Predicting the Risk Factors of Second Primary Cancer in Patients with Hepatocellular Carcinoma.

Screening for cancer and improved treatments have not only improved treatment outcomes and patient survival but have also led to an increase in the number of second primary cancers (SPCs). Hepatocellular carcinoma has been a common occurrence in Taiwan over the past decade. The mortality rate is second only to malignant tumors of lung cancer, and it also represents the fourth highest cancer medical expenditure. This study aimed to use machine learning to identify the risk factors for Hepatocellular carcinoma survivors. Of 378,445 datasets, including 15,251 from patients with SPCs, were collected; 18 predictive variables were considered risk factors for SPCs based on the physician panel discussion. The machine learning techniques employed included support vector machine, C5 decision tree, and random forest. SMOTE (Synthetic Minority Oversampling Technique) sampling method was used to resolve the imbalance problem. The results showed that the top 5 risk factors for SPCs were tumor size, clinical stage, surgery, total bilirubin, and BCLC Stage. The support vector machine method had the highest predicted accuracy (0.7673). The risk factors extracted from the classification models and association rules will be used to provide valuable information for HCC therapy.

Utility of Acute Physiology and Chronic Health Evaluation (APACHE II) in Predicting Mortality in Patients with Pyogenic Liver Abscess: A Retrospective Study.

Pyogenic liver abscess (PLA) is a major life-threatening disease with varied clinical features. This study aimed to determine predictors of mortality in patients with PLA using criteria determined upon admission. We retrospectively examined the data of 324 hospitalized adults in whom liver abscesses were confirmed using abdominal ultrasound and/or computed tomography. The relationship between various risk factors was assessed using multivariate analysis. A total of 109 (33.6%) patients were admitted to the intensive care unit (ICU). The overall mortality rate was 7.4% and was higher among ICU patients than non-ICU patients (21.1% vs. 0.5%, p < 0.001). PLA patients with an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥18 had a 19.31-fold increased risk, and those with concomitant infections had a 34.33-fold increased risk of 30-day mortality according to multivariate analysis. The estimated area under the receiver operating characteristic curve for predicting 30-day mortality revealed that APACHE II score ≥18 (sensitivity of 75% and specificity of 84%, p < 0.0001) had better discriminative power than Sequential Organ Failure Assessment (SOFA) ≥6 (sensitivity of 81% and specificity of 66%, p < 0.0001). APACHE II has shown better discrimination ability than SOFA in predicting mortality in PLA patients. To improve outcomes in patients with PLA, future management strategies should focus on high-risk patients.

Treatment of chronic hepatitis C regiments containing with recombinant interferon in patients with sustained virological response predicts risk of hepatocellular carcinoma: A meta-analysis.

Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.

Maintenance interferon therapy in chronic hepatitis C patients who failed initial antiviral therapy: A meta-analysis.

OBJECTIVES: To evaluate the effect of pegylated interferon maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy. METHODS: This is a meta-analysis of 6 randomized controlled trials that met the eligibility criteria. In all, 2438 chronic hepatitis C patients who failed to achieve sustained virologic response after initial treatment with pegylated interferon and ribavirin (antiviral therapy nonresponders or relapsers) were enrolled; 1237 patients received maintenance therapy (Maintenance group) and 1201 received no treatment (Observation group). RESULTS: The pooled analyses found that patients in the Maintenance group had a significantly higher rate of normal alanine aminotransferase than did patients in the Observation group (pooled odds ratio [OR] 4.436, 95% confidence interval [CI] 1.225-16.064, P = .023), but there was no significant difference between the 2 groups in the incidence of hepatocellular carcinoma (pooled OR 0.872, 95% CI 0.501-1.519, P = .630), or the mortality rate (pooled OR 1.564, 95% CI 0.807-3.032, P = .185). CONCLUSIONS: Interferon-based maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy improved liver inflammation as indicated by blood chemistry (alanine aminotransferase).

Exploring Oral Cancer Patients' Preference in Medical Decision Making and Quality of Life.

Little is known about the clinical effects of shared medical decision making (SMDM) associated with quality of life about oral cancer? To understand patients who occurred potential cause of SMDM and extended to explore the interrelated components of quality of life for providing patients with potential adaptation of early assessment. All consenting patients completed the SMDM questionnaire and 36-Item Short Form (SF-36). Regression analyses were conducted to find predictors of quality of life among oral cancer patients. The proposed model predicted 57.4% of the variance in patients' SF-36 Mental Component scores. Patient mental component summary scores were associated with smoking habit (ß=-0.3449, p=0.022), autonomy (ß=-0.226, p=0.018) and Control preference (ß=-0.388, p=0.007). The proposed model predicted 42.6% of the variance in patients' SF-36 Physical component scores. Patient physical component summary scores were associated with higher education (ß=0.288, p=0.007), employment status (ß=-0.225, p=0.033), involvement perceived (ß=-0.606, p=0.011) and Risk communication (ß=-0.558, p=0.019). Future research is necessary to determine whether oral cancer patients would benefit from early screening and intervention to address shared medical decision making.

Decisional Conflict in Work-Related Hand Trauma Patients.

Often, clinical decision making of reconstructive procedure is coupled and their concurrent resolution by interacting stakeholders is required. This study was to give new insight into the tradeoff method to elicit the utility function first and then the probability weighting function, to determine if and how stakeholder engagement can contribute to managing decisional conflict processes. The proposed methodology is illustrated through three subjects (physician, patient and family member). We found that significant evidence of probability weighting both at the aggregate level and at the individual subject level. The pattern of probability weights is consistent with an inverse shaped probability weighting function: Small probabilities are overweighed and intermediate and large probabilities are underweight. In addition, the degree of upper subadditivity exceeds the degree of lower subadditivity. Finally, the proposed procedure can reduce clinical risk by considering stakeholders' behavior attribute and providing physicians the effective support need for quality decision making.

Complicated skin and soft tissue infection with Mycobacterium fortuitum following excision of a sebaceous cyst in Taiwan.

Mycobacterium fortuitum group (M. fortuitum), also known as rapidly growing Mycobacteria, can cause pyogenic infections in human beings, most commonly in immunocompromised patients. Herein, we present a 40-year-old immunocompetent male patient who underwent planned excision of a sebaceous cyst in the abdominal wall. He suffered from tender erythematous lesions with purulent discharge around the healing wound that developed 2 weeks after surgery. Gram stain, bacterial and fungal culture results of the wound were negative. A diagnosis of non-tuberculous mycobacteria was made from a wound culture from the area of operative debridement, which was subsequently confirmed to be M. fortuitum group using PCR-restriction fragment length polymorphism analysis of the hsp65 gene. The patient received 4 weeks of parenteral imipenem/cilastatin 500 mg every 6 hours and amikacin 500 mg every 12 hours, plus oral clarithromycin 500 mg twice daily, and the wound recovered completely. He was discharged and followed up regularly at our outpatient clinic, and continued taking oral ciprofloxacin and clarithromycin 500 mg twice daily for 6 months. This case highlights the importance of strict aseptic precautions even during minor procedures, and also the characteristics of M. fortuitum infections in immunocompetent patients, which usually develop as localized postsurgical wound infections. We also share our experience in successfully treating a M. fortuitum complicated skin and soft tissue infection.

The clinical management of cesarean section-acquired Mycobacterium abscessus surgical site infections.

INTRODUCTION: Rapidly growing mycobacteria (RGM) can cause a broad spectrum of both community and healthcare-associated infections in humans. The aim of this study was to report the clinical management and outcomes of successive patients following cesarean delivery with healthcare-associated surgical site infections (SSIs) caused by RGM. METHODOLOGY: Patients who were admitted to Chung Shan Medical University Hospital, Taichung, Taiwan, between September 2006 and July 2008, and who developed SSIs following cesarean delivery at an obstetrics hospital and were then referred to our hospital, were enrolled. Demographic characteristics of the patients and clinical isolates were obtained retrospectively and an environmental investigation was performed. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the hsp65gene and pulsed-field gel electrophoresis (PFGE) of large genomic DNA restriction fragments were applied to differentiate Mycobacterium species. RESULTS: Seventeen patients were diagnosed with RGM infections by microbiology and/or histopathology. Mycobacterial isolates by PCR-RFLP analysis from 15 patients revealed Mycobacterium abscessus (M. abscessus) and M. lentiflavum. Most of the patients received surgical debridement and combination antimicrobial therapy and were eventually cured. CONCLUSIONS: Our study demonstrates the potential that RGM infections have in causing healthcare-associated SSIs. Surgery plus prolonged combination antimicrobial therapy seemed to be an effective option for the management of M. abscessus infections.

Down-regulation of granulocyte-macrophage colony-stimulating factor by 3C-like proteinase in transfected A549 human lung carcinoma cells.

BACKGROUND: Severe Acute Respiratory Syndrome (SARS) is a severe respiratory illness caused by a novel virus, the SARS coronavirus (SARS-CoV). 3C-like protease (3CLpro) of SARS-CoV plays a role in processing viral polypeptide precursors and is responsible of viral maturation. However, the function of 3CLpro in host cells remains unknown. This study investigated how the 3CLpro affected the secretion of cytokines in the gene-transfected cells. RESULTS: From immunofluorescence microscopy, the localization of c-myc tagged 3CLpro was detected both in the cytoplasm and nucleus of transfected A549 cells. Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly decreased in 3CLpro-transfected cells by both RT-PCR and ELISA, but without changes in other cytokines, i.e., IL-1ß, IL-6, IL-8, IL12p40, TNF-α, and TGF-ß. Furthermore, the protein levels of NF-kB decreased in 3CLpro-transfected A549 cells when compared to EGFP transfected cells. CONCLUSIONS: Our results suggest that the 3CLpro may suppress expression of GM-CSF in transfected A549 cells through down-regulation of NF-kB production.

Proteomics analysis of A375 human malignant melanoma cells in response to arbutin treatment.

Although the toxicogenomics of A375 human malignant melanoma cells treated with arbutin have been elucidated using DNA microarray, the proteomics of the cellular response to this compound are still poorly understood. In this study, we performed proteomic analyses to investigate the anticancer effect of arbutin on the protein expression profile in A375 cells. After treatment with arbutin (8 microg/ml) for 24, 48 and 72 h, the proteomic profiles of control and arbutin-treated A375 cells were compared, and 26 differentially expressed proteins (7 upregulated and 19 downregulated proteins) were identified by MALDI-Q-TOF MS and MS/MS. Among these proteins, 13 isoforms of six identical proteins were observed. Bioinformatic tools were used to search for protein function and to predict protein interactions. The interaction network of 14 differentially expressed proteins was found to be correlated with the downstream regulation of p53 tumor suppressor and cell apoptosis. In addition, three upregulated proteins (14-3-3G, VDAC-1 and p53) and five downregulated proteins (ENPL, ENOA, IMDH2, PRDX1 and VIME) in arbutin-treated A375 cells were validated by RT-PCR analysis. These proteins were found to play important roles in the suppression of cancer development.

Proteomics analysis of kojic acid treated A375 human malignant melanoma cells.

Although the toxicogenomics of kojic acid treated A375 human malignant melanoma cells has been elucidated, the proteomics of cellular response is still poorly understood. We performed proteomic analysis to investigate the anticancer effect of kojic acid on protein expression profile in A375 cells. A375 cells were treated with kojic acid at 8 microg/mL for 24, 48, and 72 h. With the use of 2-D PAGE and MALDI-Q-TOF MS and MS/MS analyses, proteomic profiles of A375 cells between control and kojic acid treatment were compared, and 30 differentially expressed proteins, containing 2 up-regulated proteins and 28 down-regulated proteins, were identified. Among these proteins, 17 isoforms of 5 identical proteins were observed and 11 chaperone proteins showed the high proportion of protein spots with 36.7% of total proteins. Bioinformatic tools were used to search for protein function and prediction of protein interaction. Sixteen differentially expressed proteins exhibited interaction network linked to the downstream regulations of p53 tumor suppressor and cell apoptosis, which may lead to suppress the melanogenesis and tumorigenesis of kojic acid treated A375 cells. In addition, GRP75, VIME and 2AAA were validated by Western blot analysis, whereas GRP75, 2AAA, HS90B, ENPL and KPYM were validated by RT-PCR. Therefore, these proteins play the important roles in cancer progression and may be potential biomarkers that are useful for diagnostic and therapeutic applications of malignant melanoma cancer.

Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by paclitaxel.

BACKGROUND: Paclitaxel, an antineoplastic drug, inhibits cell growth and cell cycle progression and induces apoptosis in human leukemia HL-60 cells. Caspase-3 plays a direct role in proteolytic cleavage of cellular proteins responsible for progression to apoptosis. METHODS: We examined the cell morphology and apoptosis in HL-60 cells after exposure to paclitaxel and measured caspase-3 activities with or without z-VAD-fmk (a broad-spectrum caspase inhibitor) pretreatment by flow cytometric analysis and Western blotting. RESULTS: Together, our results were (1) paclitaxel mainly induced G2/M cell cycle arrest in HL-60 cells (p<0.001); (2) time (p<0.001)- and dose-dependent (p<0.001) apoptosis of HL-60 cells was induced by paclitaxel; (3) in HL-60 cells, z-VAD-fmk blocked paclitaxel-induced apoptosis (12 h: p<0.001; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.001) and caspase-3 activation (12 h: p<0.05; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.01). CONCLUSIONS: These results suggest that paclitaxel can induce G2/M cell cycle transition and apoptosis via caspase-3 activity in HL-60 cells.