Associations of nutrition impact symptoms with dietary intake and eating-related distress in patients with advanced cancer.

BACKGROUND & AIMS: There is no definition of nutrition impact symptoms (NISs) in cancer care. Moreover, there is a lack of evidence on the associations of NISs with dietary intake and eating-related distress (ERD) in advanced cancer. Therefore, this study aimed to determine the associations of NISs with dietary intake and ERD in patients with advanced cancer. METHODS: This study entailed a secondary analysis of a multicenter self-reported questionnaire designed to develop measurements that assess ERD experienced by patients. Participants evaluated their dietary intake and 19 symptoms regarded as NISs using a 10-point scale. To determine the association between dietary intake and the number of NISs with a score ≥4, estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. Furthermore, to assess the association between ERD and the number of NISs with a score ≥4, multiple regression analysis was performed. RESULTS: A total of 302 patients were included in the analysis. The higher the number of NISs with a score ≥4, the lower the dietary intake tended to be. In the logistic regression model, significantly higher adjusted ORs than in the no NISs with a score ≥4 group were observed in the 4-6 NISs group, 7-9 NISs group, and 10 or more group (0.19 [95% CI, 0.07-0.52], p = 0.001; 0.11 [95% CI, 0.03-0.42], p = 0.001; 0.07 [95% CI, 0.01-0.36], p = 0.002, respectively). In the multiple regression analysis, the number of NISs with a score ≥4 was identified as one of the factors significantly associated with ERD. CONCLUSIONS: Having 4 or more NISs with a score ≥4 was shown to be predictive of the likelihood of reduced dietary intake. Furthermore, the higher the number of NISs with a score ≥4, the more likely the eating-related quality of life was impaired in advanced cancer.

Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia.

BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

Successful Management of Terminal Delirium With Transdermal Blonanserin Patch in a Terminally Ill Cancer Patient.

Delirium is a distressing condition in terminally ill cancer patients, often treated with antipsychotics. Administering them orally, subcutaneously, or intravenously can be challenging in severely agitated patients. Transdermal antipsychotic patches offer an alternative, but their use for terminal delirium remains underexplored. We present the case of a 73-year-old man with advanced diffuse large B cell lymphoma who developed severe mixed delirium during third-line chemotherapy. Nonpharmacological interventions and oral risperidone plus intravenous haloperidol failed to improve his condition. Subsequently, a transdermal blonanserin patch was applied, resulting in the resolution of hallucinations on day 1 and agitation on day 3, allowing improved communication. The patch was easily applied daily without notable adverse events. However, he deteriorated a week later with an estimated survival of days, ultimately requiring continuous midazolam for refractory agitation. This case underscores the potential of transdermal blonanserin patches for delirium in terminally ill cancer patients, emphasizing the need for future prospective studies.

Fluid retention and weight loss in refractory cancer cachexia.

OBJECTIVES: It is unknown to what extent the fluid retention (FR) status disrupts the detection of weight loss rate (WLR) in adult patients with advanced cancer. This study aimed to determine the association of FR status with WLR. METHODS: This study was a secondary analysis of a prospective cohort study. FR was evaluated as follows: oedema (0, no; 1, yes), pleural effusion (0, no; 1, yes but asymptomatic; 2, symptomatic) and ascites (0, no; 1, yes but asymptomatic; 2, symptomatic). Patients were divided into three groups according to their FR scores: no-FR (0), moderate-FR (1-2) and high-FR (3-5). Multiple regression analysis was performed. RESULTS: Four hundred and twenty patients were categorised: no-FR group (n=164), moderate-FR group (n=158) and high-FR group (n=98). The prevalence of oedema, pleural effusion and ascites was 63.9%, 27.8% and 36.7% in the moderate-FR group, and 93.9%, 61.3% and 82.6% in high-FR group. The means of WLR were 9.2, 8.4 and 3.8 in the groups. The high-FR group and the FR score of 5 were correlated with WLR (estimate -4.71, 95% CI -7.84 to -1.58; estimate -10.29, 95% CI -17.84 to -2.74). CONCLUSIONS: The coexistence of FR was significantly correlated with WLR.

Malignancy-related ascites in palliative care units: prognostic factor analysis.

OBJECTIVES: The prognostic factors in patients with malignancy-related ascites (MA) have been poorly investigated. This study aimed to evaluate both the prognostic impact of MA on terminally ill patients with cancer and the prognostic factors in those with MA. METHODS: This was a post hoc analysis of a multicentre, prospective cohort study. Patients with advanced cancer admitted to palliative care units at 23 institutions and aged≥18 years were enrolled between January and December 2017. Overall survival (OS) was compared according to MA. A multivariate analysis was conducted to explore prognostic factors in patients with MA. RESULTS: Of 1896 eligible patients, gastrointestinal and hepatobiliary pancreatic cancers accounted for 42.5%. 568 (30.0%) of the total had MA. Patients with MA had significantly shorter OS than those without MA (median, 14 vs 22 days, respectively; HR, 1.55; 95% CI, 1.39 to 1.72; p<0.01). A multivariate analysis showed that MA was a poor prognostic factor (HR, 1.30; 95% CI, 1.13 to 1.50; p<0.01) and that among patients with MA, significant poor prognostic factors were liver metastasis, moderately to severely reduced oral intake, delirium, oedema, gastric cancer, high serum creatinine, high serum C reactive protein, high serum total bilirubin, dyspnoea and fatigue, while significant good prognostic factors were female sex, good performance status, high serum albumin and colorectal cancer. CONCLUSIONS: MA had a negative impact on survival in terminally ill patients with cancer. A multivariate analysis revealed several prognostic factors in patients with terminal cancer and MA.

Human Adipose-Derived Endothelial Progenitor Cells Accelerate Epithelialization of Radiation Ulcers in Nude Mice.

BACKGROUND: Cotransplantation of adipose-derived stem cells (ASCs) and endothelial progenitor cells has shown superior angiogenic effects compared with ASCs alone in recent animal studies. However, endothelial progenitor cells could only be collected from blood vessels or bone marrow. Thus, the authors have established a method for purifying adipose-derived endothelial progenitor cells (AEPCs). The authors hypothesized that AEPCs would enhance the therapeutic effect of ASCs on radiation ulcers. METHODS: Seven-week-old male nude mice (BALB/cAJcl-nu/nu) were irradiated on the dorsal skin (total 40 Gy); 12 weeks later, 6-mm-diameter wounds were created. The mice were then treated with subcutaneous injection of human ASCs [1 × 10 5 ( n = 4)], human AEPCs [2 × 10 5 or 5 × 10 5 ( n = 5)], combinations of those [ASCs 1 × 10 5 plus AEPCs 2 × 10 5 ( n = 4) or 5 × 10 5 ( n = 5)], or only vehicle ( n = 7). The nonirradiated group was also prepared as a control ( n = 6). The days required for macroscopic epithelialization was compared, and immunostaining for human-derived cells and vascular endothelial cells was performed at day 28. RESULTS: AEPC-ASC combination-treated groups healed faster than the ASC-treated group (14 ± 0 days versus 17 ± 2 days; P < 0.01). Engraftment of the injected cells could not be confirmed. Only the nonirradiated mice had significantly higher vascular density (0.988 ± 0.183 × 10 -5 /µm -2 versus 0.474 ± 0.092 × 10 -5 /µm 2 ; P = 0.02). CONCLUSION: The results suggested therapeutic potentials of AEPCs and an enhanced effect of combination with ASCs. This study is a xenogenic transplantation model, and further validation in an autologous transplantation model is needed. CLINICAL RELEVANCE STATEMENT: Human AEPCs and their combination with ASCs accelerated epithelialization of radiation ulcers in nude mice. The authors suggest that administration of humoral factors secreted from AEPCs (eg, treatment with culture-conditioned media) could be used for the same purpose.

Psychological symptom burden associated with malignant wounds: Secondary analysis of a prospective cohort study.

OBJECTIVES: Patients with malignant wounds suffer from physical and psychological symptom burden. Despite psychological support being required, the impact of malignant wounds on patients' psychological distress is poorly investigated. We evaluated psychological distress associated with malignant wounds for patients at their end of life. METHODS: This study used the secondary analysis of the results of a large prospective cohort study, which investigated the dying process among patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prevalence of moderate to severe psychological symptom burden, evaluated by the Integrated Palliative Care Outcome Scale (IPOS)-feeling at peace scores of 2-4. In addition, the factors affecting psychological symptoms were investigated. The quality of death was also evaluated upon death using the Good Death Scale score. RESULTS: Out of the total 1896 patients, 156 had malignant wounds (8.2%). Malignant wounds were more common in female and young people. The breast, head, and neck were the most prevalent primary sites. More patients with malignant wounds had IPOS-feeling at peace scores of 2-4 than patients without malignant wounds (41.0% vs. 31.3%, p = 0.024). Furthermore, psychological distress was associated with moderate to severe IPOS-pain and the frequency of dressing changes. The presence of malignant wounds did not affect the quality of death. SIGNIFICANCE OF RESULTS: This study showed increased psychological distress due to malignant wounds. Patients with malignant wounds require psychological support in addition to the treatment of physical symptoms for maintaining their quality of life.

Improved Symptom Change Enhances Quality of Dying in Patients With Advanced Cancer: An East Asian Cross-Cultural Study.

BACKGROUND: Symptom burdens tend to increase for patients with cancer and their families over the disease trajectory. There is still a lack of evidence on the associations between symptom changes and the quality of dying and death. In this context, this research investigated how symptom changes influence the quality of dying and death. METHODS: This international prospective cohort study (the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED), 2017-2019) included 22, 11, and 4 palliative care units across Japan, South Korea, and Taiwan. Eligible participants were adults (Japan and Korea, ≥18 years; Taiwan, ≥20 years) with locally advanced or metastatic cancer. Physical and psychological symptoms were assessed by physicians upon admission and within 3 days before death. Death quality was assessed using the Good Death Scale (GDS), developed in Taiwan. Univariate and multivariate regression analyses were used to identify correlations between symptom severity changes and GDS scores. RESULTS: Among 998 patients (542 [54.3%] men and 456 [45.7%] women; mean [SD] age = 70.1 [± 12.5] years), persistent dyspnea was associated with lower GDS scores when compared to stable dyspnea (ß = -0.427, 95% CI = -0.783 to -0.071). Worsened (-1.381, -1.932 to -0.831) and persistent (-1.680, -2.701 to -0.659) delirium were also significantly associated with lower GDS scores. CONCLUSIONS: Better quality of dying and death was associated with improved symptom control, especially for dyspnea and delirium. Integrating an outcome measurement for the quality of dying and death is important in the management of symptoms across the disease trajectory in a goal-concordant manner.

Cancer Pain Management in Patients Receiving Inpatient Specialized Palliative Care Services.

CONTEXT: Cancer pain is a common complication that is frequently undertreated in patients with cancer. OBJECTIVES: This study is aimed at assessing the time needed to achieve cancer pain management goals through specialized palliative care (SPC). METHODS: This was a multicenter, prospective, longitudinal study of inpatients with cancer pain who received SPC. Patients were continuously followed up until they considered cancer pain management successful, and we estimated this duration using the Kaplan-Meier method. We investigated the effectiveness of pain management using multiple patient-reported outcomes (PROs) and quantitative measures, including pain intensity change in the Brief Pain Inventory. A paired-sample t-test was used to compare the pain intensity at the beginning and end of the observation period. RESULTS: Cancer pain management based on the PROs was achieved in 87.9% (385/438) of all cases. In 94.5% (364/385) of these cases, cancer pain management was achieved within 1 week, and the median time to pain management was 3 days (95% confidence interval [CI], 2-3). The mean worst pain intensity in the last 24 h at the start and end of observation were 6.9 ± 2.2 and 4.0 ± 2.3, respectively, with a difference of -2.9 (95% CI, -3.2 to -2.6; p < 0.01). Overall, 81.6% of the patients reported satisfaction with cancer pain management, and 62 adverse events occurred. CONCLUSION: SPC achieved cancer pain management over a short period with a high level of patient satisfaction resulting in significant pain reduction and few documented adverse events.

How different are accuracies of clinicians' prediction of survival by assessment methods?

BACKGROUND: No standardized method has been established for evaluating the accuracy of a clinicians' prediction of survival (CPS). Till now, no study has compared the accuracy of CPS according to the evaluation methods using the same dataset. We aimed to examine the accuracy of CPS by different statistical approaches in patients with far-advanced cancer. METHODS: The current study was a secondary analysis of an international multicenter prospective cohort study. Newly admitted patients with advanced cancer were enrolled in palliative care units (PCUs) in Japan, Korea, and Taiwan. We obtained the temporal CPS at enrollment. The patients were classified into groups of days (≤7 days) and weeks (≤30 days) based on CPS and actual survival (AS). We evaluated the accuracy of CPS by the distribution, area under the receiver operating characteristics curve (AUROCs), and an estimate ±33% of AS. RESULTS: A total of 2,571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. As for the "days" category, the distribution of AS is larger than that of CPS, however, the results are reversed in the "weeks" category. The AUROCs showed over 80% discrimination for both the "days" and "weeks" categories. Accurate CPS within ±33% of AS was approximately 30% in both "days" and "weeks" categories. CONCLUSIONS: We showed a discrepancy of approximately 30-80% in the accuracy of CPS among three different analysis methods: distribution, AUROC, and AS comparison. Considering the low accuracy of AS comparisons, clinicians should provide a wide range of survival time. CPS was able to effectively discriminate and may be useful for risk stratification.

Symptoms and Prognoses of Patients With Breast Cancer and Malignant Wounds in Palliative Care Units: The Multicenter, Prospective, Observational EASED Study.

BACKGROUND: This study sought to investigate the symptoms and prognoses of patients with breast cancer and malignant wounds in the palliative care unit setting. METHODS: This study was a sub-group analysis of a multicenter, prospective, observational study. Patients admitted to 23 palliative care units in Japan between January and December 2017 were enrolled. Data of patients with breast cancer were extracted. We compared demographic characteristics, symptoms, and prognoses by breast cancer malignant wound status. The primary outcome was overall survival. Secondary outcomes included Palliative Prognostic Index (PPI) score, malignant wound characteristics, and symptom burden. RESULTS: Of 1896 patients, 131 (6.9%) had breast cancer. In this cohort, 44 (33.6%) patients had malignant wounds. Most malignant wounds (88%) were on the back and chest. Malignant wounds were associated with skin redness, erosion, necrosis, or fistula. Symptoms included bleeding, exudate, odor, and pain. Twenty-eight patients (63.6%) needed dressing changes and 14 (31.8%) patients experienced bleeding. None died due to bleeding. In the malignant wounds group, 32 (72.8%) patients had used an opioid dose equivalent to 38 mg of oral morphine daily, compared to 25 mg by 57 (65.5%) patients in the non-malignant wounds group (P = .26). Median PPI scores at hospital admission were 4.5 vs 6.5 (P = .08). Median survival was 23 vs 21 days (P = .48). CONCLUSIONS: Patients with malignant wounds had a distinct symptom burden profile and tended to use a higher dose of opioids. The effect of malignant wounds on survival was unclear.

In situ hybridization analysis of odorant receptor expression in the olfactory organ of the pig-nosed turtle Carettochelys insculpta.

The turtle olfactory organ consists of upper (UCE) and lower (LCE) chamber epithelium, which send axons to the ventral and dorsal portions of the olfactory bulbs, respectively. Generally, the UCE is associated with glands and contains ciliated olfactory receptor neurons (ORNs), while the LCE is devoid of glands and contains microvillous ORNs. However, the olfactory organ of the pig-nosed turtle Carettochelys insculpta appears to be a single olfactory system morphologically: there are no associated glands; ciliated ORNs are distributed throughout the olfactory organ; and the olfactory bulb is not divided into ventral and dorsal portions. In this study, we analyzed the expression of odorant receptors (ORs), the major olfactory receptors in turtles, in the pig-nosed turtle olfactory organ, via in situ hybridization. Of 690 ORs, 375 were classified as class I and 315 as class II. Some class II ORs were expressed predominantly in the posterior dorsomedial walls of the nasal cavity, while other class II ORs and all class I ORs examined were expressed in the remaining region. These results suggest that the pig-nosed turtle olfactory organ can be divided into two regions according to the expression of ORs.

Low serum creatinine as a prognostic marker in advanced cancer.

OBJECTIVES: To evaluate whether low serum creatinine levels are associated with poor outcomes in patients with advanced cancer. METHODS: This is a secondary analysis of a prospective cohort study. Patients were divided into three groups according to their baseline serum creatinine levels. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: 809 males were divided: male-low group (n=192), male-normal group (n=403) and male-high group (n=214). 808 females were divided: female-low group (n=239), female-normal group (n=389) and female-high group (n=180). Significant differences were observed in survival rates between the high and normal groups in the males and females (both log-rank p<0.001). Significantly higher risks of mortality were observed in the Cox proportional hazard model for the high group than for the normal group in both sexes (adjusted HR 1.292, 95% CI 1.082 to 1.542; adjusted HR 1.316, 95% CI 1.094 to 1.583, respectively). High serum creatinine was associated with shorter survival than normal creatinine, while low serum creatinine was not. CONCLUSIONS: Low serum creatinine levels did not have prognostic abilities in this population.

Prediction of Survival in Patients with Advanced Cancer: A Narrative Review and Future Research Priorities.

This paper aimed to summarize the current situation of prognostication for patients with an expected survival of weeks or months, and to clarify future research priorities. Prognostic information is essential for patients, their families, and medical professionals to make end-of-life decisions. The clinician's prediction of survival is often used, but this may be inaccurate and optimistic. Many prognostic tools, such as the Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and Prognosis in Palliative Care Study, have been developed and validated to reduce the inaccuracy of the clinician's prediction of survival. To date, there is no consensus on the most appropriate method of comparing tools that use different formats to predict survival. Therefore, the feasibility of using prognostic scales in clinical practice and the information wanted by the end users can determine the appropriate prognostic tool to use. We propose four major themes for further prognostication research: (1) functional prognosis, (2) outcomes of prognostic communication, (3) artificial intelligence, and (4) education for clinicians.

Irradiation affects adipose-derived stem cells and wound healing depending on radiation dose and frequency.

BACKGROUND: Radiation therapies are often associated with permanent devitalization in the surrounding tissue. We hypothesized that stem cells are damaged depending on each irradiation dose and frequency of fractionated radiotherapies, which results in impaired tissue function including wound healing capacity. METHODS: To test the hypothesis, susceptibility of human adipose-derived stem cells (ASCs) to a single irradiation (0-10 Gy) was assessed in vitro. In vivo chronic radiation effects were also assessed on the mouse dorsal skin (N=4-5) for 6 months after a total of 40 Gy irradiation (0 Gy as control) using one of three fractionated protocols (2 Gy daily for 20 days, 10 Gy weekly for 4 weeks, or 10 Gy monthly for 4 months). Oxygen partial pressure, oxygen saturation of hemoglobin, and dorsal skin viscoelasticity were periodically measured, and wound healing and tissue immunohistology were compared at 6 months. RESULTS: A single irradiation of cultured human ASCs resulted in a dose-dependent increase in cell death up to 2 Gy but with no further increases between 2 and 10 Gy. Most of the apoptotic ASCs were in the proliferation phase. Among the three in vivo irradiation protocols, the 2 Gy×20 group had the most severe chronic tissue damage (i.e., skin dysfunction, subcutaneous atrophy, and depletion of CD34+ stem cells) 6 months after the irradiation. Wound healing was also impaired most significantly in the 2 Gy×20 group. CONCLUSIONS: These results have important clinical implications for surgeons and radiotherapists such as the timing of surgical interventions and the optimization of fractionation protocols.Clinical Relevance Statement: Irradiation damages stem cells depending on the radiation dose and frequency. Using the ultimately optimized protocol, we can minimize the long-term functional deficits of radiated tissue without losing anti-cancer efficacy of radiation therapy.

Validation of the Japanese version of the full and short form Trust in Oncologist Scale.

OBJECTIVES: This study aimed to validate the Japanese versions of the Trust in Oncologist Scale (TiOS-J) and the TiOS-Short Form (TiOS-SF-J). METHODS: A cross-sectional web-based survey was conducted among cancer patients in Japan. The forward-backward translation method was used to develop the TiOS-J. The web-based survey was mailed to 633 people, of whom 309 responded. After 2 weeks, 103 among the 156 first-time respondents completed the second survey to verify the reliability of the retest method. The validity was evaluated by exploratory factor analysis (EFA), confirmatory factor analysis (CFA), Spearman's correlation coefficients between the Patient Satisfaction Questionnaire-Japanese, willingness to recommend the oncologist, trust in health care, and number of oncological consultations. To evaluate reliability, Cronbach's α and test-retest correlation were calculated. RESULTS: The theoretically driven four-factor model and the EFA-driven one-factor model of the full-form TiOS-J (18 items) did not result in an acceptable fit; however, CFA supported the one-dimensionality of the 5 items from the TiOS-SF-J (χ2 (5) = 12.36, p = 0.03, goodness-of-fit index = 0.984, adjusted goodness-of-fit index = 0.952, comparative fit index = 0.991, and root mean square error of approximation = 0.069). With regard to the reliability of TiOS-J and TiOS-SF-J, the Cronbach's alpha values were 0.94 and 0.89, respectively; the test-retest values were 0.82 and 0.78. SIGNIFICANCE OF RESULTS: This study indicated that the TiOS-J and TiOS-SF-J are valid and reliable instruments for measuring patients' trust in their oncologists and can be used to assess trust in oncologists for both clinical and research purposes.

Continuous Deep Sedation for Psycho-Existential Suffering: A Multicenter Nationwide Study.

Background: There is ongoing debate on whether continuous deep sedation (CDS) for psycho-existential suffering is appropriate. Objective: We aimed to (1) clarify clinical practice of CDS for psycho-existential suffering and (2) assess its impact on patients' survival. Methods: Advanced cancer patients admitted to 23 palliative care units in 2017 were consecutively enrolled. We compared patients' characteristics, CDS practices, and survival between those receiving CDS for psycho-existential suffering ± physical symptoms and only for physical symptoms. Results: Of 164 patients analyzed, 14 (8.5%) received CDS for psycho-existential suffering ± physical symptoms and only one of them (0.6%) solely for psycho-existential suffering. Patients receiving CDS for psycho-existential suffering, compared with those only for physical symptoms, were likely to have no specific religion (p = 0.025), and desired (78.6% vs. 22.0%, respectively; p < 0.001) and requested a hastened death more frequently (57.1% vs. 10.0%, respectively; p < 0.001). All of them had a poor physical condition with limited estimated survival, and mostly (71%) received intermittent sedation before CDS. CDS for psycho-existential suffering caused greater physicians' discomfort (p = 0.037), and lasted for longer (p = 0.029). Dependency, loss of autonomy, and hopelessness were common reasons for psycho-existential suffering that required CDS. The survival time after CDS initiation was longer in patients receiving it for psycho-existential suffering (log-rank, p = 0.021). Conclusion: CDS was applied to patients who suffered from psycho-existential suffering, which often associated with desire or request for a hastened death. Further studies and debate are warranted to develop feasible treatment strategies for psycho-existential suffering.

In situ hybridization analysis of olfactory receptor expression in the sea turtle olfactory organ.

The olfactory organ of turtles consists of an upper chamber epithelium (UCE) with associated glands, and a lower chamber epithelium (LCE) devoid of glands. The UCE and LCE are referred to as the air-nose and the water-nose, respectively, because the UCE is thought to detect airborne odorants, while the LCE detects waterborne odorants. However, it is not clear how the two are used in the olfactory organ. Odorant receptors (ORs) are the major olfactory receptors in turtles; they are classified as class I and II ORs, distinguished by their primary structure. Class I ORs are suggested to be receptive to water-soluble ligands and class II ORs to volatile ligands. This study analyzed the expression of class I and II ORs in hatchlings of the green sea turtle, Chelonia mydas, through in situ hybridization, to determine the localization of OR-expressing cells in the olfactory organ. Class I OR-expressing cells were distributed mainly in the LCE, implying that the LCE is receptive to waterborne odorants. Class II OR-expressing cells were distributed in both the UCE and LCE, implying that the entire olfactory organ is receptive to airborne odorants. The widespread expression of class II ORs may increase opportunities for sea turtles to sense airborne odorants.

Difficulty swallowing and food bolus obstruction in advanced cancer: association with the cachexia-related quality of life.

BACKGROUND: Swallowing disorders including difficulty swallowing and food bolus obstruction, result in reduced dietary intake-a common occurrence that leads to cachexia in patients with advanced cancer. This study examined the effects of swallowing difficulty and food bolus obstruction on cachexia-related quality of life (QOL). METHODS: This study secondarily analyzed data from a self-reported questionnaire survey of adult patients with advanced cancer at 11 palliative care services. Difficulty swallowing and food bolus obstruction were measured using the 11-point Numeric Rating Scale (NRS), whereas dietary intake and cachexia-related QOL were assessed using the Ingesta-Verbal/Visual Analog Scale and the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Subscale. A multiple logistic regression model was employed to determine the factors associated with varying degrees of difficulty swallowing and food bolus obstruction. RESULTS: Of the invited 495 patients, 378 agreed to participate (response rate 76.4%). After excluding participants with missing data, the data of 332 participants were analyzed; 26.5% had difficulty swallowing (NRS ≥1) and 28.3% had food bolus obstruction (NRS ≥1). Multivariate analysis revealed a substantial association between difficulty swallowing and food bolus obstruction and a decrease in cachexia-related QOL, regardless of performance status and the existence of cachexia. The coefficients for difficulty swallowing and food bolus obstruction were -6.34 [95% confidence interval (CI): -9.55 to -3.14, P<0.001] and -5.88 (95% CI: -8.68 to -3.09, P<0.001), respectively. CONCLUSIONS: Cachexia-related QOL deteriorated as difficulty swallowing and food bolus obstruction worsened; thus, healthcare providers must diagnose and treat swallowing disorders in a timely manner to prevent progression of cachexia and improve cachexia-related QOL.