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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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background/Objective
Facilitating death preparedness is important for improving cancer patients' quality of death and dying. We aimed to identify factors associated with the four death‐preparedness ...states (no‐preparedness, cognitive‐only, emotional‐only, and sufficient‐preparedness) focusing on modifiable factors.
Methods
In this cohort study, we identified factors associated with 314 Taiwanese cancer patients' death‐preparedness states from time‐invariant socio‐demographics and lagged time‐varying modifiable variables, including disease burden, physician prognostic disclosure, patient‐family communication on end‐of‐life (EOL) issues, and perceived social support using hierarchical generalized linear modeling.
Results
Patients who were male, older, without financial hardship to make ends meet, and suffered lower symptom distress were more likely to be in the emotional‐only and sufficient‐preparedness states than the no‐death‐preparedness‐state. Younger age (adjusted odds ratio 95% confidence interval = 0.95 0.91, 0.99 per year increase in age) and greater functional dependency (1.05 1.00, 1.11) were associated with being in the cognitive‐only state. Physician prognostic disclosure increased the likelihood of being in the cognitive‐only (51.51 14.01, 189.36) and sufficient‐preparedness (47.42 10.93, 205.79) states, whereas higher patient‐family communication on EOL issues reduced likelihood for the emotional‐only state (0.38 0.21, 0.69). Higher perceived social support reduced the likelihood of cognitive‐only (0.94 0.91, 0.98) but increased the chance of emotional‐only (1.09 1.05, 1.14) state membership.
Conclusions
Death‐preparedness states are associated with patients' socio‐demographics, disease burden, physician prognostic disclosure, patient‐family communication on EOL issues, and perceived social support. Providing accurate prognostic disclosure, adequately managing symptom distress, supporting those with higher functional dependence, promoting empathetic patient‐family communication on EOL issues, and enhancing perceived social support may facilitate death preparedness.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. ...The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. Method We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. Result A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). Conclusion The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC. Keywords: Metastatic urothelial carcinoma, Variant histology, Immune checkpoint inhibitors, Real-world data
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Preparing family surrogates for patient death and end‐of‐life (EOL) decision making may reduce surrogate decisional conflict and regret. Preparedness for patient death involves cognitive ...and emotional preparedness. We assessed the associations of surrogates' death‐preparedness states (that integrate both cognitive and emotional preparedness for patient death) with surrogates' decisional conflict and regret.
Methods
Associations of 173 surrogates' death‐preparedness states (no, cognitive‐only, emotional‐only, and sufficient preparedness states) with decisional conflict (measured by the Decision Conflict Scale) and heightened decisional regret (Decision Regret Scale scores >25) were evaluated using hierarchical linear modeling and hierarchical generalized linear modeling, respectively, during a longitudinal observational study at a medical center over cancer patients' last 6 months.
Results
Surrogates reported high decisional conflict (mean standard deviation = 41.48 6.05), and 52.7% of assessments exceeded the threshold for heightened decisional regret. Surrogates in the cognitive‐only preparedness state reported a significantly higher level of decisional conflict (β = 3.010 95% CI = 1.124, 4.896) than those in the sufficient preparedness state. Surrogates in the no (adjusted odds ratio AOR 95% CI = 0.293 0.113, 0.733) and emotional‐only (AOR 95% CI = 0.359 0.149, 0.866) preparedness states were less likely to suffer heightened decisional regret than those in the sufficient preparedness state.
Conclusions
Surrogates' decisional conflict and heightened decisional regret are associated with their death‐preparedness states. Improving emotional preparedness for the patient's death among surrogates in the cognitive‐only preparedness state and meeting the specific needs of those in the no, emotional‐only, and sufficient preparedness states are actionable high‐quality EOL‐care interventions that may lessen decisional conflict and decisional regret.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
We aimed to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive gonadotropin‐releasing hormone (GnRH) agonist (GnRHa) ...therapy and those who receive GnRH antagonist therapy.
Methods
Using the Taiwan National Health Insurance Research Database, we analyzed data by comparing 666 participants receiving GnRH antagonists and 1332 propensity score‐matched participants treated with GnRHa in a 1:2 fashion during the period from May 1, 2015, to September 30, 2018. Cox proportional‐hazards models were used to estimate the treatment effect on CV outcomes. Furthermore, we conducted an in vitro study to investigate the effect of a GnRHa (leuprolide) or a GnRH antagonist (degarelix) on matrix metalloproteinase‐9 (MMP‐9) expression and invasion ability in THP‐1 differentiated macrophages.
Results
GnRH antagonist therapy was associated with a lower risk of composite CV events of myocardial infarction, ischemic stroke, or CV death (hazard ratio HR, 0.48; 95% confidence interval CI, 0.25–0.90) than GnRHa therapy, with a mean follow‐up period of 1.21 years. Significantly lower risks of CV death (HR, 0.21; 95% CI, 0.06–0.70) and all‐cause mortality (HR, 0.77; 95% CI, 0.61–0.97) were observed in the GnRH antagonist group. In the in vitro study, leuprolide, but not degarelix, significantly increased the expression of MMP‐9 activity and the invasive ability of THP‐1 differentiated macrophages through gelatin zymography and the matrix invasion assay, respectively.
Conclusion
GnRH antagonists were associated with reduced risk CV events compared with the GnRHa among patients with PCa, which may be through effects on macrophages.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Activated T regulatory (Treg) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated Treg cells and the progression of human colon cancer. We ...designed a cross‐sectional study of CD4+Foxp3+ T cells from peripheral blood, primary tumor and nontumor colon tissue of 42 patients with colon cancer and correlated the percentages of different subgroups of Treg cells with colon cancer stage. The phenotypes, cytokine‐release patterns and suppression ability of these Treg cells were analyzed. We found that Treg cells increased significantly in both peripheral blood and cancer tissue. In addition, the Treg cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing Treg cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated Treg cells (Foxp3hiCD45RA−) and nonsuppressive Treg cells (Foxp3loCD45RA−), but not resting Treg cells (Foxp3lowCD45RA+), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated Treg cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T‐cell antigen‐4. Activated Treg cells, however, secreted significantly lower levels of effector cytokines (interleukin‐2, tumor necrosis factor‐α and interferon‐γ) than did resting Treg cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, Treg cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated Treg cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.
What's new?
Activated T regulatory (Treg) cells suppress the immune response, and can interfere with immunological attacks on cancer cells. This study examined levels of Treg cells in human colorectal cancer, and found that cancer tissue and peripheral blood contained more activated Treg cells than healthy tissue. Also, the presence of activated Treg cells correlated with tumor metastases, suggesting these cells might be an important key to improving immune therapeutic strategies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with ...either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%,
= 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months,
= 0.078) and OS (median, not reached vs. 26.8 months,
= 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months,
< 0.001) and OS (median, not reached vs. 24.4 months,
= 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This cohort study investigated factors associated with 336 Taiwanese family caregivers' emotional and cognitive preparedness for death of a loved one with terminal cancer. Caregivers' ...death-preparedness states (no-death-preparedness as reference, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) were previously identified. Associations of factors with these states were determined by a hierarchical generalized linear model. Financial hardship decreased caregivers' likelihood for the emotional-death-preparedness-only and sufficient-death-preparedness states. Physician prognostic disclosure increased membership in the cognitive-death-preparedness-only and sufficient-death-preparedness states. The better the quality of the patient-caregiver relationship, the higher the odds for the emotional-death-preparedness-only and sufficient-death-preparedness states, whereas the greater the tendency for caregivers to communicate end-of-life issues with their loved one, the lower the odds for emotional-death-preparedness-only state membership. Stronger coping capacity increased membership in the emotional-death-preparedness-only state, but perceived social support was not associated with state membership. Providing effective interventions tailored to at-risk family caregivers' specific needs may facilitate their death preparedness.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Latency-associated peptide (LAP) - expressing regulatory T cells (Tregs) are important for immunological self-tolerance and immune homeostasis. In order to investigate the role of LAP in human ...CD4⁺Foxp3⁺ Tregs, we designed a cross-sectional study that involved 42 colorectal cancer (CRC) patients. The phenotypes, cytokine-release patterns, and suppressive ability of Tregs isolated from peripheral blood and tumor tissues were analyzed. We found that the population of LAP-positive CD4⁺Foxp3⁺ Tregs significantly increased in peripheral blood and cancer tissues of CRC patients as compared to that in the peripheral blood and tissues of healthy subjects. Both LAP⁺ and LAP⁻ Tregs had a similar effector/memory phenotype. However, LAP⁺ Tregs expressed more effector molecules, including tumor necrosis factor receptor II, granzyme B, perforin, Ki67, and CCR5, than their LAP⁻ negative counterparts. The in vitro immunosuppressive activity of LAP⁺ Tregs, exerted via a transforming growth factor-β-mediated mechanism, was more potent than that of LAP⁻ Tregs. Furthermore, the enrichment of LAP⁺ Treg population in peripheral blood mononuclear cells (PBMCs) of CRC patients correlated with cancer metastases. In conclusion, we found that LAP⁺ Foxp3⁺ CD4⁺ Treg cells represented an activated subgroup of Tregs having more potent regulatory activity in CRC patients. The increased frequency of LAP⁺ Tregs in PBMCs of CRC patients suggests their potential role in controlling immune response to cancer and presents LAP as a marker of tumor-specific Tregs in CRC patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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