Low cytoplasmic casein kinase 1 epsilon expression predicts poor prognosis in patients with hepatocellular carcinoma.

Casein kinase 1 epsilon (CK1ε) is a member of the casein kinase 1 (CK1) family, which comprises highly conserved and ubiquitous serine/threonine protein kinases. Recent studies have demonstrated that CK1ε plays a role in human cancers; however, the role of CK1ε in hepatocellular carcinoma (HCC) remains unclear. The study used immunohistochemistry to examine CK1ε expression in 230 HCC specimens by tissue microarray (TMA) and assessed the effect of CK1ε knockdown on migration of human hepatoma cells in vitro. The immunohistochemical analyses showed that low CK1ε expression was significantly correlated with tumor differentiation (p = 0.008), T classification (p = 0.016), tumor vascular invasion (p = 0.002), and cancer stage (p = 0.010). The univariate and multivariate analyses showed that patients with low CK1ε expression had a considerably lower OS rate than that of the patients with high CK1ε expression (p = 0.041, hazard ratio = 1.4; p = 0.039, hazard ratio = 1.4). Moreover, CK1ε small interfering RNA (siRNA) treatment exerted an invasion-promoting effect in human hepatoma cells. In conclusion, our data indicated that low CK1ε expression is correlated with a low survival rate and CK1ε may play a role as a tumor suppressor in hepatocarcinogenesis.

Casein kinase 1 epsilon expression predicts poorer prognosis in low T-stage oral cancer patients.

Casein kinase 1 is a group of ubiquitous serine/threonine kinases that are involved in normal cellular functions and several pathological conditions, such as DNA repair, cell cycle progression, cytokinesis, differentiation, and apoptosis. Recent studies have indicated that casein kinase 1-epsilon (CK1ε) and casein kinase 1-delta (CK1δ) expression has a role in human cancers. We investigated the associations between CK1ε and CK1δ expression and the clinical parameters of oral cancer using immunohistochemical study methods on oral squamous cell carcinoma specimens. The results of our immunohistochemical analysis showed that the loss of CK1ε expression was greatly associated with a poor four-year survival rate in oral cancer patients (p = 0.002). A Kaplan-Meier analysis showed that patients who had a loss of CK1ε expression had a considerably poorer overall survival rate than patients who had positive CK1ε expressions (p = 0.022). A univariate analysis revealed that patients who had a loss of CK1ε expression had considerably poorer overall survival (OS) than patients who had positive expression (p = 0.024, hazard ratio (HR) = 1.7). In conclusion, our data indicated that the loss of cytoplasmic CK1ε expression is greatly associated with poor survival and might be an adverse survival factor.

Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis.

Although the pan-genotypic direct-acting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. We evaluated the real-world safety and efficacy of two pan-genotypic regimens (Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir) for HCV-infected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua Christian Care System that commenced treatment between August 2018 and December 2020. This retrospective study evaluated the efficacy and safety of pan-genotypic direct-acting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment. Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow-up during treatment and one more patient after treatment. A total of four patients died. However, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%). Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotype-undetermined HCV infection real-world settings.

Ultrasound-Guided Femoral Nerve Block in Geriatric Patients with Hip Fracture in the Emergency Department.

Background and Objectives: Systemic analgesics, including opioids, are commonly used for acute pain control in traumatic hip fracture patients in the emergency department (ED). However, their use is associated with high rates of adverse reactions in the geriatric population. As such, the aim of this study was to investigate the impact of lidocaine-based single-shot ultrasound-guided femoral nerve block (USFNB) on the standard care for acute pain management in geriatric patients with traumatic hip fracture in the ED. Methods: This retrospective, single-center, observational study included adult patients aged ≥60 years presenting with acute traumatic hip fracture in the ED between 1 January 2017 and 31 December 2020. The primary outcome measure was the difference in the amount of opioid use, in terms of morphine milligram equivalents (MME), between lidocaine-based single-shot USFNB and standard care groups. The obtained data were evaluated through a time-to-event analysis (time to meaningful pain relief), a time course analysis, and a multivariable analysis. Results: Overall, 607 adult patients (USFNB group, 66; standard care group, 541) were included in the study. The patients in the USFNB group required 80% less MME than those in the standard care group (0.52 ± 1.47 vs. 2.57 ± 2.53, p < 0.001). The multivariable Cox proportional hazards regression models showed that patients who received USFNB achieved meaningful pain relief 2.37-fold faster (hazard ratio (HR) = 2.37, 95% confidence intervals (CI) = 1.73−3.24, p < 0.001). Conclusions: In geriatric patients with hip fractures, a lidocaine-based single-shot USFNB can significantly reduce opioid consumption and provide more rapid and effective pain reduction.

Comparison of the sixth, seventh, and eighth editions of the American Joint Committee on Cancer Tumor-Node-Metastasis staging system for gastric cancer: A single institution experience.

ABSTRACT: In 2018, the eighth edition of the American Joint Committee on Cancer Tumor-Node-Metastasis classification and staging system was implemented. Few reports were made comparing the performance of different editions of the American Joint Committee on Cancer (AJCC) system. Therefore, this study aimed to examine the prognostic predictability from the sixth to the eighth editions of the AJCC staging system for gastric cancer.A total of 414 patients with gastric cancer who underwent surgery at Changhua Christian Hospital from January 2007 to December 2017 were enrolled in the study. To identify the prognostic factors for gastric cancer death, univariate and multivariate analyses were performed. The homogeneity and discrimination abilities of the sixth to eighth editions of the staging system were compared using the likelihood ratio chi-square test, linear trend chi-square test, and Akaike information criterion.The sixth edition of the staging system had the lowest Akaike information criterion value, suggesting a better prognostic stratification than other editions. From the result of the likelihood ratio chi-square test, the T and N staging systems of the seventh and eighth editions had better homogeneity and discriminatory ability than the sixth edition. The eighth edition had better prognostic performance in patients at stage III compared with the seventh edition.The AJCC seventh and eighth editions had improved prognostic predictability of the T and N factors compared with the sixth edition. However, the overall staging performance of the eighth edition is not superior compared to the sixth edition. Further studies with larger sample size should be conducted to compare the performance of different editions of the AJCC staging system for different ethnic populations.

Clinical features and treatment of inflammatory bowel disease in a low-incidence area: A hospital-based retrospective cohort study in Taiwan.

ABSTRACT: Inflammatory bowel disease (IBD) has emerged in the Asia-Pacific area over the past 2 decades. There is a paucity of clinical data regarding real-world experience of patients with IBD from low endemic area such as Taiwan. Therefore, the present study aimed to review the clinical features of patients with IBD form a tertiary center from Taiwan.A total of 163 patients with IBD were identified from the electronic clinical database of Changhua Christian Hospital. Demographic data of the patients and clinical features of the disease pattern were retrospectively reviewed.There was a higher proportion (62.6%) of patients diagnosed with ulcerative colitis (UC). Patients with Crohn disease (CD) and UC had male predominance. The median age of diagnosis was younger in patients with CD than in patients with UC (CD vs UC: 31 vs 40 years, P = .0423). The disease distribution of UC was as follows: E1 (15.7%), E2 (47.1%), and E3 (37.3%). The disease distribution of CD was as follows: L1 (36.1%), L2 (14.8%), L3 (42.6%), and L4 (6.5%). The majority of patients with CD had a complicated presentation with B2 (32.8%) and B3 (32.8%). Patients with CD had a higher bowel resection rate than patients with UC. Patients with CD were more likely to be treated with immunomodulator and biologics and those with UC were more likely to be treated with 5-aminosalicylic acid (5-ASA). A trend of decreased bowel resection for patients with IBD and less severe phenotype of patients with CD were observed after 2015.UC with male predominance was the predominant type of IBD in the study. Patients with CD are likely to have a complicated disease course, requiring a higher demand of biologic therapy than patients with UC.

A Nomogram for Predicting Laparoscopic and Endoscopic Cooperative Surgery during the Endoscopic Resection of Subepithelial Tumors of the Upper Gastrointestinal Tract.

BACKGROUND: Considering the widespread use of esophagogastroduodenoscopy, the prevalence of upper gastrointestinal (GI) subepithelial tumors (SET) increases. For relatively safer removal of upper GI SETs, endoscopic submucosal dissection (ESD) has been developed as an alternative to surgery. This study aimed to analyze the outcome of endoscopic resection for SETs and develop a prediction model for the need for laparoscopic and endoscopic cooperative surgery (LECS) during the procedure. METHOD: We retrospectively analyzed 123 patients who underwent endoscopic resection for upper GI SETs between January 2012 and December 2020 at our institution. Intraoperatively, they underwent ESD or submucosal tunneling endoscopic resection (STER). RESULTS: ESD and STER were performed in 107 and 16 patients, respectively. The median age was 55 years, and the average tumor size was 1.5 cm. En bloc resection was achieved in 114 patients (92.7%). The median follow-up duration was 242 days without recurrence. Perforation occurred in 47 patients (38.2%), and 30 patients (24.4%) underwent LECS. Most perforations occurred in the fundus. Through multivariable analysis, we built a nomogram that can predict LECS requirement according to tumor location, size, patient age, and sex. The prediction model exhibited good discrimination ability, with an area under the curve (AUC) of 0.893. CONCLUSIONS: Endoscopic resection is a noninvasive procedure for small upper-GI SETs. Most perforations can be successfully managed endoscopically. The prediction model for LECS requirement is useful in treatment planning.

Predictive values of stool-based tests for mucosal healing among Taiwanese patients with ulcerative colitis: a retrospective cohort analysis.

BACKGROUND/PURPOSE: Over the past two decades, ulcerative colitis (UC) has emerged in the Asia Pacific area, and its treatment goal has shifted from symptom relief to endoscopic remission. Endoscopy is the gold standard for the assessment of mucosal healing; however, it is an invasive method. Fecal calprotectin (FC) is a non-invasive stool-based inflammatory marker which has been used to monitor mucosal healing status, but it is expensive. By contrast, the immune fecal occult blood test (iFOBT) is a widely utilized stool-based screening tool for colorectal cancer. In this study, we compared the predictive values of iFOBT and FC for mucosal healing in Taiwanese patients with UC. METHODS: A total of 50 patients with UC identified via the electronic clinical database of Changhua Christian Hospital, Taiwan, were retrospectively enrolled from January 2018 to July 2019. Results of iFOBT, FC level, and blood tests as well as Mayo scores were reviewed and analyzed. Colonic mucosa was evaluated using the endoscopic Mayo subscore. RESULTS: The average age of the patients was 46 years, and 62% of the patients were men. Disease distribution was as follows: E1 (26%), E2 (40%), and E3 (34%). Complete mucosal healing (Mayo score = 0) was observed in 30% of patients. Endoscopic mucosal healing with a Mayo score of 0 or 1 was observed in 62% of the patients. Results of FC and iFOBT were compared among patients with and without mucosal healing. Predictive cutoff values were analyzed using receiver operating characteristics curves. iFOBT and FC had similar area under the curve for both complete mucosal healing (0.813 vs. 0.769, respectively, p = 0.5581) and endoscopic mucosal healing (0.906 vs. 0.812, respectively, p = 0.1207). CONCLUSION: In daily clinical practice, FC and iFOBT do not differ in terms of predictive values for mucosal healing among Taiwanese patients with UC.

Implementation of human factors engineering approach to improve environmental cleaning and disinfection in a medical center.

Background: Inadequate hospital cleaning may contribute to cross-transmission of pathogens. It is important to implement effective cleaning for the safe hospital environment. We conducted a three-phase study using human factors engineering (HFE) approach to enhance environmental cleanliness. Methods: This study was conducted using a prospective interventional trial, and 28 (33.3%) of 84 wards in a medical center were sampled. The three-phases included pre-intervention analysis (Phase 1), implementing interventions by HFE principles (Phase 2), and programmatic analysis (Phase 3). The evaluations of terminal cleaning and disinfection were performed using the fluorescent marker, the adenosine triphosphate bioluminescence assay, and the aerobic colony count method simultaneously in all phases. Effective terminal cleaning and disinfection was qualified with the aggregate outcome of the same 10 high-touch surfaces per room. A score for each high-touch surface was recorded, with 0 denoting a fail and 10 denoting a pass by the benchmark of the evaluation method, and the total terminal cleaning and disinfection score (TCD score) was a score out of 100. Results: In each phase, 840 high-touch surfaces were collected from 84 rooms after terminal cleaning and disinfection. After the interventions, the TCD score by the three evaluation methods all showed significant improved. The carriage incidence of multidrug-resistant organism (MDRO) decreased significantly from 4.1 per 1000 patient-days to 3.6 per 1000 patient-days (P = .03). Conclusion: The HFE approach can improve the thoroughness and the effectiveness of terminal cleaning and disinfection, and resulted in a reduction of patient carriage of MDRO at hospitals. Larger studies are necessary to establish whether such efforts of cleanliness can reduce the incidence of healthcare-associated infection.

Anatomical location-based nodal staging system is superior to the 7th edition of the American Joint Committee on Cancer staging system among patients with surgically resected, histologically low-grade gastric cancer: A single institutional experience.

BACKGROUND: A hybrid topographic and numeric lymph node (LN) staging system for gastric cancer, which was recently proposed by Japanese experts as a simple method with a prognostic predictive power comparable to the N staging of the American Joint Committee on Cancer (AJCC) Tumor-node-metastasis classification, has not yet been validated in other Asian countries. This study aimed to examine the prognostic predictability of the hybrid staging system with the current AJCC staging system in gastric cancer. METHODS: Overall, 400 patients with gastric cancer who underwent surgery at Changhua Christian Hospital from January 2007 to December 2017 were included in the study. Univariate and multivariate analyses were performed to identify prognostic factors for gastric cancer-related death. Homogeneity and discrimination abilities of the two staging systems were compared using likelihood ratio chi-square test, linear trend chi-square test, Harrell's c-index, and bootstrap analysis. RESULTS: One-third of the LN-positive patients were reclassified into the new N and Stage system. The concordance rates of the two staging systems and the N staging between the two staging systems were 0.810 and 0.729, respectively. Harrell's c-indices for the stage and N staging were higher in the 7th AJCC staging system than the hybrid staging system (c-index for stage, 0.771 vs 0.764; c-index for nodal stage, 0.713 vs 0.705). Stratification of the patients according to the histological grade revealed that Harrell's c-indices for the stage and N stage of the hybrid staging system were comparable with those of the 7th AJCC staging system (c-index for AJCC stage vs hybrid stage, 0.800 vs 0.791; c-index for AJCC N stage vs hybrid N stage, 0.746 vs 0.734) among patients with histologically lower grade gastric cancer. The performance of the new nodal staging system was better than that of the 7th AJCC staging system by likelihood ratio and linear trend tests and bootstrap analysis in the low-grade group. CONCLUSIONS: The hybrid anatomical location-based classification may have better prognostic predictive ability than the 7th AJCC staging system for LN metastasis of low-grade gastric cancer. Further studies involving different ethnic populations are necessary for the validation of the new staging system.

Effects of Acupressure on Sleep Quality and Psychological Distress in Nursing Home Residents: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of acupressure with sham acupressure in older-adult nursing home residents presenting with poor sleep quality and psychological distress. DESIGN: Prospective, randomized, double-blind, sham-controlled trial. SETTING AND PARTICIPANTS: Sixty-two nursing home residents with poor sleep quality and psychological distress participated in this study. Participants were randomly assigned to an experimental group (n = 31) receiving acupressure at true acupoints (Baihui, Juque, Neiguan, Tianzhu, and Yongchung) or control group (n = 31) receiving acupressure at sham points. All participants received 20 minutes of acupressure before sleeping 3 times a week for 8 weeks. All participants were blinded to group allocation. MEASURES: Sleep quality and psychological distress were measured using the Pittsburgh Sleep Quality Index and the Kessler Psychological Distress scale, respectively. Both groups' outcomes were assessed by assessors blinded to group allocation at the baseline, the end of the intervention, and 1 month after the intervention. RESULTS: The experimental group demonstrated significantly more improvement in sleep quality than did the control group at the end of the intervention (10.5 vs 13.3) and 1 month after the intervention (8.3 vs 14.2; both P ≤ .001). Moreover, the experimental group had lower psychological distress levels than did the control group at 1 month after the intervention (14.6 vs 17.9, P = .05). Furthermore, significant differences in mean sleep quality (F = 60.8, P < .001) and psychological distress (F = 24.6, P < .001) were observed in the experimental group between the measurements at baseline and after the intervention. CONCLUSIONS: Acupressure at true acupoints improves sleep quality, reduces psychological distress, and provides more clinically beneficial effects compared with that at sham points. Future studies should examine whether these effects are maintained in the long term.

Application of a fluorescent marker with quantitative bioburden methods to assess cleanliness.

BACKGROUND: Improvement of environmental cleaning in hospitals has been shown to decrease in-hospital cross transmission of pathogens. Several objective methods, including aerobic colony counts (ACCs), the adenosine triphosphate (ATP) bioluminescence assay, and the fluorescent marker method have been developed to assess cleanliness. However, the standard interpretation of cleanliness using the fluorescent marker method remains uncertain. OBJECTIVE: To assess the fluorescent marker method as a tool for determining the effectiveness of hospital cleaning. DESIGN: A prospective survey study. SETTING: An academic medical center. METHODS: The same 10 high-touch surfaces were tested after each terminal cleaning using (1) the fluorescent marker method, (2) the ATP assay, and (3) the ACC method. Using the fluorescent marker method under study, surfaces were classified as totally clean, partially clean, or not clean. The ACC method was used as the standard for comparison. RESULTS: According to the fluorescent marker method, of the 830 high-touch surfaces, 321 surfaces (38.7%) were totally clean (TC group), 84 surfaces (10.1%) were partially clean (PC group), and 425 surfaces (51.2%) were not clean (NC group). The TC group had significantly lower ATP and ACC values (mean ± SD, 428.7 ± 1,180.0 relative light units [RLU] and 15.6 ± 77.3 colony forming units [CFU]/100 cm2) than the PC group (1,386.8 ± 2,434.0 RLU and 34.9 ± 87.2 CFU/100 cm2) and the NC group (1,132.9 ± 2,976.1 RLU and 46.8 ± 119.2 CFU/100 cm2). CONCLUSIONS: The fluorescent marker method provided a simple, reliable, and real-time assessment of environmental cleaning in hospitals. Our results indicate that only a surface determined to be totally clean using the fluorescent marker method could be considered clean.