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Stress-induced condensation of mRNA and protein into massive cytosolic clusters is conserved across eukaryotes. Known as stress granules when visible by imaging, these structures remarkably have no broadly accepted biological function, mechanism of formation or dispersal, or even molecular composition. As part of a larger surge of interest in biomolecular condensation, studies of stress granules and related RNA/protein condensates have increasingly probed the biochemical underpinnings of condensation. Here, we review open questions and recent advances, including the stages from initial condensate formation to accumulation in mature stress granules, mechanisms by which stress-induced condensates form and dissolve, and surprising twists in understanding the RNA components of stress granules and their role in condensation. We outline grand challenges in understanding stress-induced RNA condensation, centering on the unique and substantial barriers in the molecular study of cellular structures, such as stress granules, for which no biological function has been firmly established.

Background : This phase 1b study investigated safety and activity of combined checkpoint inhibition (CPI) with programmed death-ligand 1 (PD-L1) antibody atezolizumab plus cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab in NSCLC. Patients and Methods : Eligible patients had previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) or melanoma. A standard 3+3 dose escalation investigated atezolizumab (600-1200 mg IV every 3 weeks) plus ipilimumab starting at 1 mg/kg, administered as a single dose or 4 doses, administered every 3 weeks. The expansion stage included a cohort previously treated with atezolizumab. Patients were monitored for safety and tolerability; response was evaluated every 6 weeks. Results : Twenty-seven patients were enrolled, 4 with melanoma and 23 with NSCLC; here, we focus on data for the NSCLC population. Three of 23 patients (13.0%) received prior CPI. No dose-limiting toxicities were reported during dose escalation; dose expansion occurred with atezolizumab 1200 mg plus 1 cycle of ipilimumab 1 mg/kg. Most common treatment-emergent adverse events (AEs) were dyspnea (39%) and cough (35%); treatment-related grade ≥3 AEs occurred in 11 patients (48%), most frequently pneumonitis (17%) and amylase or lipase elevation (9% each). Six of 23 NSCLC patients (26%) achieved confirmed responses, 5 of whom (25%) were CPI-naive. Median duration of response was 23.0 (95% CI, 3.2-36.9) months overall and 36.9 (95% CI, 2.9-36.9) months in CPI-naive patients. Conclusion : Preliminary efficacy of atezolizumab plus ipilimumab was observed in metastatic NSCLC. The combination had manageable toxicity, with a safety profile consistent with those of the individual agents. MicroAbstract : Dual checkpoint inhibitor therapy with atezolizumab (anti–PD-L1) and ipilimumab (anti–CTLA-4) may improve outcomes in locally advanced or metastatic NSCLC. This phase 1b study investigated atezolizumab plus ipilimumab in 23 patients with previously treated NSCLC. The combination had manageable toxicity and demonstrated preliminary clinical activity. Further elucidation of biomarkers to optimally select patients for checkpoint inhibitor therapy may be required.

The functional lumen imaging probe provides objective measurements of the gastroesophageal junction during laparoscopic anti-reflux surgery. There is a lack of data on how functional lumen imaging probe measurements change at follow-up. We aim to describe our institutional experience in performing functional lumen imaging probe during postoperative endoscopy after laparoscopic anti-reflux surgery.A prospectively maintained database was queried. Patients who had postoperative endoscopic functional lumen imaging probe measurements between March 2018 and June 2021 were assessed at different time points from their index laparoscopic anti-reflux surgery using paired t test. Standardized quality of life questionnaires were collected for up to 2 years. Group comparisons were made using the Wilcoxon rank-sum test.Fifty-eight patients who underwent laparoscopic anti-reflux surgery (magnetic sphincter augmentation or fundoplication) had postoperative functional lumen imaging probe. Thirty-two intraoperative functional lumen imaging probe values were compared with their postoperative functional lumen imaging probe. Fundoplication values did not differ. Postoperative functional lumen imaging probe distensibility index for magnetic sphincter augmentation patients was decreased (P = .04). Functional lumen imaging probe measurements for all postoperative endoscopies showed that magnetic sphincter augmentation had the lowest distensibility index (P.01). Dysphagia as a reason for endoscopy had a decrease in distensibility index (P = .03).Functional lumen imaging probe measurements after fundoplication persist at long-term follow up while patients may have a tighter gastroesophageal junction after magnetic sphincter augmentation. Functional lumen imaging probe has the potential to assess the success or failure after laparoscopic anti-reflux surgery and optimize patient outcomes.

Objective : Catholic Religious and Ethical Directives restrict access to contraception, yet offering contraception during a delivery hospitalization facilitates birth spacing and is a convenient option for patients during the postpartum period. We assessed patient and provider experiences with hospital transparency around postpartum contraceptive care in Illinois Catholic hospitals. Study Design : We interviewed 44 participants with experience in Illinois Catholic hospitals: 21 patients, and 23 providers, including clinicians, nurses, doulas, and postpartum program staff. We used an open-ended interview approach, with a semi-structured guide focused on postpartum contraceptive care. We conducted interviews by phone between November 2019 and June 2020. We audio-recorded interviews, transcribed them verbatim, and coded transcripts in Dedoose. We developed narrative memos for each code, identifying themes and sub-themes. We organized these in a matrix for analysis and present here themes regarding hospital transparency that emerged across interviews. Results : Many patients knew they were delivering in a Catholic hospital; however, few were aware that Catholic policies limited their healthcare options. Patients expressed a desire for hospitals to be transparent, even “very vocal,” about religious restrictions and described consequences of restrictions on patient care. Patients lacked information to make contraceptive decisions, experienced limits on or delays in care, and some lost continuity with trusted providers. Consequences for providers included moral distress in trying to provide care using workarounds such as documenting false medical diagnoses. Conclusions : Religious restrictions on postpartum contraception restrict access, cause unnecessary delays in care, and lead to misdiagnosis and marginalization of contraceptive care. Restrictions also cause moral distress to providers who balance career repercussions and professional integrity with patient needs. Implications : To protect patient autonomy, especially during the vulnerable postpartum period, Catholic hospitals should increase transparency regarding limitations on reproductive health care. Insurers and policy-makers should guarantee that patients have the option to receive care at hospitals without these limitations and facilitate public education about what to expect at Catholic facilities.

Obtaining a clear Critical View of Safety helps prevent bile duct injuries during laparoscopic cholecystectomy, which can be improved with a structured Safe Critical View of Safety curriculum. We aimed to determine whether the improvement in obtaining Critical View of Safety postcurriculum is retained long-term.A safe Critical View of Safety curriculum was previously implemented for all surgeons who perform laparoscopic cholecystectomy at a regional health system. Recordings of laparoscopic cholecystectomy cases were collected 1 year after completion of the curriculum, deidentified and randomly ordered, and then graded by 2 blinded expert surgeons using a 6-point Critical View of Safety assessment tool.A total of 12 surgeons with average experience of 17.9 ± 6.3 years in practice participated in the study. The majority (83%) had performed700 laparoscopic cholecystectomies, and 4 surgeons (33%) reported 2 or more bile duct injuries in their career. Controlling for gallbladder pathology, Critical View of Safety scores improved from 1.7 ± 0.4 to 4.0 ± 0.4 (P.001) immediately after completion of the curriculum. However, there was a small decrease in Critical View of Safety score after 1 year (3.2 ± 0.3 from 4.0 ± 0.4, P = .055), while still significantly higher compared to precurriculum (3.2 ± 0.3 vs 1.7 ± 0.4, P.001). Acute care surgeons had lower Critical View of Safety retention scores compared to general surgeons (1.8 ± 0.5 vs 3.3 ± 0.4, P = .01) and minimally invasive surgeons (1.8 ± 0.5 vs 3.8 ± 0.5, P.01).A structured curriculum helped improve practicing surgeons' attainment of obtaining the Critical View of Safety during laparoscopic cholecystectomy. However, this improvement decreased after 1 year, suggesting some decay in knowledge retention over time. Therefore, continued educational interventions on Critical View of Safety and safe laparoscopic cholecystectomy may be needed to enhance long-term retention.

Purpose Older adults with head and neck cancer have increased postoperative complications, longer hospital stays, and higher rates of mortality. Geriatric assessment (GA) provides a measure of overall health status and is preferable to using age alone for assessing fitness for surgery. We sought to determine whether a patient's frailty as determined by a novel electronic GA is associated with outcomes after head and neck cancer (HNC) surgery. Methods We conducted a retrospective review of 159 patients aged 75 and older referred to the Geriatrics Service at Memorial Sloan Kettering Cancer Center for pre-operative evaluation prior to undergoing HNC surgery. All patients completed the electronic Rapid Fitness Assessment (eRFA) within 60 days prior to surgery. The accumulated geriatric deficit (AGD) score includes twelve domains from the eRFA with a point assigned for each domain in which there is a deficit and a final point related to comorbidities. Three other metrics were individually assessed: age, Karnofsky Performance Scale (KPS), and number of comorbidities. We utilized multivariable linear regression and t-tests to determine whether frailty is associated with longer length of hospital stay, 30-day intensive care unit (ICU) admission, and 30-day and 90-day postoperative mortality. Results Patients with a higher AGD score spent more time in the hospital post-operatively (1.0 day increase per unit increase in AGD; 95% CI: 0.21–1.9; p = 0.015). Lower KPS was also associated with statistically significant longer length of stay (−2.70 day change per increasing index KPS; 95% CI: −4.30 – −1.00; days; p = 0.002), while age and comorbidity were not found to be statistically associated with length of stay. Higher AGD score remained significantly associated with longer length of stay on multivariable analysis (0.93 day increase per unit increase in AGD; 95% CI 0.15–1.71; p = 0.019). AGD was the only metric associated with increased risk of ICU admission (6.6 vs 5.0 geriatric deficits for those admitted vs not admitted to ICU; p = 0.024). Conclusions Frailty is associated with increased length of hospital stay and ICU admission in older adults with HNC undergoing surgery. GA can be used to counsel patients on the expected postoperative course.

Nonalcoholic fatty liver disease (NAFLD) affects more than 25% of the adult population worldwide and is associated with significant clinical and economic burden.1 However, heterogeneous definitions and inaccurate terminology contribute to variations in prevalence estimates and may not comprehensively incorporate complex metabolic dysfunctions that exist. An international expert panel consensus proposed updated nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), and associated criteria to more accurately capture this complex multisystem metabolic disorder.2 Although it has not replaced NAFLD, the term MAFLD has been positively received given it more comprehensively incorporates the metabolic derangements that contribute to risk of fatty liver and it may be more practical for clinicians to identify patients with fatty liver.3 We describe prevalence of MAFLD among US adults based on these recently proposed nomenclature and definition.2.

PURPOSE: To investigate hemiretinal asymmetry in radial peripapillary capillary vessel area density (VAD) of healthy, glaucoma suspect, and glaucoma eyes of varying severity and its diagnostic utility for glaucoma. DESIGN: Population-based, cross-sectional study. METHODS: 6×6-mm optic disc scans were collected on optical coherence tomography angiography (OCTA) to obtain VAD and on OCT to measure circumpapillary retinal nerve fiber layer (RNFL) thickness. Hemiretinal difference in VAD (hdVAD) was defined as the absolute difference between superior and inferior hemiretinal VAD. Age-adjusted multivariable linear regression of hdVAD on glaucoma severity was performed. Area under curves (AUCs) were calculated from predicted probabilities generated by multiple logistic regression of glaucoma severity on age-adjusted single and combined parameters. RESULTS: 1043 eyes of 1043 participants (587 healthy, 270 suspect, 67 mild, 54 moderate, 65 severe glaucoma) were included. After age adjustment, mean hdVAD was similar between healthy and suspect (P = 0.225), higher in mild versus suspect (P < 0.001), higher in moderate versus mild (P = 0.018), but lower in severe versus moderate (P = 0.001). AUCs of hdVAD were highest for discriminating mild (0.685) and moderate (0.681) glaucoma from healthy. Combining hdVAD and global RNFL (gRNFL) yielded the highest AUCs of all parameters for mild (0.817) and any POAG (0.859) and resulted in significantly better diagnostic accuracy than either hdVAD or gRNFL alone (P < 0.05 for all comparisons). CONCLUSIONS: hdVAD is higher in early glaucoma and may help with early detection when damage is focal, but its diagnostic ability appears less robust in advanced glaucoma when damage is diffuse.

Summary The first catalytic asymmetric synthesis of N–N axially chiral compounds has been accomplished via a quinidine catalyzed N-allylic alkylation reaction. These N–N axially chiral frameworks are a new addition to the families of axially chiral molecules and to the atropisomerism involving heteroatom(s), e.g., N, O, and S. The reaction takes place smoothly under mild conditions and displays excellent functional group tolerance, allowing facile access to a variety of N–N axially chiral 1-aminopyrroles and 3-aminoquinazolinones in high yields and excellent enantioselectivities. DFT calculations have been applied to understand the origin of enantioselectivity and provide guidance for the design of additional molecules of this type. The investigation of N–N axis atropisomerism holds promise for new discoveries in medicinal chemistry and asymmetric catalysis.

A healthy pregnancy depends on complex interrelated biological adaptations involving placentation, maternal immune responses, and hormonal homeostasis. Recent advances in high-throughput technologies have provided access to multiomics biological data that, combined with clinical and social data, can provide a deeper understanding of normal and abnormal pregnancies. Integration of these heterogeneous datasets using state-of-the-art machine-learning methods can enable the prediction of short- and long-term health trajectories for a mother and offspring and the development of treatments to prevent or minimize complications. We review advanced machine-learning methods that could: provide deeper biological insights into a pregnancy not yet unveiled by current methodologies; clarify the etiologies and heterogeneity of pathologies that affect a pregnancy; and suggest the best approaches to address disparities in outcomes affecting vulnerable populations.

Peroral endoscopic myotomy (POEM) has previously been shown to be equally if not more expensive than laparoscopic Heller myotomy (LHM). We compare perioperative outcomes and charges between POEM and LHM at a single institution.Outcomes and charge data of 33 patients who underwent LHM and 126 patients who underwent POEM were analyzed. Patients who did not present electively were excluded.There were no demographic differences between groups. Patients who underwent POEM had a significantly shorter mean operative time and median length of stay (both p 0.001). Patients who underwent POEM stopped narcotics earlier and had faster return to activities of daily living (both p 0.05). When adjusted for inflation, POEM incurred less in hospital charges than LHM (35.5 ± 12.8 vs 30.7 ± 10.3 in thousands of US dollars, p = 0.006).Patients who underwent POEM compared to LHM had significantly better perioperative outcomes. Our results suggest POEM may be the more cost-effective option.

Dedicated post-operative radiological evaluation following ophthalmologic procedures is relatively uncommon. However, given the ever-growing ophthalmologic procedural advancements and the increasing utilization of neuroimaging for myriad indications, the orbits are often imaged incidentally in a delayed post-procedural state. Regardless of the clinical scenario, it is important for neuroradiologists and other specialists commonly exposed to orbital imaging to be aware of both expected and abnormal post-operative imaging findings because misinterpreted normal features or unrecognized complications can result in vision-threatening delays in treatment or mismanagement. In this review article, we discuss many common ophthalmologic procedures, their indications, and most likely complications. We also provide illustrative operative photographs and radiological imaging examples. By understanding the surgical intent, recognizing the devices that are commonly used, and developing familiarity with the appearance of post-operative complications, pitfalls in interpretation can be avoided and patient outcomes ultimately improved.

Background Despite national guidelines emphasizing the importance of vaccination or documenting immunity to hepatitis A virus and hepatitis B virus for patients with chronic liver disease, the success of adhering to these recommendations is suboptimal. We aim to evaluate the prevalence of vaccination or documented reactivity to hepatitis A antibody and hepatitis B surface antibody among US adults with chronic liver disease. Methods Using 2011-2018 National Health and Nutritional Examination Survey data, adults with nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis B, and hepatitis C were evaluated to determine prevalence of vaccination (self-reported completion) and hepatitis A antibody reactivity or hepatitis B surface antibody reactivity. Results Overall prevalence of vaccination or hepatitis A antibody reactivity was lowest among individuals with nonalcoholic fatty liver disease (60.8%; 95% confidence interval [CI], 57.9-63.6) and alcoholic liver disease (61.8%; 95% CI, 59.0-64.6), and highest among individuals with hepatitis B (82.9%; 95% CI, 76.8-89.0). Prevalence of vaccination or hepatitis B surface antibody reactivity was much lower: 38.6% (95% CI, 35.7-41.4) in nonalcoholic fatty liver disease, 40.7% (95% CI, 34.4-47.0) in chronic hepatitis C virus, and 47.1% (95% CI, 44.3-49.9) in alcoholic liver disease. Conclusion Among US adults with chronic liver disease, prevalence of vaccination or documented reactivity to hepatitis A antibody and hepatitis B surface antibody was alarmingly low. These observations are particularly concerning given that underlying chronic liver disease increases risks of severe liver injury and decompensation from acute hepatitis A or hepatitis B infections.

Purpose To compare the performance of a novel convolutional neural network (CNN) classifier and human graders in detecting angle closure in EyeCam (Clarity Medical Systems, Pleasanton, California, USA) goniophotographs. Design Retrospective cross-sectional study. Methods Subjects from the Chinese American Eye Study underwent EyeCam goniophotography in 4 angle quadrants. A CNN classifier based on the ResNet-50 architecture was trained to detect angle closure, defined as inability to visualize the pigmented trabecular meshwork, using reference labels by a single experienced glaucoma specialist. The performance of the CNN classifier was assessed using an independent test dataset and reference labels by the single glaucoma specialist or a panel of 3 glaucoma specialists. This performance was compared to that of 9 human graders with a range of clinical experience. Outcome measures included area under the receiver operating characteristic curve (AUC) metrics and Cohen kappa coefficients in the binary classification of open or closed angle. Results The CNN classifier was developed using 29,706 open and 2,929 closed angle images. The independent test dataset was composed of 600 open and 400 closed angle images. The CNN classifier achieved excellent performance based on single-grader (AUC = 0.969) and consensus (AUC = 0.952) labels. The agreement between the CNN classifier and consensus labels (κ = 0.746) surpassed that of all non-reference human graders (κ = 0.578-0.702). Human grader agreement with consensus labels improved with clinical experience (P = 0.03). Conclusion A CNN classifier can effectively detect angle closure in goniophotographs with performance comparable to that of an experienced glaucoma specialist. This provides an automated method to support remote detection of patients at risk for primary angle closure glaucoma.

Renal failure can be divided into acute kidney injury and chronic kidney disease. Both are common and result in increased patient morbidity and mortality. The etiology is multifactorial and differentiation of acute kidney injury from chronic kidney disease includes clinical evaluation, laboratory tests, and imaging. The main role of imaging is to detect treatable causes of renal failure such as ureteral obstruction or renovascular disease and to evaluate renal size and morphology. Ultrasound is the modality of choice for initial imaging, with duplex Doppler reserved for suspected renal artery stenosis or thrombosis. CT and MRI may be appropriate, particularly for urinary tract obstruction. However, the use of iodinated and gadolinium-based contrast should be evaluated critically depending on specific patient factors and cost-benefit ratio. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

BACKGROUND Peroral endoscopic pyloromyotomy, or gastric peroral endoscopic myotomy, is a novel endoscopic procedure for the treatment of refractory gastroparesis. We present a simulation-based curriculum using an "into-the-fire" approach with hands-on pre- and post-tests to teach this procedure. METHODS Six, 1-day peroral endoscopic pyloromyotomy courses were taught by an expert surgical endoscopist in 2018 to 2019. The curriculum is composed of a series of pretraining tests, lectures, mentored hands-on instruction, and post-training tests using porcine models. Both pre- and post-testing included a confidence survey, a knowledge-based written test, and a specific assessment form for the peroral endoscopic pyloromyotomy procedure. Participants' scores were analyzed using paired t tests. RESULTS Twenty-eight practicing physicians participated. After completing the curriculum, participants had improved confidence scores (10.5 ± 5.2 vs 19.4 ± 3.6; P < .001), written test scores (6.8 ± 1.6 vs 8.0 ± 1.1; P < .001), and hands-on performance scores (23.6 ± 3.4 vs 29.3 ± 1.4; P < .001) with marked improvement in all components of the peroral endoscopic pyloromyotomy procedure. Postcourse surveys showed 93% of participants had performed or intended to perform the peroral endoscopic pyloromyotomy procedure within the next year. CONCLUSION Our simulation curriculum with an into-the-fire approach to teach peroral endoscopic pyloromyotomy is effective in improving practitioner knowledge, confidence, and technical skills, leading to an increase in the adoption of this procedure.

We examined whether a key psychological trait-resilience, defined as one's ability to recover quickly from difficulties-contributes to the frail phenotype in patients with cirrhosis. Included were 300 adult patients with cirrhosis who underwent outpatient physical frailty testing using the Liver Frailty Index and resilience testing using the Connor-Davidson Resilience Scale (CD-RISC). The Liver Frailty Index was categorized as robust, prefrail-robust, prefrail-frail, and frail; CD-RISC was categorized using population norms as: least, less, more, and most resilient. Linear regression was used to assess factors associated with frailty (by the Liver Frailty Index per 0.1 unit change). Among the most resilient, only 10% were frail; among the least resilient, 29% were frail. In univariable analysis, resilience was strongly associated with the Liver Frailty Index (coef = -0.13 per point increase; 95% confidence interval [CI], -0.20 to -0.60; P .001) and remained significantly associated with frailty in multivariable adjustment (coef = -0.13, 95% CI -0.19 to -0.07; P .001). Low resilience is strongly associated with the frail phenotype in patients with cirrhosis. Given that resilience is modifiable, our data suggest that effective interventions to mitigate frailty should include strategies to build resilience in patients with low baseline resilience.

Background & aims Lack of effective medical therapies for primary sclerosing cholangitis (PSC) leads to continued disease progression to end-stage liver disease requiring liver transplantation (LT). Few studies have specifically evaluated whether ethnic disparities in LT outcomes exist among adults awaiting LT. We aimed to evaluate ethnicity-specific differences in LT outcomes among adults with PSC in the US. Methods We retrospectively evaluated US adults (aged ≥ 18 years) with PSC without hepatocellular carcinoma listed for LT using the 2005–2017 United Network for Organ Sharing database. Ethnicity-specific differences in overall waitlist survival and probability of receiving LT were evaluated using competing risks regression analyses and adjusted multivariable Cox proportional hazards models. Overall survival after LT was evaluated with Kaplan-Meier methods and multivariable Cox proportional hazards models. Results Among 4046 patients with PSC listed for LT (69.2% men, 82.2% non-Hispanic white, 12.4% African American, 3.9% Hispanic, 1.6% Asian), significantly higher risk of waitlist death was men vs. women (Standardized hazard ratio (SHR) = 1.50, 95% CI: 1.05–2.12, P = 0.025), but no ethnicity-specific differences were observed. Compared with non-Hispanic whites, Hispanics had significantly lower probability of receiving LT (SHR = 0.73, 95% CI: 0.54–0.98, P = 0.035). Among patients with PSC and end-stage liver disease who underwent LT, African Americans had significantly higher risk of post-LT death compared with non-Hispanic whites (SHR = 1.68, 95% CI: 1.21–2.32, P = 0.002). Conclusions Among a large cohort of US adults with PSC awaiting LT, significant ethnicity-specific disparities in LT outcomes were observed. Lower probability of LT in Hispanics and significantly higher risk of post-LT death in African Americans were observed.

BACKGROUND: Direct-acting antivirals (DAAs) are expected to improve outcomes for patients with hepatitis C virus (HCV) infection after liver transplantation (LT). We aim to evaluate trends in post-LT outcomes with availability of DAAs. METHODS: We retrospectively evaluated US adults transplanted from January 1, 2002, to March 31, 2018, using the United Network for Organ Sharing Registry, stratified by pre-DAA (January 1, 2002– to December 31, 2013) vs. post-DAA (January 1, 2014–, to March 31, 2018) eras. Adjusted multivariate Cox regression analyses and competing risk models evaluated likelihood of graft failure, death, and retransplantation (re-LT). RESULTS: Among 97,147 patients, 30.2% had HCV infection and 19.4% had hepatocellular carcinoma (HCC). Of all patients, 31.9% experienced graft failure, 27.1% died after LT, and 4.7% underwent re-LT. The post-DAA era experienced lower likelihood of graft failure (hazard ratio [HR] = 0.69, p

To validate the performance of PI-RADS v2 for detection of clinically significant prostate cancer (csPca, Gleason ≥7) within the context of a new fusion biopsy program.Patients with a PI-RADS v2 assessment category assigned on pre-biopsy mpMRI between March 2015 and November 2017 were identified. Diagnostic performance of PI-RADS v2 was calculated using fusion biopsy results as reference standard using receiver operating characteristic curve analysis. Patient and lesion characteristics were analyzed with one-way ANOVA and Wilcoxon rank sum test.Of 83 patients with 175 lesions, 115/175 (65.7%) were benign, 21/175 (12%) were Gleason 6, and 39/175 (22.3%) were Gleason ≥7. csPCa rates were 0% (0/5) for PI-RADS 1, 7.4% (2/27) for PI-RADS 2, 5.8% (3/52) for PI-RADS 3, 31.2% (24/77) for PI-RADS 4, and 71.4% (10/14) for PI-RADS 5 (p 0.0001). For prediction of csPCa, patient-level AUC was 0.68 and lesion-level AUC was 0.77. Biopsy threshold of PI-RADS ≥3 was 92.6% sensitive and 22.1% specific. A threshold of PI-RADS ≥4 was 87.2% sensitive and 58.1% specific. Rate of csPca detection on concurrent standard 12 core biopsy only was 6.7%.PI-RADS v2 assessment categories assigned prior to biopsy predict pathologic outcome reasonably well in a new prostate fusion biopsy program. Biopsy threshold of PI-RADS ≥3 is highly sensitive. A threshold of ≥4 increases specificity but misses some csPCa.

Summary: Background & aims: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally. We aim to evaluate prevalence and predictors of hepatic fibrosis among NAFLD patients, focusing on metabolic co-morbidities and dietary patterns. Methods: Quest Diagnostics laboratory data from 2017 to 2018 were used to identify NAFLD patients using a stepwise algorithm based on laboratory data and ICD-9/10 codes. Prevalence of fibrosis was assessed using a step-wise AST to platelet ratio index (APRI) algorithm. Multivariate logistic regression evaluated predictors of ≥F2 fibrosis or cirrhosis. Prevalence of fibrosis was stratified by U.S. Department of Health and Human Services geographic regions and compared with region-specific data on metabolic diseases and dietary patterns (fruit and vegetable intake) using 2017 Behavioral Risk Factor Surveillance System. Results: Among NAFLD patients, proportion of patients with APRI >2.0 was 1.58%, increasing to 3.05% (APRI > 1.5), 6.81% (APRI > 1.0), 12.67% (APRI > 0.7), and 21.87% with APRI >0.5. Increasing metabolic co-morbidities was associated with higher odds of fibrosis. Compared to patients with no metabolic co-morbidities, odds of >F2 fibrosis was OR 2.61 (95% CI 2.57–2.65, p

PurposeTo investigate the relationship between corneal hysteresis (CH) and anterior lamina cribrosa surface (ALCS) displacement over time in a cohort of patients with glaucoma.DesignProspective observational case series.MethodsIn this study, 147 eyes from 96 glaucoma or glaucoma suspect patients were followed for a mean of 3.5 years and 7.9 visits. Baseline CH measurements were obtained using the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments Inc, Depew, New York, USA). The mean anterior lamina cribrosa surface depth (ALCSD) and choroidal thickness were by automated segmentation of spectral-domain optical coherence tomography (SD-OCT) scans. The rate of change of ALCSD was calculated using linear mixed effects models. Relationship between baseline CH and follow-up ALCSD rate of change was adjusted for confounding factors, including age, intraocular pressure (IOP), and choroidal thickness.ResultsThe mean baseline CH was 9.4mm Hg (95% confidence interval [CI] 9.1-9.7). Overall, the ALCS was displaced posteriorly at a rate of 0.78μm/y (95% CI-1.82, 0.26). Seventeen eyes (11.5%) showed a significant posterior displacement of ALCS, whereas 22 eyes (15.0%) showed a significant anterior displacement of ALCS. The choroidal thickness thinned at a rate of-1.09μm/y during the follow-up (P= .001). Multivariable mixed modeling showed that choroidal thinning, lower IOP change, and lower corneal hysteresis were significantly associated with posterior ALCS displacement over time (P= .034, P= .037, and P= .048). Each 1mm lower CH was associated with 0.66μm/y posterior displacement of the ALCS.ConclusionsLower corneal hysteresis was significantly associated with posterior displacement of the anterior lamina cribrosa over time. These data provide additional support for lower corneal hysteresis being a risk factor for glaucoma progression.