With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.
Biomarkers/*blood ; DNA, Viral/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/prevention & control ; Humans ; Liver Cirrhosis/etiology ; Organic Anion Transporters, Sodium-Dependent/genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Symporters/genetics

Hepatitis B virus (HBV) is responsible for more than 50% of hepatocellular carcinoma (HCC) in HBV hyperendemic areas, such as the Asia-Pacific region. Several hepatitis B viral factors are involved in HBV-related hepatocarcinogenesis. Hepatitis B viral load is the most important risk factor of HCC development. In addition, HBV integration, HBV genotype C, and core-promoter mutations are also associated with a risk of HCC development. For untreated chronic hepatitis B (CHB) patients, the estimated HCC incidence rates per 100 patient-years were 0.03–0.17 in inactive carriers, 0.07–0.42 in asymptomatic carriers, 0.12–0.49 in chronic hepatitis, and 2.03–3.37 in cirrhosis. Complementary to HBV DNA, serum levels of the hepatitis B surface antigen and hepatitis B core-related antigen (HBcrAg) can predict the occurrence of HCC for untreated patients with low and intermediate viral loads, respectively. For patients receiving antiviral therapy, the risks of HCC occurrence 40–60% lower than those for untreated patients. Patients treated with residual detectable HBV DNA or intrahepatic cccDNA still have a risk of HCC. Serum levels of HBcrAg, M2BPGi and fibrosis-4 are predictive of the risk of HCC development in treated patients. Several well-developed HCC risk scores can help clinicians identify high-risk CHB patients for HCC surveillance, regardless of treatment status. These strategies can help minimize the threat of HCC and prolong survival in CHB patients.

INTRODUCTIONColorectal cancer is the most common form of malignancy in Taiwan and the third leading cause of death from cancer, preceded only by lung and hepatic cancers. Colorectal cancer is typically treated by surgical intervention and/or chemotherapy and radiotherapy, if necessary. To date, 5-fluorouracil (5-FU) is the most commonly used anti-cancer chemotherapy drug. However, patients commonly experience resistance to the drug therefore limiting its efficiency. In this study, we measured the expression of rTSbeta in human colon cancer as a novel 5-FU resistance marker.

MATERIALS AND METHODSWe collected 172 colon cancer samples from 4 different hospitals (including 21 pairs of colon cancer biopsies and 151 pathologic slides of colon cancer). In vitro, we measured the cytotoxicity of 5-FU and 5-FU plus leucovorin in H630 and H630-1 colon cancer cell lines.

RESULTSThe results revealed that rTSbeta was expressed in 115 (66.9 %) pathology samples and that tumour expression was higher than in corresponding normal tissue. Survival rates of up to 5 years following treatment was significantly higher for patients without rTSbeta expression than for those with rTSbeta expression (P = 0.0023). In vitro, H630-1 (with rTSbeta overexpression) had significantly higher IC50 of 5-FU than did H630. IC50 of 5-FU decreased when leucovorin was added.

CONCLUSIONSResults indicate a close relationship between rTSbeta expression and resistance to the drug 5-FU in human colorectal cancer. These results provide further evidence for rTSbeta expression as a novel 5-FU resistance marker of colorectal cancer.

Biomarkers ; Cell Line, Tumor ; drug effects ; Colorectal Neoplasms ; drug therapy ; Cytological Techniques ; Drug Resistance, Neoplasm ; physiology ; Fluorouracil ; pharmacology ; therapeutic use ; Humans ; In Vitro Techniques ; Taiwan ; Thymidylate Synthase ; genetics ; metabolism

PURPOSE: Many studies supported that vegetarians have a lower risk of cardiac diseases and mortality, partly due to better blood pressure and serum cholesterol profiles. However, the inflammatory markers, especially lipoprotein-associated phospholipase A2 (Lp-PLA2), have not been well-studied. This study aimed to compare inflammatory markers and conventional risk factors between vegetarians and omnivores. MATERIALS AND METHODS: One hundred and seventy-three vegetarians and 190 omnivores were studied. Fasting blood samples were obtained to compare levels of glucose, total cholesterol, triacylglycerol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, homocysteine, Lp-PLA2 activity, and high-sensitivity C-reactive protein (hs-CRP). RESULTS: Vegetarians had higher serum levels of the following markers: hs-CRP (1.8 +/- 3.4 vs. 1.2 1.8 mg/L, respectively; p = 0.05), homocysteine (9.39 +/- 3.22 vs. 7.62 +/- 2.41 micromol/L, respectively; p < 0.01), and triacylglycerol (96.91 +/- 59.56 vs. 84.66 +/- 43.24 mg/dL, respectively; p < 0.05). Vegetarians also had lower levels of Lp-PLA2 (18.32 +/- 7.19 10-3 micromol/min/mL vs. 20.22 8.13 10-3 micromol/min/mL; p < 0.05), total cholesterol (180.62 +/- 36.55 mg/dL vs. 192.73 +/- 36.57 mg/dL; p < 0.01), LDL cholesterol (118.15 +/- 32.8 vs. 126.41 +/- 34.28 mg/dL; p < 0.05), and HDL cholesterol (55.59 +/- 13.30 vs. 62.09 +/- 14.52 mg/dL, p < 0.01). Multivariate analyses demonstrated that a vegetarian diet increases the chances for high serum hs-CRP and low Lp-PLA2 activity. CONCLUSION: In addition to lower total cholesterol, LDL-cholesterol, and HDL-cholesterol, Taiwanese female vegetarians have lower serum Lp-PLA2 activity but higher levels of hs-CRP, homocysteine, and triacylglyerol. It might be due to geographic differences of vegetarian diets, and further studies are needed.
1-Alkyl-2-acetylglycerophosphocholine Esterase/*blood ; Adult ; Asian Continental Ancestry Group ; C-Reactive Protein/metabolism ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; *Diet, Vegetarian ; Female ; Homocysteine/blood ; Humans ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Taiwan ; Triglycerides/blood

INTRODUCTIONProblem-based learning (PBL) embraces principles of good learning and teaching. It is student-directed, fosters intrinsic motivation, promotes active learning, encourages peer teaching, involves timely feedback, and can support student self and peer assessment. The most important function of the assessment process is to enhance student learning, to improve the curriculum and to improve teaching.

MATERIALS AND METHODSTo improve the PBL tutorial in Chung Shan Medical University, we developed an online evaluation system containing the evaluation forms for students, tutor, self and peer. The Cronbach alpha reliability coefficients were 0.9480, 0.9103, and 0.9198 for the Student, Tutor and Self and Peer Evaluation Form, respectively. The online evaluations were mandatory to both students and tutors, and the information was completely anonymous.

RESULTS AND CONCLUSIONSThe survey response rates of the online evaluations ranged from 95.6% to 100%. The online evaluations provided a documented feedback to the students on their knowledge, skills and attitudes. Correspondingly, tutors too received feedback from students in evaluating their performance on the appropriateness and effectiveness of tutoring the group. Although there was an initial lack of coordination regarding responsibilities and how to use the online system for both students and the Faculty, the system enabled us to look into how effective our PBL course had been, and it provided both process and outcome evaluations. Our strategy for evaluating the success of PBL is only at its initial stage; we are in an ongoing process of collecting outcome data for further analysis which will hopefully provide more constructive information to the PBL curricula.

Education, Medical ; standards ; Educational Measurement ; Humans ; Online Systems ; Pilot Projects ; Problem-Based Learning ; methods ; Taiwan ; Universities

The Acute Disease Quality Initiative advocates multidisciplinary care for the survivors of acute kidney injury (AKI). The bundled care strategy recognizes the role of pharmacists. However, their specific contributions in this context remain underexplored. Methods: This retrospective study examined the efficacy of pharmacist-led post-AKI pharmaceutical care in outpatient settings at a single center. Adults with recent AKI during hospitalization, maintaining an estimated glomerular filtration rate <45 mL/min/1.73 m2 postdischarge, were enrolled in a multidisciplinary team care program from March 2022 to January 2023, with a 6-month follow-up period. Pharmacist-delivered care adhered to international multidisciplinary consensus guidelines. Efficacy was evaluated by analyzing medication-related recommendations, medication adherence, nephrotoxic drug utilization, and renoprotective medication usage before and after the intervention. Results: A total of 40 patients were referred to the pharmacist-managed clinic. Of these, 33 patients (mean age, 63 ± 15 years; 60.6% male) attended the clinic. Nineteen patients completed follow-up visits. The pharmacist provided 14 medication-related recommendations to relevant physicians, with 10 of these recommendations (71.4%) being accepted. There was a significant decrease in the use of modifiable nephrotoxic drugs (p = 0.03). However, no significant improvements were noted in medication adherence or the utilization of renoprotective medications. Conclusion: Our study underscores the potential benefits of pharmacist-led post-AKI bundled care strategy in outpatient settings. We observed a significant reduction in the utilization of modifiable nephrotoxic drugs, indicating the effectiveness of pharmacist interventions in optimizing medication regimens to mitigate renal harm.

Background: Coracoacromial ligament transfer is the traditional procedure for treating chronic acromioclavicular separation, but it is significantly inferior to ligament reconstruction according to biomechanical and clinical studies. However, ligament reconstruction carries the risk of complications of graft loosening and peri-tunnel fractures. Currently, there is no ligament reconstruction procedure optimal for preventing such complications. The purpose of this study was to describe and retrospectively analyze the clinical and radiological outcomes of a “duo-figure-8” autogenic graft wrapping technique, which was used to concomitantly reconstruct the acromioclavicular and coracoclavicular ligaments. Methods: Preoperative, immediate postoperative, and final follow-up oputcomes were evaluated in 10 enrolled patients. Radiographic outcomes were indicated by the bilateral difference of the coracoclavicular distance (CCD) and overlapping length of the acromioclavicular joint (OLac). Quality of reduction was classified into 4 grades according to bilateral CCD difference into overreduction (< 0 mm), anatomic reduction (0–4 mm), partial loss of reduction (4–8 mm), and recurrent dislocation (> 8 mm). Clinical outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) and Constant scores. Results: The mean side-to-side differences for CCD were 11.9 mm (preoperative), −0.1 mm (immediate postoperative), and 3.4 mm (final follow-up); those for OLac were 9.4 mm (preoperative) and 2.7 mm (final follow-up). CCD and OLac outcomes significantly improved at final follow-up (p < 0.05). At the immediate postoperative stage, 6 and 4 patients had overreduction and anatomic reduction, respectively. At final follow-up, 7 and 3 patients had anatomic reduction and partial loss of reduction, respectively. The magnitude of improvement of ASES scores for patients with anatomic reduction and partial loss of reduction (p = 0.20) was 18.1 and 20.0, respectively. The magnitude of improvement of Constant scores in patients with anatomic reduction and partial loss of reduction (p = 0.25) was 19.9 and 22.3, respectively. Conclusions The technique yielded acceptable functional outcomes in patients with anatomic reduction or partial loss of reduction. The “duo-figure-8” wrapping method—a single autogenic tendon graft passing beneath the coracoid process with a tendonknot fixation over the distal clavicle and looping around the acromion intramedullary—did not increase the risk of peri-tunnel fractures over the clavicle, coracoid process, or acromion.

Background: Coracoacromial ligament transfer is the traditional procedure for treating chronic acromioclavicular separation, but it is significantly inferior to ligament reconstruction according to biomechanical and clinical studies. However, ligament reconstruction carries the risk of complications of graft loosening and peri-tunnel fractures. Currently, there is no ligament reconstruction procedure optimal for preventing such complications. The purpose of this study was to describe and retrospectively analyze the clinical and radiological outcomes of a “duo-figure-8” autogenic graft wrapping technique, which was used to concomitantly reconstruct the acromioclavicular and coracoclavicular ligaments. Methods: Preoperative, immediate postoperative, and final follow-up oputcomes were evaluated in 10 enrolled patients. Radiographic outcomes were indicated by the bilateral difference of the coracoclavicular distance (CCD) and overlapping length of the acromioclavicular joint (OLac). Quality of reduction was classified into 4 grades according to bilateral CCD difference into overreduction (< 0 mm), anatomic reduction (0–4 mm), partial loss of reduction (4–8 mm), and recurrent dislocation (> 8 mm). Clinical outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) and Constant scores. Results: The mean side-to-side differences for CCD were 11.9 mm (preoperative), −0.1 mm (immediate postoperative), and 3.4 mm (final follow-up); those for OLac were 9.4 mm (preoperative) and 2.7 mm (final follow-up). CCD and OLac outcomes significantly improved at final follow-up (p < 0.05). At the immediate postoperative stage, 6 and 4 patients had overreduction and anatomic reduction, respectively. At final follow-up, 7 and 3 patients had anatomic reduction and partial loss of reduction, respectively. The magnitude of improvement of ASES scores for patients with anatomic reduction and partial loss of reduction (p = 0.20) was 18.1 and 20.0, respectively. The magnitude of improvement of Constant scores in patients with anatomic reduction and partial loss of reduction (p = 0.25) was 19.9 and 22.3, respectively. Conclusions The technique yielded acceptable functional outcomes in patients with anatomic reduction or partial loss of reduction. The “duo-figure-8” wrapping method—a single autogenic tendon graft passing beneath the coracoid process with a tendonknot fixation over the distal clavicle and looping around the acromion intramedullary—did not increase the risk of peri-tunnel fractures over the clavicle, coracoid process, or acromion.

Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI’s pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2·insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.