Publications by authors named "Wen-Chi Chou"

211 Publications

Liposomal irinotecan pre-emptive dose reduction in patients with pancreatic ductal adenocarcinoma: 667 patients' experience within a population-based study.

Ther Adv Med Oncol 2021 20;13:17588359211058255. Epub 2021 Nov 20.

Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 5 Fu-Hsing Street, 333 Kwei-Shan Shiang, Taoyuan.

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is currently the standard second-line treatment for patients with pancreatic ductal adenocarcinoma (PDAC) after previous failed gemcitabine-based therapy. This population-based study aimed to evaluate the efficacy and safety of nal-IRI + 5-FU/LV and the association of pre-emptive nal-IRI dosing with treatment outcomes in patients with PDAC.

Methods: We retrospectively enrolled a total of 667 consecutive patients with PDAC who received nal-IRI plus 5-FU/LV treatment between August 2018 and November 2020 at 9 medical centers in Taiwan. Patients were allocated into groups according to pre-emptive nal-IRI dosing (⩾75%, 50-74%, <50%) for comparison of treatment efficacy and safety.

Results: The median overall survival (OS) and time to treatment failure (TTF) were 5.9 months [95% confidence interval (CI), 5.3-6.5] and 2.8 months (95% CI, 2.6-3.0), respectively. The median OS was 6.5 months (95% CI, 5.7-6.7), 5.0 months (95% CI, 3.4-6.5), and 4.1 months (95% CI, 2.7-5.6), respectively, among the ⩾75%, 50-74%, and <50% pre-emptive nal-IRI dosing groups, whereas the median TTF of the three groups was 3.0 months (95% CI, 2.6-3.4), 2.6 months (95% CI, 2.3-2.9), and 1.9 months (95% CI, 1.6-2.2), respectively. Pre-emptive nal-IRI dosing <50% was an independent negative prognostic factor for OS and TTF in multivariate analyses. The most common severe adverse events were neutropenia (22.9%), anemia (21.1%), and hypokalemia (15.4%). Patients in the <50% pre-emptive nal-IRI dosing group had a significantly lower incidence of neutropenia and non-neutropenic infection than those in the other groups.

Conclusion: Our results support the use of nal-IRI + 5-FU/LV as standard clinical practice for treating patients with PDAC based on this large population-based study. Our findings encourage physicians to provide adequate doses of nal-IRI in order to achieve better outcomes without compromising safety profiles.
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http://dx.doi.org/10.1177/17588359211058255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606735PMC
November 2021

Association of frailty and chemotherapy-related adverse outcomes in geriatric patients with cancer: a pilot observational study in Taiwan.

Aging (Albany NY) 2021 11 8;13(21):24192-24204. Epub 2021 Nov 8.

Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Background: With the rapid growth of the elderly population and the increasing incidence of cancer, an increasing number of geriatric patients are receiving cancer treatment, making the selection of appropriate treatment an important issue. Increasing studies have confirmed that frailty can predict adverse outcomes in geriatric patients with cancer after treatment, but local data from Taiwan are lacking. Therefore, this study aimed to investigate the correlation between frailty and chemotherapy-related adverse outcomes in geriatric patients with cancer.

Material And Methods: A total of 234 geriatric patients aged ≥65 years with cancer receiving chemotherapy were enrolled during the study period of September 2016 to November 2018. The collected data included: patients' basic demographics and Comprehensive Geriatric Assessment (CGA) before treatment, chemotherapy-related adverse outcomes, unexpected hospitalizations, and emergency department visits within 3 months of treatment. We investigated the association between frailty and chemotherapy-related adverse outcomes in geriatric patients with cancer using the chi-square test and logistic regression analysis.

Results: The prevalence of frailty in geriatric patients with cancer was 58.1%. Age, marital status, main caregiver, cancer type, and Eastern Cooperative Oncology Group performance status, and physical fitness were factors associated with frailty. Frail geriatric patients with cancer were at higher risk of chemotherapy-related adverse outcomes, such as grades 3-4 thrombocytopenia (odds ratio [OR] = 11.13, = 0.021) and grades 3-4 hyponatremia (OR = 12.03, = 0.017), than non-frail patients, and they were at increased risk of unexpected hospitalizations (OR = 2.15, = 0.025) and emergency department visits (OR = 1.99, = 0.039).

Conclusions: Frailty is a common problem in geriatric patients with cancer and significantly impacts chemotherapy-related adverse outcomes. Our findings suggest that geriatric patients with cancer should undergo frail assessment prior to chemotherapy as a reference to guide future treatment decisions.
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http://dx.doi.org/10.18632/aging.203673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610137PMC
November 2021

Paclitaxel and Carboplatin Cisplatin and 5-Fluorouracil in Concurrent Chemoradiotherapy in Patients With Esophageal Cancer.

In Vivo 2021 Nov-Dec;35(6):3391-3399

Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.;

Background/aim: Cisplatin with 5-fluouracil (Cis/5Fu) and paclitaxel with carboplatin (Pac/Car) are common regimens used in concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal cancer (EC). Here, we aimed to compare the survival outcomes and treatment-related toxicities between these regimens in neoadjuvant CCRT in patients with locally advanced EC.

Patients And Methods: One hundred and thirty-six patients with locally advanced EC (98% squamous cell carcinoma) were prospectively recruited between 2016 and 2017 in a non-randomized manner. Patients were categorized into two groups according to the chemotherapeutic agents administered (Pac/Car group, n=87; Cis/5Fu group, n=47) in CCRT to compare the survival outcome and severe adverse event (sAE) incidence.

Results: Forty-two patients (85.7%) and 80 patients (91.4%) in the Cis/5Fu and Pac/Car groups completed pre-planned CCRT (p=0.26), respectively. The Cis/5Fu group presented a higher incidence of non-hematological sAE than the Pac/Car group (69.45% vs. 51.7%, p=0.049). Patients in the Pac/Car group showed a higher rate of surgical resection than those in the Cis/5Fu group (49.4% vs. 22.4%, p<0.001). After a median follow-up duration of 22.0 months (range=1.9-31.8), the 2-year survival rate was 56.9% for patients in the Pac/Car group and 28.7% for the Cis/5Fu group. The hazard ratio (HR) of overall survival was 0.45 (95%CI=0.28-0.72, p=0.001) in the comparison between the groups.

Conclusion: Overall, neoadjuvant CCRT with Pac/Car is associated with a better survival outcome, higher surgical resection rate, and better safety profiles than Cis/5Fu in patients with locally advanced EC.
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http://dx.doi.org/10.21873/invivo.12638DOI Listing
October 2021

Impact of Frailty on Treatment Outcome in Patients With Locally Advanced Esophageal Cancer Undergoing Concurrent Chemoradiotherapy.

Anticancer Res 2021 Oct;41(10):5213-5222

Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.;

Background/aim: The clinical significance of frailty status on treatment outcome in patients with esophageal cancer (EC) has been seldom explored. This study aimed to evaluate the impact of pretreatment frailty on treatment-related toxicity and survival outcome in patients with EC undergoing concurrent chemoradiotherapy (CCRT).

Patients And Methods: Patients aged ≥20 years and with newly diagnosed locally advanced EC receiving neoadjuvant radiotherapy and concurrent chemotherapy with weekly administration of carboplatin and paclitaxel for 5 weeks were prospectively enrolled. A pretreatment frailty assessment was performed within 7 days before CCRT initiation. The primary endpoint was treatment-related toxicity and complications of CCRT while the secondary endpoint was overall survival.

Results: A total of 87 patients were enrolled, 41 (47%) and 46 (53%) of whom were allocated in the frail and fit group, respectively. Frail patients had a significantly higher incidence of having at least one severe hematological adverse event (63.4% vs. 19.6%, p<0.001), higher risk of emergent room visiting [relative risk 3.72; 95% confidence interval (CI)=1.39-9.91; p=0.009] and hospitalization (relative risk 3.85; 95% CI=1.03-11.2; p=0.013) during the course of CCRT, when compared to fit patients. Overall survival showed significant worsening in the frail group [adjusted hazard ratio (HR)=2.12; 95% CI=1.01-4.42; p=0.046].

Conclusion: Frailty is associated with increase of treatment-related toxicities and poor survival outcome in EC patients undergoing CCRT. Our study suggested that pretreatment frailty assessment is imperative to serve as a predictor and prognostic factor for all adult patients with EC undergoing CCRT.
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http://dx.doi.org/10.21873/anticanres.15340DOI Listing
October 2021

Factors associated with distinct prognostic-awareness-transition patterns over cancer patients' last 6 months of life.

Cancer Med 2021 Nov 30;10(22):8029-8039. Epub 2021 Sep 30.

Division of Hematology-Oncology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.

Background: Cancer patients may develop prognostic awareness (PA) heterogeneously, but predictors of PA-transition patterns have never been studied. We aimed to identify transition patterns of PA and their associated factors during cancer patients' last 6 months.

Methods: For this secondary-analysis study, PA was assessed among 334 cancer patients when they were first diagnosed as terminally ill and monthly till they died. PA was categorized into four states: (a) unknown and not wanting to know; (b) unknown but wanting to know; (c) inaccurate awareness; and (d) accurate awareness. The first and last PA states estimated by hidden Markov modeling were examined to identify their change patterns. Factors associated with distinct PA-transition patterns were determined by multinomial logistic regressions focused on modifiable time-varying variables assessed in the wave before the last PA assessment to ensure a clear time sequence for associating with PA-transition patterns.

Results: Four PA-transition patterns were identified: maintaining accurate PA (56.3%), gaining accurate PA (20.4%), heterogeneous PA (7.8%), and still avoiding PA (15.6%). Reported physician-prognostic disclosure increased the likelihood of belonging to the maintaining-accurate-PA group than to other groups. Greater symptom distress predisposed patients to be in the still-avoiding-PA than the heterogeneous PA group. Patients with higher functional dependence and more anxiety/depressive symptoms were more and less likely to be in the heterogeneous PA group and in the still-avoiding-PA group, respectively, than in the maintaining- and gaining-accurate PA groups.

Conclusions: Cancer patients heterogeneously experienced PA-transition patterns over their last 6 months. Physicians' prognostic disclosure, and patients' symptom distress, functional dependence, and anxiety/depressive symptoms, all modifiable by high-quality end-of-life care, were associated with distinct PA-transition patterns.
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http://dx.doi.org/10.1002/cam4.4321DOI Listing
November 2021

Concurrent Chemoradiotherapy Induces Body Composition Changes in Locally Advanced Head and Neck Squamous Cell Carcinoma: Comparison between Oral Cavity and Non-Oral Cavity Cancer.

Nutrients 2021 Aug 26;13(9). Epub 2021 Aug 26.

Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 333007, Taiwan.

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 ( = 69) and NOCC ( = 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.
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http://dx.doi.org/10.3390/nu13092969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472371PMC
August 2021

Caregivers' Death-Preparedness States Impact Caregiving Outcomes and Patients' End-of-Life Care.

J Pain Symptom Manage 2021 Sep 24. Epub 2021 Sep 24.

Division of Hematology-Oncology (W-C. C, M-M.H, P.J.S., W-C.S., J.-S.C., W-C.C., S.T.T.), Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan, Republic of China; School of Nursing (M.H.H., S.T.T.), Chang Gung University, Tao-Yuan, Taiwan, Republic of China; Department of Nursing (S.T.T.), Chang Gung Memorial Hospital at Kaohsiung, Taiwan, Republic of China. Electronic address:

Background/objective: Preparing family caregivers, cognitively, emotionally, and behaviorally, for their relative's death is an actionable component of high-quality end-of-life care. We aimed to examine the never-before-examined associations of conjoint cognitive prognostic awareness and emotional preparedness for death with caregiving outcomes and end-of-life care received by cancer patients.

Design/setting/participants/main Measures: For this longitudinal study, associations of death-preparedness states (no-death-preparedness, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) with subjective caregiving burden, depressive symptoms, and quality of life (QOL) and patients' end-of-life care (chemotherapy and/or immunotherapy, cardiopulmonary resuscitation, intensive care unit care, intubation, mechanical ventilation support, vasopressors, nasogastric tube feeding, and hospice care) were evaluated using multivariate hierarchical linear and logistic regression modeling, respectively, for 377 caregivers in cancer patients' last 6 months and 1 month, respectively.

Key Results: Caregivers in the cognitive-death-preparedness-only state experienced a higher level of subjective caregiving burden than those in the sufficient-death-preparedness state. Caregivers in the no-death-preparedness and cognitive-death-preparedness-only states reported significantly more depressive symptoms and worse QOL than those in the sufficient-death-preparedness state. Cancer patients with caregivers in the sufficient-death-preparedness state were less likely to receive chemotherapy and/or immunotherapy, intubation, mechanical ventilation, and nasogastric tube feeding than patients with caregivers in other death-preparedness states. However, patients' receipt of hospice care was not associated with their caregivers' death-preparedness states.

Conclusion: Family caregivers' death-preparedness states were associated with caregiving outcomes and their relative's end-of-life care. Cultivating caregivers' accurate prognostic awareness and improving their emotional preparedness for their relative's death may facilitate more favorable end-of-life-caregiving outcomes and may limit potentially nonbeneficial end-of-life care.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.09.012DOI Listing
September 2021

Associations of death-preparedness states with bereavement outcomes for family caregivers of terminally ill cancer patients.

Psychooncology 2021 Sep 22. Epub 2021 Sep 22.

Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan, ROC.

Objective: Death preparedness involves cognitive prognostic awareness and emotional acceptance of a relative's death. Effects of retrospectively assessed cognitive prognostic awareness and emotional preparedness for patient death have been individually investigated among bereaved family caregivers. We aimed to prospectively examine associations of caregivers' death-preparedness states, determined by conjoint cognitive prognostic awareness and emotional preparedness for death, with bereavement outcomes.

Methods: Associations of caregivers' death-preparedness states (no-death-preparedness, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) at last preloss assessment with bereavement outcomes over the first two bereavement years were evaluated among 332 caregivers of advanced cancer patients using hierarchical linear models with the logit-transformed posterior probability for each death-preparedness state.

Results: Caregivers with a higher logit-transformed posterior probability for sufficient death-preparedness state reported less prolonged-grief symptoms, lower likelihoods of severe depressive symptoms and heightened decisional regret, and better mental health-related quality of life (HRQOL). Caregivers with a higher logit-transformed posterior probability for no-death-preparedness state reported less prolonged-grief symptoms, a lower likelihood of severe depressive symptoms, and better mental HRQOL. A higher logit-transformed posterior probability for cognitive-death-preparedness-only state was associated with bereaved caregivers' higher likelihood of heightened decisional regret, whereas that for emotional-death-preparedness-only state was not associated with caregivers' bereavement outcomes.

Conclusions: Caregivers' bereavement outcomes were associated with their preloss death-preparedness states, except for physical health-related QOL. Interventions focused on not only cultivating caregivers' accurate prognostic awareness but also adequately preparing them emotionally for their relative's forthcoming death are actionable opportunities for high-quality end-of-life care and are urgently warranted to facilitate caregivers' bereavement adjustment.
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http://dx.doi.org/10.1002/pon.5827DOI Listing
September 2021

Associations between Family Satisfaction with End-of-Life Care and Chart-Derived, Process-Based Quality Indicators in Intensive Care Units.

J Palliat Med 2021 Sep 1. Epub 2021 Sep 1.

Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan, Republic of China.

Evidence linking process-based, high-quality end-of-life (EOL) care indicators to family satisfaction with EOL care in intensive care units (ICUs) remains limited. This study aimed to fill this gap. For this exploratory, prospective, longitudinal observational study, 278 family members were consecutively recruited from medical ICUs at two medical centers in Taiwan. Family satisfaction with ICU care was surveyed in the first month after patient death using the Family Satisfaction in the ICU questionnaire (FS-ICU). Associations between FS-ICU scores and process-based quality indicators collected over the patient's ICU stay were examined using generalized estimating equations. Documentation of process-based indicators of high-quality EOL care was generally associated with higher scores for both the FS-ICU Care and FS-ICU Decision-Making domains. Higher family satisfaction with ICU care was significantly associated with physician-family prognostic communication ( [95% confidence interval (CI)]: 3.558 [2.963 to 4.154]), a do-not-resuscitate (DNR) order in place at death (23.095 [17.410 to 28.779]), and death without cardiopulmonary resuscitation (CPR) (13.325 [11.685 to 14.965]). Family members' satisfaction with decision making was positively associated with documentation of social worker involvement (4.767 [0.663 to 8.872]), a DNR order issued (10.499 [0.223 to 20.776]), and withdrawal of life-sustaining treatments (LSTs) before death (2.252 [1.834 to 2.670]). EOL care processes are associated with family satisfaction with EOL care in ICUs. Bereaved family members' satisfaction with EOL care in ICUs may be improved by promoting physician-family prognostic communication and psychosocial support, facilitating a DNR order and death without CPR, and withdrawing LSTs for patients dying in ICUs.
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http://dx.doi.org/10.1089/jpm.2021.0304DOI Listing
September 2021

Comorbidity, Radiation Duration, and Pretreatment Body Muscle Mass Predict Early Treatment Failure in Taiwanese Patients with Locally Advanced Oral Cavity Squamous Cell Carcinoma after Completion of Adjuvant Concurrent Chemoradiotherapy.

Diagnostics (Basel) 2021 Jul 2;11(7). Epub 2021 Jul 2.

Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 333007, Taiwan.

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; = 0.044), radiation duration (HR, 1.092; 95% CI, 1.015-1.174; = 0.018) and the pretreatment body muscle mass (HR, 0.578; 95% CI, 0.345-0.957; = 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.
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http://dx.doi.org/10.3390/diagnostics11071203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306647PMC
July 2021

Course and predictors of posttraumatic stress-related symptoms among family members of deceased ICU patients during the first year of bereavement.

Crit Care 2021 08 5;25(1):282. Epub 2021 Aug 5.

Department of Nursing, Chang Gung Memorial Hospital at Kaohsiung, Tao-Yuan, Taiwan, R.O.C.

Background/objective: Death in intensive care units (ICUs) may increase bereaved family members' risk for posttraumatic stress disorder (PTSD). However, posttraumatic stress-related symptoms (hereafter as PTSD symptoms) and their precipitating factors were seldom examined among bereaved family members and primarily focused on associations between PTSD symptoms and patient/family characteristics. We aimed to investigate the course and predictors of clinically significant PTSD symptoms among family members of deceased ICU patients by focusing on modifiable quality indicators for end-of-life ICU care.

Method: In this longitudinal observational study, 319 family members of deceased ICU patients were consecutively recruited from medical ICUs from two Taiwanese medical centers. PTSD symptoms were assessed at 1, 3, 6, and 13 months post-loss using the Impact of Event Scale-Revised (IES-R). Family satisfaction with end-of-life care in ICUs was assessed at 1 month post-loss. End-of-life care received in ICUs was documented over the patient's ICU stay. Predictors for developing clinically significant PTSD symptoms (IES-R score ≥ 33) were identified by multivariate logistic regression with generalized estimating equation modeling.

Results: The prevalence of clinically significant PTSD symptoms decreased significantly over time (from 11.0% at 1 month to 1.6% at 13 months post-loss). Longer ICU stays (adjusted odds ratio [95% confidence interval] = 1.036 [1.006, 1.066]), financial insufficiency (3.166 [1.159, 8.647]), and reported use of pain medications (3.408 [1.230, 9.441]) by family members were associated with a higher likelihood of clinically significant PTSD symptoms among family members during bereavement. Stronger perceived social support (0.937 [0.911, 0.965]) and having a Do-Not-Resuscitate (DNR) order issued before the patient's death (0.073 [0.011, 0.490]) were associated with a lower likelihood of clinically significant PTSD symptoms. No significant association was observed for family members' satisfaction with end-of-life care (0.988 [0.944, 1.034]) or decision-making in ICUs (0.980 [0.944, 1.018]).

Conclusions: The likelihood of clinically significant PTSD symptoms among family members decreased significantly over the first bereavement year and was lower when a DNR order was issued before death. Enhancing social support and facilitating a DNR order may reduce the trauma of ICU death of a beloved for family members at risk for developing clinically significant PTSD symptoms.
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http://dx.doi.org/10.1186/s13054-021-03719-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340476PMC
August 2021

Real-World Effectiveness of Adjuvant Oxaliplatin Chemotherapy in Stage III Colon Cancer: A Controlled Interrupted Time Series Analysis.

Front Pharmacol 2021 29;12:693009. Epub 2021 Jun 29.

Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

The real-world effectiveness of oxaliplatin in stage III colon cancer has not been determined in a large-scale population. We aimed to assess the real-world impact of adjuvant oxaliplatin treatment on the survival of these patients. Based on Taiwan cancer registry, we evaluated 17,801 patients with resected stage III colon cancer, including 14,168 patients receiving adjuvant chemotherapy and 3,633 not receiving adjuvant chemotherapy as the control group between 2004 and 2014. We used the controlled interrupted time-series analysis to assess the three-year disease-free survival and five-year overall survival rates before (2004-2008) and after (2009-2014) the addition of oxaliplatin. The introduction of oxaliplatin was associated with no significant improvement in the slopes (per half-year) of the three-year disease-free survival rate (0.2%, 95% CI: -1.7∼2.2%) and five-year overall survival rate (0.6%, 95% CI: -1.8∼3%). The patients receiving oxaliplatin-based chemotherapy also showed no significant increase in the slopes (per half-year) of the three-year disease-free survival rate (0.6%, 95% CI: -1.4∼2.6%) and five-year overall survival rate (1%, 95% CI: -1.5∼3.5%). The nonsignificant results were consistent across subgroup analyses of age (<70 vs. ≥70 years), recurrence risk (T1-3 or N1 vs. T4 or N2), and cycle of oxaliplatin use (≤6 vs. >6). However, oxaliplatin-based chemotherapy significantly increased the slope (per half-year) of the five-year OS (2%, 95% CI: 0.2∼3.8%) for patients in the high-risk group (T4 or N2). The present results were robust in several sensitivity analyses. Among real-world patients with stage III colon cancer, the introduction of oxaliplatin does not yield a significant improvement in survival. Future work should identify the subpopulation(s) of patients who benefit significantly from the addition of oxaliplatin.
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http://dx.doi.org/10.3389/fphar.2021.693009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276019PMC
June 2021

Establishment of a Pretreatment Nomogram to Predict the 6-Month Mortality Rate of Patients with Advanced Biliary Tract Cancers Undergoing Gemcitabine-Based Chemotherapy.

Cancers (Basel) 2021 Jun 23;13(13). Epub 2021 Jun 23.

Department of Internal Medicine, Division of Haematology-Oncology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, 333 Taoyuan, Taiwan.

Background: The estimation of mortality risk among patients diagnosed with advanced cancer provides important information for clinicians and patients in clinical practice. Currently, gemcitabine-based chemotherapy regimens are the standard treatment for patients with advanced biliary tract cancer (BTC). We aimed to develop a nomogram to predict the 6-month mortality rate among patients with advanced BTC to help physicians evaluate treatment options and outcomes.

Patients: We conducted a retrospective analysis to evaluate the 6-month mortality rate among patients with advanced BTC who underwent gemcitabine-based chemotherapy from 2012 to 2018. Data regarding pretreatment factors and the clinical response to treatment were collected. Univariate and multivariate analyses were performed to identify independent factors for nomogram creation.

Results: A total of 202 advanced BTC patients who were treated with gemcitabine-based chemotherapy were included in this analysis. No difference in survival was identified between patients undergoing gemcitabine monotherapy and those treated with gemcitabine combined with other cytotoxic agents. The univariate analysis revealed 10 significant factors, while the multivariate analysis identified four independent factors, including gender, monocyte to lymphocyte ratio (MLR), alkaline phosphatase (ALP), and liver metastasis, which were used to establish the nomogram. The performance of this nomogram for the prediction of 6-month mortality risk was found to be promising and feasible based on logistic regression.

Conclusion: A nomogram based on four independent pretreatment factors, including gender, MLR, ALP, and liver metastasis, was established to predict the 6-month mortality risk in patients with advanced BTC; it can provide clinicians and patients with additional information when evaluating treatment outcomes.
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http://dx.doi.org/10.3390/cancers13133139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268608PMC
June 2021

Utility of Palliative Prognostic Index in Predicting Survival Outcomes in Patients With Hematological Malignancies in the Acute Ward Setting.

Am J Hosp Palliat Care 2021 Jul 1:10499091211028820. Epub 2021 Jul 1.

Division of Hema-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Background: The palliative prognostic index (PPI) predicts the life expectancy of patients with terminally ill cancer in hospice settings. This study aimed to evaluate PPI as a prognostic tool for predicting the life expectancy of patients with hematological malignancies admitted to the acute ward.

Methods: A total of 308 patients with hematological malignancies admitted to the hematological ward at a medical center between January 2016 and December 2017 were consecutively enrolled. PPI was scored within 24 h of admission. All patients were categorized into 3 groups by PPI for comparing survival and in-hospital mortality rates.

Results: The median survival times were 38.4, 3.6, and 1.1 months for patients with good, intermediate, and poor prognostic group, respectively. The hazard ratio was 2.31 (95% CI 1.59-3.35, p < 0.001) when comparing the intermediate and good prognosis groups, and 3.90 (95% CI 2.52-6.03, p < 0.001) when comparing the poor and good prognosis groups. Forty-five (14.6%) patients died at discharge; in-hospital mortality rates among the good, intermediate, and poor prognostic groups were 9.0%, 23.4%, and 46.4%, respectively. The adjusted odds ratio for in-hospital mortality was 1.96 (95% CI, 0.80-4.82, p = 0.14) and 5.25 (95% CI, 2.01-13.7, p < 0.001) for patients in the intermediate and poor prognostic groups compared to those in the good prognostic group.

Conclusion: PPI is an accurate prognostic tool for predicting survival times and in-hospital mortality rates in patients with hematological malignancies in an acute ward setting. PPI could assist clinicians in discussing end-of-life issues and in referring patients with hematological malignancies to palliative care.
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http://dx.doi.org/10.1177/10499091211028820DOI Listing
July 2021

A novel computational framework for genome-scale alternative transcription units prediction.

Brief Bioinform 2021 Nov;22(6)

School of Mathematics, Shandong University, Jinan 250200, China.

Alternative transcription units (ATUs) are dynamically encoded under different conditions and display overlapping patterns (sharing one or more genes) under a specific condition in bacterial genomes. Genome-scale identification of ATUs is essential for studying the emergence of human diseases caused by bacterial organisms. However, it is unrealistic to identify all ATUs using experimental techniques because of the complexity and dynamic nature of ATUs. Here, we present the first-of-its-kind computational framework, named SeqATU, for genome-scale ATU prediction based on next-generation RNA-Seq data. The framework utilizes a convex quadratic programming model to seek an optimum expression combination of all of the to-be-identified ATUs. The predicted ATUs in Escherichia coli reached a precision of 0.77/0.74 and a recall of 0.75/0.76 in the two RNA-Sequencing datasets compared with the benchmarked ATUs from third-generation RNA-Seq data. In addition, the proportion of 5'- or 3'-end genes of the predicted ATUs, having documented transcription factor binding sites and transcription termination sites, was three times greater than that of no 5'- or 3'-end genes. We further evaluated the predicted ATUs by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. The results suggested that gene pairs frequently encoded in the same ATUs are more functionally related than those that can belong to two distinct ATUs. Overall, these results demonstrated the high reliability of predicted ATUs. We expect that the new insights derived by SeqATU will not only improve the understanding of the transcription mechanism of bacteria but also guide the reconstruction of a genome-scale transcriptional regulatory network.
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http://dx.doi.org/10.1093/bib/bbab162DOI Listing
November 2021

Alpha-fetoprotein for Gastric Cancer Staging: An Essential or Redundant Tumor Marker?

Anticancer Res 2021 May;41(5):2711-2718

Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.;

Background/aim: This study was designed to clarify the value of routine alpha-fetoprotein (AFP) testing for patients with gastric cancer (GC).

Patients And Methods: A total of 905 patients with newly diagnosed GC and available pretreatment carcinoembryonic antigen (CEA), cancer-related antigen 19-9 (CA19-9), and AFP data from 2010 to 2016 were collected for comparison of tumor stage and survival.

Results: In total, 139 patients (15.4%), 155 patients (17.1%), and 27 patients (3.0%) had elevated CEA, CA19-9, and AFP levels, respectively. The c-index values of elevated AFP levels in predicting stage IV disease and the 1-year mortality rate were 0.564 (95%CI=0.520-0.608) and 0.594 (95%CI=0.553-0.635), respectively, which were significantly lower than those of CEA (0.673 and 0.665) and CA19-9 (0.619 and 0.618).

Conclusion: Elevated AFP is rare in patients with newly diagnosed GC. Routine AFP sampling would not provide a higher survival prediction in GC patients than CEA or CA19-9.
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http://dx.doi.org/10.21873/anticanres.15052DOI Listing
May 2021

Clinical and Immunologic Responses to a B-Cell Epitope Vaccine in Patients with HER2/neu-Overexpressing Advanced Gastric Cancer-Results from Phase Ib Trial IMU.ACS.001.

Clin Cancer Res 2021 Jul 20;27(13):3649-3660. Epub 2021 Apr 20.

Imugene Limited, Sydney, Australia.

Purpose: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988).

Patients And Methods: A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1.

Results: IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses.

Conclusions: IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3742DOI Listing
July 2021

Impact of Pancreatic Resection on Survival in Locally Advanced Resectable Gastric Cancer.

Cancers (Basel) 2021 Mar 14;13(6). Epub 2021 Mar 14.

Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.

Whether gastric adenocarcinoma (GC) patients with adjacent organ invasion (T4b) benefit from aggressive surgery involving pancreatic resection (PR) remains unclear. This study aimed to clarify the impact of PR on survival in patients with locally advanced resectable GC. Between 1995 and 2017, patients with locally advanced GC undergoing radical-intent gastrectomy with and without PR were enrolled and stratified into four groups: group 1 (G1), pT4b without pancreatic resection (PR); group 2 (G2), pT4b with PR; group 3 (G3), positive duodenal margins without Whipple's operation; and group 4 (G4), cT4b with Whipple's operation. Demographics, clinicopathological features, and outcomes were compared between G1 and G2 and G3 and G4. G2 patients were more likely to have perineural invasion than G1 patients (80.6% vs. 50%, < 0.001). G4 patients had higher lymph node yield (40.8 vs. 31.3, = 0.002), lower nodal status ( = 0.029), lower lymph node ratios (0.20 vs. 0.48, < 0.0001) and higher complication rates (45.2% vs. 26.3%, = 0.047) than G3 patients. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly longer in G1 than in G2 (28.1% vs. 9.3%, = 0.003; 32% vs. 13%, = 0.004, respectively). The 5-year survival rates did not differ between G4 and G3 (DFS: 14% vs. 14.4%, = 0.384; OS: 12.6% vs. 16.4%, = 0.321, respectively). In conclusion, patients with T4b lesion who underwent PR had poorer survival than those who underwent resection of other adjacent organs. Further Whipple's operation did not improve survival in pT3-pT4 GC with positive duodenal margins.
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http://dx.doi.org/10.3390/cancers13061289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001184PMC
March 2021

Depressive-Symptom Trajectories From End-of-Life Caregiving Through the First 2 Bereavement Years for Family Caregivers of Advanced Cancer Patients.

J Pain Symptom Manage 2021 10 29;62(4):699-708. Epub 2021 Mar 29.

Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan, ROC; School of Nursing, Chang Gung University, Tao-Yuan, Taiwan, ROC; Department of Nursing, Chang Gung Memorial Hospital at Kaohsiung, Taiwan, ROC. Electronic address:

Background: Family caregivers' distinct depressive-symptom trajectories are understudied and have been examined independently during end-of-life (EOL) caregiving or bereavement, making it difficult to validate two competing hypotheses (wear-and-tear vs. relief) of caregiving effects on bereavement. Existing studies may also miss short-term heterogeneity in depressive symptoms during the immediate postloss period due to lengthy delays in the first postloss assessment.

Purpose: This secondary-analysis study examined distinct depressive-symptom trajectories for caregivers of advanced cancer patients from EOL caregiving through the first 2 bereavement years with closely spaced assessments.

Methods: Depressive symptoms were measured monthly during EOL caregiving and 1, 3, 6, 13, 18, and 24 months postloss among 661 caregivers using the Center for Epidemiologic Studies-Depression scale. Depressive-symptom trajectories were identified using latent-class growth analysis while controlling for gender and age.

Results: We identified seven distinct depressive-symptom trajectories (prevalence) characterized by the timing, intensity, and duration of depressive symptoms: minimal-impact resilience (20.4%), recovery (34.0%), preloss-grief only (21.6%), delayed symptomatic (9.1%), relief (5.9%), prolonged symptomatic (6.5%), and chronically persistent distressed (2.5%).

Conclusion: Caregivers of advanced cancer patients responded heterogeneously to the stresses of EOL caregiving and bereavement. The majority of caregivers was resilient while providing caregiving and quickly rebounded to healthy levels of psychological functioning during bereavement, whereas a minority experienced delayed-symptomatic, prolonged-symptomatic, or chronically-persistent-distressing depressive-symptom trajectories. Linking caregivers' psychological experiences from caregiving through bereavement by closely spaced assessments can more comprehensively illustrate their depressive-symptom trajectories, which confirm both the wear-and-tear and relief hypotheses, and help in targeting interventions for distinct depressive-symptom trajectories.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.03.018DOI Listing
October 2021

A comparison of the MNA-SF, MUST, and NRS-2002 nutritional tools in predicting treatment incompletion of concurrent chemoradiotherapy in patients with head and neck cancer.

Support Care Cancer 2021 Sep 11;29(9):5455-5462. Epub 2021 Mar 11.

Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Background: Concurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT.

Material And Methods: Three nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded.

Results: A total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9-6.3% and 14.5-18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801-0.837, p<0.001 for all) and accurately predicted the incompletion of CCRT. MNA-SF had the highest performance in predicting treatment-related toxicity, including emergency room visits, need for hospitalization, any grade III or higher hematological adverse events, and critical body weight loss, compared to the other tools.

Conclusions: MNA-SF, MUST, and NRS2002 were all shown to be competent tools for prediction of treatment incompletion and treatment-related toxicity in HNC patients undergoing CCRT. We suggest implementing nutritional assessment prior to treatment to improve the rate of treatment completion and to reduce treatment-related toxicity in HNC patients.
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http://dx.doi.org/10.1007/s00520-021-06140-wDOI Listing
September 2021

Role of the Appendicular Skeletal Muscle Index for Predicting the Recurrence-Free Survival of Head and Neck Cancer.

Diagnostics (Basel) 2021 Feb 14;11(2). Epub 2021 Feb 14.

Osteoporosis Prevention and Treatment Center, Chang Gung Memorial Hospital, Keelung 222, Taiwan.

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; = 0.030). There was at least 5% reduction in total lean and fat mass ( < 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.
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http://dx.doi.org/10.3390/diagnostics11020309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918727PMC
February 2021

High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial.

Radiother Oncol 2021 05 3;158:146-154. Epub 2021 Mar 3.

Department of Radiation Oncology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan; Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, and Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan. Electronic address:

Purpose: Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC.

Methods And Materials: Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software.

Results: In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9.

Conclusion: Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.
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http://dx.doi.org/10.1016/j.radonc.2021.02.037DOI Listing
May 2021

Comparative prognostic value of different preoperative complete blood count cell ratios in patients with oral cavity cancer treated with surgery and postoperative radiotherapy.

Cancer Med 2021 03 23;10(6):1975-1988. Epub 2021 Feb 23.

Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.

Background: We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT).

Methods: We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest.

Results: The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656-0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478-0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high-risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p < 0.03)-with a borderline significance being evident for DC in patients with T4 disease (p = 0.058).

Conclusions: A high pretreatment NLR was an independent unfavorable risk factor for both OS and DC in patients with OSCC who underwent surgery and PORT. No other preoperative complete blood count parameters and cell ratios were found to have prognostic significance.
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http://dx.doi.org/10.1002/cam4.3738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957172PMC
March 2021

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.

BMC Microbiol 2021 02 18;21(1):53. Epub 2021 Feb 18.

Infectious Disease & Microbiome Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.

Background: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs.

Results: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions.

Conclusion: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI.

Trial Registration: Clinical trial registration number: ClinicalTrials.gov NCT01776021 .
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http://dx.doi.org/10.1186/s12866-021-02106-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890861PMC
February 2021

Distinct Death-Preparedness States by Combining Cognitive and Emotional Preparedness for Death and Their Evolution for Family Caregivers of Terminally Ill Cancer Patients Over Their Last 6 Months of Life.

J Pain Symptom Manage 2021 09 6;62(3):503-511. Epub 2021 Feb 6.

Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taiwan; Chang Gung University, School of Nursing, Taiwan; Department of Nursing, Chang Gung Memorial Hospital at Kaohsiung, Taiwan. Electronic address:

Context: To identify caregivers' death-preparedness states by combining cognitive and emotional preparedness for their loved one's death as well as their evolution over cancer patients' last 6 months, which have never been explored.

Methods: Death-preparedness states and their evolution were examined by hidden Markov modeling among 393 caregivers of cancer patients.

Results: Four death-preparedness states were identified: no death preparedness, cognitive death preparedness only, emotional death preparedness only, and sufficient death preparedness. Caregivers in the no-death-preparedness state had neither accurate cognitive prognostic awareness (PA) nor adequate emotional preparedness for death. Caregivers in the sufficient-death-preparedness state reported accurate PA and adequate emotional preparedness for death. In the cognitive- and emotional-death-preparedness-only states, caregivers were accurately aware of the patient's prognosis and adequately emotionally prepared for his/her forthcoming death only, respectively. Prevalence of the sufficient-death-preparedness state fluctuated within a narrow range (40.8%-43.2%) over the patient's last six months. Proportions of caregivers decreased in the emotional-death-preparedness-only (19.5%-6.5%) and no-death-preparedness (21.0%-8.2%) states, whereas prevalence of the cognitive-death-preparedness-only state increased substantially (16.3%-44.4%) to become the most prevalent state as death approached.

Conclusion: Caregivers of cancer patients heterogeneously experienced combined cognitive and emotional preparedness for death. About 40% of caregivers consistently had sufficient death preparedness over their loved one's dying process. Evaluating these different aspects of death preparedness could be an important approach in high-quality end-of-life care by not only cultivating caregivers' cognitive PA, but also facilitating their emotional preparedness for the patient's death, thus helping caregivers prepare well for their loved one's forthcoming death.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.01.131DOI Listing
September 2021

Conjoint cognitive and emotional death-preparedness states and their changes within cancer patients' last 6 months.

Psychooncology 2021 05 4;30(5):691-698. Epub 2021 Jan 4.

Department of Internal Medicine, Division of Hematology-Oncology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC.

Background/objective: Cognitive prognostic awareness (PA) and emotional preparedness for death are distinct but related concepts that have rarely been investigated conjointly and without considering the dynamic nature of death preparedness. To fill this gap, this secondary-analysis study identified distinct patterns/states of death preparedness and their changes within cancer patients' last 6 months.

Methods: Distinct death-preparedness states, determined by conjoint cognitive PA and emotional preparedness for death, as well as their changes between consecutive times were identified and estimated, respectively, by latent transition modeling with hidden Markov modeling among 383 cancer patients within their last 6 months.

Results: Four death-preparedness states (prevalence) were initially identified: no death preparedness (17.1%), cognitive death preparedness only (23.3%), emotional death preparedness only (39.9%), and sufficient death preparedness (19.7%). Patients in the no-death-preparedness state had neither accurate PA nor adequate emotional preparedness for death. The sufficient-death-preparedness state was characterized by both accurate PA and adequate emotional preparedness for death. In the cognitive- and emotional-death-preparedness-only states, patients were accurately aware of their prognosis and adequately emotionally prepared for their forthcoming death only, respectively. As death approached, state prevalence fluctuated within a narrow range for the no- and sufficient-death-preparedness states, whereas prevalence of cognitive- and emotional-death-preparedness-only states increased and decreased substantially, respectively.

Conclusion: Cancer patients heterogeneously experienced conjoint cognitive PA and emotional preparedness for death, and prevalence of death-preparedness states changed substantially as death approached. Effective interventions are warranted to cultivate cognitive PA and facilitate emotional death-preparedness to improve end-of-life-care quality, thereby helping patients achieve a good death.
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http://dx.doi.org/10.1002/pon.5614DOI Listing
May 2021

Prognostic significance of the preoperative systemic immune-inflammation index in patients with oral cavity squamous cell carcinoma treated with curative surgery and adjuvant therapy.

Cancer Med 2021 01 16;10(2):649-658. Epub 2020 Dec 16.

Department of Radiation Oncology, Proton and Radiation Therapy Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Objectives: To investigate the prognostic value of the preoperative systemic immune-inflammation index (SII) in patients with oral cavity squamous cell carcinoma (OC-SCC) treated with curative surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CCRT).

Materials And Methods: We retrospectively reviewed the clinical records of patients with OC-SCC who received surgery and postoperative adjuvant RT/CCRT between January 2005 and December 2012. Blood samples were drawn in the 2 weeks preceding surgery. SII was calculated by multiplying the absolute neutrophil and platelet counts, and then, divided by the absolute lymphocyte count, and its optimal cutoff value was identified using the Youden's index. The study endpoints included overall survival (OS), local control (LC), regional control (RC), and distant control (DC).

Results: The study sample consisted of 993 patients (58.8% of them treated with CCRT). The optimal cutoff value for SII was 810.6. A total of 347 (34.9%) study participants had high preoperative SII values. After allowance for potential confounders in multivariable analysis, high SII values were independently associated with less favorable DC (adjusted hazard ratio [HR] = 1.683, p = 0.001) and OS (adjusted HR = 1.466, p < 0.001). No independent association between SII and LC/RC was observed.

Conclusion: Increased SII values predict poor DC and OS in patients with OC-SCC treated with curative resection and adjuvant RT/CCRT. Owing to the higher risk of systemic failure in this patient group, a thorough follow-up surveillance schedule may be advisable pending independent confirmation of our data.
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http://dx.doi.org/10.1002/cam4.3650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877364PMC
January 2021

Evaluating if an Advance Care Planning Intervention Promotes Do-Not-Resuscitate Orders by Facilitating Accurate Prognostic Awareness.

J Natl Compr Canc Netw 2020 12 2;18(12):1658-1666. Epub 2020 Dec 2.

3Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan, ROC.

Background: Issuing do-not-resuscitate (DNR) orders has seldom been an outcome in randomized clinical trials of advance care planning (ACP) interventions. The aim of this study was to examine whether an ACP intervention facilitating accurate prognostic awareness (PA) for patients with advanced cancer was associated with earlier use of DNR orders.

Patients And Methods: Participants (n=460) were randomly assigned 1:1 to the experimental and control arms, with 392 deceased participants constituting the final sample of this secondary analysis study. Participants in the intervention and control arms had each received an intervention tailored to their readiness for ACP/prognostic information and symptom-management education, respectively. Effectiveness in promoting a DNR order by facilitating accurate PA was determined by intention-to-treat analysis using multivariate logistic regression with hierarchical linear modeling.

Results: At enrollment in the ACP intervention and before death, 9 (4.6%) and 8 (4.1%) participants and 168 (85.7%) and 164 (83.7%) participants in the experimental and control arms, respectively, had issued a DNR order, without significant between-arm differences. However, participants in the experimental arm with accurate PA were significantly more likely than participants in the control arm without accurate PA to have issued a DNR order before death (adjusted odds ratio, 2.264; 95% CI, 1.036-4.951; P=.041). Specifically, participants in the experimental arm who first reported accurate PA 31 to 90 days before death were significantly more likely than their counterparts in the control arm who reported accurate PA to have issued a DNR order in the next wave of assessment (adjusted odds ratio, 13.365; 95% CI, 1.989-89.786; P=.008). Both arms issued DNR orders close to death (median, 5-6 days before death).

Conclusions: Our ACP intervention did not promote the overall presence of a DNR order. However, our intervention facilitated the issuance of NDR orders before death among patients with accurate PA, especially those who reported accurate PA 31 to 90 days before death, but it did not facilitate the issuance of DNR orders earlier than their counterparts in the control arm.ClinicalTrial.gov Identification: NCT01912846.
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http://dx.doi.org/10.6004/jnccn.2020.7601DOI Listing
December 2020

End-of-Life-Care Quality in ICUs Is Associated With Family Surrogates' Severe Anxiety and Depressive Symptoms During Their First 6 Months of Bereavement.

Crit Care Med 2021 01;49(1):27-37

Department of Nursing, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan, Republic of China.

Objectives: Evidence linking end-of-life-care quality in ICUs to bereaved family members' psychologic distress remains limited by methodological insufficiencies of the few studies on this topic. To examine comprehensively the associations of family surrogates' severe anxiety and depressive symptoms with end-of-life-care quality in ICUs over their first 6 months of bereavement.

Design: Prospective, longitudinal, observational study.

Setting/participants: Family surrogates (n = 278) were consecutively recruited from seven medical ICUs at two academically affiliated medical centers in Taiwan.

Measurements And Statistical Analysis: Family surrogates' anxiety and depressive symptoms were assessed 1, 3, and 6 months postloss using the Hospital Anxiety and Depression Scale. Family satisfaction with end-of-life care in ICUs was assessed 1-month postloss by the Family Satisfaction in the ICU questionnaire. Patients' end-of-life care was documented over the patient's ICU stay. Associations of severe anxiety and depressive symptoms (scores ≥ 8 for each subscale) with end-of-life-care quality in ICUs (documented by patient care received and family satisfaction with end-of-life care in ICUs) were examined by multivariate logistic regression models with generalized estimating equation.

Main Results: Prevalence of severe anxiety and depressive symptoms decreased significantly over time. Surrogates' lower likelihood of severe anxiety or depressive symptoms 3-6 month postloss was associated with death without cardiopulmonary resuscitation, withdrawing life-sustaining treatments, and higher family satisfaction with end-of-life care in ICUs. Bereaved surrogates' higher likelihood of these symptoms was associated with physician-surrogate prognostic communication and conducting family meetings before patients died.

Conclusions: End-of-life-care quality in ICUs is associated with bereaved surrogates' psychologic well-being. Enhancing end-of-life-care quality in ICUs by improving the process of end-of-life care, for example, promoting death without cardiopulmonary resuscitation, withdrawing life-sustaining treatments, and increasing family satisfaction with end-of-life care, can lighten bereaved family surrogates' severe anxiety symptoms and severe depressive symptoms.
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http://dx.doi.org/10.1097/CCM.0000000000004703DOI Listing
January 2021

Human Brain Dynamics Reflect the Correctness and Presentation Modality of Physics Concept Memory Retrieval.

Front Hum Neurosci 2020 31;14:331. Epub 2020 Aug 31.

Institute for Neural Computation, University of California, San Diego, San Diego, CA, United States.

Human memory retrieval is the core cognitive process of the human brain whenever it is processing the information. Less study has focused on exploring the neural correlates of the memory retrieval of scientific concepts when presented in word and picture modalities. Fewer studies have investigated the differences in the involved brain regions and how the brain dynamics in these regions would associate with the accuracy of the memory retrieval process. Therefore, this study specifically focused on investigating the human brain dynamics of participants when they retrieve physics concepts in word vs. pictorial modalities, and whether electroencephalogram (EEG) activities can predict the correctness of the retrieval of physics concepts. The results indicated that word modality induced a significant stronger right frontal theta augmentation than pictorial modality during the physics concepts retrieval process, whereas the picture modality induced a significantly greater right parietal alpha suppression than the word modality throughout the retrieval process spurred by the physics concept presentations. In addition, greater frontal midline theta augmentation was observed for incorrect responses than the correct responses during retrieve physics concepts. Moreover, the frontal midline theta power has greater negative predictive power for predicting the accuracy of physics concepts retrieval. In summary, the participants were more likely to retrieve physics concepts correctly if a lower amount of theta were allocated during the maintaining period from 2,000 ms through 3,500 ms before making responses. It provides insight for our future application of brain computer interface (BCI) in real-time science learning. This study implies that the lower frontal midline theta power is associated with a lower degree of cognitive control and active maintenance of representations as participants approach a correct answer.
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http://dx.doi.org/10.3389/fnhum.2020.00331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488981PMC
August 2020
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