Context.— Generative artificial intelligence (GAI) technologies are likely to dramatically impact health care workflows in clinical pathology (CP). Applications in CP include education, data mining, decision support, result summaries, and patient trend assessments. Objective.— To review use cases of GAI in CP, with a particular focus on large language models. Specific examples are provided for the applications of GAI in the subspecialties of clinical chemistry, microbiology, hematopathology, and molecular diagnostics. Additionally, the review addresses potential pitfalls of GAI paradigms. Data Sources.— Current literature on GAI in health care was reviewed broadly. The use case scenarios for each CP subspecialty review common data sources generated in each subspecialty. The potential for utilization of CP data in the GAI context was subsequently assessed, focusing on issues such as future reporting paradigms, impact on quality metrics, and potential for translational research activities. Conclusions.— GAI is a powerful tool with the potential to revolutionize health care for patients and practitioners alike. However, GAI must be implemented with much caution considering various shortcomings of the technology such as biases, hallucinations, practical challenges of implementing GAI in existing CP workflows, and end-user acceptance. Human-in-the-loop models of GAI implementation have the potential to revolutionize CP by delivering deeper, meaningful insights into patient outcomes both at an individual and a population level.
Radiotherapy with 15 × 2.633 Gy vs. 20 × 2.0 Gy in Patients with Malignant Spinal Cord Compression and Favorable Survival Prognoses: A Secondary Analysis of the RAMSES-01 Trial
Many patients with malignant spinal cord compression (MSCC) who are not candidates for neurosurgery receive radiotherapy alone. This study compared 15 × 2.633 Gy over three weeks to 20 × 2.0 Gy over four weeks in patients with favorable survival prognoses. The outcomes of 34 patients treated with 15 × 2.633 Gy (equivalent dose 41.6 Gy10) in the RAMSES-01 trial were compared to 239 patients from an existing database receiving 20 × 2.0 Gy using propensity-score-adjusted Cox and logistic regression models. All patients had favorable survival prognoses. Endpoints included local progression-free survival (LPFS), improvement of motor function, post-treatment ambulatory status, and overall survival (OS). After propensity score adjustment, the 12-month rates of LPFS and OS were 98.1% (RAMSES-01 cohort) vs. 91.6% (p = 0.265) and 79.1% vs. 82.2% (p = 0.704), respectively. Regarding improvement of motor function, 15 × 2.633 Gy appeared superior (p = 0.073). No significant difference was observed regarding ambulatory status (p = 0.822). The three-week regimen for MSCC has similar outcomes and reduces treatment time when compared to a four-week regimen.
Reproductive Experiences of Physicians in Medical and Surgical Subspecialties
Objective: To evaluate the reproductive experiences of physicians across gender and specialty. Patients and Methods: Between November and December 2021, we surveyed nontrainee physicians of all genders at a single quaternary institution using a modified version of an existing survey instrument. Experiences with family planning, fertility, pregnancy, and parental leave were assessed. Results: There were 422 completed responses. Respondents reported a higher prevalence of infertility as compared to the general U.S. population (26% versus 19%), with no difference in infertility or obstetrical complications by specialty. Most respondents (75%) reported stigma regarding having children in medicine, and 71% reported delaying childbearing. These trends were strongest in the subanalysis of female respondents. Forty-five percent of respondents reported that their work increased the risk for subfertility, infertility, or pregnancy complications. Surgeons were significantly more likely to report physically demanding work conditions (75% versus 30%, p < 0.001), radiation exposure (39% versus 14%, p < 0.001), and bloodborne pathogen exposure (25% versus 12%, p = 0.03) as occupational reproductive hazards. Only 55% of respondents with a pregnancy history reported ever taking parental leave. Among those who took less than the full amount offered, 63% cited concerns about falling behind educationally or professionally as significantly influencing this decision. Conclusions: These results support previous trends showing delayed childbearing and increased infertility among physicians while shedding new light on stigma associated with childbearing and parental leave. A better understanding of the reproductive experiences of physicians is critical to recruiting and retaining a skilled workforce and fostering career and life satisfaction in this profession.
The Perceived Inclusivity of Sex Education Scale – 2: Sex Education Inclusivity and Health Outcomes Among Gender Diverse Individuals
Abstract Kidney injury is a major medical burden and one of the most common reasons for hospitalization and poor life quality. Kidney injury can include acute kidney injury, chronic kidney disease, and immune-mediated kidney diseases most of which have no definitive therapy. The spleen is a secondary lymphoid organ in the reticuloendothelial system that plays an important role in protecting the body from various diseases. Notably, spleen tyrosine kinase, a non-receptor tyrosine kinase, is a crucial player that aids in immunity and protection and is highly expressed in the kidney and hematopoietic cells. It has been shown that alterations in spleen tyrosine kinase function or expression could lead to a wide range of diseases and abnormalities. Over the past decade, the role of spleen and spleen tyrosine kinase in multiple kidney diseases has emerged. Evidence suggests that modulating the spleno-renal connection through activation of the cholinergic anti-inflammatory pathway can be a promising strategy for protecting against kidney injury. Imitating the protective function of the spleen through interleukin-10-extracellular vesicles can also be of therapeutic value. In addition, evidence showed that inhibition of the spleen tyrosine kinase leads to amelioration of the kidney injury. However, further exploration and long-term studies are needed to unravel the spleno-renal connection, as well as the efficacy of spleen tyrosine kinase inhibitors, before they can be used as means for treatment of kidney injury. Graphical Abstract
One Size Fits Small: The Narrow Utility for Plasma Metagenomics
Abstract Metagenomic sequencing of plasma has been advertised by Karius, Inc. as a way to diagnose a variety of infectious syndromes. Due to the lack of robust evidence of clinical utility, our laboratory began actively stewarding Karius testing. Microbiology Directors recommended cancelation of Karius orders when certain criteria were identified. We set out to review Karius test requests in a 52-month period of stewardship, during which we recommended cancellation on 21 of 57 orders (37%). Of Karius tests sent on samples with negative conventional testing, only 3 (7%) had positive results for Karius with plausible explanatory etiologies. Of these three cases, two were empirically covered for the positive finding without improvement and one case was never treated. Twelve (29%) had positive results that were noted by infectious diseases (ID) to reflect insignificant detections. Given the 4-fold higher detection of insignificant Karius results, we set out to systematically analyze the literature for the experience of insignificant detections at other centers. When we compared studies that included healthy controls or had clinical adjudication of positive Karius findings by ID physicians, we found a median of 17.5% of individual patients that had positive insignificant detections of potential pathogenic bacteria or fungi. The most frequently detected species were as likely to be clinically adjudicated to be insignificant as they were to be significant within the same studies. Overall, these findings highlight limited utility of Karius testing and a need for careful stewardship, not only to ensure it is sent on patients who may benefit, but also to ensure results of potential pathogens are interpreted cautiously.
Breast care considerations for transgender and gender-diverse patients
Transgender and gender-diverse (TGD) persons represent a small but growing population in the United States. Accessing inclusive, equitable, and evidence-based healthcare remains a challenge for this patient population. Many TGD persons seek gender-affirming care, including gender-affirming hormonal therapy (GAHT) and gender-affirming surgery (GAS), to help ameliorate the physical and mental aspects of their gender incongruence. Both GAHT and GAS induce clinically important histopathologic and anatomic changes in breast tissue. Consequently, breast care in TGD persons has become an increasingly recognized topic of importance in gender-affirming care. However, there remains a scarce but growing base of literature specifically addressing the unique healthcare needs of breast care in TGD patients. This article will review how to establish trusting patient–provider relationships for TGD patients, gender inclusivity in breast clinics and imaging centers, the influence of GAHT and GAS on breast tissue, breast cancer screening recommendations and barriers, and breast cancer risk and treatment considerations in TGD persons.
Bridging Gaps in Health Literacy for Cleft Lip and Palate: The Role of Artificial Intelligence and Interactive Educational Materials
Objective Our goal is to address the health literacy gap concerning cleft lip and palate using artificial intelligence (AI), specifically OpenAI's ChatGPT-4, to enhance the readability of patient educational materials (PEMs). Additionally, we aim to explore the integration of interactive educational materials into these resources. Design A cross-sectional study. Setting Websites of craniofacial teams approved by the American Cleft Palate-Craniofacial Association (ACPA). Patients/Participants PEMs collected from these websites. Interventions First, we examined the PEMs for interactive educational content such as videos, photos, case examples, and audio clips. Subsequently, we used the WebFX online readability calculator and Grammarly to evaluate the texts’ readability and clarity. After that, we used ChatGPT-4 to simplify the PEM texts to a 6th-grade reading level and re-evaluated their readability and clarity. Main Outcome Measure(s) Readability levels (grade level) and clarity scores of PEMs before and after AI modification, and the presence of interactive educational content. Results Initial evaluations using the Flesch-Kincaid Grade Level formula showed that the texts were written at a median 9th-grade reading level. Modifications using ChatGPT-4 significantly improved readability, achieving a median 6th-grade level and enhanced clarity. Only 27% of the websites featured interactive educational content, indicating a gap in utilizing educational enhancements. Conclusion The use of AI improved the readability and clarity of patient educational materials, aligning with recommended standards. However, the underutilization of interactive tools suggests a need for broader integration of these resources to optimize patient education and engagement.
Poster 339: Outcomes of Anterior Cruciate Ligament Reconstruction in Competitive Ice Hockey Players: Outcomes, Reoperations, and Return to Play at 7 Years Mean Follow-Up
Objectives: Ice hockey is a physically demanding sport, with young athletes prone to anterior cruciate ligament (ACL) injuries. Currently, there is a paucity of data examining the results of ACL reconstruction (ACLR) in competitive hockey players. The purpose of this study was to assess return to hockey (RTH) and reoperation rates following ACLR for ACL injuries in a cohort of competitive hockey players. Methods: All competitive ice hockey players (including, youth, high school, juniors, collegiate, or professional) with a history of ACL injury and subsequent ACLR at a single academic institution between 2000 and 2022 were identified. Exclusion criteria included ACL injuries that did not occur during hockey, history of ACLR prior to hockey injury, and recreational hockey players. Graft failure was defined as a retear (as determined via clinical or advanced imaging evaluation) and/or revision ACLR. Results: Ultimately, 50 knees in 44 hockey players were included at a mean (± standard deviation) follow-up time of 7.0 years ± 5.4 years (Table 1). The mean age at the time of index surgery was 18.9 years ± 3.0 years, with 38 males (76%), and the distribution of bone-patellar tendon-bone (BPTB) and hamstring tendon (HT) autografts was 40 (80%) and 10 (20%), respectively. RTH occurred in 66% of hockey players at a mean of 10.2 months ± 6.2 months. Graft failure occurred in 9 knees (18%) at a mean of 5.9 years ± 5.8 years after the index ACLR. All patients who sustained a retear underwent reoperation. Kaplan-Meier survivorship free from surgical failure of the entire cohort was 94% at 1 year, 88% at 5 years, 74% at 10 years, and 67% at 15 years (Figure 1A). BPTB autograft demonstrated a lower failure rate compared with HT autograft (13% vs 40%; P = 0.041) and was associated with better survival compared with HT autograft up to 15 years after the index ACLR (80% vs 39%; P = 0.047; Figure 1B). Conclusions: ACL injury remains a concern for competitive hockey players after ACLR. Return to competitive ice hockey was observed in 66% of athletes after ACLR, with 18% of hockey players experiencing graft failure and undergoing subsequent reoperation. BPTB autograft was associated with better survival than HT autograft.
Poster 295: Evidence Suggesting Beneficial Effects of Platelet-Rich Plasma Over Alternative Injections for Knee Osteoarthritis Is Fairly Robust: A Systematic Review and Statistical Fragility Index-Based Meta-Analysis of Randomized Controlled Trials
Objectives: Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown. The purpose of this study is to evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies. Methods: All RCTs comparing PRP to alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse fragility index (RFI) were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from one or more trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect. Results: In total, this analysis included outcomes from 1993 patients with a mean (± standard deviation) age of 58.0 ± 3.8 years. The mean number of events required to reverse significance (FI) was 4.57 ± 5.85. This corresponded to a fragility quotient of 0.060 ± 0.075, meaning the significance of the results was contingent on 6 events per 100 participants. For non-significant outcome events, the mean number of events required to reverse statistical nonsignificance (RFI) was 4.41 ± 2.22. This corresponded to a reverse fragility quotient of 0.065 ± 0.056, meaning the non-significance of the results was contingent on 6.5 events per 100 participants (Figure 1). Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared to hyaluronic acid (p = 0.002, odds ratio 95% CI = 2.19 [1.33-3.62]) (Figure 2) as well as higher rates of patient-reported symptom relief (p = 0.019, odds ratio [95% CI] = 1.55 [1.07-2.24]) (Figure 3), not requiring a reintervention after the initial injection treatment (p = 0.002, odds ratio [95% CI] = 2.17 [1.33-3.53]) (Figure 4), and achieving the minimal clinically important difference (MCID) for pain improvement (p = 0.007, odds ratio [95% CI] = 6.19[1.63-23.42]) when compared to all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50. Conclusions: Individual RCTs evaluating PRP for knee OA possess slight robustness. Upon meta-analysis, PRP demonstrated a significant advantage over HA as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared to alternative, nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and healthcare. Future RCTs and meta-analyses should consider reporting fragility indices and quotients to facilitate interpretation of results in their proper context. In addition, the robustness of these findings suggests that reconsideration of the American Academy of Orthopaedic Surgeons clinical practice guidelines around the use of PRP for knee OA may be warranted.