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Owing to the increasing worldwide burden of liver diseases, the crucial need for safe and effective interventions for treating end-stage liver failure has been a very productive line of inquiry in the discipline of hepatology for many years. Liver transplantation is recognized as the most effective treatment for end-stage liver disease; however, the shortage of donor organs, high medical costs, and lifelong use of immunosuppressive agents represent major drawbacks and demand exploration for alternative treatments. Stem cell-based therapies have been widely studied in the field of liver diseases and are considered to be among the most promising therapies. Herein, we review recent advances in the application of stem cell-related therapies in liver disease with the aim of providing readers with relevant knowledge in this field and inspiration to spur further inquiry.

PURPOSE: Quality payment programs aim to adjust payments on the basis of quality and cost; however, few quality metrics exist in radiation oncology. This study evaluates and predicts the top spenders (TS) after radiation therapy (RT). MATERIALS AND METHODS: Patient characteristics, cancer details, treatments, toxicity, and survival data were collected for patients treated with RT at Mayo Clinic from 2007 to 2016. Standardized costs were obtained and adjusted for inflation. TSs were identified as those with greater than 93rd percentile costs (≥ $120,812). Prediction models were developed to predict TSs using training and validation sets using information available at consultation, after RT, and at last follow-up. RESULTS: A total of 15,131 patients were included and 1,065 TSs identified. Mean cost overall was $55,290 (median, $39,996) for all patients. Prediction models 1, 2, and 3 had concordance statistics of 0.83 to 0.83, 0.85 to 0.85, and 0.87 to 0.88, respectively in training and validation, indicating excellent prediction of TSs. Factors that were most predictive of TSs included stage N/A and stage 4 ( v stage 0; odds ratio [OR], 18.23 and 8.44, respectively; P < .001); hematologic, upper GI, skin and lung cancers ( v breast; OR, 11.45, 7.69, 3.81, and 2.43, respectively; P < .01); immunotherapy, surgery, and chemotherapy use (OR, 4.36, 2.51, and 1.61, respectively; P < .01); hospitalizations within 90 days of RT (OR, 2.26; P < .01); or death during the episode (OR, 1.56; P < .01). CONCLUSION: This is the first study of its kind to predict with high accuracy the highest spenders in radiation oncology. These patients may benefit from pre-emptive management to mitigate costs, or may require exclusion or adjustment from quality payment programs.

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background This repeated cross-sectional survey study was conducted to determine the prevalence of, and factors associated with, burnout, distress, and depression among anesthesiology residents and first-year graduates. We hypothesized that heavy workload and student debt burden were associated with a higher risk of physician burnout, distress, and depression, and that perception of having adequate workplace resources, work–life balance, and social support were associated with a lower risk. Methods Physicians beginning U.S. anesthesiology residency between 2013 and 2016 were invited to take online surveys annually from their clinical anesthesia year 1 to 1 yr after residency graduation. The Maslach Burnout Inventory, the Physician Well-Being Index, and the Harvard Department of Psychiatry/National Depression Screening Day Scale were used to measure burnout, distress, and depression, respectively. Logistic regression analyses were conducted to examine whether self-reported demographics, personal, and professional factors were associated with the risk of burnout, distress, and depression. Results The response rate was 36% (5,295 of 14,529). The prevalence of burnout, distress, and depression was 51% (2,531 of 4,966), 32% (1,575 of 4,941), and 12% (565 of 4,840), respectively. Factors associated with a lower risk of all three outcomes included respondents’ perceived workplace resource availability, (odds ratio = 0.51 [95% CI, 0.45 to 0.57] for burnout; 0.51 [95% CI, 0.45 to 0.56] for distress; 0.52 [95% CI, 0.45 to 0.60] for depression) and perceived ability to maintain work–life balance (0.61 [95% CI, 0.56 to 0.67] for burnout; 0.50 [95% CI, 0.46 to 0.55] for distress; 0.58 [95% CI, 0.51 to 0.65] for depression). A greater number of hours worked per week and a higher amount of student debt were associated with a higher risk of distress and depression, but not burnout. Conclusions Burnout, distress, and depression are notable among anesthesiology residents. Perceived institutional support, work–life balance, strength of social support, workload, and student debt impact physician well-being.

This study compared anesthesiology residency graduates’ written certification examination performance before and after the American Board of Anesthesiology (ABA) introduced the staged examination system. After equating test scores using common test items, the first 2 cohorts (2013, 2014) in the staged system scored 7.1 points and 8.3 points higher than the 2011 baseline cohort in the former examination system. The 2013 and 2014 cohorts’ pass rates (94.2% and 95.9%) were also higher than the 2011 and 2012 cohorts (91.9% and 92.6%) if a common standard had been applied. The staged examination system may be associated with improved knowledge of anesthesiology graduates.

SummaryWe aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea–hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/− periodic limb movements during sleep (5 ≤ apnea–hypopnea index < 30 events per hr), − obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, − obstructive sleep apnea/− periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time‐ and frequency‐domain heart rate variability measures were calculated over 5‐min periods of stable stage 2 non‐rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea–hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea–hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea–hypopnea index and low periodic limb movement index, and compared with those with low apnea–hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea–hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.

Abstract We report a 73-year-old man with Val142Ile transthyretin (TTR) amyloidosis and an atypical clinical presentation of upper-extremity–predominant neuropathy without significant autonomic or cardiac involvement. TTR familial amyloid polyneuropathy commonly presents as length-dependent sensorimotor polyneuropathy with marked and early autonomic involvement. Multiple pathogenic mutations in TTR gene have been identified, of which Val50Met is commonly associated with TTR familial amyloid polyneuropathy, and Val142Ile is commonly associated with familial amyloid cardiomyopathy. Our patient is from a nonendemic region, without family history for amyloidosis. Predominant upper-extremity neuropathy, without significant cardiac or autonomic involvement, distinguishes this case from previously reported Val142Ile-mutated TTR amyloidosis.

BackgroundInducible co-stimulator (ICOS) is a CD28-related molecule exclusively expressed on activated T cells and plays a critical role in modulating the immune response in breast cancer. The blockage of ICOS pathway has been shown to inhibit the activity of Type 2 T helper cells, thus potentially protecting against cancer growth. The current study aims to investigate the correlation between inducible co-stimulator ligand (ICOSL) expression in tumor tissues and the prognoses of patients with invasive breast cancer.MethodsTumor samples from 562 Chinese patients with invasive breast carcinomas were collected between 2003 and 2010. The expression of ICOSL on breast tumor and adjacent non-cancerous tissue was determined via immunohistochemistry. The overall survival (OS) of patients with positive and negative ICOSL expression were described using Kaplan–Meier curves, respectively. Parametric correlation method was used to analyze the correlation between ICOSL expression and other clinicopathological parameters. ICOSL was selected as a dependent variable for multivariate analysis.ResultsPositive ICOSL expression was identified on the plasma membrane in both cytoplasm and the nucleus of breast cancer cells. Membrane-expressed ICOSL is determined as an independent prognostic factor for OS in breast cancer but without significantly correlating with other clinicopathologic parameters such as age, menopausal status, depth of invasion, lymph node metastasis status, histologic classification, etc.ConclusionOur study suggests that the up-regulated expression of ICOSL protein in breast tumor cells can be associated with poor prognoses in invasive breast carcinomas.

Background and objectives To evaluate the growth pattern of kidney cyst number and cyst volume in association with kidney size, demographics, and genotypes in autosomal dominant polycystic kidney disease. Design, setting, participants, & measurements Kidney cyst number and cyst volume were measured from serial magnetic resonance images, giving a maximum follow-up of 14.23 years, from 241 patients with autosomal dominant polycystic kidney disease (15–46 years old at baseline). The growth pattern was analyzed, in association with sex, age, height-adjusted total kidney volume, and genotype, using linear mixed models of repeated measurements and tests of interactions with age (as a time-dependent covariate) to assess rates of change over time. Models were also fit using Irazabal class. Genotypic groups were characterized as either ( 1 ) PKD1 truncating, PKD1 nontruncating, and PKD2 plus patients with no mutation detected; or ( 2 ) in combination with PKD1 mutation strength groups. Results Imaging and genetic data were collected (at least one visit) for 236 participants. The mean height-adjusted total cyst number increased exponentially over time from a baseline value of 762 to 1715 at the last clinic visit, while the mean height-adjusted total cyst volume increased exponentially from 305 to 770 ml. Height-adjusted total kidney volume, height-adjusted total cyst number, and height-adjusted total cyst volume were all highly correlated over time. Female participants and participants with larger height-adjusted total kidney volume at baseline showed smaller rates of change in the log of height-adjusted total cyst number and cyst volume. PKD1 was associated with significant increases in both cyst number and volume at a given age, but genotype did not significantly affect the rate of growth. Conclusions Both height-adjusted total cyst number and height-adjusted total cyst volume increased exponentially and more than doubled over 14.23 years of follow-up. Compared with PKD2 plus no mutation detected, PKD1 was associated with a greater cyst number and volume at a given age, but no significant difference in the rate of growth.