Implementation and Analysis of a 5-Year Online Esophageal Motility Curriculum for Gastroenterology Fellows.

BACKGROUND: Motility disorders are frequently encountered in gastroenterology (GI) practice, yet a national structured training curriculum for GI fellows in motility disorders is lacking. Since GI fellowships vary considerably in opportunities for specialized esophageal motility (EM) training, novel educational technology may be leveraged to provide standardized EM curriculum to train GI fellows in esophageal manometry. METHODS: GI fellows participated in an online EM learning program at a single academic center from 2017 to 2022. Fellows answered case-based questions and were provided with evidence-based, corrective feedback related to core EM learning objectives. The primary outcome was change in knowledge and comfort in interpretation and clinical application of EM studies. RESULTS: Sixty-nine fellows actively participated in the online EM curriculum. 65 fellows completed a pre-curriculum test, and 54 fellows completed a post-curriculum test. There was a cumulative improvement between pre-curriculum test and post-curriculum test scores from 70 to 87%, respectively (p < 0.001). Fellows had a mean improvement of 19% in questions as they progressed through the curriculum. Prior to enrolling in the EM course, 26% of fellows felt comfortable in interpreting EM studies compared to 54% of fellows after completion of the program (p < 0.001). CONCLUSION: An online, technology-based curriculum was effective in educating GI fellows on core competencies of EM. Fellows demonstrated improvement in proficiency of clinically important EM studies and increased comfort in interpreting EM studies. Further studies are needed to evaluate the use of technology-based learning to widely disseminate a structured training curriculum in EM, particularly in training programs without a motility presence.

Gaining Consensus Around Patient Risk Groups and Prognostic Profiles to Guide CMV Management Among Patients With Allogeneic Hematopoietic Stem Cell Transplant: Insights From a Delphi Panel With Hematopoietic Stem Cell Transplant Experts.

INTRODUCTION: This study aimed to characterize patient risk groups and prognostic profiles to optimize clinical decision-making and guide appropriate medical cytomegalovirus (CMV) management among patients with allogeneic hematopoietic stem cell transplant (HSCT). METHODS: Between 8/2021 and 2/2022, a 3-round modified Delphi study was conducted to generate consensus among 10 international experts in HSCT and infectious diseases. Experts were asked about treatment and prognoses for patients in 7 distinct clinical scenarios. Furthermore, experts were asked to risk-stratify patients by pre-/post-transplant characteristics. Consensus around opting for/against a treatment was observed if ≥75% or <25% of experts reported ≥50% likelihood to recommend or if treatments were ranked inside/outside the top 2 options and ≥75% of experts were within 1 SD of mean ranks. RESULTS: Experts agreed on several unmet needs in CMV disease management post-HSCT, particularly avoidance of treatment-limiting toxicities with conventional CMV therapy and the emergence of both refractory and drug-resistant treatment failures. Experts considered CMV viral load, resistance profile, and route of administration as critical to treatment selection. For newer CMV therapeutic options, experts listed a lack of long-term use data, concerns over potential resistance, high cost, and limited availability as challenges restricting adoption and successful patient management. CONCLUSIONS: Experts achieved consensus around patient risk stratifications and factors influencing therapeutic options. Recommendations emerging from this Delphi study may support practicing physicians when confronted with challenging CMV scenarios in patients with HSCT.

Atypical Presentation Delays Treatment of Pediatric Testicular Torsion.

OBJECTIVE: The aim of the study is to identify patient- and care-related factors associated with time to treatment for acute testicular torsion and the likelihood of testicular loss. METHODS: Data were retrospectively collected for patients 18 years and younger who had surgery for acute testicular torsion between April 1, 2005, and September 1, 2021. Atypical symptoms and history were defined as having abdominal, leg, or flank pain, dysuria, urinary frequency, local trauma, or not having testicular pain. The primary outcome was testicular loss. The primary process measure was time from emergency department (ED) triage to surgery. RESULTS: One hundred eleven patients were included in descriptive analysis. The rate of testicular loss was 35%. Forty-one percent of all patients reported atypical symptoms or history. Eighty-four patients had adequate data to calculate time from symptom onset to surgery and time from triage to surgery and were included in analyses of factors affecting risk of testicular loss. Sixty-eight patients had adequate data to evaluate all care-related time points and were included in analyses to determine factors affecting time from ED triage to surgery. On multivariable regression analyses, increased risk of testicular loss was associated with younger age and longer time from symptom onset to ED triage, while longer time from triage to surgery was associated with reporting atypical symptoms or history.The most frequently reported atypical symptom was abdominal pain, in 26% of patients. These patients were more likely to have nausea and/or vomiting and abdominal tenderness but equally likely to report testicular pain and swelling and have testicular findings on examination. CONCLUSIONS: Patients presenting to the ED with acute testicular torsion reporting atypical symptoms or history experience slower transit from arrival in the ED to operative management and may be at greater risk of testicular loss. Increased awareness of atypical presentations of pediatric acute testicular torsion may improve time to treatment.

The impact of procedural activities on musculoskeletal pain experienced by pregnant surgeons.

BACKGROUND: Two-thirds of surgeons report work-related musculoskeletal disorders (WRMD). There is limited data on WRMD symptoms experienced by pregnant surgeons. METHODS: We distributed an electronic survey via personal contacts to attending and trainee surgeons across six academic institutions to assess the impact of procedural activities and surgical ergonomics (SE) on WRMD symptoms during pregnancy. RESULTS: Fifty-three respondents were currently or had been pregnant while clinically active, representing 93 total pregnancies. 94.7% reported that symptoms were exacerbated by workplace activities during pregnancy and 13.2% took unplanned time off work as a result. Beyond 24 weeks of pregnancy, 89.2% of respondents continued to operate/perform procedures, 81.7% worked >24-h shifts and 69.9% performed repetitive lifting >50 pounds. No respondents were aware of any institutional pregnancy-specific SE policies. CONCLUSIONS: Procedural activities can exacerbate pain symptoms for the pregnant surgeon. SE best practices during pregnancy warrant further attention.

The role of facebook support groups for women with benign urologic conditions.

OBJECTIVE: To understand the availability and content of patient support groups on social media platforms. MATERIALS AND METHODS: Five prevalent benign, urologic conditions affecting adult women were selected for analysis. Facebook support groups for these conditions were identified. Groups specific to one urologic condition and with at least 400 members were included, and groups for pediatric and malignant conditions were excluded. Each support group was analyzed for member count, posts per month, and period of activity. The 100 most recent posts in the largest support groups were manually reviewed and further categorized into content subsections. RESULTS: A total number of 56 Facebook support groups were identified that satisfied the inclusion/exclusion criteria. Interstitial cystitis (IC) had 25 groups (68 466 members; 4825 posts), pelvic organ prolapse (POP) had 14 groups (72 342; 3067), UTI had nine groups (36 414; 3204), overactive bladder and/or urinary incontinence (OAB/UI) had seven groups (8246; 306), urinary retention had one group (1168; 118). Across all groups, post content was predominantly informational support (77.6%). Remaining post content was both informational and emotional support (10.0%), emotional support only (7.6%), or unrelated to either informational or emotional support (4.8%). CONCLUSION: Individuals with benign urologic conditions are utilizing social media support groups predominantly to seek and share informational support from patient peers. The number of existing groups as well as the level of activity and number of members within individual support groups varies significantly between different urologic conditions. This suggests that there is an unmet need for accessible informational content for patients who suffer with benign urological conditions.

Engaging and Empowering Female Urologists in Academic Publishing and Peer Review.

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Current exposure to Female Pelvic Medicine and Reconstructive Surgery faculty during urology residency.

INTRODUCTION: Contemporary US resident exposure to Female Pelvic Medicine and Reconstructive Surgery (FPMRS) faculty during urology residency is unknown. METHODS: Accredited US urology residencies were identified through the American Urological Association (AUA). Accredited, urology-based FPMRS fellowships were identified through the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction. The number of faculty and residency positions were obtained from program AUA profiles if they were last modified within the current application cycle; this information was obtained from program websites if AUA profiles were outdated. Data on faculty fellowship training was manually extracted from program websites. A quality control cross-check of program and faculty training characteristics was performed through direct communication with 5% of programs. RESULTS: Of 139 accredited residency programs assessed, 10.8% were affiliated with an accredited, urology-based FPMRS fellowship. In total, 29.5% of residency programs, representing 25% of US urology residents, had neither a FPMRS fellowship nor any FPMRS certified faculty. The national FPMRS faculty-to-resident ratio was 1:10.8, and 7.4% of faculty at all residency programs were FPMRS certified. In comparison, faculty-to-resident ratios for other subspecialties were: 1:4.7 for pediatrics, 1:3.6 for oncology, 1:5.9 for minimally invasive surgery/endourology, 1:14.2 for trauma/reconstruction, and 1:11.8 for andrology or male sexual/reproductive health. The FPMRS faculty-to-resident ratio was 1:5.1 in programs with a urology-based FPMRS fellowship compared with 1:13.4 in programs without a FPMRS fellowship. CONCLUSIONS: 30% of US urology residency programs lack FPMRS trained faculty. Even when FPMRS faculty are on staff, the field is often underrepresented relative to other urologic subspecialties. Further studies are required to ascertain if inadequate exposure to FPMRS cases and mentors during training contribute to the shortage of urology residents who choose to specialize in FPMRS. This link has important implications for the current shortage of FPMRS providers.

Spatially resolved single-cell translatomics at molecular resolution.

The precise control of messenger RNA (mRNA) translation is a crucial step in posttranscriptional gene regulation of cellular physiology. However, it remains a challenge to systematically study mRNA translation at the transcriptomic scale with spatial and single-cell resolution. Here, we report the development of ribosome-bound mRNA mapping (RIBOmap), a highly multiplexed three-dimensional in situ profiling method to detect cellular translatome. RIBOmap profiling of 981 genes in HeLa cells revealed cell cycle-dependent translational control and colocalized translation of functional gene modules. We mapped 5413 genes in mouse brain tissues, yielding spatially resolved single-cell translatomic profiles for 119,173 cells and revealing cell type-specific and brain region-specific translational regulation, including translation remodeling during oligodendrocyte maturation. Our method detected widespread patterns of localized translation in neuronal and glial cells in intact brain tissue networks.

The Utility of Renal Mass Biopsy in Shared Decision-Making for Renal Mass Treatment.

OBJECTIVE: To evaluate the utility of renal mass biopsy (RMB) in shared decision-making for renal mass treatment. Underutilization of RMB for patients with renal masses is due in part to physicians believing that results have limited clinical utility. MATERIALS AND METHODS: This was a prospective study of all patients referred for RMB from October 2019 to October 2021. Patients and physicians completed pre- and post-RMB questionnaires. Questionnaires assessed both parties' perceived utility of RMB and the impact of biopsy results on treatment preference using Likert scales. RESULTS: We enrolled 22 patients with a mean age of 66years (SD 14.5) and mean renal tumor size 3.1 cm (SD 1.4). Five were lost to follow-up (three pre-RMB, two post-RMB). Pre-RMB, 100% of patients believed that a biopsy would help them choose a treatment and 45% were unsure of their treatment preferences. After RMB, 92% perceived their biopsy results as useful and only 9% were unsure of treatment preference. Overall, 100% of patients were glad they had a biopsy. Results led patients and physicians to change their treatment preference in 57% and 40% of cases, respectively. Patients and physicians disagreed about treatment in 81% of cases prior to biopsy, but in only 25% of cases after biopsy. CONCLUSION: Discordance between patient and physician treatment preference for renal masses is higher in the absence of RMB data. Select patients are willing to undergo RMB and RMB data can increase patient confidence and comfort in a shared decision-making approach for renal mass treatment.

Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape.

Spatiotemporal regulation of the cellular transcriptome is crucial for proper protein expression and cellular function. However, the intricate subcellular dynamics of RNA remain obscured due to the limitations of existing transcriptomics methods. Here, we report TEMPOmap-a method that uncovers subcellular RNA profiles across time and space at the single-cell level. TEMPOmap integrates pulse-chase metabolic labeling with highly multiplexed three-dimensional in situ sequencing to simultaneously profile the age and location of individual RNA molecules. Using TEMPOmap, we constructed the subcellular RNA kinetic landscape in various human cells from transcription and translocation to degradation. Clustering analysis of RNA kinetic parameters across single cells revealed 'kinetic gene clusters' whose expression patterns were shaped by multistep kinetic sculpting. Importantly, these kinetic gene clusters are functionally segregated, suggesting that subcellular RNA kinetics are differentially regulated in a cell-state- and cell-type-dependent manner. Spatiotemporally resolved transcriptomics provides a gateway to uncovering new spatiotemporal gene regulation principles.

Factors Related to Differential Treatment and Practice Limitations Amongst Urologists: A Report of American Urological Association 2021 Census Data.

OBJECTIVE: To assess rates of urologist-reported differential treatment in practice and practice limitations based on characteristics of urologists... identity. MATERIALS AND METHODS: The 2021 AUA Census samples were linked with the United States (US) practicing urologist population file and assigned proper sample weighting to adjust for non-response bias. Responses to 2 questions of the Census related to (1) (negative) differential treatment experienced in practice and (2) limitations in patients/diagnoses seen in practice due to different aspects of respondent...s identity were evaluated. Responses were stratified based on self-reported gender (female vs male) and race (White vs non-White); results were compared using a chi-squared test. RESULTS: A total of 1742 urologists, representing 13,790 practicing US urologists through post-stratified weighting, responded to the Census. Overall, amongst those who answered the relevant questions, 16.3% reported having experienced differential treatment in practice due to their identity and 6.1% reported being limited in patients/diagnoses seen in practice due to their identity. Women were more likely than men to have experienced differential treatment (75.0% vs.ß10.2%, P.ß<.ß.001) and to be limited in patients/diagnoses seen in practice (27.0% vs.ß3.7%, P.ß<.ß.001). Similarly, non-White respondents were more likely than White urologists to both have experienced differential treatment (30.4% vs.ß14.1%, P.ß<.ß.001) and to be limited in patients/diagnoses seen in practice (12.8% vs.ß5.0%, P.ß<.ß.001). CONCLUSION: Female and non-White urologists are more likely to experience differential treatment in their practice and limitations in the scope of their practice. Further studies are needed to characterize these experiences and explore the etiologies of these differences.

Protein-protein interfaces in molecular glue-induced ternary complexes: classification, characterization, and prediction.

Molecular glues are a class of small molecules that stabilize the interactions between proteins. Naturally occurring molecular glues are present in many areas of biology where they serve as central regulators of signaling pathways. Importantly, several clinical compounds act as molecular glue degraders that stabilize interactions between E3 ubiquitin ligases and target proteins, leading to their degradation. Molecular glues hold promise as a new generation of therapeutic agents, including those molecular glue degraders that can redirect the protein degradation machinery in a precise way. However, rational discovery of molecular glues is difficult in part due to the lack of understanding of the protein-protein interactions they stabilize. In this review, we summarize the structures of known molecular glue-induced ternary complexes and the interface properties. Detailed analysis shows different mechanisms of ternary structure formation. Additionally, we also review computational approaches for predicting protein-protein interfaces and highlight the promises and challenges. This information will ultimately help inform future approaches for rational molecular glue discovery.

Gaining consensus around patient risk groups and prognostic profiles to guide CMV management among patients with solid organ transplant: Insights from a Delphi panel with SOT experts.

INTRODUCTION: This study aimed to characterize patient risk groups and respective prognostic profiles to optimize clinical decision-making and guide appropriate medical cytomegalovirus (CMV) management among patients with solid organ transplant (SOT). METHODS: Between September 2021 and February 2022, a three-round modified Delphi study was conducted to generate consensus among 14 international experts in virology and organ transplantation. Experts were asked about treatment and prognoses for patients in seven distinct clinical scenarios. Furthermore, experts were asked to risk-stratify patients by pre-/post-transplant characteristics. Consensus around opting for/against a treatment was observed if ≥75% or <25% of experts reported ≥50% likelihood to recommend or if treatments were ranked inside/outside the top two options and ≥75% of experts were within 1 standard deviation of the mean rank. RESULTS: Experts agreed on several unmet needs in CMV disease management post-SOT, particularly avoidance of treatment-limiting toxicities with conventional CMV therapy and emergence of both primary refractory and drug resistant treatment failures. Experts considered CMV viral load, resistance profile, and route of administration as critical to treatment selection. For newer CMV therapeutic options, experts listed lack of long-term use data, concerns over potential resistance, high cost and limited availability as challenges restricting adoption, and successful patient management. CONCLUSION: Experts achieved consensus around patient risk stratifications and factors influencing therapeutic options. Recommendations emerging from this Delphi study may support practicing physicians when confronted with challenging CMV scenarios in SOT patients, but additional experiences with newer anti-CMV agents are needed to re-validate expert consensus and update post-transplant CMV guidelines.

Impact of donor kidney biopsy on kidney yield and posttransplant outcomes.

Procurement biopsy is performed to determine kidney quality, but evidence supporting such association is poor. We investigated the impact of glomerulosclerosis percentage (GS%) on kidney yield and patient outcomes. Information on deceased kidney donors from July 1, 2017, to June 30, 2019, was collected. Association between GS% and kidney yield (number of kidneys procured per donor) and posttransplant graft and patient outcomes were studied. Maximal GS% and minimal GS% were calculated to determine the relationship between GS% and kidney yield; minimal GS% only for correlation with posttransplant outcomes. Multinomial logistic regression and Cox models with least absolute shrinkage and selection operator were used to analyze the association of GS% with kidney yield and posttransplant outcomes, respectively. The kidney yield was 1.63 when maximal GS% and minimal GS% were <5%, but was 0.88 when both GS% were >20%. The hazard ratio for graft failure 1 year after transplant was 1.05 when minimal GS% was 16% to 20%, but was 1.3 for GS% of >20%. The hazard ratio for mortality increased from 1 to 1.2 when minimal GS% reached >20%. In summary, higher GS% was associated with lower kidney yield and inferior posttransplant outcomes. Incorporation of GS% into Scientific Registry of Transplant Recipients models may reassure organ procurement organizations and transplant centers pursuing kidneys with relatively high GS% levels, thereby reducing kidney discard rates.

Racial Disparities in Endoscopy Cancellations During the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic has disrupted healthcare delivery including elective endoscopy. We aimed to determine the prevalence of endoscopy cancellations in the COVID-19 era and identify patient characteristics associated with cancellation due to the pandemic. METHODS: Medical charts were reviewed for adults who cancelled an outpatient endoscopic procedure from 5/2020 to 8/2020. The association of patient characteristics with cancellation of endoscopy due to COVID-19 was assessed using logistic regression. RESULTS: There were 652 endoscopy cancelations with 211 (32%) due to COVID-19, 384 (59%) due to non-COVID reasons, and 57 (9%) undetermined. Among COVID-19 related cancellations, 75 (36%) were COVID-19 testing logistics related, 121 (57%) were COVID-19 fear related, and 15 (7%) were other. On adjusted analysis, the odds of cancellation due to COVID-19 was significantly higher for black patients (OR 2.04, 95% CI 1.07-3.88, p = 0.03), while patients undergoing EGD (OR 0.56, 95% CI 0.31-0.99, p = 0.05) or advanced endoscopy (OR 0.18, 95% CI 0.07-0.49, p = 0.001) had lower odds of cancellation. The odds of cancelling due to COVID-19 testing logistics was significantly higher among black patients (OR 3.12, 95% CI 1.03-9.46, p = 0.05) and patients with Medi-Cal insurance (OR 2.89, 95% CI 1.21-6.89, p = 0.02). CONCLUSION: Black race is associated with an increased risk of COVID-19 related cancellation. Specifically, black patients and those with Medi-Cal are at increased risk of cancellation related to logistics of obtaining pre-endoscopy COVID-19 testing. Racial and socioeconomic disparities in access to endoscopy may be further amplified by the COVID-19 pandemic and warrant further study.

Ergonomic Considerations in Urologic Surgery.

PURPOSE OF REVIEW: This paper aims to discuss the various work-related musculoskeletal disorders (WRMDs) among urologists and provide an overview of the latest recommendations to improve awareness of ergonomic principles that can be applied in the operating room, with special consideration of challenges faced during pregnancy. RECENT FINDINGS: Urologists suffer from a large burden of WRMDs. The main drivers of pain associated with the various surgical approaches include repetitive movements, static and awkward body positions, and the use of burdensome equipment. Pregnant surgeons are at an even greater risk of WRMDs and face high rates of pregnancy complications. Laparoscopy, endoscopy, robot-assisted surgeries, and open surgeries present unique ergonomic challenges for the practicing urologist. Proper posture and equipment use, optimal operating room setup, intraoperative stretching breaks, and an emphasis on teaching ergonomic principles can reduce the risk of WRMDs. Surgeons are also at increased risk of WRMDs during pregnancy but may continue to operate while taking measures to limit physical exertion and fatigue. Improving awareness of and incorporating ergonomic principles early in a urologist's career may reduce the risk of injury and improve operative performance and longevity.

Urodynamic findings in female patients with nocturia: An age-matched case-control study.

INTRODUCTION: Nocturia negatively impacts the quality of life and is associated with poor general health, but our understanding of its etiologies is incomplete. Urodynamic studies (UDS) findings in patients with nocturia are not well described and may help guide management. Our objective was to compare UDS findings with age-matched patients with and without nocturia. MATERIALS AND METHODS: We retrospectively reviewed UDS findings of 1124 patients (2010-2017). A total of 484 (43%) presented with nocturia and 821 (73%) were female. Female patients were separated into age-matched groups with and without nocturia. Urinary symptoms, past medical diagnoses, demographic information, and UDS findings were compared. RESULTS: A total of 596 female patients were included, 298 (50%) with nocturia and 298 without. Past medical history, including diabetes mellitus and cardiovascular disease, did not differ between groups. Patients with nocturia were more likely to have pelvic pain (p = 0.0014) and other daytime symptoms (frequency, urgency, and urgency incontinence). On UDS, patients with nocturia were more likely to have bladder outlet obstruction (BOO) (p = 0.025) and dysfunctional voiding (DV) (p < 0.0001). There was no difference in the frequency of detrusor overactivity (DO). Bladder capacity and postvoid residual volumes were lower, though not significantly, in the nocturia group. CONCLUSIONS: When comparing UDS findings in contemporary, age-matched groups of female patients with and without nocturia, we found only BOO and DV to be associated with nocturia. While the treatment of nocturia is often aimed at managing DO, our data suggest that this may not be the primary urodynamic correlation with nocturia. Further studies are needed to assess whether successful treatment of BOO and DV can improve nocturia.

Differences in management of pregnant women with obstructing infected ureteral stones: A population-based analysis.

OBJECTIVES: Obstructing ureteral stones complicated by urinary tract infection are urologic emergencies that require prompt decompression. We explore the association of pregnancy with rates of and delays in decompression in a cohort of women of reproductive age. METHODS: Using the National Inpatient Sample from 2010 to 2015, a cross-sectional, descriptive analysis of women of reproductive age (15 to 44 years old) diagnosed with obstructing ureteral stones and urinary tract infection was performed and stratified by pregnancy status. Survey-weighted regression models were used to assess the association of pregnancy on decompression, delays in decompression, and hospital length of stay. Additional exploratory analyses on the association of timing and type of decompression with maternal-fetal outcomes were performed. RESULTS: A weighted total of 38 783 hospitalizations were identified, with 6.1% of admissions occurring in pregnant women. On multivariable regression, pregnant women with obstructing ureteral stones and urinary tract infection were 38% less likely of undergoing decompression (adjusted OR: 0.62; p < 0.001) compared with nonpregnant women. Among those decompressed, pregnant women had greater odds of delayed decompression (adjusted OR: 2.28; p < 0.001) and longer length of stay (adjusted IRR: 1.11; p = 0.007). Delayed decompression among pregnant women was associated with increased rates of C-section, early or threatened labor, fetal distress, and umbilical cord complications. CONCLUSIONS: Overall, pregnant women had reduced odds of decompression, as well as increased odds of delayed decompression, when compared with nonpregnant women of reproductive age. Delays in decompression among pregnant women were also associated with increased maternal and fetal complications.