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Abstract This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.

Background: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. Methods: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Background: Postoperative delirium (POD) is a common surgical complication in elderly patients. As frailty is a relatively novel concept, its clinical significance for POD has seldom been examined. This study aimed to investigate the association between frailty and POD in aged cancer patients undergoing elective abdominal surgery in Taiwan. Methods: We prospectively enrolled 345 consecutive patients aged ≥65 years with newly diagnosed cancer who underwent elective abdominal surgery between 2016 and 2018. Frailty assessment was performed using the Comprehensive Geriatric Assessment (CGA). POD was assessed daily using the Confusion Assessment Method from postoperative day 1 until discharge. Patients were allocated into fit and frail groups. Results: POD occurred in 19 (5.5%) of 345 patients. POD incidence was 1.6%, 3.1%, 4.8%, 11.5%, and 10.0% in patients with 0, 1, 2, 3, and 4+ frail conditions, respectively, which presented a positive linear correlation among patients with an increased number of frail conditions and POD incidence. Based on CGA, 159 (46.1%) and 186 (53.9%) patients were allocated to fit and frail groups, respectively. POD incidence was 2.5% and 8.1% for the fit and frail groups, respectively. Frailty status was an independent risk factor for POD occurrence in multivariate analysis. Conclusion: Our study identified frailty as an independent risk factor for POD in aged Taiwanese cancer patients undergoing elective abdominal surgery. Given the high prevalence of frailty among older cancer patients, preoperative assessment is important to identify high risk of POD and to improve the quality of postoperative care.

Abstract Background The conventional written tests and professional assessment have limitation in fair judgement of clinical competence. Because the examiners may not have total objectivity and may lack standardization throughout the assessment process. We sought to design a valid method of competence assessment in medical and nursing specialties. This work was aimed to develop an Objective Structured Clinical Exam (OSCE) to evaluate novice nursing practitioners’ clinical competency, work stress, professional confidence, and career satisfaction. Methods A Quasi-experimental study (pre-post). Fifty-five novice nursing practitioners received the OSCE three-months following their graduation, which consisted of four stations: history taking, physical examination, problem-directed management, interpersonal communication, and the required techniques of related procedures. The examiners had to complete an assessment checklist, and the participants had to complete a pre-post questionnaire (modified from a Nursing Competency Questionnaire, a Stress scale, and Satisfaction with Learning scale). Results Among the novice nursing practitioners, 41 of them (74.5 %) passed the exam with a mean score of 61.38 ± 8.34. There was a significantly higher passing rate among nurses who were working in medical-surgical wards (85.7 %) and the intensive care unit-emergency department (77.8 %) compared to novice nursing practitioners working in other units. All the novice nursing practitioners at Station A had poor performance in assessing patients with a fever. OSCE performance was more associated with educational attainment and work unit, rather than the gender. Finally, the participants showed statistically significant increases in their clinical competency, confidence in their professional competence, satisfaction with the clinical practice, and decreased work stress after the OSCE. Conclusions We found that the OSCE process had a positive educational effect, in providing a meaningful and accurate assessment of the competence of novice nursing practitioners. An appropriate OSCE program is vital for novice nursing practitioners, educators, and administrators. The effective application of OSCEs can help novice nursing practitioners gain confidence in their clinical skills.

Background: This study aimed to investigate the role of circulating tumor cells (CTCs) and circulating cancer stem-like cells (cCSCs) before and after one cycle of chemotherapy and assessed the effects of early changes in CTCs and cCSCs on the outcomes of patients with metastatic breast cancer. Methods: Patients with stage IV invasive ductal carcinoma of the breast who received first-line chemotherapy between April 2014 and January 2016 were enrolled. CTCs and cCSCs were measured before the first cycle of chemotherapy (baseline) and on day 21, before the second cycle of chemotherapy commenced; a negative selection strategy and flow cytometry protocol were employed. Results: CTC and cCSC counts declined in 68.8 and 45.5% of patients, respectively. Declines in CTCs and cCSCs following the first chemotherapy cycle were associated with superior chemotherapy responses, longer progression-free survival (PFS), and longer overall survival (OS). An early decline in cCSCs remained an independent prognostic indicator for OS and PFS in multivariate analysis. Conclusions: A cCSC decline after one cycle of chemotherapy for metastatic breast cancer is predictive of a superior chemotherapy response and longer PFS and OS, implying that cCSC dynamic monitoring may be helpful in early prediction of treatment response and prognosis.

BackgroundFactor V (FV) deficiency is a rare disease, with a low incidence rate in Asia. Therefore, the F5 mutation in the Taiwanese population is poorly understood.MethodsA Chinese family with FV deficiency was included, and the patient and his family members underwent mutation analysis. Then, patients from Keelung City (Taiwan) were screened for F5 polymorphism; the Chang Gung Human Database was used to determine single-nucleotide variants in the non-FV-deficient patient population.ResultsEight mutation sites on the F5 gene locus, including exon 16 homozygote Met1736Val and seven heterozygous mutations, including Asp68His, were found. Moreover, Met1736Val was found to be the dominant mutation in people living in the Taiwan community, and this result was compared with the records of the Chang Gung Human Database. The above-mentioned polymorphisms may result in a variable incidence of FV deficiency in Keelung City, thereby facilitating carrier diagnosis and prenatal diagnosis in most FV-deficient families.ConclusionThe homozygote Met1736Val and the co-inheritance of the Asp68His F5 gene are unique and worthy of screening in FV-deficient patients.

Abstract Background The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. Methods We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). Results: Overall, the patients who experienced grade 1–2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27–0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24–1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21–0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17–0.69, p = 0.003) than patients without any of these irAEs. Conclusions Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1–2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.

Background Whether the prevalence of frailty and its clinical significance are relevant to treatment outcomes in younger (aged < 65 years) cancer patients remains uncertain. This study aimed to evaluate the impact of frailty on treatment outcomes in younger cancer patients with head and neck and esophageal malignancy. Material and methods This multicenter prospective study recruited 502 patients with locally advanced head and neck and esophageal cancer during 2016–2017 in Taiwan, aged 20–64 years who received curative-intent concurrent chemoradiotherapy (CCRT) as first-line antitumor treatment. Baseline frailty assessment using geriatric assessment (GA) was performed for each patient within 7 days before CCRT initiation. Results Frailty was observed in 169 (33.7%) of 502 middle-aged patients. Frail patients had significantly higher incidences of chemotherapy incompletion (16.6% versus 3.3%, P < .001) and radiotherapy incompletion (16.6% versus 3.6%, P < .001) than fit patients. During CCRT, frail patients had a significantly higher percentage of hospitalizations (42.0% versus 24.6%, P < .001) and a trend toward a higher percentage of emergency room visits (37.9% versus 30.0%, P = .08) than fit patients. Frail patients more likely had a significantly higher incidence of grade ≥ 3 adverse events than fit patients during CCRT. The 1-year survival rate was 68.7% and 85.2% (hazard ratio 2.56, 95% confidence interval 1.80–3.63, P < .001) for frail and fit patients, respectively. Conclusions This study demonstrated the significance of pretreatment frailty on treatment tolerance, treatment-related toxicity, and survival outcome in younger patients with head and neck and esophageal cancer undergoing CCRT. While GA is commonly targeted toward the older population, frailty assessment by GA may also be utilized in younger patients for decision-making guidance and prognosis prediction.

Neuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocortin receptors to modulate feeding behavior. In this study, we expressed novel agrp promoters, including different lengths of the 5’ flanking regions of the agrp gene (4749 bp) in the zebrafish genome. We used the agrp promoter to derive the enhanced green fluorescent protein (EGFP)-nitroreductase (NTR) fusion protein, allowing expression of the green fluorescence signal in the AgRP neurons. Then, we treated the transgenic zebrafish AgRP4.7NTR (Tg [agrp-EGFP-NTR]) with metronidazole to ablate the AgRP neurons in the larvae stage and observed a decline in their appetite and growth. The expression of most orexigenic and growth hormone/insulin-like growth factor axis genes decreased, whereas that of several anorexigenic genes increased. Our findings demonstrate that AgRP is a critical regulator of neuronal signaling for zebrafish appetite and energy intake control. Thus, AgRP4.7NTR can be used as a drug-screening platform for therapeutic targets to treat human appetite disorders, including obesity. Furthermore, the unique agrp promoter we identified can be a powerful tool for research on AgRP neurons, especially AgRP neuron-mediated pathways in the hypothalamus, and appetite.

Background: The overlapping clinical presentations of limb-girdle muscular dystrophy (LGMD) and idiopathic inflammatory myopathy (IIM) make clinical diagnosis challenging. This study provides a comprehensive evaluation of the distributions and characteristics of muscle fat substitution and edema and aims to differentiate those two diseases.Methods: This retrospective study reviewed magnetic resonance imaging (MRI) of seventeen patients with pathologically proved diagnosis, comprising 11 with LGMD and 6 with IIM. The fat-only and water-only images from a Dixon sequence were used to evaluate muscle fat substitution and edema, respectively. The degrees of muscle fat substitution and edema were graded and compared using the appropriate statistical methods.Results: In LGMD, more than 50% of patients had high-grade fat substitution in the majority of muscle groups in the thigh and calf. However,

Lipid metabolism dysfunction is related to clinical disorders including obesity, cancer, liver steatosis, and cardiomyopathy. Impaired lipolytic enzymes result in altered release of free fatty acids. The dramatic change in dyslipidemia is important in lipotoxic cardiomyopathy. Adipose triglyceride lipase (ATGL) catalyzes the lipolysis of triacylglycerol to reduce intramyocardial triglyceride levels in the heart and improve myocardial function. We examined the role of ATGL in metabolic cardiomyopathy by developing an Atgl knockout (ALKO) zebrafish model of metabolic cardiomyopathy disease by continuously expressing CRISPR/Cas9 protein and atgl gene guide RNAs (gRNAs). The expressed Cas9 protein bound to four gRNAs targeting the atgl gene locus, facilitating systemic gene KO. Ablation of Atgl interfered with lipid metabolism, which induced hyperlipidemia and hyperglycemia. ALKO adults and embryos displayed hypertrophic hearts. ALKO presented a typical dilated cardiomyopathy profile with a remarkable reduction in four sarcomere genes (myosin heavy chain 7-like, actin alpha cardiac muscle 1b, myosin binding protein C3, and troponin T type 2a) and two Ca2+ handling regulator genes (tropomyosin 4b and ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2b). Immune cell infiltration in cardiac tissue of ALKO provided direct evidence of advanced metabolic cardiomyopathy. The presently described model could become a powerful tool to clarify the underlying mechanism between metabolic disorders and cardiomyopathies.

This prospective study investigated how exercise impacted chronological changes in anthropometrics, body composition, prostate-specific antigen (PSA) level and prognostic nutrition index (PNI) in high-risk prostate cancer (PCa) patients on androgen deprivation therapy (ADT). The patients were divided into either the usual care or exercise group. All patients received measurements a week before ADT initiation, six- and twelve months after treatment. The exercise group received both aerobic and resistance training. The analysis was conducted using appropriate statistical methods. There were 45 males enrolled (age 67.4 ± 8 years and BMI 25.5 ± 3.6 kg/m2). Profound changes were observed at six months follow-up. The exercise group showed a significant increase in the trunk and leg lean mass, and a lesser loss of total and arm lean mass. A significant decrease in PSA was also observed among the exercise group. PNI and PSA were significantly associated with regional lean mass. Exercise can prevent loss or even increase lean mass in high-risk PCa, especially in the early stage of ADT treatment. Moreover, a strong bond between lean mass and PNI and PSA further underscores the importance of early and continuous exercise interventions.

Abstract Background We previously developed a robust prognostic model (GS model) to predict the survival outcome of patients with advanced pancreatic cancer (APC) receiving palliative chemotherapy with gemcitabine plus S‐1 (GS). This study aimed to validate the application of the GS model in APC patients receiving chemotherapy other than the GS regimen. Patients and methods We retrospectively analyzed 727 APC patients who received first‐line palliative chemotherapy other than the GS regimen between 2010 and 2016 at four institutions in Taiwan. The patients were categorized into three prognostic groups based on the GS model for comparisons of survival outcome, best tumor response, and in‐group survival differences with monotherapy or combination therapy. Results The median survival times for the good, intermediate, and poor prognostic groups were 13.4, 8.4, and 4.6 months, respectively. The hazard ratios for the comparisons of intermediate and poor to good prognostic groups were 1.51 (95% confidence interval [CI]), 1.22‐1.88, P

Few prospective cohort trials have investigted the effect of pretreatment nutritional and inflammatory status on the clinical outcome of patients with cancer and optimal performance status and assessed the interplay between nutrition, inflammation, body composition, and circulating metabolites before treatment. Here, 50 patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2 were prospectively recruited along with 43 healthy participants. Before concurrent chemoradiotherapy, compared with healthy controls, the cancer group showed lower levels of histidine, leucine, and phenylalanine and had low values in anthropometric and body composition measurements; however, the group displayed higher ornithine levels, more malnutrition, and severe inflammation. Pretreatment advanced Glasgow prognostic score (1 and 2) status was the sole prognostic factor for 3-year mortality rate and was associated with age and serum histidine levels in patients with cancer. Thus, even at the same tumor stage and ECOG PS, patients with LAHNSCC, poor nutrition, and high inflammation severity at baseline may have inferior survival outcomes than those with adequate nutrition and low inflammation severity. Assessment of pretreatment nutritional and inflammatory status should be included in the enrollment criteria in future studies.

The immunomodulatory effects of regulatory T cells (Tregs) and co-signaling receptors have gained much attention, as they help balance immunogenic and immunotolerant responses that may be disrupted in autoimmune and infectious diseases. Drug hypersensitivity has a myriad of manifestations, which ranges from the mild maculopapular exanthema to the severe Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS). While studies have identified high-risk human leukocyte antigen (HLA) allotypes, the presence of the HLA allotype at risk is not sufficient to elicit drug hypersensitivity. Recent studies have suggested that insufficient regulation by Tregs may play a role in severe hypersensitivity reactions. Furthermore, immune checkpoint inhibitors, such as anti-CTLA-4 or anti-PD-1, in cancer treatment also induce hypersensitivity reactions including SJS/TEN and DRESS/DIHS. Taken together, mechanisms involving both Tregs as well as coinhibitory and costimulatory receptors may be crucial in the pathogenesis of drug hypersensitivity. In this review, we summarize the currently implicated roles of co-signaling receptors and Tregs in delayed-type drug hypersensitivity in the hope of identifying potential pharmacologic targets.

ObjectiveMetabolic syndrome (MetS) gains more attention due to high prevalence of obesity, diabetes and hypertension among adults. Although obesity, diabetes and hypertension can certainly compromise health-related quality of life (HRQoL), the correlations of sociodemographic factors, quality of life and MetS remains unclear. This study aims to investigate the association between HRQoL and MetS in an Asian community of the sociodemographic characteristics.Research design and methodsWe performed a cross-sectional study by recruiting 2588 Taiwanese patients aged ≥30 years between August 2015 and August 2017. Sociodemographic data and anthropometric variables were obtained from medical records and physical examination. Meanwhile, HRQoL was assessed by 36-Item Short-Form Health Survey questionnaires.ResultsThe overall prevalence of MetS was 32.8%. Multivariate analysis revealed that age ≥65 years (OR=1.987, p

Only few prospective cohort trials have evaluated the risk factors for the 2-year mortality rate between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC): oral cavity cancer with adjuvant concurrent chemoradiotherapy (CCRT) (OCC) and non-oral cavity cancer with primary CCRT (NOCC), under the recommended calorie intake and investigated the interplay among calorie supply, nutrition–inflammation biomarkers (NIBs), and total body composition change (TBC), as assessed using dual-energy X-ray absorptiometry (DXA). Patients with LAHNSCC who consumed at least 25 kcal/kg/day during CCRT were prospectively recruited. Clinicopathological variables, blood NIBs, CCRT-related factors, and TBC data before and after treatment were collected. Factor analysis was performed to reduce the number of anthropometric and DXA-derived measurements. Cox proportional hazards models were used for analysis. We enrolled 123 patients with LAHNSCC (69 with OCC and 54 with NOCC). The mean daily calorie intake correlated with the treatment interval changes in total body muscle and fat. Patients consuming ≥30 kcal/kg/day had lower pretreatment levels but exhibited fewer treatment interval changes in anthropometric and DXA measurements than patients consuming

Few prospective cohort trials have evaluated the difference in treatment-interval total body composition (TBC) changes assessed by dual-energy X-ray absorptiometry (DXA) between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC) receiving concurrent chemoradiotherapy (CCRT): oral cavity cancer with adjuvant CCRT (OCC) and non-oral cavity with primary CCRT (NOCC). This study prospectively recruited patients with LAHNSCC. Clinicopathological variables, blood nutritional/inflammatory markers, CCRT-related factors, and TBC data assessed by DXA before and after treatment were collected. Multivariate linear regression analysis identified the factors associated with treatment-interval changes in body composition parameters, including lean body mass (LBM), total fat mass (TFM), and bone mineral content (BMC). A total of 127 patients (OCC (n = 69) and NOCC (n = 58)) were eligible. Body composition parameters were progressively lost during CCRT in both subgroups. Extremities lost more muscle mass than the trunk for LBM, whereas the trunk lost more fat mass than the extremities for TFM. BMC loss preferentially occurred in the trunk region. Different factors were independently correlated with the interval changes of each body composition parameter for both OCC and NOCC subgroups, particularly mean daily calorie intake for LBM and TFM loss, and total lymphocyte count for BMC loss. In conclusion, treatment-interval TBC changes and related contributing factors differ between the OCC and NOCC subgroups.

Few prospective cohort trials have evaluated the potential risk factors of early treatment failure of locally advanced oral cavity squamous cell carcinoma (LAOCSCC) patients following the completion of postoperative adjuvant concurrent chemoradiotherapy (CCRT). We collected clinicopathological variables, nutrition-inflammatory markers and total body composition data assessed by dual-energy X-ray absorptiometry (DXA) before and after CCRT. A factor analysis was used to reduce the number of DXA-derived parameters. Cox proportional hazard models were applied to determine the risk factors associated with early treatment failure defined as tumor progression or death within 180 days of CCRT completion. A total of 69 patients were eligible for analysis. After CCRT, the body weight, body mass index, nutritional markers, and muscle mass decreased, whereas C-reactive protein level increased. Five factors reflecting different body composition statuses were identified. A total of 21 patients (30.4%) developed early treatment failure. Comorbidities (hazard ratio ((HR)), 2.699; 95% confidence interval ((CI)), 1.005–7.913; p = 0.044), radiation duration (HR, 1.092; 95% CI, 1.015–1.174; p = 0.018) and the pretreatment body muscle mass (HR, 0.578; 95% CI, 0.345–0.957; p = 0.037) independently contributed to early treatment failure. Comorbidities, longer radiation duration, and lower pretreatment body muscle mass are predictive factors for early treatment failure in LAOCSCC patients following postoperative adjuvant CCRT completion.

Background: This study investigates whether the appendicular skeletal muscle index (ASMI) was an independent prognostic predictor for patients with locally advanced head and neck cancer (LAHNC) receiving concurrent chemoradiotherapy (CCRT) and whether there were any differences in lean mass loss in different body regions during CCRT. Methods: In this prospective study, we analyzed the clinicopathological variables and the total body composition data before and after treatment. The factors associated with the 2-year recurrence-free survival rate (RFSR) were analyzed via logistic regression analysis. Results: A total of 98 patients were eligible for analysis. The body weight, body mass index, and all parameters of body composition significantly decreased after CCRT. The pretreatment ASMI was the only independent prognostic factor for predicting the 2-year RFSR (hazard ratio, 0.235; 95% confidence interval, 0.062–0.885; p = 0.030). There was at least 5% reduction in total lean and fat mass (p < 0.001); however, the highest lean mass loss was observed in the arms (9.5%), followed by the legs (7.2%), hips (7.1%), waist (4.7%), and trunk (3.6%). Conclusions: The pretreatment ASMI was the only independent prognostic predictor for the 2-year RFSR of LAHNC patients undergoing CCRT. Asynchronous loss of lean mass may be observed in different body parts after CCRT.

Study on the impact of pretreatment malnutrition on treatment outcomes in locally advanced head and neck cancer (LAHNC) patients is still lacking. We prospectively collected various malnutrition assessment methods including nutrition indexes, inflammatory biomarkers, and lean body mass index (LBMI) data before treatments. The one year mortality rate was assessed, and the factors associated with this outcome were investigated. Furthermore, the association between malnutrition assessment methods was examined. A total of 113 patients were enrolled. By prognostic stratification based on the prognostic nutritional index (PNI) and platelet-to-lymphocyte ratio (PLR) combination, the low PNI/high PLR group had highest and the high PNI/low PLR group had the lowest mortality rate. Furthermore, the PNI was positively correlated with the LBMI, and the PLR was inversely correlated with the LBMI. PNI and PLR were found to be independent prognostic factors of one year mortality and also associated with the loss of muscle.

Background: The time schedules for response evaluation of epidermal growth factor receptor-tyrosine kinase Inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients are still ill-defined. Methods: Stage IIIB/IV patients with histologically proven NSCLC were enrolled in this study if the tumor cells bore EGFR mutations other than T790M. Eligible patients were treated with either 250 mg of gefitinib or 150 mg of erlotinib once daily. The early response rate [computed tomography (CT) scan on Day 14], definitive response rate determined on Day 56, progression-free survival (PFS), overall survival (OS), and toxicity profile were assessed prospectively. Results: Thirty-nine patients were enrolled in this study. A total of 29 patients (29/39, 74.4%) achieved partial response (PR). Twenty-one patients (21/39, 53.8%) had early radiological response on Day 14. The early radiological response rate in patients with PR was 72.4% (21/29). Only eight patients without a PR on early CT still ended with PR. Among the 29 patients with PR, the PFS (8.1 months) and OS (18.3 months) of the 21 patients with early CT response were shorter than those of the 8 patients without early CT response (11.9 and 24.0 months for PFS and OS, respectively). But the survival differences were statistically non-significant. Conclusions: A very high percentage (72.4%, 21/29) of NSCLC patients with EGFR mutations with PR demonstrates early radiological response to EGFR-TKIs, which would advocate early radiological examination for EGFR-TKI therapy in NSCLC patients.

Dasatinib is a potent second-generation tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia. The most common adverse event associated with dasatinib therapy is fluid retention, including pleural effusion. Dasatinib-related chylothorax has rarely been reported. The clinical manifestations, pathophysiology, management, and prognosis are not fully understood. Here we report a 40-year-old woman presenting with chylothorax following dasatinib use. We propose the hypothesis of its mechanism as well as offering a review of the relevant literature.

Limited studies have assessed the associations of pretreatment serum glutamine level with clinicopathological characteristics and prognosis of colorectal cancer (CRC) patients. This study focuses on clarifying the clinical significance of baseline serum glutamine level in CRC patients. We retrospectively examine 123 patients with newly diagnosed CRC between 2009 and 2011. The associations of pretreatment serum glutamine level with clinicopathological characteristics, proinflammatory cytokines, overall survival (OS), and progression-free survival (PFS) were analyzed. We executed univariate and multivariate analyses to assess the associations between serum glutamine level and clinicopathological variables able to predict survival. Low glutamine levels were associated with older age, advanced stage, decreased albumin levels, elevated carcinoembryonic antigen levels, higher C-reactive protein levels, higher modified Glasgow prognostic scores, and higher proinflammatory cytokine levels. Furthermore, patients with low glutamine levels had poorer OS and PFS than those with high glutamine levels (p < 0.001 for both). In multivariate analysis, pretreatment glutamine level independently predicted OS (p = 0.016) and PFS (p = 0.037) in CRC patients. Pretreatment serum glutamine level constitutes an independent prognostic marker to predict survival and progression in CRC patients.

Taiwan is only now beginning to offer palliative care to patients who do not have cancer. This study aimed to document the polysymptomatic presentation of illness in Taiwanese patients with late-stage nonmalignant disease and to evaluate the potential benefits of palliative care for these patients. The results may help to educate healthcare personnel regarding the need for and importance of palliative treatment as comprehensive, appropriate end-of-life care for patients with nonmalignant disease. Methods: We retrospectively analyzed 115 patients without cancer hospitalized in a community hospital in Taiwan: 61 had organic brain disease, 31 had chronic obstructive pulmonary disease, 17 had chronic renal failure, 14 had congestive heart failure, 12 had liver cirrhosis, and 20 had multiple illnesses. The median age was 81 years (interquartile range 69–86 years), and 51% of patients were enrolled from intensive care. Symptoms and their severity were analyzed. Patients' and their families' understanding of the diagnosis and prognosis and “Do Not Resuscitate” (DNR) consent were evaluated pre- and post-palliative care. Results: The four leading symptoms were fatigue (96%), fever (86%), cough (81%), and dyspnea (79%). No significant differences in symptom prevalence were found between different sexes, ages, performance statuses, ward locations, or underlying diseases, except for fewer episodes of dizziness, more frequent episodes of cough in patients older than 80 years, and more episodes of jaundice in ward service subjects. Only the presence of abdominal distension differed significantly between surviving and deceased patients (22.9% vs. 40.3%; p=0.004). After the start of palliative care, patients' DNR consent increased (105/115 before, 114/115 after). Patients' recognition of the diagnosis and prognosis increased from 13 to 64, respectively, with a simultaneous increase in family members' recognition (66 before, 114 after). Conclusion: Hospice care with good symptom control is warranted for patients with late-stage nonmalignant disease who need appropriate end-of-life care. Medical personnel need education in the importance of palliative care and the identification of patients who could benefit from it. In addition, patients should be informed of its availability.

miR-27b has emerged as a regulatory hub in cholesterol and lipid metabolism, and as a potential therapeutic target for treating atherosclerosis and obesity. However, the impact of miR-27b on lipid levels in vivo remains to be determined. Zebrafish lipids are normally stored as triacylglycerols (TGs) and their main storage sites are visceral, intramuscular, and subcutaneous lipid depots, and not blood vessels and liver. In this study, we applied microRNA-sponge (miR-SP) technology and generated zebrafish expressing transgenic miR-27b-SP (C27bSPs), which disrupted endogenous miR-27b activity and induced intravascular lipid accumulation (hyperlipidemia) and the early onset of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Oil Red O staining predominantly increased in the blood vessels and livers of larvae and juvenile C27bSPs, indicating that miR-27b depletion functionally promoted lipid accumulation. C27bSPs also showed an increased weight gain with larger fat pads, resulting from adipocyte hyperplasia. Molecular analysis revealed that miR-27b depletion increased the expression of genes that are associated with lipogenesis and the endoplasmic reticulum (ER). Moreover, miR-27b-SP increased peroxisome proliferator-activated receptor γ (PPAR-γ), CCAAT enhancer binding protein-α (C/EBP-α, and sterol regulatory element binding transcription factor 1c (SREBP-1c) expression and contributed to lipogenesis and adipogenesis. Conclusion: Our results suggest that miR-27b-SP acts as a lipid enhancer by directly increasing the expression of several lipogenic/adipogenic transcriptional factors, resulting in increased lipogenesis and adipogenesis. In this study, miR-27b expression improved lipid metabolism in C27bSPs, which suggests that miR-27b is an important lipogenic factor in regulating early onset of hyperlipidemia and adipogenesis in zebrafish.