-resistant extra-intestinal infections. ST131 E. coli frequently produce extended-spectrum β-lactamases (ESBLs), which confer resistance to many β-lactam antibiotics and make infections difficult to treat. We sequenced the genomes of 154 ESBL-producing E. coli clinical isolates belonging to the ST131 lineage from patients at the University of Pittsburgh Medical Center (UPMC) between 2004 and 2018. Isolates belonged to the well described ST131 clades A (8%), B (3%), and C (89%). Time-dated phylogenetic analysis estimated that the most recent common ancestor (MRCA) for all clade C isolates emerged around 1989, consistent with previous studies. We identified multiple genes potentially under selection in clade C, including the cell wall assembly gene ftsI, the LPS biosynthesis gene arnC, and the yersiniabactin uptake receptor fyuA. Diverse ESBL-encoding genes belonging to the blaCTX-M, blaSHV, and blaTEM families were identified; these genes were found at varying numbers of loci and in variable numbers of copies across isolates. Analysis of ESBL flanking regions revealed diverse mobile elements that varied by ESBL type. Overall, our findings show that ST131 subclade C dominated among patients and uncover possible signals of ongoing adaptation within this ST131 lineage.

Corneal Collagen Cross-linking for Keratoconus in Pediatric and Developmentally Delayed Patients.

Corneal cross-linking (CXL) is the standard of care in patients with keratoconus but presents unique challenges in children and developmentally delayed patients. We present our clinical decision-making algorithm, CXL surgical technique, and outcomes in these groups. A retrospective chart review was undertaken at a tertiary referral center of all patients who underwent CXL for keratoconus at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between October 1, 2017, and April 1, 2021. Demographic information along with preoperative, intraoperative, and postoperative ophthalmic examination findings were collected. The main outcome measures were indications of CXL, postoperative complications, and visual acuity (VA). Forty-eight eyes of 34 patients [21 patients (30 eyes) with developmental delay (DD) and 13 patients (18 eyes) with no DD (NDD)] underwent epithelium-off, standard CXL. General anesthesia was used for CXL in all patients except for 3 with NDD. A temporary central tarsorrhaphy was performed in all patients with DD and 7 patients with NDD. The remaining got a bandage contact lens. There were no immediate postoperative complications. A trend toward improvement in VA was noted postoperatively. The mean logMAR VA (with habitual correction) was 0.67 preoperatively and 0.57 postoperatively (P = 0.3) in DD and 0.52 and 0.36, respectively (P = 0.13), in NDD. This retrospective review presents a technique for assessment and treatment of keratoconus in children and those with DD. Our technique ensures timely diagnosis and provides a safe method for CXL in these groups. Temporary central tarsorrhaphy is a well-tolerated option to reduce postoperative pain.

Community pharmacists’ attitudes toward and practice of pharmacy-based harm reduction services in Pittsburgh, PA: a descriptive survey

BackgroundIn Pittsburgh, PA, legal changes in recent decades have set the stage for an expanded role for community pharmacists to provide harm reduction services, including distributing naloxone and non-prescription syringes (NPS). In the wake of the syndemics of the COVID-19 pandemic and worsening overdose deaths from synthetic opioids, we examine knowledge, attitudes, and practices of harm reduction services among community pharmacists in Pittsburgh and identify potential barriers of expanded pharmacy-based harm reduction services.MethodsWe provided flyers to 83 community pharmacies within a 5-mile radius of the University of Pittsburgh Medical Center to recruit practicing community pharmacists to participate in an anonymous electronic survey. We used a 53-question Qualtrics survey consisting of multiple-choice, 5 or 6 point-Likert scale, and open-ended questions adapted from 5 existing survey instruments. Survey measures included demographics, knowledge, attitudes, and practices of harm reduction services (specifically naloxone and NPS provision), and explored self-reported barriers to future implementation. Data was collected July–August 2022. We conducted descriptive analysis using frequencies and proportions reported for categorical variables as well as means and standard deviations (SD) for continuous variables. We analyzed open-ended responses using inductive content analysis.ResultsEighty-eight community pharmacists responded to the survey. 90% of participants agreed pharmacists had a role in overdose prevention efforts, and 92% of participants had previously distributed naloxone. Although no pharmacists reported ever refusing to distribute naloxone, only 29% always provided overdose prevention counseling with each naloxone distributed. In contrast, while 87% of participants had positive attitudes toward the usefulness of NPS for reducing disease, only 73% of participants ever distributed NPS, and 54% had refused NPS to a customer. Participants endorsed a lack of time and concerns over clientele who used drugs as the most significant barriers to offering more comprehensive harm reduction services.ConclusionsOur findings highlight that while most community pharmacists have embraced naloxone provision, pharmacy policies and individual pharmacists continue to limit accessibility of NPS. Future expansion efforts for pharmacy-based harm reduction services should not only address the time and labor constraints identified by community pharmacists, but also fear-based policy and stigma toward people who inject drugs and harm reduction more broadly.

Extraction of sleep information from clinical notes of Alzheimer's disease patients using natural language processing.

Alzheimer's disease (AD) is the most common form of dementia in the United States. Sleep is one of the lifestyle-related factors that has been shown critical for optimal cognitive function in old age. However, there is a lack of research studying the association between sleep and AD incidence. A major bottleneck for conducting such research is that the traditional way to acquire sleep information is time-consuming, inefficient, non-scalable, and limited to patients' subjective experience. We aim to automate the extraction of specific sleep-related patterns, such as snoring, napping, poor sleep quality, daytime sleepiness, night wakings, other sleep problems, and sleep duration, from clinical notes of AD patients. These sleep patterns are hypothesized to play a role in the incidence of AD, providing insight into the relationship between sleep and AD onset and progression. A gold standard dataset is created from manual annotation of 570 randomly sampled clinical note documents from the adSLEEP, a corpus of 192000 de-identified clinical notes of 7266 AD patients retrieved from the University of Pittsburgh Medical Center (UPMC). We developed a rule-based natural language processing (NLP) algorithm, machine learning models, and large language model (LLM)-based NLP algorithms to automate the extraction of sleep-related concepts, including snoring, napping, sleep problem, bad sleep quality, daytime sleepiness, night wakings, and sleep duration, from the gold standard dataset. The annotated dataset of 482 patients comprised a predominantly White (89.2%), older adult population with an average age of 84.7 years, where females represented 64.1%, and a vast majority were non-Hispanic or Latino (94.6%). Rule-based NLP algorithm achieved the best performance of F1 across all sleep-related concepts. In terms of positive predictive value (PPV), the rule-based NLP algorithm achieved the highest PPV scores for daytime sleepiness (1.00) and sleep duration (1.00), while the machine learning models had the highest PPV for napping (0.95) and bad sleep quality (0.86), and LLAMA2 with finetuning had the highest PPV for night wakings (0.93) and sleep problem (0.89). Although sleep information is infrequently documented in the clinical notes, the proposed rule-based NLP algorithm and LLM-based NLP algorithms still achieved promising results. In comparison, the machine learning-based approaches did not achieve good results, which is due to the small size of sleep information in the training data. The results show that the rule-based NLP algorithm consistently achieved the best performance for all sleep concepts. This study focused on the clinical notes of patients with AD but could be extended to general sleep information extraction for other diseases.

Impact of Weight Gain on Cardiovascular Outcomes in Patients With Atrial Fibrillation.

The long-term impact of weight gain (WG) on cardiovascular outcomes among patients with atrial fibrillation (AF) is unclear. We studied 62 871 (mean age, 72±12, 43% women) adult patients with AF evaluated at the University of Pittsburgh Medical Center between January 1, 2010, and May 13, 2021. Serial body mass index, risk factors, comorbidities, and subsequent death and hospitalization were ascertained and stratified according to percentage WG (≥0% to <5%, ≥5% to <10%, and ≥10%). Over 4.9±3.19 years of follow-up, 27 114 (43%) patients gained weight (61%, ≥0% to <5%; 23%, ≥5% to <10%; 16%, ≥10%). Patients with progressive WG were incrementally younger (P<0.001) women (40%, 42%, and 47%) with lower median household income (P=0.002) and active smoking (8%, 13% and 13%), and they were less likely to be on a non-vitamin K oral anticoagulant (39%, 37%, and 32%). WG was incrementally associated with a significant increase in risk of hospitalization for AF (≥10% WG; hazard ratio [HR], 1.2 [95% CI, 1.2-1.3]; P<0.0001), heart failure (≥10% WG; HR, 1.44 [95% CI, 1.3-1.6]; P<0.001; ≥5% to <10% WG; HR, 1.17 [95% CI, 1.1-1.2]; P<0.001), myocardial infarction (≥10% WG; HR, 1.2 [95% CI, 1.3-1.6]; P<0.001) and all-cause stroke (4.2%, 4.3%, and 5.6%) despite significantly lower mean CHADS2Vasc score (2.9±1.7, 2.7±1.6, and 2.7±1.7). Patients with more WG were significantly more likely to receive cardiac and electrophysiologic interventions. Among patients with AF, WG is incrementally associated with increased hospitalization for cardiovascular causes, particularly heart failure, stroke, myocardial infarction, and AF.

Post-traumatic Total Hip Arthroplasty After Acetabular Fractures: Benefits of the Hardinge Approach.

Post-traumatic arthritis is a common sequelae after undergoing open reduction and internal fixation (ORIF) of acetabular fractures. This often necessitates conversion to total hip arthroplasty (THA) to help alleviate pain and improve function for these patients. Unfortunately, dislocation rates for post-traumatic THA have been alarmingly high especially when the posterior approachhas been used.In the setting of prior soft tissue disruption, the theoretical risk of dislocation is even greater. Conversely, the lateral or the abductor-split approach (Hardinge) is associated with decreased dislocation rates. In this retrospective case series, we evaluated the dislocation rate of the Hardinge approach on patients who underwent THA after developing post-traumatic arthritis after acetabulum ORIF.All patients who matched CPT code 27132 (Repair, Revision, and/or Reconstruction Procedures on the Pelvis and Hip Joint), from January 2009 to December 2019, and treated by the senior author, were pulled from the electronic medical record at the University of Pittsburgh Medical Center. Thirty-one of the resultant 110 were treated with THA for post-traumatic arthrosis through a lateral, abductor-splitting Hardinge approach and met the inclusion criteria for further study. Our case series involves 31 patients who underwent post-traumatic THA through a Hardinge approach: the mean age at the time of index acetabular ORIF is 48.5 years, the mean age at the time of THA is 53.5 years, and the mean interval between ORIF and ultimate THA was five years. The mean length of follow-up after THA was 22.4 months.Overall, patients did well with an all-cause revision rate of 9.7%, with no revision performed for loosening of either the acetabular or femoral component. One patient developed an infection. No patient in our group sustained a dislocation, and all implants were stable without evidence of radiographic loosening at the final follow-up. This study found satisfactory results withpatients undergoing THA via lateral or abductor split approach (Hardinge) for post-traumatic arthritis after acetabular ORIF. The use of a Hardinge approach for post-traumatic reconstruction of the hip may be protective against dislocation without increasing baseline risks in this difficult patient population.

Enhancing post-traumatic stress disorder patient assessment: leveraging natural language processing for research of domain criteria identification using electronic medical records

BackgroundExtracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities.MethodsIn our study, we created a natural language processing (NLP) workflow to analyze electronic medical record (EMR) data and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, all-mpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh Medical Center. Subsequently, we showcased the significance of our approach by extracting and visualizing RDoC information in two use cases: (i) across multiple patient populations and (ii) throughout various disease trajectories.ResultsThe sentence transformer model demonstrated high F1 macro scores across all RDoC domains, achieving the highest performance with a cosine similarity threshold value of 0.3. This ensured an F1 score of at least 80% across all RDoC domains. The study revealed consistent reductions in all six RDoC domains among PTSD patients after psychotherapy. We found that 60.6% of PTSD women have at least one abnormal instance of the six RDoC domains as compared to PTSD men (51.3%), with 45.1% of PTSD women with higher levels of sensorimotor disturbances compared to men (41.3%). We also found that 57.3% of PTSD patients have at least one abnormal instance of the six RDoC domains based on our records. Also, veterans had the higher abnormalities of negative and positive valence systems (60% and 51.9% of veterans respectively) compared to non-veterans (59.1% and 49.2% respectively). The domains following first diagnoses of PTSD were associated with heightened cue reactivity to trauma, suicide, alcohol, and substance consumption.ConclusionsThe findings provide initial insights into RDoC functioning in different populations and disease trajectories. Natural language processing proves valuable for capturing real-time, context dependent RDoC instances from extensive clinical notes.

CASTOR1 phosphorylation as a predictor of survival in male patients with KRAS-mutated lung adenocarcinoma.

e20015 Background: Lung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. This study focuses on the predictive value of phosphorylated cytosolic arginine sensor for mTORC1 subunit 1 at S14 (pCASTOR1) in lung adenocarcinoma (LUAD) patients, specifically in males with KRAS mutations. Methods: This retrospective study, approved by University of Pittsburgh IRB, utilized formaline-fixed paraffin embedded primary tissues from two independent cohorts of patients who underwent thoracic surgical procedures at the University of Pittsburgh Medical Center (UPMC) from 2002 to 2011. Comprehensive clinical, demographical and pathological information was obtained from UPMC Cancer Registry, with cases lacking incomplete information excluded from analysis. Study endpoints included overall survival (OS) and relapse-free survival (RFS). An antibody targeting pCASTOR1 was employed to analyze LUAD tumor and adjacent non-tumor lung tissues from both cohorts. A pathologist, blinded to patient information and survival outcomes, conducted scoring in 5% increments. Scores were categorized as low or high pCASTOR1 based on second or third quartile. Correlations between pCASTOR1 scores and OS/RFS were examined, stratifying by clinical, pathological, demographic, or genotype data. Univariate OS and RFS analyses were conducted using the Kaplan-Meier method and log-rank test, while multivariate survival significance was assessed via Cox regression analysis. Additionally, unpaired T-tests were utilized to compare pCASTOR1 levels between non-tumor and tumor cells. A significance threshold of p &lt; 0.05 was applied for all analyses. Results: Tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells in both cohorts (P &lt; 0.05). High pCASTOR1 scores predicted poor OS (HR = 3.3, P = 0.0008) and RFS (HR = 3.0, P = 0.0035) in male patients with KRAS mutations in Cohort 1. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Cohort 2, comprised solely of smokers with incomplete genotype information, validated these findings, with high pCASTOR1 scores correlating with worse OS (HR = 4.8, P = 0.0363). Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations in Cohort 1, and worse OS (HR = 5.0, P = 0.0069) and RFS (HR = 5.0, P = 0.0069) in Cohort 2, akin to late-stage patients. Conclusions: Elevated pCASTOR1 score serves as a robust biomarker predicting poor OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup.

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 &lt; 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&amp;lt; 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&amp;lt; 0.001). This remained significant when adjusted for age, menopausal status, or ethnicity (p&amp;lt; 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% women) 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% women) 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 (men 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]; women 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.

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).