Hidden curricula in academic medicine: Streamlining success for early career scholars from majority and diverse backgrounds.

The hidden curriculum (HC), or implicit norms and values within a field or institution, affects faculty at all career stages. This study surveyed affiliates of a junior faculty training program (n = 12) to assess the importance of HC topics for junior faculty, mentors, and institutional leaders. For non-diverse junior faculty and their mentors, work-life balance, research logistics, and resilience were key HC topics. Coping with bias and assertive communication were emphasized for diverse junior faculty and mentors. Institutional norms and vision were essential for leaders, while networking was important for all groups. Future research should explore HC needs and potential interventions.

Academic Promotions in Medicine: An Appraisal of Fairness.

OBJECTIVE: To investigate whether the process of conferring academic rank or components of the promotion packet contribute to the lack of parity in academic advancement for women and individuals underrepresented in medicine (URMs). PATIENTS AND METHODS: We retrospectively reviewed prospective promotion applications to the position of associate professor or professor at Mayo Clinic from January 2, 2015, through July 1, 2019. Individuals with doctorate degrees who applied for either rank were included in the study. Data collected included demographic characteristics, curriculum vitae at time of application, committee score sheets, and deferral and approval decisions. Deferral rates for women compared with men and for URMs compared with non-URMs was the primary outcome. RESULTS: Of 462 people who applied for associate professor, 10% (n=46) were deferred. Those promoted had worked longer at Mayo Clinic (median, 6 years vs 2 years; P=.01), had more mentees (median, 6 vs 4; P=.02), authored more publications (median [interquartile range (IQR)], 39 [32-52] vs 30 [24-35]; P<.001), and were more likely to be on a National Institutes of Health or institutional grant (P<.05). Of the 320 people who applied for professor, 8.8% (n=28) were deferred. Those promoted had authored more publications (median [IQR], 77 [60-99] vs 56 [44-66]; P<.001) and were less likely to hold an elected office to a professional society (22.6% vs 39.3%; P=.05). There was no significant association between deferral status and sex (P>.4) or race/ethnicity (P>.9) for either rank. CONCLUSION: The process for academic advancement for professorships does not contribute to the gap in promotion rates for women and URMs.

Associations between childhood adversity and age at natural menopause.

OBJECTIVE: Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause. METHODS: This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders. RESULTS: A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, -3.2 to 0.6; P = 0.18). CONCLUSIONS: Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause.

Development and use of a novel tool for assessing and improving researcher embeddedness in learning health systems and applied system improvements.

This paper outlines the development, deployment and use, and testing of a tool for measuring and improving healthcare researcher embeddedness - i.e., being connected to and engaged with key leverage points and stakeholders in a health system. Despite the widely acknowledged importance of embeddedness for learning health systems and late-stage translational research, we were not aware of useful tools for addressing and improving embeddedness in scholar training programs. We developed the MN-LHS Embeddedness Tool covering connections to committees, working groups, leadership, and other points of contact across four domains: patients and caregivers; local practice (e.g., operations and workflows); local institutional research (e.g., research committees and agenda- or initiative-setting groups); and national (strategic connections within professional groups, conferences, etc.). We used qualitative patterns and narrative findings from 11 learning health system training program scholars to explore variation in scholar trajectories and the embeddedness tool's usefulness in scholar professional development. Tool characteristics showed moderate evidence of construct validity; secondarily, we found significant differences in embeddedness, as a score, from baseline through program completion. The tool has demonstrated simple, practical utility in making embeddedness an explicit (rather than hidden) part of applied and learning health system researcher training, alongside emerging evidence for validity.

Training the next generation of learning health system scientists.

Introduction: The learning health system (LHS) aligns science, informatics, incentives, stakeholders, and culture for continuous improvement and innovation. The Agency for Healthcare Research and Quality and the Patient-Centered Outcomes Research Institute designed a K12 initiative to grow the number of LHS scientists. We describe approaches developed by 11 funded centers of excellence (COEs) to promote partnerships between scholars and health system leaders and to provide mentored research training. Methods: Since 2018, the COEs have enlisted faculty, secured institutional resources, partnered with health systems, developed and implemented curricula, recruited scholars, and provided mentored training. Program directors for each COE provided descriptive data on program context, scholar characteristics, stakeholder engagement, scholar experiences with health system partnerships, roles following program completion, and key training challenges. Results: To date, the 11 COEs have partnered with health systems to train 110 scholars. Nine (82%) programs partner with a Veterans Affairs health system and 9 (82%) partner with safety net providers. Clinically trained scholars (n = 87; 79%) include 70 physicians and 17 scholars in other clinical disciplines. Non-clinicians (n = 29; 26%) represent diverse fields, dominated by population health sciences. Stakeholder engagement helps scholars understand health system and patient/family needs and priorities, enabling opportunities to conduct embedded research, improve outcomes, and grow skills in translating research methods and findings into practice. Challenges include supporting scholars through roadblocks that threaten to derail projects during their limited program time, ranging from delays in access to data to COVID-19-related impediments and shifts in organizational priorities. Conclusions: Four years into this novel training program, there is evidence of scholars' accomplishments, both in traditional academic terms and in terms of moving along career trajectories that hold the potential to lead and accelerate transformational health system change. Future LHS training efforts should focus on sustainability, including organizational support for scholar activities.

Evaluating the Link Between Self-Reported Endometriosis and Female Sexual Dysfunction.

BACKGROUND: Studies have found that women with endometriosis have a higher risk of female sexual dysfunction (FSD). AIM: To evaluate the relationship between self-reported endometriosis and FSD utilizing validated surveys. METHODS: A cross-sectional analysis was conducted among sexually active women aged 18-90 who presented to 3 Mayo Clinic sites from 2015 to 2021. FSD was determined utilizing a combined endpoint of Female Sexual Function Index score ≤ 26.55 and Female Sexual Distress Scale-Revised score ≥ 11. Associations between history of endometriosis and FSD were evaluated by fitting 3 multivariable logistic models and were stratified by menopause status. In the first model, the association was adjusted for age, BMI, race/ethnicity, marital status, and education. The second model adjusted for the variables in Model 1 and hormone therapy, hormonal contraceptive use, self-reported history of abuse within the last year, and co-morbidities including the history of diabetes, heart disease, hypertension, osteoporosis, and stroke. The third model adjusted for the variables in Model 1, Model 2, and anxiety, depression, relationship satisfaction, and SSRI/SNRI use. OUTCOMES: The outcomes included self-reported endometriosis and female sexual dysfunction determined utilizing a combined endpoint of Female Sexual Function Index score ≤ 26.55 and Female Sexual Distress Scale-Revised score ≥ 11. RESULTS: Of 7118 patients (mean age 51.3), 92.2% were white, 78.4% were peri- or postmenopausal, 8.7% reported endometriosis history, and 57.2% met the criteria for FSD. Women with endometriosis were more likely to be overweight or obese, be smokers, have had a history of heart disease and osteoporosis, have had anxiety and depressed mood, have had a hysterectomy and bilateral salpingo-oophorectomy, and have used hormone therapy. Compared to those without endometriosis, women with endometriosis were significantly more likely to have FSD only among premenopausal women (74.2% vs 57.4%). Similarly, in multivariable analysis the relationship was only seen for premenopausal women in all 3 models (Model 1: OR 2.74 (95% CI 1.43-5.27); Model 2: OR 2.55 (95% CI 1.30-5.04); Model 3: OR 2.30 (95% CI 1.13-4.68)). CLINICAL IMPLICATIONS: These findings highlight the opportunity for healthcare practitioners to evaluate sexual function in premenopausal women with endometriosis. For peri and postmenopausal women with endometriosis, the risk of FSD was lower than for premenopausal women with endometriosis. STRENGTHS AND LIMITATIONS: This study analyzed the association between endometriosis and FSD in women by menopause status using validated tools that included a measure of distress associated with sexual dysfunction. Limitations include its cross-sectional design which does not allow for determination of the direction of this association. CONCLUSION: The risk for FSD associated with endometriosis depends on menopause status. Endometriosis increased the odds of FSD only in premenopausal women. Kling JM, Ghaith S, Smith T, et al. Evaluating the Link Between Self-Reported Endometriosis and Female Sexual Dysfunction. J Sex Med 2022;19:1533-1561.

Changing the face of academic medicine: an equity action plan for institutions.

In recent years, there have been concerted efforts to better recruit, support, and retain diverse faculty, staff, and trainees in academic medicine. However, many institutions lack comprehensive and strategic plans to provide support to retain and recruit individuals from historically underrepresented groups. In this article, we itemize specific mechanisms through which institutions can support diverse individuals with the goal of improving inclusion and belonging in the workforce to better reflect the diversity of the intended patient and research participant population.

Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. METHODS: Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17 controls. Over 90% of bile samples were from patients with perihilar CCA. Stool was obtained from 31 patients with PSC (11 were matched to bile), 16 with CCA with PSC (10 matched to bile), and 11 with CCA without PSC (6 matched to bile). Microbiota composition was assessed using 16SrRNA-marker-based sequencing and was compared between groups. RESULTS: Bile has a unique microbiota distinguished from negative DNA controls and stool. Increased species richness and abundance of Fusobacteria correlated with duration of PSC and characterized the biliary microbiota in CCA. Stool microbiota composition showed no significant differences between groups. CONCLUSIONS: We identified a unique microbial signature in the bile of patients with increased duration of PSC or with CCA, suggesting a role for microbiota-driven inflammation in the pathogenesis and or progression to perihilar CCA. Further studies are needed to test this hypothesis.

Prospective Study Assessing Impact of Ethylene Oxide Sterilization on Endoscopic Ultrasound Image Quality.

BACKGROUND & AIMS: Duodenoscope-associated transmission of infections has raised questions about efficacy of endoscope reprocessing using high-level disinfection (HLD). Although ethylene oxide (ETO) gas sterilization is effective in eradicating microbes, the impact of ETO on endoscopic ultrasound (EUS) imaging equipment remains unknown. In this study, we aimed to compare the changes in EUS image quality associated with HLD vs HLD followed by ETO sterilization. METHODS: Four new EUS instruments were assigned to 2 groups: Group 1 (HLD) and Group 2 (HLD + ETO). The echoendoscopes were assessed at baseline, monthly for 6 months, and once every 3 to 4 months thereafter, for a total of 12 time points. At each time point, review of EUS video and still image quality was performed by an expert panel of reviewers along with phantom-based objective testing. Linear mixed effects models were used to assess whether the modality of reprocessing impacted image and video quality. RESULTS: For clinical testing, mixed linear models showed minimal quantitative differences in linear analog score (P = .04; estimated change, 3.12; scale, 0-100) and overall image quality value (P = .007; estimated change, -0.12; scale, 1-5) favoring ETO but not for rank value (P = .06). On phantom testing, maximum depth of penetration was lower for ETO endoscopes (P < .001; change in depth, 0.49 cm). CONCLUSIONS: In this prospective study, expert review and phantom-based testing demonstrated minimal differences in image quality between echoendoscopes reprocessed using HLD vs ETO + HLD over 2 years of clinical use. Further studies are warranted to assess the long-term clinical impact of these findings. In the interim, these results support use of ETO sterilization of EUS instruments if deemed clinically necessary.

Lessons Learned from Clinical and Translational Science Faculty and Student Survey as COVID-19 Pandemic Continues to Shift Education Online.

INTRODUCTION: As the pandemic continues with new variants emerging, faculty and students require support with education's rapid shift to the virtual space. The Mayo Clinic Center for Clinical and Translational Science curriculum team works closely with faculty to support a smooth transition to offering graduate courses in a virtual learning environment. The aim of the present project was to explore faculty and student perceptions of these remote learning strategies to gain an understanding of the innovations required to improve future educational offerings. METHODS: All faculty and learners involved in nine Clinical and Translational Science courses in spring 2020 were invited to participate in a web-based questionnaire. Quantitative analysis was performed on closed-ended items, including 5-point Likert-scale questions used to assess the range of views. Qualitative free-text responses were independently analyzed for repetitive themes and summarized. Additionally, comparisons of faculty and course evaluations and student grade point averages (GPAs) from the in-person courses and their subsequent virtual course offerings were considered. RESULTS: Survey results indicated several positive impacts with moving courses into the virtual environment, including increased accessibility as well as more student-centered education. Learners joining from sites outside of the originating campus were especially grateful for the virtual classroom because they felt newly integrated within classes. Faculty and course evaluations, as well as student GPAs, remained consistent. CONCLUSION: New COVID-19 variants continue to shift education online, and innovative ideas are required to further improve future virtual course offerings. Increased engagement is warranted, both from faculty to incorporate activities designed specifically for a virtual classroom, and from students to increase participation by activating their microphones and webcams. Greater opportunities for global involvement and connectedness arise. Finally, this project advocates for adequate eLearning staffing to support quality online education as the need for pedagogical and technical provision continues.

Collaborative biostatistics and epidemiology in academic medical centres: A survey to assess relationships with health researchers and ethical implications.

The role of collaborative biostatisticians and epidemiologists in academic medical centers and how their degree type, supervisor type, and sex influences recognition and feelings of respect is poorly understood. We conducted a cross-sectional survey of self-identified biostatisticians and epidemiologists working in academic medical centers in the US or Canada. The survey was sent to 341 contacts at 125 institutions who were asked to forward the survey invitation to faculty and staff at their institution and posted on Community sections of the American Statistical Association website. Participants were asked a variety of questions including if they felt pressured to produce specific results, whether they had intellectual and ethical freedom to pursue appropriate use of statistical methods in collaborative research, and if they felt their contributions were appropriately recognized by collaborators. We received responses from 314 biostatisticians or related methodologists. A majority were female (59%), had a doctorate degree (52%), and reported a statistician or biostatistician supervisor (69%). Overall, most participants felt valued by their collaborators, but that they did not have sufficient calendar time to meet deadlines. Doctoral-level participants reported more autonomy in their collaborations than master's level participants. Females were less likely to feel recognized and respected compared to males. The survey results suggest that while most respondents felt valued by their collaborators, they have too many projects and need more time to critically review research. Further research is needed to understand why response differs by sex and how these responses fluctuate over time.

Predictors of Jaundice Resolution and Survival After Endoscopic Treatment of Primary Sclerosing Cholangitis.

The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow-up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1-year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1-year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1-point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5-0.79) in the validation set. Independent predictors of death or transplant during follow-up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1-point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant-free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.

Evaluation of the academic achievements of clinician health services research scientists involved in "pre-K" career development award programs.

INTRODUCTION: Research career development awards (CDAs) facilitate development of clinician-scientists. This study compared the academic achievements of individuals in a structured institutional "pre-K" CDA program, the Mayo Clinic Kern Scholars program, with individuals who applied for but were not admitted to the Kern program ("Kern applicants"), and awardees of other unstructured internal CDAs. METHODS: This was a longitudinal cohort study of clinicians engaged in research at Mayo Clinic between 2010 and 2019. The primary outcome was time to the 15th new peer-reviewed publication after the program start, adjusted for baseline number of publications. Secondarily, we described successful awarding of federal funding by the NIH or VA. RESULTS: The median (IQR) number of baseline publications was highest among Kern Scholars compared to Kern Applicants or other CDA awardees [16 (12, 29) vs 5 (1, 11) and 8 (5, 16); P < 0.001]. After adjustment for baseline publications, the time to 15th new publication was significantly shorter for Kern Scholars than for the two comparator groups (P<0.001). Similar findings were observed with total new publications within 5 years (P < 0.001), as well as number of new first-/last-author publications within 5 years (P < 0.001). The overall frequency of K-awards, R-awards (or equivalent), or any funding were similar between groups, with the exception of R03 awards, which were significantly more common among Kern Scholars (P = 0.002). CONCLUSION: The Kern Scholars program is a successful training model for clinician-scientists that demonstrated comparatively greater acceleration of scholarly productivity than other internal CDA programs.

Building a framework for inclusion in health services research: Development of and pre-implementation faculty and staff attitudes toward the Diversity, Equity, and Inclusion (DEI) plan at Mayo Clinic.

OBJECTIVE: To mitigate the impact of racism, sexism, and other systemic biases, it is essential for organizations to develop strategies to address their diversity, equity and inclusion (DEI) climates. The objective of this formative evaluation was to assess Mayo Clinic Department of Health Sciences Research (HSR) faculty and staff perceptions toward a proposed departmental DEI plan and to explore findings by diversity and professional subgroups. MATERIALS AND METHODS: Key plan components include recruitment and support for diverse individuals; training for all HSR employees and leaders; and a review system to capture diversity and inclusion feedback for leaders. Additional activities include building inclusion "nudges" into existing performance reviews. To assess pre-implementation beliefs about specific plan components, we polled attendees at a departmental staff meeting in July 2020. RESULTS: Overall, respondents (n = 162) commonly endorsed a blinded promotion review process and DEI training for all staff and leaders as most important. In contrast, respondents expressed less support for plan activities related to "nudges." However, attitudes among certain diversity or professional groups toward specific plan activities diverged from their non-diversity group counterparts. Qualitative feedback indicated awareness of the need to address DEI issues. DISCUSSION: Overall, HSR faculty and staff respondents conveyed support for the plan. However, some specific plan activities were perceived differently by members of certain diversity or professional subgroups. CONCLUSION: These findings present a DEI framework on which other institutions can build and point to future directions for how DEI activities may be differentially perceived by impacted faculty and staff.

Risk of Symptomatic Kidney Stones During and After Pregnancy.

RATIONALE & OBJECTIVE: There are several well-known anatomical and physiological changes during pregnancy that could contribute to kidney stone formation, but evidence that they increase the risk of kidney stones during pregnancy is lacking. We determined whether there was an increased risk of a first-time symptomatic kidney stone during and after pregnancy. STUDY DESIGN: A population-based matched case-control study. SETTING & PARTICIPANTS: 945 female first-time symptomatic kidney stone formers aged 15-45 years and 1,890 age-matched female controls in Olmsted County, MN, from 1984-2012. The index date was the date of onset of a symptomatic kidney stone for both the case and her matched controls. EXPOSURE: The primary exposure was pregnancy with assessment for variation in risk across different time intervals before, during, and after pregnancy. Medical records were manually reviewed to determine the conception and delivery dates for pregnancies. OUTCOME: Medical record-validated first-time symptomatic kidney stone. ANALYTICAL APPROACH: Conditional and unconditional multivariable logistic regression analysis. RESULTS: Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in women was similar in the first trimester (OR, 0.92; P=0.8), began to increase during the second trimester (OR, 2.00; P=0.007), further increased during the third trimester (OR, 2.69; P=0.001), peaked at 0 to 3 months after delivery (OR, 3.53; P<0.001), and returned to baseline by 1year after delivery. These associations persisted after adjustment for age and race or for diabetes mellitus, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies. Having a prior pregnancy (delivery date>1year ago) was also associated with a first-time symptomatic kidney stone (OR, 1.27; P=0.01). LIMITATIONS: Observational study design in a predominantly White population. The exact timing of stone formation cannot be determined. CONCLUSIONS: Pregnancy increases the risk of a first-time symptomatic kidney stone. This risk peaks close to delivery and then improves by 1 year after delivery, though a modest risk of a kidney stone still exists beyond 1 year after delivery.

Natural History of Clinical, Laboratory, and Echocardiographic Parameters of a Primary Hyperoxaluria Cohort on Long Term Hemodialysis.

Background: Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). Though systemic oxalate deposition is well-known, the natural history of PH1 during RRT has not been systematically described. In this study, we describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT. Methods: Patients with PH1 enrolled in the Rare Kidney Stone Consortium PH Registry who progressed to require RRT, had ≥2 plasma oxalate (pOx) measurements 3-36 months after start of RRT, and at least one pair of pOx measurements between 6 and 18 months apart were retrospectively analyzed. Clinical, echocardiographic, and laboratory results were obtained from the Registry. Results: The 17 PH1 patients in our cohort had a mean total HD hours/week of 17.4 (SD 7.9; range 7.5-36) and a range of age of RRT start of 0.2-75.9 years. The average change in plasma oxalate (pOx) over time on RRT was -0.74 [-2.9, 1.4] µmol/L/month with the mean pOx never declining below 50 µmol/L. Over time on RRT, oxalosis progressively developed in multiple organ systems. Echocardiography performed on 13 subjects showed worsening of left ventricular global longitudinal strain correlated with pOx (p < 0.05). Conclusions: Even when a cohort of PH1 patients were treated with intensified RRT, their predialysis pOx remained above target and they developed increasing evidence of oxalosis. Echocardiographic data suggest that cardiac dysfunction could be related to elevated pOx and may worsen over time.

Automated radiomic analysis of CT images to predict likelihood of spontaneous passage of symptomatic renal stones.

PURPOSE: To evaluate the ability of a semi-automated radiomic analysis software in predicting the likelihood of spontaneous passage of urinary stones compared with manual measurements. METHODS: Symptomatic patients visiting the emergency department with suspected stones in either kidney or ureters who underwent a CT scan were included. Patients were followed for up to 6 months for the outcome of a trial of passage. Maximum stone diameters in axial and coronal images were measured manually. Stone length, width, height, max diameter, volume, the mean and standard deviation of the Hounsfield units, and morphologic features were also measured using automated radiomic analysis software. Multivariate models were developed using these data to predict subsequent spontaneous stone passage, with results expressed as the area under a receiver operating curve (AUC). RESULTS: One hundred eighty-four patients (69 females) with a median age of 56 years were included. Spontaneous stone passage occurred in 114 patients (62%). Univariate analysis demonstrated an AUC of 0.83 and 0.82 for the maximum stone diameter determined manually in the axial and coronal planes, respectively. Multivariate models demonstrated an AUC of 0.82 for a model including manual measurement of maximum stone diameter in axial and coronal planes. The same AUC was found for a model including automatic measurement of maximum height and diameter of the stone. Further addition of morphological parameters measured automatically did not increase AUC beyond 0.83. CONCLUSION: The semi-automated radiomic analysis of urinary stones shows similar accuracy compared with manual measurements for predicting urinary stone passage. Further studies are needed to predict clinical impacts of reporting the likelihood of urinary stone passage and improving inter-observer variation using automatic radiomic analysis software.

Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure.

BACKGROUND: The precise concentrations of full-length parathyroid hormone (PTH1-84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure are unknown. METHODS: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantify PTH1-84 and PTH fragments in serum of 221 patients with progressive renal dysfunction. Following capture by matrix-bound amino-terminal or carboxyl-terminal region-specific antibodies and elution from matrix, PTH1-84 and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay. RESULTS: Full-length PTH1-84 and 8 PTH fragments (PTH28-84, 34-77, 34-84, 37-77, 37-84, 38-77, 38-84, and 45-84) were unequivocally identified and were shown to increase significantly when an eGFR declined to ≤17-23 mL/min/1.73m2. Serum concentrations of PTH1-84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. In patients with an eGFR of <30 mL/min/1.73 m2, serum PTH concentrations measured using LC-HRMS were significantly lower than PTH measured using an iPTH immunoassay. PTH7-84 and oxidized forms of PTH1-84 were below the limit of detection (30 and 50 pg/mL, respectively). CONCLUSIONS: LC-HRMS identifies circulating PTH1-84, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in patients with progressive renal failure. Serum PTH1-84 and its fragments markedly rise when an eGFR decreases to ≤17-23 mL/min/1.73 m2. PTH concentrations measured using LC-HRMS tend to be lower than those measured using an iPTH immunoassay, particularly in severe chronic renal failure. Our data do not support the existence of circulating PTH7-84 and oxidized PTH1-84.