Symptoms and health-related quality of life in patients with newly diagnosed multiple myeloma: a multicenter prospective cohort study.

OBJECTIVE: Existing cross-sectional observational studies indicate that patients with multiple myeloma experience negative physical and psychological symptoms and low health-related quality of life. The study aim was to determine symptom prevalence, health-related quality of life and symptoms associated with health-related quality of life in patients with newly diagnosed multiple myeloma. METHODS: This multicenter longitudinal cohort study was conducted in four hospitals in Japan. Patients with newly diagnosed multiple myeloma were asked to report their symptom intensity and health-related quality of life using validated questionnaires at three points: at diagnosis (T1), 1 month (T2) and 12 months after diagnosis (T3). Symptoms associated with health-related quality of life were explored using a mixed-effects model. RESULTS: A total of 106 patients completed the assessment at T1. The symptoms more than 30% of patients reported were pain, disturbed sleep and distress at T1, pain, dry mouth, disturbed sleep and fatigue at T2, fatigue, numbness of tingling and pain and numbness or tingling at T3. Pain and depression were significantly associated with health-related quality of life negatively. CONCLUSIONS: The finding suggests that more than 30% of multiple myeloma patients suffered from pain and various symptoms and they received suboptimal palliative care within a year after starting initial chemotherapy. Pain and depression should be the main targets of interventions to improve health-related quality of life in this population.

Factors associated with suicidal ideation in patients with multiple myeloma.

Patients with multiple myeloma are at risk of suicide. The study objective was to investigate the clinical risk factors of suicidal ideation among multiple myeloma patients. Consecutive inpatients with a new primary diagnosis of multiple myeloma were recruited. Patients were asked to complete the Patient Health Questionnaire-9 to measure suicidal ideation and depression. Patient demographic and biomedical characteristics (age, gender, education, marital status, employment, performance status and cancer stage) and pain and depression scores were analyzed as potential factors associated with suicidal ideation. Of the 79 patients, 10 [12.6% (95% confidence interval: 7-22)] had suicidal ideation. The results of a logistic regression analysis showed that being unmarried, less advanced cancer stage and depression were significantly associated with the presence of suicidal ideation. These findings suggest that a non-negligible proportion of patients with multiple myeloma experience suicidal ideation and that several multidimensional factors are significantly associated.

Depressive symptoms during the first month of chemotherapy and survival in patients with hematological malignancies: A prospective cohort study.

OBJECTIVE: The objective of the study is to investigate depressive symptoms before and after the initiation of chemotherapy and their impact on overall survival (OS) among patients with hematological malignancies. METHODS: We performed a prospective analysis of consecutive patients with newly diagnosed malignant lymphoma or multiple myeloma enrolled between September 2010 and March 2016. We evaluated depression symptoms at two time points: before starting chemotherapy (T1) and 1 month later (T2), using PHQ-9 and known prognostic factors. We allocated participants with depressive symptoms at T1 and/or T2 to a depression group that was subdivided as follows: new depressive symptoms at T2, ("new-onset"), remission of depressive symptoms at T2 ("remission"), and persistent depressive symptoms from T1 to T2 ("persistent"). The main outcome, OS, was evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards modeling. RESULTS: Of the 294 eligible participants, we analyzed 255 patients, including 83 with depression. There were 19 participants in the new-onset, 38 in the remission, and 26 in the persistent depression group. The OS of participants with depression was significantly shorter than that of those without depression (adjusted hazard ratio [AjHR] 2.43; 95% confidence interval [CI] 1.43-4.12; P < .001). Using the never-depressive symptoms group as a reference group, AjHRs were as follows: new-onset, 1.91 (95% CI, 0.77-4.75; 0.166); remission, 2.98 (95% CI, 1.55-5.74; 0.001), and persistent, 2.17 (95%CI, 1.01-4.68; 0.047). CONCLUSIONS: Among patients with mature lymphoid malignancy, the group with depression at baseline had a poorer survival, both in the group that remained depressive and the group that recovered from depressive symptoms.

Comparative study of MAFLD as a predictor of metabolic disease treatment for NAFLD.

A novel concept of Metabolic Associated Fatty Liver Disease (MAFLD) was proposed, incorporating metabolic abnormalities such as obesity and diabetes, which are risk factors that affect the prognosis. Non-Alcoholic Fatty Liver Disease (NAFLD), entails fat accumulation in the liver without alcohol consumption and is often linked to obesity, insulin resistance, and metabolic syndrome. However, the broad nature of the disease concept has hindered prognosis accuracy. In this study, we assess the contribution of the impact of diagnostic criteria for MAFLD on metabolic disease progression compared to conventional diagnostic criteria for NAFLD. A total of 7159 patient who were presented to the health screening center in Tokai University Hospital both in 2015 and 2020 were included in the study. Fatty liver was diagnosed using abdominal ultrasonography. The diagnostic criteria for NAFLD were consistent with the global guidelines based on alcohol consumption. The diagnostic criteria for MAFLD were based on the International Consensus Panel. Medications (anti-hypertensive, diabetic, and dyslipidemia medications) were evaluated by self-administration in the submitted medical questionnaire. A total of 2500 (34.9%) participants were diagnosed with fatty liver (FL +), 1811 (72.4%) fit both NAFLD and MAFLD diagnostic criteria (overlap), 230 (9.2%) fit only the NAFLD diagnostic criteria (NAFLD group) and 404 (16.1%) fit the MAFLD diagnostic criteria (MAFLD group) at 2015. Over the next 5 years, medication rates increased in the NAFLD group for anti-hypertensive, + 17 (7.4%); diabetes, + 3 (1.3%); and dyslipidemia, + 32 (13.9%). In contrast, the only-MAFLD group showed a more significant increase with + 49 (12.1%), + 21 (5.2%), and + 49 (12.1%), for the respective medications, indicating a substantial rise in patients starting new medications. Our analysis of repeated health check-ups on participants revealed that the diagnostic criteria for MAFLD are more predictive of future treatment for metabolic disease than conventional diagnostic criteria for NAFLD.

Specialized Palliative Care and Intensity of End-of-Life Care Among Adolescents and Young Adults with Cancer: A Medical Chart Review.

Purpose: Adolescents and young adults (AYAs) with cancer often undergo aggressive end-of-life (EOL) care. We evaluated whether specialized palliative care (SPC) involvement is associated with the receipt of intensive EOL care among AYAs. Methods: This retrospective study included patients with cancer treated between the ages of 15 and 39 years at a university hospital, who died during 2009-2022. The primary outcome was high-intensity EOL (HI-EOL) care, which was defined as ≥1 session of intravenous chemotherapy <14 days from death or during the final 30 days of life, ≥1 hospitalization at an intensive care unit, >1 emergency room admission, or >1 hospitalization at an acute care unit during the final 30 days of life. We determined predictors of outcomes using multiple logistic regression models. Results: We analyzed 132 AYAs (75 with SPC involvement), of whom 42.4% (95% confidence interval [CI]: 33.9%-51.3%) underwent HI-EOL care. The prevalence of HI-EOL care was significantly lower in those who had SPC involvement than in those without SPC involvement (adjusted odds 0.30; 95% CI: 0.13-0.69; p = 0.005). Using no SPC involvement group as a reference, the adjusted odds for SPC involvement ≤60 days and >60 days were 0.71 (95% CI: 0.18-2.78; p = 0.63) and 0.22 (95% CI: 0.09-0.57; p = 0.002), respectively. Conclusion: In AYAs with cancer, SPC involvement and duration were associated with a lower incidence of HI-EOL care. Thus, integrating SPC into oncology may improve EOL care for AYAs.

Estimated Elovl6 and delta-5 desaturase activities might represent potential markers for insulin resistance in Japanese adults.

Purpose: Results from a recent study indicated that lower stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with metabolically unhealthy obesity. However, this has not been extensively studied in the Japanese population. Methods: We recruited 291 Japanese subjects with serum free fatty acid profiles undergoing health examinations. Whole serum desaturase activity was estimated as the product: precursor ratio -SA/PA ratio for elongation of long-chain fatty acid family member 6 (Elovl6) and AA/DGLA for delta-5 desaturase (D5D). The determinants of Elovl6 and D5D activity were investigated using multiple regression analyses. Results: The Elovl6 and D5D activities exhibited a negative correlation with the logmatic-transformed TG/HDL-C ratio and TyG index. Multiple regression analyses revealed that the TG/HDL-C ratio and TyG index were negatively associated with Elovl6 and D5D activities. Most atherogenic markers were worse in the low Elovl6 or D5D activity group than in the high Elovl6 or D5D activity group. When study subjects were further stratified by TG levels, most atherogenic markers were the worst in the highest TG group in either the lowest Elovl6 or lowest D5D activity groups. Conclusion: The estimated Elovl6 and D5D activities might be useful markers of insulin resistance in Japanese subjects.

Association of High-Density Lipoprotein Subclasses Levels with Sleep Duration and Other Lifestyles in Middle-Aged and Elderly Women: Cross-Sectional Study.

Objective: We aimed at investigating the association of high-density lipoprotein subclasses (HDL2-C and HDL3-C) levels with sleep duration, in comparison to other lifestyles in middle-aged and elderly women. Materials and Methods: A total of 69 women aged older than 40 who underwent "Anti-aging Health Checkups" were enrolled in the study. The analyses were conducted for all the subjects using personal data regarding clinical characteristics and lifestyle. Sleep duration was categorized into two groups of less than or more than 6 hrs. First, an analysis was performed to assess the correlation of two major HDL subclasses with various factors. Next, a multiple regression analysis was conducted to identify the association for each HDL2-C and HDL3-C with lifestyles such as sleep duration, daily breakfast, dinner time, habitual exercise, and drinking. Moreover, we examined the associations between HDL2-C and sleep duration combined with other lifestyle factors such as dinner time, daily breakfast, habitual exercise, and drinking. Results: In comparison to lifestyles, sleep duration had a strong association with only HDL2-C after adjustment for confounders. The "less 6 hrs sleep" group in combination with the "no exercise habit" or the "routine drinking habit" significantly decreased HDL2-C levels more than the assumed reference group. Regarding breakfast, there is a significant association between the "less than 6 hrs sleep with no daily breakfast" and the "more than 6 hrs sleep with daily breakfast." Conclusion: The results of this study may suggest that sufficient sleep might be significant for maintaining appropriate HDL2-C levels in middle-aged and elderly women under the condition that lifestyle might change during the ongoing COVID-19 pandemic.

The effect of haptic stimulation simulating heartbeats on the regulation of physiological responses and prosocial behavior under stress: The influence of interoceptive accuracy.

Research has discovered the modulatory effect of peripheral stimulation simulating altered bodily signals on emotion. Whether such an effect varies depending on one's interoceptive accuracy (IAc) remains unclear. Therefore, we provided haptic stimulation simulating participants' slowed-down heartbeats or no stimulation while they engaged in socially stressful tasks to examine whether participants reacted differently depending on their IAc. Results showed that haptic stimulation exhibited the opposite effect on participants with different levels of IAc for both heart rate and heart rate variability (HRV). When receiving the stimulation, participants with higher IAc showed less increased heart rate and more elevated HF than participants with lower IAc. In contrast, in the absence of stimulation, an opposite pattern of response depending on participants' IAc was observed. The modulatory effect of stimuli and IAc on prosocial behavior was not significant. Individual differences in IAc were shown to affect how one perceives/responds to altered bodily signals.

Comparative analysis of plant isochorismate synthases reveals structural mechanisms underlying their distinct biochemical properties.

Isochorismate synthase (ICS) converts chorismate into isochorismate, a precursor of primary and secondary metabolites including salicylic acid (SA). SA plays important roles in responses to stress conditions in plants. Many studies have suggested that the function of plant ICSs is regulated at the transcriptional level. In Arabidopsis thaliana, the expression of AtICS1 is induced by stress conditions in parallel with SA synthesis, and AtICS1 is required for SA synthesis. In contrast, the expression of NtICS is not induced when SA synthesis is activated in tobacco, and it is unlikely to be involved in SA synthesis. Studies on the biochemical properties of plant ICSs are limited, compared with those on transcriptional regulation. We analyzed the biochemical properties of four plant ICSs: AtICS1, NtICS, NbICS from Nicotiana benthamiana, and OsICS from rice. Multiple sequence alignment analysis revealed that their primary structures were well conserved, and predicted key residues for ICS activity were almost completely conserved. However, AtICS1 showed much higher activity than the other ICSs when expressed in Escherichia coli and N. benthamiana leaves. Moreover, the levels of AtICS1 protein expression in N. benthamiana leaves were higher than the other ICSs. Construction and analysis of chimeras between AtICS1 and OsICS revealed that the putative chloroplast transit peptides (TPs) significantly affected the levels of protein accumulation in N. benthamiana leaves. Chimeric and point-mutation analyses revealed that Thr531, Ser537, and Ile550 of AtICS1 are essential for its high activity. These distinct biochemical properties of plant ICSs may suggest different roles in their respective plant species.

The value of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein as a predictive marker for hepatitis C virus-related complications after systemic chemotherapy.

Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) was developed recently as a predictive marker of progression to liver fibrosis and hepatocellular carcinoma (HCC) in patients seropositive for hepatitis C virus (HCV). We retrospectively analyzed 16 HCV-seropositive patients who received systemic chemotherapy for hematologic malignancies to evaluate the usefulness of WFA(+)-M2BP for predicting HCV-related complications. These were defined as the onset of significant liver damage (LD) with increased HCV RNA levels, leading to interrupted or discontinued chemotherapy or the occurrence of HCC after chemotherapy. Baseline WFA(+)-M2BP levels were determined using preserved serum samples. The median level of WFA(+)-M2BP was 1.59 [cutoff index (C.O.I.) value range 0.38-6.66]. With a median follow-up of 623 days (range 120-2404), LD and HCC were observed in three and two patients, respectively. Detectable HCV RNA and WFA(+)-M2BP ≥2.0 C.O.I. at baseline were identified as risk factors for these HCV-related complications (P = 0.034 and P = 0.005, respectively). The sensitivity, specificity, and positive and negative predictive values of the WFA(+)-M2BP level (cutoff point: 2.0 C.O.I.) for the occurrence of HCV-related complications were 100.0, 81.8, 71.4, and 100.0 %, respectively. WFA(+)-M2BP may be a useful marker for the prediction of HCV-related complications in HCV-seropositive patients following systemic chemotherapy.

Phase I study of once weekly treatment with bortezomib in combination with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma.

Proteasome inhibitors (PIs) in combination with immunomodulatory drugs (IMiDs) have been shown to be effective against relapsed/refractory multiple myeloma (RRMM). To determine the optimal dosing schedule of once weekly bortezomib (BTZ) combined with lenalidomide (LEN) and dexamethasone (DEX), especially in the outpatient setting, we conducted a phase I dose escalation study. A 21-day cycle of BTZ 1.3 mg/m(2) on days 1 and 8, LEN 10 mg/day (cohort 1) or 15 mg/day (cohort 2) on days 1-14, and DEX 20 mg/day on days 1, 2, 8, and 9 was administered. Three patients were enrolled in each cohort. No dose-limiting toxicity was observed in either cohort. Although hematological toxicities estimated as >grade 3 were common, non-hematological toxicities of grade 3 or higher were rare. Two cases of newly diagnosed peripheral neuropathy (PN) were observed, while no grade 3/4 PN was observed. Two patients achieved partial response and two achieved stable disease. The recommended doses of BTZ and LEN were determined to be 1.3 mg/m(2) and 15 mg, respectively. Combination therapy of once weekly BTZ with LEN and DEX was well tolerated and shows promise as a regimen for patients with RRMM previously treated with both PIs and IMiDs.

Plant DNA-damage repair/toleration 100 protein repairs UV-B-induced DNA damage.

We report the characterization of VvDRT100-L, a grape DNA-damage repair/toleration 100 protein. VvDRT100-L has nine leucine-rich repeats and belongs to the plant DRT100 protein family. VvDRT100-L is expressed abundantly in green organs of grapevines, including tendrils, leaves, and green berry skins. The overexpression of VvDRT100-L in Arabidopsis plants decreased the number of abasic sites and the frequency of DNA single-strand breaks in the DNA damaged by UV-B irradiation, whereas UV-B irradiation markedly increased the number of abasic sites and the frequency of DNA single-strand breaks in T-DNA insertion mutant drt100 plants. VvDRT100-L-overexpressing plants remained viable and noticeably healthy under lethal UV doses, suggesting that VvDRT100-L may enhance UV tolerance in plant. Taken together, we concluded that VvDRT100-L might play an important role in the repair and toleration of UV-B-induced DNA damage. These findings would help us better understand how plants acquire UV stress acclimation, tolerance and DNA repair.