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Abstract Background This study explored the career development experiences of Korean medical educators who have forged their paths amid dynamic medical education landscapes. Additionally, it explored their career development process by introducing a protean career theoretical framework, that is, an individual-led career development theory. Methods This study employed Interpretative Phenomenological Analysis (IPA) to gather in-depth insights regarding the experiences of medical educators who have successfully built their careers in Korea. Semi-structured interviews were conducted with nine medical educators to investigate the significance of these experiences. The emerging themes were categorised based on the protean career theory during data analysis. Results The findings revealed that medical educators navigated their careers in line with the protean career development model, characterised by protean career orientation, process and outcomes. Their experiences in the medical education domain were aligned with eight factors of the protean career model – self-direction, intrinsic work values, awareness, adaptability, agency, subjective career success, objective career success and organisational commitment. Conclusion In the context of less structured career pathways and a rapidly evolving regional environment, medical educators have developed individual-driven careers with self-direction and intrinsic values, formed their identities and demonstrated flexibility and proactive strategies. Hence, the protean career model successfully explains the characteristics of self-directed career development for medical educators, while emphasising the need for organisational support.

Introduction: Proteinuria presents a challenging complication during systemic therapy for hepatocellular carcinoma (HCC). This study aims to identify risk factors for proteinuria in patients with HCC treated with atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic treatment. Methods: A retrospective analysis was conducted on 622 consecutive patients with unresectable HCC who received Atezo/Bev or LEN as first-line systemic treatment between October 2013 and October 2022. Cumulative incidence of proteinuria was estimated using Kaplan-Meier curves and compared using log-rank tests. Risk factors for proteinuria were identified using Cox proportional-hazard models, along with propensity score-matched and subgroup analyses. Results: Among 367 patients treated with Atezo/Bev and 255 with LEN, the cumulative incidence of proteinuria at 12 months was 27.5%. In the multivariable analysis, Atezo/Bev treatment (adjusted HR [aHR]: 1.57; 95% CI: 1.03–2.42), diabetes (aHR: 1.64; 95% CI: 1.03–2.61), hypertension (aHR: 2.27; 95% CI: 1.04–4.97), Child-Pugh class B (aHR: 3.43; 95% CI: 1.34–8.78), macrovascular invasion (MVI; aHR: 1.58; 95% CI: 1.04–2.38), and an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 (aHR: 3.21; 95% CI: 1.84–5.62) were identified as risk factors for proteinuria. A higher risk of proteinuria in Atezo/Bev patients compared with LEN was consistently observed in the PS-matched cohort, particularly pronounced in subgroups with MVI (HR: 2.84; 95% CI: 1.23–6.54) compared with those without MVI (HR: 1.31; 95% CI: 0.69–2.47). Conclusions: Patients treated with Atezo/Bev as first-line systemic treatment for HCC exhibited a higher risk of proteinuria compared with those with LEN, particularly when accompanied by MVI.

Backgrounds/Aims This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. Methods We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Results Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (P

Background/Aims: With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance. Methods: Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR. Results: The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Time-dependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC. Conclusions: aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

Background/Aims Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. Methods We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. Results The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (P=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. Conclusions Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.

Abstract The terrestrial ecosystem in East Asia mainly consists of semi-arid regions that are sensitive to climate change. Therefore, gross primary productivity (GPP) in East Asia could be highly variable and vulnerable to climate change, which can significantly affect the local carbon budget. Here, we examine the spatial and temporal characteristics of GPP variability in East Asia and its relationship with climate factors over the last three decades. We detect an abrupt decrease in GPP over Eastern China-Mongolia region around the year 2000. This is attributed to an abrupt decrease in precipitation associated with the phase shift of the Pacific decadal oscillation (PDO). We also evaluate the reproducibility of offline land surface models to simulate these abrupt changes. Of the twelve models, eight were able to simulate this abrupt response, while the others failed due to the combination of an exaggerated CO2 fertilization effect and an underrated climate impact. For accurate prediction, it is necessary to improve the sensitivity of the GPP to changes in CO2 concentrations and the climate system.

ABSTRACTPurpose. Lack of health care providers’ knowledge about the experience and needs of individuals with disabilities contribute to health care disparities experienced by people with disabilities. Using the Core Competencies on Disability for Health Care Education, this mixed methods study aimed to explore the extent the Core Competencies are addressed in medical education programs and the facilitators and barriers to expanding curricular integration. Method. Mixed-methods design with an online survey and individual qualitative interviews was used. An online survey was distributed to U.S. medical schools. Semi-structured qualitative interviews were conducted via Zoom with five key informants. Survey data were analyzed using descriptive statistics. Qualitative data were analyzed using thematic analysis. Results. Fourteen medical schools responded to the survey. Many schools reported addressing most of the Core Competencies. The extent of disability competency training varied across medical programs with the majority showing limited opportunities for in depth understanding of disability. Most schools had some, although limited, engagement with people with disabilities. Having faculty champions was the most frequent facilitator and lack of time in the curriculum was the most significant barrier to integrating more learning activities. Qualitative interviews provided more insight on the influence of the curricular structure and time and the importance of faculty champion and resources. Conclusions. Findings support the need for better integration of disability competency training woven throughout medical school curriculum to encourage in-depth understanding about disability. Formal inclusion of the Core Competencies into the Liaison Committee on Medical Education standards can help ensure that disability competency training does not rely on champions or resources.

Summary: Background: The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association between statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC. Methods: A nationwide cohort study was performed with data from the National Health Insurance Service Database in Korea. Among 65,101 HCC patients who underwent hepatic resection between January 2002 and December 2017, we included 21,470 patients. For validation, a hospital-based cohort of 3366 patients with very early or early-stage HCC who received curative-intent hepatic resection between January 2010 and December 2018 was analyzed. Recurrence-free survival (RFS) and overall survival (OS) was compared between statin users and non-users. Findings: Among the nationwide cohort of 21,470 patients, 2399 (11.2%) used statins and 19,071 (88.8%) did not. Among the hospital cohort of 3366 patients, 363 (10.8%) used statins and 3003 (89.2%) did not. In the propensity score-matched nationwide cohort, statin users had better RFS (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.56–0.64; P

Background/Aim The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. Methods A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. Results The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P

Multifunctional molecules might offer better treatment of complex multifactorial neurological diseases. Monoaminergic pathways dysregulation and neuroinflammation are common convergence points in diverse neurodegenerative and neuropsychiatric disorders. Aiming to target these diseases, polypharmacological agents modulating both monoaminergic pathways and neuroinflammatory were addressed. A library of analogues of the natural product hispidol was prepared and evaluated for inhibition of monoamine oxidases (MAOs) isoforms. Several molecules emerged as selective potential MAO B inhibitors. The most promising compounds were further evaluated in vitro for their impact on microglia viability, induced production of proinflammatory mediators and MAO-B inhibition mechanism. Amongst tested compounds, 1p was a safe potent competitive reversible MAO-B inhibitor and inhibitor of microglial production of neuroinflammatory mediators; NO and PGE2. In-silico study provided insights into molecular basis of the observed selective MAO B inhibition. This study presents compound 1p as a promising lead compound for management of neurodegenerative disease.

Background/Aims: The care cascade for hepatitis C virus (HCV) infection is impeded by multiple barriers, including suboptimal anti-HCV testing, link to care, and diagnosis. We explored the changes in the care cascade of HCV for the past 20 years and its current status in a large cohort from a tertiary referral center. Methods: We analyzed 1,144,468 patients who had anti-HCV testing between January 2001 and June 2020. Metrics related to the care cascade of HCV infection and the long-term prognosis of patients were explored. Results: The seroprevalence of anti-HCV positivity was 1.8%, with a recent decreasing trend. In all, 69.9% of anti-HCV positive patients performed HCV RNA testing, with a 65.7% positivity. Patients who did not have HCV RNA testing were older and more likely to have a non-hepatocellular carcinoma malignancy, normal alanine aminotransferase level, and good liver function. Linkage times for HCV RNA testing from the anti-HCV positivity and for antiviral treatment from HCV diagnosis decreased, notably after 2015, when highly efficacious oral antiviral treatment was introduced to Korea. The average treatment uptake rate was 35.4%, which increased to 38.9% after 2015. Of the 5,302 patients analyzed for long-term prognosis, the annual incidences of hepatocellular carcinoma were 1.02 or 2.14 per 100 person-years in patients with or without a sustained virological response, respectively. Conclusions: The care cascade of HCV infection has been suboptimal for the past 20 years, despite the recent changes. More effort should be made to increase HCV RNA testing and treatment uptake.

Background/Aim We aimed to investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) in elderly patients with small hepatocellular carcinomas (HCC). Methods Eighty-three patients (89 lesions) with HCC who underwent SBRT between January 2012 and December 2018 were reviewed in this retrospective observational study. The key inclusion criteria were as follows: 1) age ≥75 years, 2) contraindications for hepatic resection or percutaneous ablative therapies, 3) no macroscopic vascular invasion, and 4) no extrahepatic metastasis. Results The patients were 75-90 years of age, and 49 (59.0%) of them were male. Most patients (94.0%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Seventy-four patients (89.2%) had Child-Pugh class A hepatic function before SBRT. The median tumor size was 1.6 cm (range, 0.7-3.5). The overall median follow-up period was 34.8 months (range, 7.3-99.3). The 5-year local tumor control rate was 90.1%. The 3-year and 5-year overall survival rate was 57.1% and 40.7%, respectively. Acute toxicity grade ≥3 was observed in three patients (3.6%) with elevated serum hepatic enzymes; however, no patient experienced a worsening of the Child-Pugh score to ≥2 after SBRT. None of the patients developed late toxicity (grade ≥3). Conclusions SBRT is a safe treatment option with a high local control rate in elderly patients with small HCC who are not eligible for other curative treatments.

Abstract Selecting an optimal donor for living donor liver transplantation is crucial for the safety of both the donor and recipient, and hepatic steatosis is an important consideration. We aimed to build a prediction model with noninvasive variables to evaluate macrovesicular steatosis in potential donors by using various prediction models. The study population comprised potential living donors who had undergone donation workup, including percutaneous liver biopsy, in the Republic of Korea between 2016 and 2019. Meaningful macrovesicular hepatic steatosis was defined as >5%. Whole data were divided into training (70.5%) and test (29.5%) data sets based on the date of liver biopsy. Random forest, support vector machine, regularized discriminant analysis, mixture discriminant analysis, flexible discriminant analysis, and deep neural network machine learning methods as well as traditional logistic regression were employed. The mean patient age was 31.4 years, and 66.3% of the patients were men. Of the 1652 patients, 518 (31.4%) had >5% macrovesicular steatosis on the liver biopsy specimen. The logistic model had the best prediction power and prediction performances with an accuracy of 80.0% and 80.9% in the training and test data sets, respectively. A cut‐off value of 31.1% for the predicted risk of hepatic steatosis was selected with a sensitivity of 77.7% and specificity of 81.0%. We have provided our model on the website (https://hanseungbong.shinyapps.io/shiny_app_up/) under the name DONATION Model. Our algorithm to predict macrovesicular steatosis using routine parameters is beneficial for identifying optimal potential living donors by avoiding superfluous liver biopsy results.

Background/Aims The safety of direct oral anticoagulants (DOACs) compared with warfarin in patients with both nonvalvular atrial fibrillation (AF) and clinically confirmed liver cirrhosis (LC) has not been well studied. We compared the risk of a major bleeding event between DOAC and warfarin treatments in this patient population. Methods A total of 238 cirrhotic patients with AF were retrospectively analyzed. The major bleeding event risk was compared between DOAC- and warfarin-treated groups. The median follow-up duration was 5.6 years. Results Among the 238 study patients with LC and AF, 128 (53.8%) received DOACs and 110 (46.2%) received warfarin. The mean patient age was 68.8 years, and 78.2% were men. A major bleeding event occurred in 10 and 20 patients in the DOAC and warfarin groups, respectively, most commonly caused by gastrointestinal bleeding (70.0%). The cumulative risk of major bleeding did not differ between the groups by log-rank test (p = 0.12). This finding did not change when using 60 propensity score-matched pairs. A multivariable Cox regression model indicated that the concomitant use of antiplatelet agents (adjusted hazard ratio [aHR], 2.06; 95% confidence interval [CI], 1.00 to 4.30; p = 0.048) and presence of esophageal or gastric varices confirmed by endoscopic examination (aHR, 2.31; 95% CI, 1.03 to 5.17; p = 0.04) were associated with major bleeding in the entire cohort. Conclusions A major bleeding event risk is not increased by DOAC compared with warfarin treatment. Antiplatelet agent use and varices are independently associated with a higher risk of major bleeding during anticoagulation.

Abstract Background To evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE). Methods Patients treated with SBRT for single viable HCC after incomplete TACE between 2012 and 2017 at Asan Medical Center (Seoul, South Korea) were included. Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up dynamic computed tomography (CT) or magnetic resonance imaging following one or more consecutive TACEs, (2) no definite tumor staining on superselective hepatic angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or CT. Doses of 10–15 Gy per fraction were given over 3–4 consecutive days. The primary outcome was local control rate at 3 years and secondary outcome included tumor response, overall survival rate, out-of-field intrahepatic recurrence-free survival, distant metastasis-free survival and treatment-related toxicities. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03. Results A total of 302 patients were analyzed. The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6–41.7) and the median tumor size was 2.0 cm (range, 0.7–6.9). The local control (LC) and overall survival rates at 3 years were 91.2 and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9–4.7), and 39.9 and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field. Conclusion SBRT could be considered a feasible salvage treatment option for HCC after incomplete TACE.

This study aimed to explore provider observations of inequitable care delivery towards COVID-19 positive patients who are Black, Indigenous, and Other People of Color (BIPOC) and/or have disabilities and to identify ways the health workforce may be contributing to and compounding inequitable care. We conducted semi-structured interviews between April and November 2021 with frontline healthcare providers from Washington, Florida, Illinois, and New York. Using thematic analysis, major themes related to discriminatory treatment included decreased care, delayed care, and fewer options for care. Healthcare providers' bias and stigma, organizational bias, lack of resources, fear of transmission, and burnout were mentioned as drivers for discriminatory treatment. COVID-19 related health system policies such as visitor restrictions and telehealth follow-ups inadvertently resulted in discriminatory practices towards BIPOC patients and patients with disabilities. As patients experience lower quality healthcare during the pandemic, COVID-19-related restrictions and policies compounded existing inequitable care for these populations.

Situs inversus totalis (SIT) is a rare anatomical condition, where all the viscera appear in its reverse position. Although minimally invasive surgery has evolved to achieve totally laparoscopic gastrectomy for gastric cancer patients with SIT, it is difficult to perform lymphadenectomy in such a transposed anatomical condition. Recently, we performed a single-port laparoscopic total gastrectomy (SPTG) for gastric cancer in a patient with SIT. No postoperative complications or dietary problems were observed. Based on this experience, we are to design a safe strategy to perform D2 lymphadenectomy during SPTG in patients with SIT.

Abstract Background The incidence of hepatocellular carcinoma (HCC) has been increasing among the elderly populations. Trans-arterial chemoembolization (TACE), a widely used first-line non-curative therapy for HCCs is an issue in geriatrics. We investigated the prognosis of elderly HCC patients treated with TACE and determined the factors that affect the overall survival. Methods We included 266 patients who were older than 65 years and had received TACE as initial treatment for HCC. We analyzed the skeletal muscle index (SMI) and visceral-to-subcutaneous fat ratio (VSR) around the third lumbar vertebrae using computed tomography scans. Muscle depletion with visceral adiposity (MDVA) was defined by falling below the median SMI and above the median VSR value sex-specifically. We evaluated the overall survival in association with MDVA and other clinical factors. Results The mean age was 69.9 ± 4.5 years, and 70.3% of the patients were men. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, 29, 136, and 101 patients were classified as BCLC 0, A, and B stages, respectively, and 79 (29.7%) had MDVA. During the median follow-up of 4.1 years, patients with MDVA had a shorter life expectancy than those without MDVA (P = 0.007) even though MDVA group had a higher objective response rate after the first TACE (82.3% vs. 75.9%, P = 0.035). Multivariate analysis revealed that MDVA (Hazard ratio [HR] 1.515) age (HR 1.057), liver function (HR 1.078), tumor size (HR 1.083), serum albumin level (HR 0.523), platelet count (HR 0.996), tumor stage (stage A, HR 1.711; stage B, HR 2.003), and treatment response after the first TACE treatment (HR 0.680) were associated with overall survival. Conclusions MDVA is a critical prognostic factor for predicting survival in the elderly patients with HCC who have undergone TACE.

Abstract Background Oral health is essential for daily living and plays a pivotal role in overall health conditions and well-being. This study evaluated the impact of self-reported oral health on geriatric conditions, institutionalization, and mortality. Methods This study analyzed the population of the Aging Study of Pyeongchang Rural Area that had undergone geriatric assessments between 2016 and 2017. The oral health status of the participants was determined using three items from the General Oral Health Assessment Index, and the participants were classified into three groups according to the total sum of the scores as good (3), fair (4–7), or poor (8–15). The outcomes were the incidence of geriatric syndromes at 2 years and the composite outcome of mortality and institutionalization. Results Among the 1189 participants, 44.1 % were women, and the mean age of the study population was 75.0 years. Good, fair, and poor oral health were observed in 597 (50.2 %), 406 (34.1 %), and 186 (15.6 %) individuals, respectively. Worsening oral health status was associated with the incidences of various geriatric syndromes at follow-up, and these associations were attenuated after adjusting for baseline demographic and geriatric parameters. Similarly, the significant association between baseline oral health status and the incidence of the composite outcome was attenuated after adjusting for demographic and geriatric parameters. Conclusions Oral health affected the geriatric health conditions in this prospective, longitudinal cohort of community-dwelling older adults. The correlations and interactions of oral health status with other functional parameters may deserve consideration as a geriatric domain.

BackgroundAddressing issues of diversity, equity, and inclusion (DEI) has become central in implementing inclusive and socially responsible rehabilitation education and clinical practice. Yet, the constructs of disability and d/Deaf identity and culture, as well as ableism and allyship are often overlooked. Or, these concepts are approached using outdated philosophical perspectives that pathologize disability and fail to prioritize the lived experiences, expertise, intersectionality, and self-identified needs of people with disabilities. A Critical Disability Studies (CDS) framework may provide a background for better understanding and responding to these issues through allyship.PurposeThis study employed a CDS framework to understand the lived experiences of ableism and allyship from faculty, staff, and students on University of Washington (UW) campuses who identify as d/Deaf, disabled/with a disability, or as having a chronic health condition.MethodsDuring 2020–2021, we conducted in-depth, semi-structured interviews and focus groups with 22 diverse undergraduate and graduate students, faculty, and staff with disabilities, one third who also identified as people of color. Encounters were audio-recorded, transcribed verbatim, and coded using constant comparison until themes emerged.ResultsFour major themes that emerged from the data are: (1) Ever-present ableism in healthcare, (2) Ableism at the intersections, (3) COVID: Surfacing ableism and expanding access, and (4) Disability allyship and healthcare partnership building. Experiences of ableism and allyship were identified at individual, group/unit, and institutional/systemic levels, though participants reported significantly fewer instances of allyship compared to experiences of ableism. Participants identified intersections between disability and other marginalized identities and juxtaposed the benefits of widespread adoption of many access-increasing practices and technologies due to the COVID-19 pandemic, while also highlighting ways in which the pandemic created new obstacles to inclusion.ConclusionsThis analysis provides insights into ways of implementing inclusive practices in rehabilitation education, practice, and beyond. Rehabilitation students, faculty, and staff may not be aware of how ableism affects their disabled peers or underpins their professional education. It is important to cultivate opportunities within professional education and clinical training to explicitly address our collective role in creating inclusive and accessible academic and healthcare experiences for our diverse community post COVID-19. Drawing on a CDS framework, the research team devised the mnemonic TRAC, which includes Training, Recognition and Representation, Attendance and Action, and Calling to account as strategic guidelines for operationalizing such opportunities.

Abstract Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although many substances have been suggested to improve the rate of embryo implantation targeting enhancement of endometrial receptivity, currently there rarely are effective evidence-based treatments to prevent or cure this condition. Here we strongly suggest minimally-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention. Chemokine CXCL12 derived from pre- and peri-implanting embryos significantly enhances the rates of embryo attachment and promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in C57BL/6 mice improved endometrial receptivity showing increased integrin β3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Thus, our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a minimally-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells’ death and also lowers monoamine neurotransmitter levels. In addition, acetylcholinesterase activity and neuroinflammation are involved in neurodegenerative diseases. Herein, we aim to achieve a multifunctional agent that inhibits the oxidative catabolism of monoamine neurotransmitters and, hence, the detrimental production of ROS while enhancing neurotransmitter levels. Such a multifunctional agent might also inhibit acetylcholinesterase and neuroinflammation. To meet this end goal, a series of aminoalkyl derivatives of analogs of the natural product hispidol were designed, synthesized, and evaluated against both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Promising MAO inhibitors were further checked for the inhibition of acetylcholinesterase and neuroinflammation. Among them, compounds 3aa and 3bc were identified as potential multifunctional molecules eliciting submicromolar selective MAO-B inhibition, low-micromolar AChE inhibition, and the inhibition of microglial PGE2 production. An evaluation of their effects on memory and cognitive impairments using a passive avoidance test confirmed the in vivo activity of compound 3bc, which showed comparable activity to donepezil. In silico molecular docking provided insights into the MAO and acetylcholinesterase inhibitory activities of compounds 3aa and 3bc. These findings suggest compound 3bc as a potential lead for the further development of agents against neurodegenerative diseases.

Abstract Background Despite constipation being a common clinical condition in older adults, the clinical relevance of constipation related to frailty is less studied. Hence, we aimed to investigate the association between chronic constipation (CC) and frailty in older adults. Methods This is a cross-sectional analysis of a population-based, prospective cohort study of 1278 community-dwelling older adults in South Korea. We used the Rome criteria to identify patients with irritable bowel syndrome with predominant constipation (IBS-C) and functional constipation (FC). We investigated whether participants consistent with the criteria for IBS-C and FC had CC. Frailty was assessed using the Cardiovascular Health Study (CHS) frailty phenotype. Results In the study population with a mean age of 75.3 ± 6.3 years, 136 (10.7%) had CC. The participants with CC were older, had higher medication burdens, and had worse physical performances compared to those without CC (All P

Introduction: Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear. Methods: This multinational, multicenter, and retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab between July 2016 and April 2019. Results: Among 71 patients treated with atezolizumab-bevacizumab, a total of 49 patients who received subsequent systemic therapy were included in this analysis; the median age was 60 years (range, 37–80) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (n = 29), lenvatinib (n = 19), and cabozantinib (n = 1), were used as second-line therapy for all patients. The objective response rate and disease control rate were 6.1 and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.8–4.9) and 14.7 months (95% CI 8.1–21.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 vs. 2.5 months; p = 0.004), although there was no significant difference in median OS (16.6 vs. 11.2 months; p = 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (n = 26, 53.1%), fatigue (n = 14, 28.6%), hypertension (n = 14, 28.6%), and diarrhea (n = 12, 24.5%). Conclusion: Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.

Background: Cabozantinib, a multiple kinase inhibitor, was recently approved for patients with previously treated unresectable hepatocellular carcinoma (uHCC). We investigated the real-world safety and efficacy profiles of cabozantinib. Methods: This multicenter retrospective study included 110 patients with uHCC who received cabozantinib after progression on other systemic treatments between October 2019 and May 2021. Results: The median age was 58 (range, 20–77) years, and 98 (89.1%) were male. Prior to cabozantinib, all patients were treated with other systemic therapies: sorafenib ( n = 104, 94.5%) and regorafenib ( n = 91, 82.7%) were the most commonly used agents. Immune checkpoint inhibitors were previously used in 93 patients (84.5%). Cabozantinib was used beyond the third-line of therapy in most patients ( n = 90, 81.8%). With a median follow-up duration of 11.9 months [95% confidence interval (CI), 10.8–17.2], the median progression-free survival (PFS) was 3.7 months (95% CI, 3.1–4.9), and the median overall survival (OS) was 7.5 months (95% CI, 5.5–9.5). The disease control rate and overall response rate (ORR) were 66.3% and 3.6%, respectively. In the Child–Pugh A cohort ( n = 88), the ORR was 4.5%, and the median PFS and OS were 4.3 months (95% CI, 3.6–5.8) and 9.0 months (95% CI, 7.5–11.7), respectively. Conclusion: Cabozantinib showed consistent efficacy outcomes with a prior phase III trial, although in this study, it was used as later-line therapy for patients who were refractory to multiple systemic treatments, including immune checkpoint inhibitors.

Background/Aims Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs. Methods A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria. Results Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events. Conclusions SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.

Regorafenib and nivolumab are drugs approved for second‐line treatment of patients with hepatocellular carcinoma (HCC) after sorafenib failure. However, the effectiveness of regorafenib and nivolumab following sorafenib has not been directly compared. This study retrospectively evaluated 373 patients with HCC who were treated with regorafenib (n = 223) or nivolumab (n = 150) after sorafenib failure between July 2017 and February 2019. Progression‐free survival (PFS; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69‐1.06; P = 0.150), time to progression (TTP; HR, 0.95; 95% CI, 0.77‐1.19; P = 0.680), and overall survival (OS; HR, 0.83; 95% CI, 0.64‐1.07; P = 0.154) did not differ significantly between groups of patients treated with regorafenib and nivolumab, findings consistently observed by multivariable‐adjusted, propensity score‐matched, and inverse probability treatment weighting (IPTW) analyses. However, the objective response rate was significantly higher in the nivolumab than in the regorafenib group (13.3% vs. 4.0%; P = 0.002). When the effectiveness of regorafenib and nivolumab was compared in nonprogressors to treatment, defined as patients who achieved complete response, partial response, or stable disease after first response evaluation, PFS (HR, 0.50; 95% CI, 0.33‐0.75; P = 0.001), TTP (HR, 0.48; 95% CI, 0.31‐0.73; P

Introduction: We evaluated the radiologic response rate of combined transarterial chemoembolization (TACE) plus radiotherapy (RT) in treatment-naïve patients with liver-confined hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI) and analyzed its clinical importance in overall survival (OS) outcomes. Methods: Patients who were treated with TACE plus RT as a first-line treatment for HCC with MVI between January 2010 and December 2015 were retrospectively reviewed. Radiologic response was assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 2- and 4-months after completion of RT. Landmark analysis at 2- and 4-months and time-dependent Cox regression analysis using response as a time-dependent covariate were performed for univariable and multivariable analyses. Results: The 2-month landmark analysis included 427 patients, and the 4-month landmark analysis included 355 patients after excluding patients without imaging studies for response evaluation at 4 months. Radiologic responses were observed in 210 (49.2%) patients at 2 months and 181 (51.8%) at 4 months. In multivariable analyses, radiologic response was identified as an independent prognosticator for OS at 2 months (median OS: responders, 23.1 months vs. non-responders, 8.0 months; hazard ratio [HR], 3.194; P < 0.001) and 4 months (median OS: responders, 26.5 months vs. non-responders, 9.3 months; HR, 4.534; P < 0.001). Conclusion: Radiologic response assessed by mRECIST was a significant prognostic factor for OS in patients with advanced-stage HCC showing MVI treated with combined TACE plus RT.

Long-term application of soil organic amendments (SOA) can improve the formation of soil organic carbon (SOC) pool as well as soil fertility and health of paddy lands. However, the effects of SOA may vary with the input amount and its characteristics. In this work, a descriptive field research was conducted during one cropping season to investigate the responses of various SOC fractions to different long-term fertilization practices in rice fields and their relationships with soil biogeochemical properties and the emission of greenhouse gases (GHG). The field sites included two conventional paddies applied with chemical fertilizer (CF) or CF + rice straw (RS) and six organic agriculture paddies applied with oilseed cake manure (OCM) + wheat straw (WS), cow manure (CM) + WS, or CM + RS. The two paddy soils treated with CM + RS had significantly higher concentrations of recalcitrant to labile C forms, such as loss-on-ignition C (LOIC; 56–73 g kg−1), Walkley–Black C (WBC; 20–25 g kg−1), permanganate oxidizable C (POXC; 835–853 mg kg−1), and microbial biomass carbon (MBC; 133–141 mg kg−1), than soils treated with other SOA. Likewise, long-term application of CM + RS seemed to be the best for regulating soil fertility parameters, such as ammonium (11–141 mg kg−1); phosphate (61–106 mg kg−1); and soluble Ca, K, and Mg (7–10, 0.5–1.2, and 1.9–3.8 mg kg−1, respectively), although the results varied with the location and soil properties of rice fields. Additionally, the two paddy sites had the largest cumulative methane emission (754–762 kg ha−1), seemingly attributed to increased microbial biomass and labile C fractions. The significant correlations of most SOC fractions with soil microbial biomass, trophic factors, and methane emissions were confirmed with multivariate data analysis. It was also possible to infer that long-term SOA application, especially with CM + RS, enhanced interaction in belowground paddy fields, contributing to soil fertility and rice production sustainability. Based on our findings, we suggest the need for analysis of various types of SOC fractions to efficiently manage soil fertility and quality of paddy fields, C sequestration, and GHG emissions.

BACKGROUND & AIM:In clinical practice, transarterial chemoembolization (TACE) has been widely used for the treatment of hepatocellular carcinoma (HCC) beyond as well as within guideline recommendations. Here we aimed to verify whether two consecutive non-responses could be an optimal criterion for creating a rule to stop TACE being performed on these patients. METHODS:This study evaluated 200 patients with HCC beyond the Milan criteria, initially treated with TACE. TACE response was determined using the mRECIST criteria via dynamic CT or MRI. Median follow-up duration was 23.9 months. RESULTS:Within the 200 patients analyzed, 183 (91.5%) were male, with a total median age of 59.8 years. The mean size of the largest tumor was 6.8 cm, with 80 (40.0%) patients with ≥4 tumors. After the first TACE procedure, complete response, partial response, stable disease, or progressive disease were observed in 48 (24.0%), 87 (43.5%), 59 (29.5%) and 6 (3.0%) of patients, respectively. 45 (22.5%) patients showed no objective response (OR) following two consecutive TACE sessions. Of these, 28 received a subsequent TACE, with a 10.7% OR rate. Patients without OR showed poorer survival when compared to patients who achieved OR after repeated TACE. Multivariable analysis showed that size of the largest tumor >5cm and high alpha-fetoprotein of >200 ng/mL were significant factors associated with failure of OR to two consecutive TACE sessions. CONCLUSION:Patients showing no OR to two consecutive TACE sessions will present a poor OR to subsequent TACE procedures. Early transition to systemic therapy may be advocated in such cases.

Background & aimHepatic resection is a treatment option for patients with hepatocellular carcinoma (HCC). However, factors associated with candidacy for resection and predictive of liver-related morbidity after resection for HCC remain unclear. This study aimed to assess candidacy for liver resection in patients with HCC and to design a model predictive of liver-related morbidity after resection.MethodsA retrospective analysis of 1,565 patients who underwent liver resection for HCC between January 2016 and December 2017 was performed. The primary outcome was liver-related morbidity, including post-hepatectomy biochemical dysfunction (PHBD), ascites, hepatic encephalopathy, rescue liver transplantation, and death from any cause within 90 days. PHBD was defined as international normalized ratio (INR) > 1.5 or hyperbilirubinemia (> 2.9 mg/dL) on postoperative day ≥ 5.ResultsThe 1,565 patients included 1,258 (80.4%) males and 307 (19.6%) females with a mean age of 58.3 years. Of these patients, 646 (41.3%) and 919 (58.7%) patients underwent major and minor liver resection, respectively. Liver-related morbidity was observed in 133 (8.5%) patients, including 77 and 56 patients who underwent major and minor resection, respectively. A total of 83 (5.3%) patients developed PHBD. Multivariate analysis identified cut-off values of the platelet count, serum albumin concentration, and ICG R15 value for predicting liver-related morbidity after resection. A model predicting postoperative liver-related morbidity was developed, which included seven factors: male sex, age ≥ 55 years, ICG R15 value ≥ 15%, major resection, platelet count < 150,000/mm3, serum albumin concentration < 3.5 g/dL, and INR > 1.1.ConclusionHepatic resection for HCC was safe with 90-day liver-related morbidity and mortality rates of 8.5% and 0.8%, respectively. The developed point-based scoring system with seven factors could allow the prediction of the risk of liver-related morbidity after resection for HCC.

Background: Only few surgeons have tried to perform laparoscopic combined resection for T4b gastric cancer. The purpose of this study was to investigate the feasibility of laparoscopic combined resection through a comparison of the clinical outcomes between cT4a and cT4b cases.Methods: We reviewed the medical charts of patients who underwent laparoscopic gastrectomy for clinically T4 gastric cancer from May 2014 and July 2018. During this period, 62 patients with serosa-positive gastric cancer underwent laparoscopic curative surgery. The patients were divided into the following groups: patients who underwent gastrectomy and combined resection for the invaded organs (combined resection group) and those who did not undergo combined organ surgery (gastrectomy only group). Clinical outcomes were compared between the gastrectomy only and combined resection groups.Results: Of 62 patients included in this study, 43 and 19 patients were included in the gastrectomy only and combined resection groups, respectively. The operation time was significantly longer in the combined resection group (364.6 ± 102.5 vs. 247.7 ± 66.1 min; p < 0.001). The incidence of grade ≥ III complications was comparable between the groups (26.3% vs. 11.6%; p = 0.147). The time from the first operation to the initiation of adjuvant chemotherapy showed no statistically significant difference between the groups (48.1 ± 45.4 days vs. 31.6 ± 9.2; p = 0.134).Conclusions: Focusing on the high quality of image and new devices of laparoscopic surgery, it is necessary to re-evaluate the oncologic outcomes of combined resection for T4b gastric cancer.

Liver cancer: The search for an early-stage indicator A protein that is highly expressed in cancer with extensive blood vessel development may provide a potential biomarker for early-stage liver cancer. Liver cancer is often not diagnosed until it is advanced and is also hard to be cured despite of advances in treatment, meaning patients often die from the disease. No tools for early detection or prognosis prediction exist, and scientists are keen to find useful biomarker molecules. Young-Hwa Chung at the University of Ulsan College of Medicine, Asan Medical Center, Seoul, and co-workers in South Korea reviewed recent research into one possible cancer-related protein, arrest-defective 1 (ARD1), known to be highly expressed in certain cancers and possibly associated with poor prognosis. While ARD1 appears to regulate pathways critical to cancer progression and promote cancer cell invasiveness, further in-depth investigations are needed to clarify its specific role in liver cancer.

Background/Aims Portal vein invasion (PVI) is a poor prognostic factor in patients with hepatocellular carcinoma (HCC). We intended to compare the effects of surgical resection and transarterial chemoembolization (TACE) with additional radiation therapy (RT) in HCC patients with PVI. Methods The subjects comprised 43 patients who underwent surgical resection for HCC with PVI without previous treatment and another 43 patients who received TACE followed by RT (TACE+RT) as initial treatment who were matched for Child-Pugh class, tumor size, and extent of PVI. Disease progression and death after the treatment were examined, and progression-free survival (PFS) and overall survival (OS) were compared between groups. Predisposing factors affecting OS were analyzed using univariate and multivariate analyses in HCC patients with PVI. Results The subjects (Age [51, 24-74; median, range], Sex [81/13; male/female], Etiology [78/1/15; hepatitis B virus {HBV}/ hepatitis C virus {HCV}/non-HBV and non-HCV]) were followed for a median of 17 (2-68) months. There were no differences in clinical or tumor characteristics between the resection and TACE+RT groups. The cumulative PFS was not significantly different between groups. The median PFS was 5.6 and 4.0 months in the resection and TACE+RT groups, respectively. However, the cumulative OS was significantly longer in patients treated with resection than in those treated with TACE+RT (P=0.04). The median OS was 26.9 and 14.2 months in the resection and TACE+RT groups, respectively. Univariate and multivariate analyses revealed that surgical resection was an independent predictive factor for better survival outcome. Conclusions Surgical resection might be an effective treatment in HCC patients with PVI.

Liver fibrosis: Reversing the damage A scaffolding protein that modulates cell signaling pathways contributes to reverse liver scarring. Liver fibrosis is caused by a build-up of scar tissue that interferes with liver function. However, the damage is reversed when the cause of injury is removed. Kyu-Won Kim at Seoul National University, South Korea, and colleagues examined the levels of A-Kinase Anchoring Protein 12 (AKAP12), a scaffolding protein that regulates the subcellular location of signaling proteins, in mouse and human livers. Levels of AKAP12 were reduced in fibrotic livers but restored when fibrosis was reversed. Mice lacking AKAP12 were unable to effectively repair the damage caused by fibrosis. Genetic analyses suggest that AKAP12 stimulates signaling through the adenosine 3′,5′-cyclic monophosphate (cAMP) pathway, which can inhibit fibrosis. These findings highlight a key role for AKAP12 in accelerating liver recovery.

Background/Aims Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion. Methods A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. Results The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps

Jejunal variceal bleeding is less common compared with esophagogastric varices in patients with portal hypertension. However, jejunal variceal bleeding can be fatal without treatment. Treatments include surgery, transjugular intrahepatic porto-systemic shunt (TIPS), endoscopic sclerotherapy, percutaneous coil embolization, and balloon-occluded retrograde transvenous obliteration (BRTO). Percutaneous coil embolization can be considered as an alternative treatment option for those where endoscopic sclerotherapy, surgery, TIPS or BRTO are not possible. Complications of percutaneous coil embolization have been reported, including coil migration. Herein, we report a case of migration of the coil into the jejunal lumen after percutaneous coil embolization for jejunal variceal bleeding. The migrated coil was successfully removed using surgery.

Endoscopic variceal ligation is the preferred endoscopic treatment method for esophageal variceal bleeding. The incidence of complications such as chest pain, bleeding, stricture formation, and aspiration pneumonia is low. We report a case wherein a malfunctioning multiple-band ligator could have potentially caused damage to the esophageal varices and massive bleeding. The equipment was safely removed using scissors and forceps. To the best of our knowledge, this is the first published report detailing the management of a case of esophageal variceal bleeding.

Prior epidemiological evidences suggest that hepatitis B virus (HBV) infection is linked to cancers other than hepatocellular carcinoma. This prospective hospital registry-based case-control study aimed to investigate the sero-epidemiological association between chronic HBV infection and various types of cancer.95,034 patients with first-diagnosed non-hepatocellular malignancy in a tertiary hospital between 2007 and 2014; and 118,891 non-cancer individuals as controls from a health promotion center were included. Cases and controls were compared for HBV surface antigen (HBsAg) positivity by conditional regression with adjustment for age, hypertension, diabetes, body mass index, alcohol consumption, smoking status and cholesterol level in both genders.An analysis of matched data indicated significant associations of HBV infection with lymphoma (adjusted odds ratio[AOR] 1.53 [95% CI 1.12-2.09] in men and 3.04 [1.92-4.82] in women) and biliary cancer (2.59[1.98-3.39] in men and 1.71[1.16-2.51] in women). Cervical (1.49[1.11-2.00]), uterine (1.69[1.09-2.61]), breast (1.16[1.02-1.32]), thyroid (1.49[1.28-1.74]), and lung cancers (1.79[1.32-2.44]) in women; and skin cancer (5.33[1.55-18.30]) in men were also significantly related to HBV infection.Chronic HBV infection is associated with several malignant disorders including lymphoma, and biliary, cervical, uterine, breast, thyroid, lung, and skin cancers. Our findings may offer additional insights into the development of these neoplasms and may suggest the need to consider HBV screening in cancer patients and cancer surveillance in HBV-infected subjects.

BACKGROUND:Combined hepatocellular-cholangiocarcinoma (cHCC-CC) can present as a hypervascular or peripherally enhancing tumor in dynamic imaging. We evaluated the effect of transarterial chemoembolization (TACE) on prognosis according to post-operative recurrence imaging patterns. METHODS:We retrospectively analyzed 42 cHCC-CC and 59 hepatocellular carcinoma (HCC-control) patients at the Asan Medical Center. We classified recurrent cHCC-CC according to enhancement pattern (globally enhancing: GE cHCC-CC, peripherally enhancing: PE cHCC-CC) and evaluated tumor response, time-to-local progression (TTPlocal), and overall survival (OS). RESULTS:The GE cHCC-CC group had a significantly higher best objective response rate (complete remission + partial response) than the PE cHCC-CC group (36% vs 0%, P = 0.005), and it was comparable to that of the HCC-control group (35.6%, P = 0.97). TTPlocal in the GE cHCC-CC group was significantly shorter than in the HCC-control group (6.6 vs 27.1 months, P < 0.001), and was not significantly different from that in the PE cHCC-CC group (5.3 months, P = 0.12). OS was 12.4 months, 52.8 months, and 67.5 months in the PE cHCC-CC, GE cHCC-CC, and HCC-control groups, respectively (Ps < 0.05). The adjusted hazard ratios (HRs) for TTPlocal and OS revealed an independent association with enhancement pattern of recurrent cHCC-CC (TTPlocal: HR 2.46; 95% CI 1.10-5.46; P = 0.03; OS: HR 5.97; 95% CI 2.38-14.96; P < 0.001). CONCLUSIONS:The GE cHCC-CC group showed better response and prognosis after TACE than the PE cHCC-CC group, but poorer response and prognosis than the HCC-control group. Enhancement patterns at recurrence were crucially associated with tumor response and overall survival.

Current revisions to the accreditation standards for occupational therapy (OT) education include proposed changes to experiential learning. The AOTA Fieldwork/Experiential Learning Ad Hoc Committee recommends that fieldwork Level I experiences be replaced with a new model of experiential education that includes the use of standardized patients and simulation (AOTA, 2017). The purpose of this article is to present critical perspectives about standardized patient simulation and disability simulation to support informed decision-making about the integration of experiential learning in OT professional education. In standardized patient simulation, actors play the roles of clients and important others in therapeutic scenarios; in disability simulation, students act out impairments in a variety of settings. While these forms of simulation are commonly used within OT education, they are critiqued for failing to present participants with authentic lived experiences of disability. This paper presents alternative approaches that would more fully align the OT curriculum with perspectives and priorities of intersectional disability communities. Recommendations to be considered by educators and educational programs include becoming familiar with relevant literature across fields and communities; developing long-term partnerships with disability organizations and community members; involving people with disabilities in the development, implementation, and evaluation of experiential learning opportunities; and providing experiential learning opportunities that take place outside educational and clinical settings and that attend to multiple intersecting dimensions of people with disabilities’ lived experiences. Together, these recommendations can help ensure that students have access to evidence-based educational approaches and best practices that accurately reflect the self-identified needs, concerns, and priorities of intersectional disability communities.

Background/AimsThere are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients.MethodsThis was a retrospective cohort study of 156 patients with chronic hepatitis C virus (HCV) infection who received combination treatment of PEG-IFN plus RBV. Blood samples from these patients were analyzed to identify the IL28B SNPs at rs12979860, rs12980275, rs8099917, and rs8103142. Association analyses were performed to evaluate the relationships between each IL28B SNP and SVRs.ResultsSeventy six patients with HCV genotype 1 and 80 with genotype non-1 were enrolled. The frequencies of rs12979860 CC and CT genotypes were 90.4% and 9.6%, respectively; those of rs12980275 AA and AG genotypes were 87.2% and 12.8%, respectively; those of rs8099917 TT and TG genotypes were 92.3% and 7.7%, respectively; and those of rs8103142 TT and CT genotypes were 90.4% and 9.6%, respectively. Among the patients with HCV genotype 1, the SVR rates were 69.7% and 80.0% for rs12979860 CC and CT, respectively (P=0.71). Among the HCV genotype non-1 patients, SVR rates were 88.0% and 100% for rs12979860 CC and CT (P=1.00), respectively.ConclusionsGenotypes of the IL28B SNP that are known to be favorable were present in most of the Korean patients with chronic hepatitis C in this study. Moreover, the IL28B SNP did not influence the SVR rate in either the HCV genotype 1 or non-1 patients. Therefore, IL28B SNP analysis might be not useful for the initial assessment, prediction of treatment outcomes, or treatment decision-making of Korean chronic hepatitis C patients.

Background/AimsThe role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients.MethodsThe expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored.ResultsThe interleukin-1-β-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues.ConclusionsThe prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.