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.

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.

Cell contact guidance via sensing anisotropy of network mechanical resistance.

Despite the ubiquitous importance of cell contact guidance, the signal-inducing contact guidance of mammalian cells in an aligned fibril network has defied elucidation. This is due to multiple interdependent signals that an aligned fibril network presents to cells, including, at least, anisotropy of adhesion, porosity, and mechanical resistance. By forming aligned fibrin gels with the same alignment strength, but cross-linked to different extents, the anisotropic mechanical resistance hypothesis of contact guidance was tested for human dermal fibroblasts. The cross-linking was shown to increase the mechanical resistance anisotropy, without detectable change in network microstructure and without change in cell adhesion to the cross-linked fibrin gel. This methodology thus isolated anisotropic mechanical resistance as a variable for fixed anisotropy of adhesion and porosity. The mechanical resistance anisotropy |Y*| -1 - |X*| -1 increased over fourfold in terms of the Fourier magnitudes of microbead displacement |X*| and |Y*| at the drive frequency with respect to alignment direction Y obtained by optical forces in active microrheology. Cells were found to exhibit stronger contact guidance in the cross-linked gels possessing greater mechanical resistance anisotropy: the cell anisotropy index based on the tensor of cell orientation, which has a range 0 to 1, increased by 18% with the fourfold increase in mechanical resistance anisotropy. We also show that modulation of adhesion via function-blocking antibodies can modulate the guidance response, suggesting a concomitant role of cell adhesion. These results indicate that fibroblasts can exhibit contact guidance in aligned fibril networks by sensing anisotropy of network mechanical resistance.

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.

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.

Outcomes of pregnancy in autoimmune hepatitis: A population-based study.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) disproportionately affects young women, which may have implications in pregnancy. However, data on pregnancy outcomes in women with AIH are limited. APPROACH AND RESULTS: Using weighted discharge data from the United States National Inpatient Sample from 2012 to 2016, we evaluated pregnancies after 20 weeks gestation and compared outcomes in AIH to other chronic liver diseases (CLD) or no CLD in pregnancy. The association of AIH with maternal and perinatal outcomes was assessed by logistic regression. Among 18,595,345 pregnancies, 935 (<0.001%) had AIH (60 with cirrhosis) and 120,100 (0.006%) had other CLD (845 with cirrhosis). Temporal trends in pregnancies with AIH remained stable from 2008 to 2016 with 1.4-6.8/100,000 pregnancies per year (p = 0.25). On adjusted analysis, the odds of gestational diabetes (GDM) and hypertensive complications (pre-eclampsia, eclampsia, or hemolysis, elevated liver enzymes, low platelets) were significantly higher in AIH compared to other CLD (GDM: OR 2.2, 95% CI: 1.5-3.9, p < 0.001; hypertensive complications: OR: 1.8, 95% CI: 1.0-3.2, p = 0.05) and also compared to no CLD in pregnancy (GDM: OR: 2.4, 95% CI: 1.6-3.6, p < 0.001; hypertensive complications: OR: 2.4, 95% CI: 1.3-4.1, p = 0.003). AIH was also associated with preterm births when compared with women without CLD (OR: 2.0, 95% CI: 1.2-3.5, p = 0.01). AIH was not associated with postpartum hemorrhage, maternal, or perinatal death. CONCLUSIONS: Rates of pregnancy in women with AIH have remained stable in recent years, although AIH is associated with notable maternal and perinatal risks, such as GDM, hypertensive complications, and preterm birth. Whether these risks are influenced by steroid use and/or AIH disease activity warrants evaluation. These data support a low risk of postpartum hemorrhage and favorable survival of mothers and infants.

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.

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.

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.

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.

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.

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.

Neuromodulation for lower urinary tract symptoms in special populations.

AIMS: Discuss the efficacy, safety, and future directions of neuromodulation in special populations of patients with neurological conditions. METHODS: A literature review was done to find meta-analyses, review articles, studies, and case reports of the use of neuromodulation, either sacral neuromodulation or percutaneous tibial nerve stimulation, in patients with various neurological conditions of interest. RESULTS: Sacral neuromodulation (SNM) and posterior tibial nerve stimulation (PTNS) appear to be safe and effective in special neurological populations of patients with multiple sclerosis (MS), Parkinson's disease (PD), and spinal cord injury (SCI). The majority of publications are smaller retrospective case series. Outcomes appear similar to those seen in nonneurogenic patients but also partly depend on disability progression. Magnetic resonance imaging (MRI) compatibility has helped to improve eligibility for SNM in these special populations. CONCLUSIONS: In a small number of studies, SNM and PTNS appear to be safe and effective in special neurological populations of patients with MS, PD, and SCI. MRI compatibility has helped to improve eligibility for SNM in these special populations. Studies looking at SNM are limited by a small number of subjects, lack of prospective trials, and selection bias. Larger, randomized studies with long-term follow up are needed to better predict response to SNM and PTNS in these populations.

Protein stability engineering insights revealed by domain-wide comprehensive mutagenesis.

The accurate prediction of protein stability upon sequence mutation is an important but unsolved challenge in protein engineering. Large mutational datasets are required to train computational predictors, but traditional methods for collecting stability data are either low-throughput or measure protein stability indirectly. Here, we develop an automated method to generate thermodynamic stability data for nearly every single mutant in a small 56-residue protein. Analysis reveals that most single mutants have a neutral effect on stability, mutational sensitivity is largely governed by residue burial, and unexpectedly, hydrophobics are the best tolerated amino acid type. Correlating the output of various stability-prediction algorithms against our data shows that nearly all perform better on boundary and surface positions than for those in the core and are better at predicting large-to-small mutations than small-to-large ones. We show that the most stable variants in the single-mutant landscape are better identified using combinations of 2 prediction algorithms and including more algorithms can provide diminishing returns. In most cases, poor in silico predictions were tied to compositional differences between the data being analyzed and the datasets used to train the algorithm. Finally, we find that strategies to extract stabilities from high-throughput fitness data such as deep mutational scanning are promising and that data produced by these methods may be applicable toward training future stability-prediction tools.

Low Rates of Advance Care Planning (ACP) Discussions Despite Readiness to Engage in ACP Among Liver Transplant Candidates.

BACKGROUND: Patients with end-stage liver disease awaiting liver transplantation (LT) are seriously ill and experience fluctuating periods of clinical decompensation. Discussion of a patient's advance care planning (ACP) wishes early in their dynamic disease course is critical to providing value-aligned care while awaiting LT. We aimed to evaluate current ACP documentation and assess readiness to engage in ACP in this population. METHODS: We conducted a retrospective study of adults undergoing LT evaluation from January 2017 to June 2017 and assessed characteristics associated with documentation using logistic regression. We then administered a survey to LT candidates from March 2018 to May 2018 to determine self-reported readiness to engage in ACP (range 1 = not at all ready to 5 = very ready). RESULTS: Among 170 LT candidates, median (interquartile range) age was 58 (53-65), 65% were men, MELDNa was 15 (11-21), and Child-Pugh A/B/C were 33/38/29%. Nine percent reported completing ACP prior to LT evaluation, but 0% had legal ACP forms or end-of-life wishes documented in the medical record. A durable power of attorney (DPOA) was discussed with 10%. In univariable analysis, white race (OR 4.16, p = 0.03) and female sex (OR 3.06, p = 0.04) were associated with ACP documentation, but Child-Pugh score and MELDNa were not. Of the 41 LT candidates who completed the ACP survey, 93% were ready to appoint a DPOA and 85% were ready to discuss end-of-life care. CONCLUSION: There is a paucity of ACP documentation and identification of DPOA among LT candidates, despite patients reporting readiness to complete ACP and appoint a DPOA. These results reveal an opportunity for tools to facilitate discussions around ACP between clinicians, patients, and their caregivers.

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

Multidimensional outcomes of suburethral synthetic midurethral sling removal.

PURPOSE: To report multidimensional outcomes encompassing pain, dyspareunia, and recurrent urinary tract infections (UTIs), following suburethral sling removal (SSR) of synthetic midurethral slings (MUS) placed for female stress urinary incontinence. METHODS: We reviewed a prospectively maintained, IRB-approved database of women undergoing SSR at our institution. Demographic data, type of sling, and symptoms along with Urogenital Distress Inventory-Short Form (UDI-6) scores both before and after SSR were analyzed. Success was defined using several modalities including patient-reported symptoms (ideal outcome) and UDI-6 questionnaire. RESULTS: From 3/2006-2/2017, 443 women underwent SSR of which 230 met study criteria with median overall follow-up of 23 months (mean 30 months). 180/230 (78%) patients reported 3 or more symptoms at presentation. Median most recent post-SSR total UDI-6 score was 38 vs. 50 at baseline (p < 0.0001). By UDI-6, 53% of patients achieved success post-SSR. An ideal outcome was attained in 22/230 (10%) patients. A modified outcome allowing for one minimally invasive anti-incontinence procedure and excluding sexual activity classified 112/230 (49%) patients as successes. CONCLUSIONS: While patients with MUS present with multiple symptoms, following SSR, there is sustained improvement in multiple symptom domains, including pain and urinary incontinence. Allowing for minimally invasive anti-incontinence procedures (not inclusive of subsequent suburethral sling), the rate of success was 49%, which was comparable to that derived from UDI-6 scores (53%).

The Range and Reproducibility of the Liver Frailty Index.

The Liver Frailty Index (LFI), composed of 3 performance-based tests (grip strength, chair stands, and balance), is a tool specifically developed in patients with cirrhosis to objectively measure physical function, a critical determinant of health outcomes. We aimed to (1) determine the range of LFI scores in adults with chronic liver disease but without cirrhosis, (2) determine the range of LFI scores in adults without known liver disease, and (3) evaluate reproducibility of the LFI in adults with cirrhosis listed for liver transplantation. Intraclass correlation coefficient (ICC) assessed interrater reliability of the LFI. Included were 91 adults with chronic liver disease, 109 adults without known liver disease, and 166 adults with cirrhosis with median Model for End-Stage Liver Disease-sodium of 16. Median (interquartile range) LFI was 3.6 (3.1-4.1) in adults with cirrhosis, 3.1 (2.5-3.7) in adults with chronic liver disease but not cirrhosis, and 2.7 (2.2-3.2) in adults without liver disease (P < 0.001). Using established LFI cutoffs for robust, prefrail, and frail categories, adults with cirrhosis or chronic liver disease were less likely to be robust (29% versus 53% versus 77%) and more likely to be prefrail (57% versus 42% versus 22%) or frail (14% versus 5% versus 1%) when compared with adults without liver disease (P < 0.001). The LFI had excellent reliability with ICC of 0.93 (95% confidence interval, 0.91-0.95). In conclusion, the LFI has external validity in noncirrhotic populations and is highly reproducible among different raters. This objective assessment tool can be implemented in outpatient clinical practice or research to operationalize the concept of physical frailty.

Are dialysis patients too frail to exercise?

Clinical manifestations of functional and morphological muscular abnormalities in dialysis patients are muscle weakness and low exercise capacity, possibly leading to a sedentary life style with low physical activity. Low cardiorespiratory fitness and muscle atrophy and weakness contribute to the development of frailty and affect patients' ability to physically navigate their environment. While many dialysis patients may appear too frail to participate in moderate-to-vigorous aerobic exercise training, those who can complete such programs appear to derive substantial benefit. Less vigorous aerobic exercise, resistance training, and alternative forms of exercise can also be beneficial. Most patients on dialysis are not too frail to perform resistance exercise of adequate intensity to achieve increases in muscle size and strength, therefore, frailty should not be considered a contraindication to exercise.