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Background: Preparing family caregivers for a patient's death is an integral component of quality end-of-life care, but temporal changes in emotional preparedness for death and its associations with caregivers' psychological well-being or quality of life (QOL) while providing end-of-life caregiving are under-researched. Our study was conducted to fill this gap.Methods: For this prospective, longitudinal study, the course of changes in adequate emotional preparedness for death and its associations with severe depressive symptoms and QOL were examined on 309 consecutive caregivers of terminally ill cancer patients by univariate and multivariate generalized estimating equation analyses, respectively.Results: Prevalence of adequate emotional preparedness for death was 57.2%, 61.3%, 54.4%, and 46.0% at 181-365, 91-180, 31-90, and 1-30 days before the patient's death, respectively, without significant changes as the patient's death approached. Adequate emotional preparedness for death was associated with caregivers' lower likelihood of severe depressive symptoms (adjusted odds ratio [95% CI]: 0.23 [0.16, 0.32], P < 0.001) but with their better QOL (adjusted β [95% CI]: 7.65 [6.38, 8.92], P < 0.001) in the patient's last year.Conclusions: Without active, effective clinical interventions to promote caregivers' emotional preparedness for death, they cannot automatically become more prepared for the patient's death over time. Adequate emotional preparedness for the patient's death benefits caregivers by its associations with a lower likelihood of depressive symptoms and better QOL. Supportive programs for caregivers of terminally ill cancer patients should focus on not only enhancing caregiving skills but also cultivating emotional preparedness for their relative's death to promote their psychological well-being and QOL. [ABSTRACT FROM AUTHOR]

The scarce research on factors associated with surrogate decisional regret overlooks longitudinal, heterogenous decisional-regret experiences and fractionally examines factors from the three decision-process framework stages: decision antecedents, decision-making process, and decision outcomes. This study aimed to fill these knowledge gaps by focusing on factors modifiable by high-quality end-of-life (EOL) care. This observational study used a prior cohort of 377 family surrogates of terminal-cancer patients to examine factors associated with their membership in the four preidentified distinct decisional-regret trajectories: resilient, delayed-recovery, late-emerging, and increasing-prolonged trajectories from EOL-care decision making through the first two bereavement years by multinomial logistic regression modeling using the resilient trajectory as reference. Decision antecedent factors: Financial sufficiency and heavier caregiving burden increased odds for the delayed-recovery trajectory. Spousal loss, higher perceived social support during an EOL-care decision, and more postloss depressive symptoms increased odds for the late-emerging trajectory. More pre- and postloss depressive symptoms increased odds for the increasing-prolonged trajectory. Decision-making process factors: Making an anticancer treatment decision and higher decision conflict increased odds for the delayed-recovery and increasing-prolonged trajectories. Making a life-sustaining-treatment decision increased membership in the three more profound trajectories. Decision outcome factors: Greater surrogate appraisal of quality of dying and death lowered odds for the three more profound trajectories. Patient receipt of anticancer or life-sustaining treatments increased odds for the late-emerging trajectory. Surrogate membership in decisional-regret trajectories was associated with decision antecedent, decision-making process, and decision outcome factors. Effective interventions should target identified modifiable factors to address surrogate decisional regret. [ABSTRACT FROM AUTHOR]

Background/purpose: To investigate the diagnostic accuracy of 68Ga-DOTATOC and 18F-FDG PET/CT to identify the primary foci in Taiwanese patients with clinically suspected neuroendocrine tumors (NET) and NET of unknown primary site.Methods: Patients with clinically suspected NET and NET of unknown primary site were eligible. All participants underwent a conventional workup (including CT, MR, endoscopic ultrasound), 68Ga-DOTATOC, and 18F-FDG PET/CT. The results of pathology and findings on clinical follow-up served as the gold standard.Results: Among the 36 patients included in the study, we were able to identify the primary tumor in 17 participants (47.2%). The overall sensitivity values of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 88%, 41%, and 53%, respectively, whereas the specificities were 100%, 100%, 68%, respectively. The areas under curve of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 0.941, 0.706, and 0.607, respectively. 68Ga-DOTATOC was more sensitive than 18F-FDG and more specific than conventional workup. Treatment changes as a result of 68Ga-DOTATOC PET/CT findings occurred in 12 (33.3%) of the 36 study participants.Conclusion: Our data confirm the usefulness of 68Ga-DOTATOC in the identification of NET. In addition, treatment modifications as a result of 68Ga-DOTATOC PET/CT findings were evident in approximately one third of NET patients. [ABSTRACT FROM AUTHOR]

Regret plays a central role in surrogate decision making. Research on decisional regret in family surrogates is scarce and lacks longitudinal studies to illustrate the heterogenous, dynamic evolution of decisional regret. To identify distinct decisional-regret trajectories from end-of-life (EOL) decision making through the first two bereavement years among surrogates of cancer patients. A prospective, longitudinal, observational study was conducted on a convenience sample of 377 surrogates of terminally ill cancer patients. Decisional regret was measured by the five-item Decision Regret Scale monthly during the patient's last six months and 1, 3, 6, 13, 18, and 24 months post loss. Decisional-regret trajectories were identified using latent-class growth analysis. Surrogates reported substantially high decisional regret (pre- and postloss mean [SD] as 32.20 [11.47] and 29.90 [12.47], respectively). Four decisional-regret trajectories were identified. The resilient trajectory (prevalence: 25.6%) showed a general low decisional-regret level with mild and transient perturbations around the time of patient death only. Decisional regret for the delayed-recovery trajectory (56.3%) accelerated before the patient's death and decreased slowly throughout bereavement. Surrogates in the late-emerging (10.2%) trajectory reported a low decisional-regret level before loss but their decisional regret increased gradually thereafter. The increasing-prolonged trajectory (6.9%) rapidly increased in decisional-regret levels during EOL decision making, peaked one-month post loss, then declined steadily but without a complete resolution. Surrogates heterogeneously suffered decisional regret from EOL decision making through bereavement as evident by four identified distinct decisional-regret trajectories. Early identification and prevention of increasing/prolonged decisional-regret trajectories is warranted. [ABSTRACT FROM AUTHOR]

Background The prognosis of patients with esophageal cancer who have poor response to chemoradiotherapy (ie, pathologic nonresponders [pNRs]) remains poor. We investigated whether the use of postoperative adjuvant therapy (AT) could improve survival in this patient group. Methods Among patients with esophageal squamous cell carcinoma who were treated with neoadjuvant chemoradiotherapy (nCRT) and operation between 2000 and 2012, pNRs (defined as those having a postoperative T stage of equal or greater pretreatment T stage or persistent nodal disease) were identified and divided into two groups according to their subsequent management (AT versus surveillance). Survival and recurrence were compared after propensity score matching for the following five factors: age, performance status, pathological lymph node status after treatment (ypN) status, severity of postoperative complications, and length of hospital stay (LOS). Results Of the 115 pNRs, 74 and 41 received AT and surveillance alone, respectively. Patients who received AT were younger, had less major postoperative complications, and a shorter LOS. A total of 32 pairs of well-balanced patients (n = 64) were selected by propensity matching. A significant benefit in terms of disease-free survival (DFS) was observed for pNRs treated with AT compared with those undergoing surveillance (3-year DFS rate: 45% versus 22.3%, p = 0.022). However, more patients in the AT group died of causes unrelated to cancer, resulting only in a borderline increase of overall survival (OS) [3-year OS rate: 34.4% versus 21.6%, p = 0.13]. Conclusions Postoperative AT can improve DFS in pNRs after nCRT. However, its use should be carefully weighed against a potential increase in the risk of treatment-related death. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity with poor prognosis. The dysregulation of Notch signaling pathway has been implicated in the OSCC tumorigenesis. However, the clinical implication of NOTCH1 mutation status in OSCC remains unelucidated. We extracted the NOTCH1 gene mutations from a whole exome sequencing dataset of 168 frozen OSCC tumor specimens and validated these NOTCH1 gene mutations by Sanger sequencing. We also assessed these NOTCH1 gene mutations and its pathological significance in our OSCC tumor tissues using immunohistochemistry. Univariate and multivariate analyses were also used to determine whether the association between NOTCH1 mutation status and prognostic factors was independent of other parameters. In this study, we have identified 44 (26.19 %) NOTCH1 gene mutations from a whole-exome sequencing of 168 OSCC formalin-fixed, paraffin-embedded (FFPE) tissue specimen. These mutations distributed in different NOTCH1 function domains, including the EGF-like repeats region, negative regulatory region, and Ankyrin repeats region. The immunohistochemical staining analysis revealed that NOTCH1 expression was increased in oral cancer tissues. In addition, of the 43 OSCC tumors with NOTCH1 mutations, we observed that the majority were negative for NOTCH1 intracellular domain 1 (NICD1) staining (76.74 %), and 10 tumors were positive for NICD1 staining (23.26 %). In conclusion, o ur study suggested that NOTCH1 expression is associated with the progression of OSCC. We also demonstrated that presence of a mutated NOTCH1 gene will help prognostic stratification in OSCC when combined with other clinicopathologic parameters. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• The prognostic impact of diagnosis-to-surgery interval (DSI) in OCSCC is unclear. • DSI ≤20 days portended a better survival than DSI 21–31 days and >31 days. • DSI >31 days (versus ≤20 days) is an independent unfavorable prognostic factor. • Shortening DSI may improve survival outcomes in patients with OCSCC. The question as to whether prolonged diagnosis-to-surgery intervals (DSIs) may compromise survival outcomes in patients with oral cavity squamous cell carcinoma (OCSCC) remains unanswered. This nationwide study was designed to address this issue. We analyzed data from 26,214 patients with first primary OCSCC identified in the Taiwanese Cancer Registry Database between 2011 and 2021. The optimal DSI cutoff was determined based on 5-year disease-specific survival (DSS) and overall survival (OS) rates using Cox regression analysis. Patients were categorized into three distinct DSI groups: ≤20 days (47 %), 21–31 days (31 %), and > 31 days (22 %). The 5-year DSS and OS rates for the ≤20/21–31/>31 days groups were 81 %/78 %/77 % and 73 %/70 %/68 %, respectively (both p < 0.0001). Patients in the ≤20 days group had a higher prevalence of pathological stages I–II. After adjustment for potential confounders in multivariable analysis, a DSI > 31 days (versus ≤ 20 days) retained independent associations with adverse outcomes at 5 years, with hazard ratios of 1.07 for both DSS and OS. Propensity score matching and multivariable analysis comparing DSI ≤ 20 days to DSI > 31 days stratified by pathological stage III–IV showed that higher DSS and OS rates were observed in patients with DSI ≤ 20 days than DSI > 31 days (68 % / 66 %, p = 0.0586; 60 % / 57 %, p = 0.0228, respectively), with hazard ratios of 1.09 for both DSS and OS. Our findings indicate that DSI is an independent predictor of 5-year DSS and OS in patients with OCSCC. A DSI exceeding 31 days, or even 21 days, may potentially decrease survival outcomes. [ABSTRACT FROM AUTHOR]

• An MDR cutoff of 0.6 is associated with 5-year survival outcomes in OCSCC. • MDR outperforms traditional margin status as a prognostic factor for OCSCC outcomes. • MDR refines risk stratification within < 5 mm and ≥ 5 mm surgical margin subgroups. • MDR may guide surgical margin modification and identify patients requiring adjuvant therapy. The prognostic significance of margin-to-depth ratio (MDR) in oral cavity squamous cell carcinoma (OCSCC) remains unclear, particularly in comparison to traditional margin status. We aimed to examine the association between MDR and clinical outcomes in a large Taiwanese cohort. A total of 18,324 patients with first primary OCSCC were categorized by margin status: positive (1013), <5 mm (8371), and ≥ 5 mm (8940). Disease-specific survival (DSS) and overall survival (OS) served as the main outcome measures. After excluding patients with positive margins (MDR = 0), the optimal MDR cutoff value for DSS and OS was 0.6. Patients with MDR > 0.6 showed significantly better 5-year DSS and OS rates (87 %, 81 %) compared to those with MDR ≤ 0.6 (71 %, 63 %) and MDR = 0 (53 %, 43 %). Multivariable analysis identified MDR ≤ 0.6 as independently associated with both DSS and OS in the entire cohort (hazard ratio [HR] = 1.34/1.32). This finding was consistent in the subgroups with surgical margins < 5 mm (HR = 1.39 for DSS and 1.38 for OS) and margins ≥ 5 mm (HR = 1.21 for both DSS and OS). In subgroups with surgical margins < 5 mm and ≥ 5 mm, an MDR > 0.6 was associated with better survival outcomes. An MDR (cutoff: 0.6) is independently associated with prognosis in OCSCC, offering improved risk stratification compared to margin status alone. While MDR may guide surgical margin modification, further research is needed to determine whether MDR could serve as a postoperative indicator for adjuvant therapy in patients with close or clear margins. [ABSTRACT FROM AUTHOR]

Abstract: Background. Tibial baseplates were occasionally reported with clinical fatigue failures. This study postulated that tibial baseplate of a specific mobile bearing design with a uniform thickness across the baseplate offers more fatigue resistance than the fixed-bearing design. Tibial baseplates of a fixed bearing and a mobile bearing design were fatigue-tested in vitro to study their fatigue resistance. Methods. Five samples of each design were tested under a sinusoidal loading between 90N and 900N at 30Hz till failure or 10 million cycles. Experimental setup followed a standard published test method. Scanning electron microscope was used for inspecting the fracture surface of the failed baseplate. Findings. Two baseplates of fixed bearing design failed before 10 million cycles. Fatigue crack advancement marks were visible on the fractured surface of the failed samples. The fractured cross-section showed that the failure started near the end of the fin, it was likely due to the stress concentration as stress singularity existed at a point of sudden geometrical change. Five mobile bearing baseplates passed the test. Design of the tibial baseplate without fin structure and with a uniform thickness across the whole baseplate could help reducing the incidence of fatigue failure. Interpretation. The prosthesis survival rate was influenced by the long-term integrity of the metallic part of the prostheses such as the tibial baseplate. This study revealed that the tibial baseplate of a mobile bearing design with a uniform thickness provided better fatigue resistance than fixed bearing one. Standardized fatigue screening of the tibial baseplate was considered important in designing knee prostheses. [Copyright &y& Elsevier]

Context: Emotional preparedness for death (hereafter called death preparedness) and prognostic awareness (PA), a distinct but related concept, each contributes to patients' practical, psychological, and interpersonal preparations for death. However, the distinction between these two concepts has never been investigated.Objectives: To evaluate the distinction between death preparedness and accurate PA by examining their agreement during cancer patients' last year and the similarity of their predictors.Methods: For this secondary analysis of a longitudinal study of death preparedness for 277 patients with cancer, agreement between death preparedness and accurate PA was evaluated by percentages and kappa coefficients, and predictors of the two outcomes were evaluated by multivariate logistic regression models with the generalized estimating equation.Results: Levels of agreement between reported death preparedness and accurate PA increased slightly (42.44%-52.85%) from 181-365 days to one to 30 days before death, with kappa values from -0.190 (-0.319, -0.061) to -0.006 (-0.106, 0.093), indicating poor agreement. Participants who were male, older, reported financial sufficiency, had fewer distressing symptoms, and perceived higher levels of social support were more likely to report death preparedness. Participants who were female, had greater than high-school educational attainment, and endured higher levels of functional dependence were more likely to report accurate PA.Conclusion: The distinction between death preparedness and accurate PA was supported by their poor agreement, lack of reciprocal associations, and two different sets of predictors. Health care professionals should not only cultivate cancer patients' accurate PA but also facilitate emotional preparation for death to achieve a good death and improve end-of-life care quality. [ABSTRACT FROM AUTHOR]

Purpose: The evidence for adjuvant therapy of oral cavity squamous cell carcinoma (OCSCC) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. Here, we examined whether adjuvant therapy should be guided by a detailed analysis of pathologic risk factors in patients with pure OCSCC.Methods and Materials: Between 2004 and 2016, we retrospectively reviewed 1200 consecutive patients with OCSCC who underwent radical surgery and neck dissection in the Chang-Gung Memorial Hospital (CGMH). Patients were divided into 3 prognostic groups. High-risk patients were those with extranodal extension (ENE) and/or positive margins (ENE/margins+, n = 267). Intermediate-risk patients were further divided into 3 subgroups: (1) patients in whom adjuvant therapy was indicated according to the CGMH but not the NCCN guidelines (NCCN[-]/CGMH[+], n = 14); (2) patients in whom adjuvant therapy was indicated by the NCCN but not the CGMH guidelines (NCCN[+]/CGMH[-], n = 160); and (3) patients in whom adjuvant therapy was indicated according to both guidelines (NCCN[+]/CGMH[+], n = 411). Low-risk patients were those for whom adjuvant therapy was not suggested in light of either guideline (NCCN[-]/CGMH[-], n = 348).Results: According to NCCN guidelines, postoperative adjuvant therapy was indicated in 69.8% of the participants. However, only 57.7% of patients were in need of adjuvant therapy by CGMH guidelines. The following 5-year outcomes were observed in the NCCN(-)/CGMH(-), NCCN(-)/CGMH(+), NCCN(+)/CGMH(-), NCCN(+)/CGMH(+), and ENE/margins+ subgroups: locoregional control, 88%/70%/83%/79%/68%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .576); distant metastases, 2%/7%/2%/9%/36%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .003); disease-specific survival, 97%/86%/94%/84%/56%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001); and overall survival, 92%/86%/87%/68%/42%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001), respectively.Conclusions: Patients in the NCCN(+)/CGMH(-) subgroup, 28% (160/571[160 + 411]) of NCCN intermediate-risk patients, had more favorable 5-year disease-specific and overall survival (94% and 87%) than the NCCN(+)/CGMH(+) subgroup. The former are unlikely to derive clinical benefits from NCCN guidelines. The 70% adjuvant therapy rate required by NCCN guidelines after radical surgery might be too high, ultimately leaving room for improvement. [ABSTRACT FROM AUTHOR]

• Several studies indicated that margins < 1 mm should be classified as positive margins in OCSCC. • Margin < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis. • Positive margins should remain a high risk factor, whereas margins < 1 mm could be considered an intermediate risk factor. While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins. [ABSTRACT FROM AUTHOR]

Context: Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.Objectives/methods: We used multivariate hierarchical linear modeling to simultaneously evaluate associations between five distinct patterns of conjoint symptom distress and functional impairment (symptom-functional states) and subjective caregiving burden, QOL, and depressive symptoms in a convenience sample of 215 family caregiver-patient dyads. Data were collected every 2 to 4 weeks over patients' last 6 months.Results: Caregivers of patients in the worst symptom-functional states (States 3-5) reported worse subjective caregiving burden and depressive symptoms than those in the best two states, but the three outcomes did not differ between caregivers of patients in State 3 and States 4-5. Caregivers of patients in State 5 endured worse subjective caregiving burden and QOL than those in State 4. Caregivers of patients in State 4 suffered worse subjective caregiving burden and depressive symptoms but comparable QOL to those in State 2.Conclusion: Patients' five distinct, conjoint symptom-functional states were significantly and differentially associated with their caregivers' worse subjective caregiving burden, QOL, and depressive symptoms while caring for patients over their last 6 months. [ABSTRACT FROM AUTHOR]

Objective: According to the AJCC 2017 Staging Manual, oral cavity squamous cell carcinoma (OCSCC) with pN2 disease (based on the AJCC 2010 criteria) and extra-nodal extension (ENE) should be classified as pN3b. We performed a detailed outcome analyses in this patient subgroup.Material and Methods: We retrospectively reviewed the clinical records of consecutive OCSCC patients who underwent radical surgery between 1996 and 2017. Patients with pN3b disease (n = 365) were divided into a pN+ ≥8/ENE ≥5 subgroup (defined by the presence of pN+ ≥8 nodes or ENE ≥5 nodes, n = 77) and a pN+ ≤7/ENE ≤4 subgroup (defined by the presence of pN+ ≤7 nodes and ENE ≤4 nodes, n = 288). Patients with pN0/pN1/pN2 (n = 1192/179/197) disease were included for comparison purposes.Results: Patients in the pN+ ≥8/ENE ≥5 subgroup had less favorable 5-year outcomes than those in the pN+ ≤7/ENE ≤4/pN2/pN1/pN0 groups (local control, 64%/79%/86%/83%/88%, p < 0.001; neck control, 55%/75%/80%/86%/93%, p < 0.001; distant metastases, 67%/28%/20%/12%/3%, p < 0.001; disease-free survival, 21%/51%/64%/72%/82%, p < 0.001; disease-specific survival, 25%/55%/71%/82%/92%, p < 0.001; overall survival, 19%/40%/54%/64%/82%, p < 0.001; respectively). Among patients with pN3b disease, multivariable analysis identified the pN+ ≥8/ENE ≥5 subgroup, lower neck (level IV/V) metastases, and depth of invasion ≥25 mm as independent adverse prognostic factors for 5-year distant metastases and survival rates.Conclusions: Patients in the pN+ ≥8/ENE ≥5 subgroup have an unfavorable prognosis and their classification as pN3b is advisable. In contrast, patients in the pN+ ≤7/ENE ≤4 subgroup should be classified as pN3a. [ABSTRACT FROM AUTHOR]

Context: Terminally ill cancer patients do not engage in end-of-life (EOL) care discussions or do so only when death is imminent, despite guidelines for EOL care discussions early in their disease trajectory. Most studies on patient-reported EOL care discussions are cross sectional without exploring the evolution of EOL care discussions as death approaches. Cross-sectional studies cannot determine the direction of association between EOL care discussions and patients' prognostic awareness, psychological well-being, and quality of life (QOL).Objectives/methods: We examined the evolution and associations of accurate prognostic awareness, functional dependence, physical and psychological symptom distress, and QOL with patient-physician EOL care discussions among 256 terminally ill cancer patients in their last six months by hierarchical generalized linear modeling with logistic regression and by arranging time-varying modifiable variables and EOL care discussions in a distinct time sequence.Results: The prevalence of physician-patient EOL care discussions increased as death approached (9.2%, 11.8%, and 18.3% for 91-180, 31-90, and 1-30 days before death, respectively) but only reached significance in the last month. Accurate prognostic awareness facilitated subsequent physician-patient EOL care discussions, whereas better patient-reported QOL and more anxiety symptoms hindered such discussions. The likelihood of EOL care discussions was not associated with levels of physical symptom distress, functional dependence, or depressive symptoms.Conclusion: Physician-patient EOL care discussions for terminally ill Taiwanese cancer patients remain uncommon even when death approaches. Physicians should facilitate EOL care discussions by cultivating patients' accurate prognostic awareness early in their cancer trajectory when they are physically and psychologically competent, with better QOL, thus promoting informed and value-based EOL care decision making. [ABSTRACT FROM AUTHOR]

A polymer composite was prepared by incorporating 5-20 wt% quaternized chitosan (Q-chitosan) nanoparticles into quaternized polyvinyl alcohol (Q-PVA) to enhance the dimensional stability and conductive properties. Compared with the pristine Q-PVA membrane, the ionic conductivity of the Q-PVA composites with 5–10 wt% Q-chitosan was improved due to increased polymeric free volume hole density. The methanol permeability is suppressed in these Q-PVA/Q-chitosan composites because of the confined swelling in the presence of the fillers, shrinking the free volume size. The Q-PVA/5%Q-chitosan composite exhibits higher peak power density (P max ) than other Q-PVA membranes in direct methanol fuel cells. A P max of 92 mW cm −2 is attained using the Q-PVA/5%Q-chitosan composite at 90 °C with 5–6 mg cm −2 catalyst loads on micro-porous layer-containing carbon cloth. The high load of 20 wt% Q-chitosan does not benefit ionic conduction and power generation, probably due to interfacial resistance at rough surfaces. Using the Q-PVA/5%Q-chitosan composite and reduced catalyst loads of 1–2 mg cm −2 on pristine carbon cloth, P max of 90 mW cm −2 can be achieved at 60 °C for both methanol and ethanol fuel cells, but declined at 90 °C due to insufficient catalysts. Overall the Q-PVA/Q-chitosan composite offers a potential electrolyte for energy devices operating in an alkaline environment. [ABSTRACT FROM AUTHOR]

In this work, mesoporous calcium-based adsorbents are prepared with the assistance of an organogel, 1,3:24-Bis (3,4-dimethylobenzylideno) sorbitol (DMDBS), which can self-assemble into nanoscale fibrillar networks and act as soft template to create mesopores. Particularly, it is found that the specific surface area of adsorbent is increased about 25 times by adding an extremely low concentration of DMDBS template (0.4 wt%) during the adsorbent production, which is much more efficient than common template materials. Additionally, the physical property and adsorption capability of calcium-based adsorbents can be tuned by control over calcination temperatures and DMDBS loadings. Under optimal preparation conditions (700 °C and 0.4 wt% DMDBS), the synthesized mesoporous adsorbent can achieve a Langmuir adsorption capacity of 48.8 mmol g−1 at pH of 7 and a removal efficiency of 70% in a mimicking natural water with the existence of NaCl. Thermodynamic analysis of equilibriums indicates that the adsorption reaction of fluoride with synthesized adsorbents from water is endothermic and spontaneous in nature. Most significantly, the results demonstrate that adsorbents with surface mesopores possess enriched ionized surface hydroxyl groups, CaO-, which act as the dominant species for fluoride attraction via electrostatic force at a neutral environment. This finding can be supported by the zeta potential analysis and surface speciation calculation. Moreover, the fluoride adsorption capacities of DMDBS-synthesized adsorbents are stable over neutral pH range of 6–8, revealing a promising potential for practical applications in fluoride-contaminated groundwater. [Display omitted] • Mesoporous Ca-based adsorbents are synthesized using organogel template. • 0.4 wt% of DMDBS template can improve the surface area of adsorbents by 25 times. • Adsorption capacity of 48.8 mmol g−1 and ΔG of −8.19 kJ mol−1 at pH of 7 is obtained. • Both electrostatic attraction and ion exchange mechanisms contribute to fluoride removal. • Ionized hydroxyl groups on adsorbent surface dominate the fluoride adsorption. [ABSTRACT FROM AUTHOR]

• NCCN maintains that END should be considered for cT1-2N0M0 OCSCC with a DOI > 3 mm. • DOI > 2.5 mm and poor differentiation predict adverse outcomes in cT1N0M0 OCSCC. • The decision to perform END should be guided by DOI and tumor differentiation. • This strategy allows avoiding END in 48.6% of patients, without compromising outcomes. According to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition. Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. The 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively. Because all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes. [ABSTRACT FROM AUTHOR]

Context: The stability of life-sustaining treatment (LST) preferences at end of life (EOL) has been established. However, few studies have assessed preferences more than two times. Furthermore, associations of LST preferences with modifiable variables of accurate prognostic awareness, physician-patient EOL care discussions, and depressive symptoms have been investigated in cross-sectional studies only.Objectives: To explore longitudinal changes in LST preferences and their associations with accurate prognostic awareness, physician-patient EOL care discussions, and depressive symptoms in terminally ill cancer patients' last year.Methods: LST preferences (cardiopulmonary resuscitation, intensive care unit [ICU] care, intubation, and mechanical ventilation) were measured approximately every two weeks. Changes in LST preferences and their associations with independent variables were examined by hierarchical generalized linear modeling with logistic regression.Results: Participants (n = 249) predominantly rejected cardiopulmonary resuscitation, ICU care, intubation, and mechanical ventilation at EOL without significant changes as death approached. Patients with inaccurate prognostic awareness were significantly more likely than those with accurate understanding to prefer ICU care, intubation, and mechanical ventilation than to reject these LSTs. Patients with more severe depressive symptoms were less likely to prefer ICU care and to be undecided about wanting ICU care and mechanical ventilation than to reject such LSTs. LST preferences were not associated with physician-patient EOL care discussions, which were rare in our sample.Conclusion: LST preferences are stable in cancer patients' last year. Facilitating accurate prognostic awareness and providing adequate psychological support may counteract the increasing trend for aggressive EOL care and minimize emotional distress during EOL care decisions. [ABSTRACT FROM AUTHOR]

Context Studies exploring the trajectories of physical-psychological-social-spiritual dying experiences frequently treat changes in these experiences as consistent across different domains and over time. Objective This prospective, longitudinal investigation was designed to characterize trajectories of the multidimensional dying experience for cancer patients in their last year of life. Methods Trajectories of physical-psychological-social-spiritual/existential dimensions and overall quality of life (QOL) were identified among 313 cancer patients using mixed-effects models to test for linear, quadratic, or cubic changes. Changes in each variable were evaluated for clinical significance using minimal important difference. Results When patients transitioned to their end of life, symptom distress, functional dependence, anxiety, and depressive symptoms slightly increased, followed by a stable status for approximately four to six months, and accelerated dramatically to the first clinically significant changes at three to four months before death. Perceived social support and post-traumatic growth declined gradually to clinically significant changes at one and four months before death, respectively. Perceived sense of burden to others increased steadily in the last year of life, with no clinically significant changes identified. Overall QOL deteriorated gradually in the last year but did not reach a clinically significant change until 2.5 months before death. Conclusion All dimensions deteriorated in the last year of life but with distinctive physical-psychological-social-spiritual/existential and overall QOL trajectories. Recognizing trajectory patterns and tipping points of accelerating deterioration in each dimension can help clinicians anticipate times of increased distress, initiate timely, effective interventions to relieve patient suffering, and facilitate high-quality end-of-life care tailored to patients' needs and preferences. [ABSTRACT FROM AUTHOR]

Abstract: Context: Since the development of palliative care in the 1980s, “do not resuscitate” (DNR) has been promoted worldwide to avoid unnecessary resuscitation in terminally ill cancer patients. Objectives: This study aimed to evaluate the effect of a palliative care consultation service (PCCS) on DNR designation and to identify a subgroup of patients who would potentially benefit from care by the PCCS with respect to DNR designation. Methods: In total, 2995 terminally ill cancer patients (with a predicted life expectancy of less than six months by clinician estimate) who received care by the PCCS between January 2006 and December 2010 at a single medical center in Taiwan were selected. Among these, the characteristics of 2020 (67.4%) patients who were not designated as DNR at the beginning of care by the PCCS were retrospectively analyzed to identify variables pertinent to DNR designation. Results: A total of 1301 (64%) of 2020 patients were designated as DNR at the end of care by the PCCS. Male gender and primary liver cancer were characteristics more predominantly found among DNR-designated patients who also had worse performance status, higher prevalence of physical distress, and shorter intervals from palliative care referral to death than did patients without DNR designation. On univariate analysis, a higher probability of DNR designation was associated with male gender, duration of care by the PCCS of more than 14 days, patients' prognostic awareness, family's diagnostic and prognostic awareness, and high Palliative Prognostic Index (PPI) scores. On multivariate analysis, duration of care by the PCCS, patients' prognostic awareness, family's diagnostic and prognostic awareness, and a high PPI score constituted independent variables predicting DNR-designated patients at the end of care by the PCCS. Conclusion: DNR designation was late in terminally ill cancer patients. DNR-designated cancer patient indicators were high PPI scores, patients' prognostic awareness, family's diagnostic and prognostic awareness, and longer durations of care by the PCCS. [Copyright &y& Elsevier]

Objective: In this study, we investigated the usefulness and limitations of EBV-DNA follow-up in patients who had treated localized nasopharyngeal carcinoma. Methods: Study subjects comprised 389 patients who had received treatment for localized nasopharyn-geal carcinoma in our department. Copy numbers of EBV-DNA in plasma were assessed by real-time quantitative PCR. Patients in whom disease recurrence was suspected underwent image evaluation, esp. PET scan, and tissue proof if it is feasible. Lesions of undermined nature were confirmed by sequen-tial follow-up. Results: Plasma EBV-DNA was detectable in 60 of 63 (95%) patients with metastatic disease and all had positive PET findings. In addition, of the 45 patients with localized recurrent disease, plasma EBV-DNA was detectable in 23 (51%) patients and positive PET scan results were obtained in 40 (89%) of the patients. Of the 284 patients who were disease free, plasma EBV-DNA was detected in 90 (32%) patients. Of the 19 patients in disease free group who were suspected disease recurrence receiving PET scanning, 7 positive PET images were found including 3 second primary malignancy and 4 non-cancer lesions. Two lymphoma cases with positive EBV-DNA value sequentially attacked before or after their NPC were diag-nosed. With the cutoff value of 400 copies/ml of EBV-DNA, the positive predict value was 73.5% and the negative predict value was 82.1%. The sensitivity was 0.46 and the specificity was 0.94. Conclusions: EBV-DNA was a good marker for detecting metastatic failure in treated localized NPC. How-ever, careful interpretation with complements from image examination was needed for locoregional fail-ure and other false positive or false negative situations. [ABSTRACT FROM AUTHOR]

Objectives: While the NCCN guidelines maintain that T4b oral cavity squamous cell carcinoma (OCSCC) should undergo either non-surgical treatments or clinical trials, promising outcomes of T4b OCSCC having surgical excision have been reported. We analyzed and compared the clinical outcomes of Taiwanese patients with pT4a and pT4b OCSCC who had undergone surgical treatment.Methods: From 2011 to 2017, a total of 4031 and 355 patients with first primary pT4a and pT4b OCSCC were identified. A propensity score (PS)-matched analysis of patients (n = 351 each) for pT4a and pT4b tumors was also performed.Results: The 5-year disease-specific and overall survival (DSS/OS) rates were more favorable in patients with pT4a than in those with pT4b OCSCC (64%/55%, p < 0.0001; 55%/43%, p < 0.0001, respectively). Compared with pT4a, those with pT4b tumors had a higher burden of the following risk factors: buccal/retromolar/hard palate subsite, male sex, depth ≥ 10 mm, and positive margins. Before PS matching, multivariable analyses revealed that pT4b tumors (versus pT4a) were an adverse prognosticator for both 5-year DSS and OS (hazard ratios: 1.32 and 1.39, respectively). However, in the PS-matched cohort, no significant differences in 5-year DSS and OS rates were observed between pT4a and pT4b OCSCC (57%/56%, p = 0.4024; 48%/44%, p = 0.1807, respectively) CONCLUSIONS: No significant outcome differences were evident between pT4b and pT4a OCSCC after PS matching. The most plausible hypothesis for the observed survival difference between T4a and T4b tumors is that it was driven by positive margins. We suggest that T4b OCSCC should undergo initial surgical excision if adequate resection is possible. [ABSTRACT FROM AUTHOR]

Objectives: The prognosis of pN3b oral cavity squamous cell carcinoma (OCSCC) remains heterogeneous. We sought to improve the prognostic stratification of patients with pN3b OCSCC through a combined analysis of FDG-PET parameters and clinicopathological risk factors (RFs).Methods: From 2001 to 2019, complete data on maximum standardized uptake values derived from FDG-PET of neck metastatic nodes (SUV-nodal-max) and clinicopathological RFs were available for 257 patients with pN3b disease.Results: Using the 5-year disease-free survival (DFS) as the outcome of interest, the optimal cutoff points for SUV-nodal-max and lymph node ratio (LNR) were 15.9 and 0.17, respectively. The 5-year DFS rates/(number of cases) for patients with pN3b disease were as follows: SUV-nodal-max < 15.9 versus ≥ 15.9, 49%(226)/21%(31), p = 0.000003; LNR < 0.17 versus ≥ 0.17, 49%(230)/17%(27), p = 0.000117; absence versus presence of neck level IV/V metastases, 49%(230)/15%(27), p = 0.000004. Multivariable analyses revealed that SUV-nodal-max ≥ 15.9, LNR ≥ 0.17, and level IV/V metastases were independent prognosticators for 5-year distant metastases (DM), DFS, disease-specific survival (DSS), and overall survival (OS) rates. Based on these variables, we devised a scoring system that identified three distinct prognostic subgroups at low (score 0, n = 190), intermediate (score 1, n = 51), and high (scores 2-3, n = 16) risk. The 5-year rates of patients with pN3b disease deemed to be at low/intermediate/high risk were as follows: DM, 31%/52%/89%; DFS, 54%/26%/0%; DSS, 59%/36%/8%; OS, 42%/31%/6%, respectively; all p < 0.001.Conclusions: A scoring system based on SUV-nodal-max, LNR, and level IV/V metastases improves the prognostic stratification of OCSCC patients with pN3b disease. [ABSTRACT FROM AUTHOR]

Objectives: pStage IVB oral cavity squamous cell carcinoma (OCSCC) is defined as either pT4b or pN3 disease. We sought to devise an improved prognostic stratification of this patient group.Methods: Between December 2003 and January 2018, we retrospectively reviewed the clinical records of 1331 consecutive patients with OCSCC who received tumor excision and neck dissection. The number of patients with pT4a/pT4b, pT1N3b/pT2N3b/pT3N3b/pT4N3b, and pStage IVA/IVB was 370/83, 3/49/42/142, and 332/295, respectively.Results: The 5-year rates of disease-free survival (DFS) and disease-specific survival (DSS) for patients with pT4a/pT4b disease were 64%/63% (p = 0.973) and 72%/69% (p = 0.672), respectively. The 5-year DFS and DSS rates for patients with pT1N3b/pT2N3b/pT3N3b/pT4N3b disease were 67%/65%/40%/42% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002) and 100%/68%/45%/49% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002), respectively. We devised a new definition for pStage IV by considering patients with pT4bN0-2 and pT1-2N3b diseases as pStage-IVA. The number of patients with pStage IVA/IVB (pT3-4N3b) was 443/184. The 5-year rates of AJCC pStage IVA/IVB and the newly proposed pStage IVA/IVB (pT3-4N3b) were as follows: DFS, 74%/52% and 72%/42%; DSS, 83%/58% and 81%/47%; respectively, all p value < 0.001.Conclusions: The clinical outcomes of pT4b and pT4a OCSCC are similar. However, patients with pT3-4N3b disease have a less favorable 5-year prognosis compared with cases with pT1-2N3b. In light of the unfavorable outcomes, pT3-4N3b disease should continue to be classified as pStage IVB. Conversely, pT4bN0-2 and pT1-2N3b diseases portend a less adverse prognosis and should therefore be downstaged to pStage IVA. [ABSTRACT FROM AUTHOR]

Objectives: This large-scale cohort study was designed to compare the clinical outcomes of Taiwanese patients with squamous cell carcinoma (SCC) of the upper versus lower gum.Methods: Between 2004 and 2017, we identified 4244 patients with first primary SCC of the gum (694 upper gum; 3550 lower gum) who were treated with surgery either with or without adjuvant therapy. Of them, 1990 patients (329 upper gum; 1661 lower gum) enrolled from 2011 to 2017 had a higher number of histopathological variables and entered subgroup analyses. Five-year disease-specific survival (DSS) and overall survival (OS) rates served as outcome measures.Results: The 5-year DSS and OS rates of patients with upper gum SCC were lower than those of cases with lower gum SCC (65%/74%, p < 0.0001; and 55%/65%, respectively, p < 0.0001). Compared with lower gum SCC, upper gum SCC had a higher prevalence of the following variables: female sex, age ≥ 65 years, pNx (without neck dissection), no-betel chewing (2011-2017), no-smoking (2011-2017), and margin status ≤ 4 mm (positive and close margins, 2011-2017). On multivariable analysis, gum subsite (upper versus lower), age (≥65 versus < 65 years), pT (T3 - 4 versus T1 - 2), pN (N1 - 3 versus N0/Nx), depth (≥10 mm versus < 10 mm, 2011-2017), ENE (present versus absent, 2011-2017), and margins (≤4 mm versus > 4 mm 2011-2017, only DSS) were identified as independent adverse prognostic factors for 5-year DSS and OS.Conclusions: Compared to lower gum SCC, upper gum SCC had less favorable 5-year outcomes. Wide resection margins are recommended to improve prognosis of upper gum SCC. [ABSTRACT FROM AUTHOR]

We prepared poly (vinylidene fluoride) (PVDF) based membranes via the phase inversion method to investigate the individual and simultaneous effects of graphene oxide (GO) and poly (vinyl pyrrolidone) (PVP) additives. It was demonstrated that the noticeable contribution of GO was to lower membrane surface charge. The principal role of PVP was to enhance membrane porosity, α-to-β phase transformation and mechanical strength. PVP also assisted GO distribution in the membrane matrix owing to their hydrogen-bonding interactions. GO-PVP-PVDF membrane showed cumulative effects in membrane physicochemical properties. In both pure water and naphthol blue black (NBB) dye solutions at pHs 4–10, the filtrate permeance increased from the pure PVDF to GO-PVDF, PVP-PVDF and GO-PVP-PVDF membranes. Therein, GO and PVP introduction provided permeance increases by one order of magnitude. All the membranes exhibited high dye rejections of ≥80.0% due to the Donnan exclusion mechanism. The membranes showed negligible dye adsorption. The stable filtration performance was demonstrated over 24-h multi-cycle filtration. The GO-PVP-PVDF membrane achieved outstanding high permeance (953–1350 L m−2 h−1 MPa−1) and excellent dye removal efficiencies (83.2–87.5%), which opened an avenue for application of this PVDF composite membrane to actual dye wastewater treatment. Image 1 • GO as a membrane electronegativity enhancer. • PVP as a membrane porosity, α-to-β phase transformation and rigidity enhancer. • GO-PVP effects are additive on membrane physical and chemical properties. • PVP introduction produces a one order of magnitude increase in membrane permeance. • High filtrate fluxes and dye rejections occur at pHs 4–10 on GO-PVP-PVDF membrane. [ABSTRACT FROM AUTHOR]

Context/objectives: To examine whether an advance care planning intervention randomized controlled trial facilitates terminally ill cancer patients' transitions to accurate prognostic awareness (PA) and the time spent in the accurate PA state in patients' last six months.Methods: Participants (N = 460) were randomized 1:1 to experimental (interactive intervention tailored to participants' readiness for advance care planning/prognostic information) and control (symptom management education) arms with similar formats. PA was categorized into four states: 1) unknown and not wanting to know; 2) unknown but wanting to know; 3) inaccurate awareness; and 4) accurate awareness. Intervention effectiveness in the two outcomes was evaluated by intention-to-treat analysis with multistate Markov modeling (effect size ≥0.2 as minimal clinically important difference).Results: The final sample constituted 188 and 184 experimental arm and control arm participants who died and were repeatedly assessed, respectively. Experimental arm participants in States 1-3 had a higher probability of shifting to accurate PA (23.0%-35.4% vs. 15.2%-26.2%) than control arm participants, and all effect sizes met the minimal clinically important difference criterion (effect sizes 0.22-0.49). In their last six months, experimental arm participants spent more time in States 3 and 4 (0.18 vs. 0.08 and 2.94 vs. 2.38 months, respectively) but less time in States 1 and 2 (2.70 vs. 3.19 and 0.18 vs. 0.36 months, respectively) (effect sizes 0.11-0.19).Conclusion: Our intervention meaningfully facilitated participants' transition toward accurate PA and more time spent in the accurate PA state (State 4). Our intervention can help health care professionals foster cancer patients' accurate PA earlier in the terminal illness trajectory to make informed end-of-life care decisions tailored to their readiness for prognostic information. [ABSTRACT FROM AUTHOR]