At what COST?: A prospective longitudinal cohort assessment of financial toxicity, quality of life, and associated risk factors in patients with plasma cell disorders.

Financial toxicity is prevalent and harmful to patients with plasma cell disorders.

Recent advancements in wastewater treatment via anaerobic fermentation process: A systematic review.

This manuscript delves into the realm of wastewater treatment, with a particular emphasis on anaerobic fermentation processes, especially dark, photo, and dark-photo fermentation processes, which have not been covered and overviewed previously in the literature regarding the treatment of wastewater. Moreover, the study conducts a bibliometric analysis for the first time to elucidate the research landscape of anaerobic fermentation utilization in wastewater purification. Furthermore, microorganisms, ranging from microalgae to bacteria and fungi, emphasizing the integration of these agents for enhanced efficiency, are all discussed and compared. Various bioreactors, such as dark and photo fermentation bioreactors, including tubular photo bioreactors, are scrutinized for their design and operational intricacies. The results illustrated that using clostridium pasteurianum CH4 and Rhodopseudomonas palustris WP3-5 in a combined dark-photo fermentation process can treat wastewater to a pH of nearly 7 with over 90% COD removal. Also, integrating Chlorella sp and Activated sludge can potentially treat synthetic wastewater to COD, P, and N percentage removal rates of 99%,86%, and 79%, respectively. Finally, the paper extends to discuss the limitations and future prospects of dark-photo fermentation processes, offering insights into the road ahead for researchers and scientists.

Outcomes of patients with multiple myeloma refractory to standard dose vs low dose lenalidomide.

Refractoriness to lenalidomide is an important factor determining the choice of therapy at first relapse in multiple myeloma (MM). It remains debatable if resistance to lenalidomide varies among MM refractory to standard doses vs low dose maintenance doses. In this study, we assessed the outcomes with subsequent therapies in patients with MM refractory to standard dose vs low dose lenalidomide. We retrospectively reviewed all patients with MM at our institution who received first line therapy with lenalidomide containing regimens, and assessed progression free survival (PFS) and overall survival for these patients for second line therapy, and with lenalidomide retreatment. For second line therapy, we found no difference in the PFS between standard dose refractory and low dose refractory groups (median PFS 14 months vs 14 months, p = 0.95), while the PFS for both these groups was inferior to the not refractory group (median PFS 30 months, p < 0.001 for both pairs). Similar trends were seen among these groups on lenalidomide retreatment, and on multivariable analysis. These data suggest that refractoriness to lenalidomide is not dose dependent, and definition of lenalidomide refractoriness should not depend on the dose of lenalidomide to which the disease was considered refractory.

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma.

Daratumumab is an anti-CD38 mAb, used frequently in combination with lenalidomide and pomalidomide. No studies compared daratumumab plus lenalidomide and dexamethasone (DRd) to daratumumab plus pomalidomide and dexamethasone (DPd) in lenalidomide-exposed multiple myeloma. We identified 504 consecutive multiple myeloma patients who received daratumumab at Mayo Clinic between January 2015 and April 2019. We excluded patients who received daratumumab in the first line, received more than four lines of therapy prior to daratumumab use, did not receive lenalidomide prior to daratumumab, or had an unknown status of lenalidomide exposure, and patients who received daratumumab combinations other than DRd or DPd. We examined the impact of using DRd compared to DPd on progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma. Out of 504 patients, 162 received DRd or DPd and were included; 67 were lenalidomide-exposed and 95 were lenalidomide-refractory. DRd was used in 76 (47%) and DPd in 86 (53%) patients. In lenalidomide-exposed multiple myeloma, there was no difference in median PFS; 34.2 months [95% confidence interval (CI), 22.8-44.6] for DRd compared to 25.2 months (95% CI, 4.9-35.3) for DPd, P  = 0.2. In lenalidomide-refractory multiple myeloma, there was no difference in median PFS; 18.6 months (95% CI, 13-32) for DRd compared to 9 months (95% CI, 5.2-14.6) for DPd, P  = 0.09. No difference in median OS was observed in DRd compared to DPd. Our study shows combining daratumumab with lenalidomide in patients with prior lenalidomide use is a viable and effective treatment option.

Analysis of Gremlin 1 Levels Following Sleeve Gastrectomy.

BACKGROUND: In the current study, we aimed to assess the levels of Gremlin 1, an adipokine with a rich repertoire of metabolic effects, in association with the glycemic and lipid parameters after sleeve gastrectomy. MATERIAL AND METHODS: This study was conducted on 31 males with obesity aged 25 to 50 years who underwent sleeve gastrectomy. Plasma Gremlin 1 levels were evaluated using enzyme-linked immunosorbent assay (ELISA) at baseline and 6-12 months after the operation, along with body mass index, insulin, glucose, and lipid profile. RESULTS: Plasma Gremlin 1 levels were elevated (148.19±17.43 vs. 193.29±19.82 ng/mL, p < 0.05) after sleeve gastrectomy. This was accompanied by a decrease in body mass index (from 51.47±1.71 to 39.23±1.56 kg/m2, p < 0.05). Insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) also exhibited a significant decrease (19.69±1.81 vs. 8.98±1.09 mIU/L and 6.52±0.98 vs. 2.57±0.036 p < 0.05, respectively) in the postoperative period. Total cholesterol levels were significantly increased after surgery (4.29±0.16 to 5.10±0.16, p < 0.05). Pearson correlation analysis showed that Gremlin 1 was positively correlated with insulin before surgery, but there was no significant correlation after surgery. CONCLUSION: The circulating Gremlin 1 levels were elevated postoperatively among our participants. The improvement in insulin sensitivity appears to be independent of the reported antagonistic effects of Gremlin 1.

Relationships Among Health Insurance Literacy, Financial Toxicity, and Sociodemographic Factors in Patients With Cancer.

PURPOSE: The objective of the study was to describe the prevalence of health insurance literacy (HIL) and investigate how patient-reported outcome measures assessing HIL are related to financial toxicity in patients with cancer. METHODS: We assessed HIL and financial toxicity in 404 patients enrolled between December 2019 and January 2021 at two medical centers in the United States. We conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to explore and test the relationships among the factors and items. We fit structural equation models (SEMs) to find the relationships among the factors and sociodemographic/clinical characteristics. RESULTS: The EFA revealed items loaded on four factors: knowledge about health insurance, confidence related to HIL (HIL confidence), information-seeking behavior related to health insurance, and financial toxicity. The four-factor CFA model had good fit statistics (comparative fit index, 0.960; Tucker-Lewis index, 0.958; root mean square error of approximation, 0.046; and standardized root mean square residual, 0.086). In SEM, income, education level, and race positively predicted knowledge about health insurance. Knowledge about health insurance and number of total lines of cancer treatment was positively associated with HIL confidence. Higher income, older age, and HIL confidence were associated with less financial toxicity. Higher levels of financial toxicity, HIL confidence, and knowledge were associated with greater information-seeking behavior. CONCLUSION: Our findings showed how different aspects of HIL are related to financial toxicity even after adjustment for sociodemographic and clinical characteristics. Future studies should investigate the longitudinal relationships among these factors to help develop interventions to mitigate financial toxicity.

Long-term outcomes of allogeneic stem cell transplant in multiple myeloma.

Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT (p = 0.03) and to have been transplanted between 2000 and 2010 (p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT.

Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma.

Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC < NL). Patients who achieved CR/sCR had higher rates of month 1 BM-MRDneg and FLC < NL. The rate of sustained BM-MRDneg was 40% (19/47). Rate of conversion from MRDpos to MRDneg was 5%(1/20). At month 1, 38%(18/47) of the BM-MRDneg were hypocellular. Recovery to normal cellularity was observed in 50%(7/14) with a median time to normalization at 12 months (range: 3-Not reached). Compared to Month 1 BM-MRDpos patients, patients who were BM-MRDneg had longer PFS irrespective of BM cellularity [PFS: 2.9 months (95% CI, 1.2-NR) vs. 17.5 months (95% CI, 10.4-NR), p < 0.0001]. Month 1 BM-MRDneg and FLC below normal were associated with prolonged survival. Our data support the continued evaluation of BM early post-CART infusion as a prognostic tool.

Response to COVID-19 Vaccination Post-CAR T Therapy in Patients With Non-Hodgkin Lymphoma and Multiple Myeloma.

COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to prescribed immunosuppressive therapy. Chimeric antigen receptor T-cell (CAR T) therapy is now widely used for NHL and MM, but little is known about seroconversion rates after COVID-19 vaccination among these populations. We evaluated SARS-CoV-2 spike-binding IgG antibody levels following COVID-19 vaccination among NHL and MM CAR T therapy recipients. Out of 104 CAR T infusions, 19 patients developed known COVID-19 infection post-CAR T. We tested 17 patients that received CAR T for antibody spike titers post COVID-19 vaccination, only 29 % (n = 5) were able to mount a clinically relevant antibody response (>250 IU/mL).

Design, synthesis, and metabolite identification of Tamoxifen esterase-activatable prodrugs.

Tamoxifen (TAM) is used in treatment of hormonal dependent breast cancer, both in premenopausal and postmenopausal women. TAM is intrinsically metabolized by CYP450 enzymes to more active metabolites. Recent reports identified CYP2D6, an enzyme involved in the conversion of TAM to the more potent 4-OH-TAM, is encoded by theCYP2D6gene, which is highly polymorphic. Women with inactive alleles are poor metabolizers; in many cases they suffer acquired TAM resistance. Herein we report synthesis and biological evaluation of novel TAM analogues. The novel analogues are designed to elude CYP2D6 metabolism. Hydrolysis of the carbamate moiety on ring C is mediated via carboxylesterases. Compound 3d [E/Z Benzyl-carbamic acid4-{2-benzyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-but-1-enyl}-phenyl ester] showed GI50 = 0.09 µM on MCF-7 and GI50 = 1.84 µM on MDA-MB231 cell lines. To further validate our hypothesis, metabolites of selected novel analogues were determined in vitro under different incubation conditions. The hydroxylated analogues were obtained under non CYP2D6 dependent conditions. Compound 8d, a benzyl carbamate derivative, was the least-stable analog and showed the highest rate of metabolism among all tested analogues. Our in silico model showed the novel flexible analogues can still adopt an antiestrogenic binding profile occupying the same pocket as 4-OH-TAM.

Impact of Pharmacist-Led Interventions to Improve Clinical Outcomes for Adults With Type 2 Diabetes at Risk of Developing Cardiovascular Disease: A Systematic Review and Meta-analysis.

ObjectiveThe aim of this systematic review and meta-analysis of randomised controlled trials is to evaluate the impact of pharmacist-led interventions on cardiovascular disease (CVD) risk factors among patients with type 2 diabetes. Method: A literature review was conducted according to PRISMA guidelines using 4 electronic databases: Embase, MEDLINE, CINHAL and the Cochrane Central Register of Controlled Trials. We searched for pharmacist interventions among adults with type 2 diabetes and cardiovascular disease in randomised controlled trials from inception to May 2021 in primary care, diabetes clinics and hospitals. The clinical outcomes measured glycosylated haemoglobin (HbA1c), blood pressure (BP) and lipid profile. The non-clinical outcomes included medication adherence, smoking, health-related quality of life and the cost of the intervention. For the meta-analysis, clinical outcomes were pooled with the random effect model in RevMan 5.3. The Cochrane risk-of-bias tool was used to assess the quality of the included studies. Results: We retrieved 223 studies,141 of which were included in the review. Ten published articles met the inclusion criteria and were included in the meta-analysis. The pharmacists delivered the interventions alone or collaboratively with other healthcare professionals in hospitals or similar settings. The overall result showed a significant reduction in HbA1c (n = 10; standard deviation in mean value [SDM]: -.53%, 95% CI: -.84, -.23) and systolic BP (n = 10; [SDM]: -.35 mmHg, 95% CI: -.51, -.20) in pharmacist intervention groups. For the non-clinical outcomes, the review revealed variable results from pharmacist intervention compared with those standard care. Conclusion: Pharmacy interventions provide evidence for pharmacists' decisive role in diabetes care management and reducing cardiovascular risk factors among adults with type 2 diabetes.

Association of Health Insurance Literacy With Financial Hardship in Patients With Cancer.

Importance: Patient-reported financial hardship is an increasing challenge in cancer care delivery. Health insurance literacy and its association with financial hardship in patients with cancer, especially after controlling for financial literacy, have not been well examined. Objective: To examine the prevalence of and factors in the association between health insurance literacy and financial literacy as well as the overall and individual domains of financial hardship and their association with health insurance literacy, both independently and when adjusted for financial literacy, in patients with cancer. Design, Setting, and Participants: This cross-sectional survey study recruited and enrolled patients from 2 separate ambulatory infusion centers at Mayo Clinic Arizona in Phoenix, Arizona, and the University of Mississippi Medical Center in Jackson, Mississippi. Adult patients aged 18 years or older were enrolled from December 2019 to February 2020 and from August to October 2020 at Mayo Clinic Arizona (n = 299) and from September 2020 through January 2021 at the University of Mississippi Medical Center (n = 105). Survey respondents received a $5 gift card. Exposures: Surveys included questions about sociodemographic characteristics, health insurance literacy and financial literacy, financial knowledge, and financial hardship and its domains (material hardship, psychological hardship, and behavioral hardship). Main Outcomes and Measures: Financial hardship was assessed using the COST-FACIT (Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy) measure and National Health Interview Survey questions to capture information about the domains of financial hardship. The Health Insurance Literacy Measure is a validated 21-item measure of a consumer's ability to select and use health insurance. Five questions from the National Financial Capability Study assessed financial literacy. Results: A total of 404 participants were enrolled in the study. Median (IQR) age of the respondents was 63 (54-71) years, and 219 were women (54%), 307 were non-Hispanic White individuals (76%), 153 (38%) had private insurance, and 289 (72%) had solid tumors. Overall financial hardship (denoted by median COST-FACIT score <27 points) was reported by 49% (95% CI, 44%-53%) of the cohort. Prevalence of financial hardship was higher using the National Health Interview Survey questions, with 68% (95% CI, 63%-72%) of respondents reporting at least 1 hardship domain (n = 276). Sixty-six percent (95% CI, 60%-69%) of respondents (n = 265) had a high level of financial literacy. The mean (SD) Health Insurance Literacy Measure score was 64.9 (13.3) points. In multivariable analyses, each 10-point increase in the Health Insurance Literacy Measure score was associated with lower odds of financial hardship (odds ratio, 0.82; 95% CI, 0.68-0.99; P = .04). However, this association was no longer significant after adjusting for financial literacy. Conclusions and Relevance: Results of this study showed that, despite a high level of health insurance literacy and financial literacy, the prevalence of financial hardship was high. Although there were lower odds of financial hardship with increased health insurance literacy, the association was no longer significant when financial literacy was added to the model, suggesting that a high level of financial literacy may help mitigate the adverse outcome of lower health insurance literacy levels in patients with cancer.

In vivo biological evaluation of sodium salt of ethyl (E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-yl)-3-(4-hydroxyphenyl) acrylate as anticancer agent.

Nowadays, quinoline scaffold is among the most vital construction compounds for the development of new drugs. The purpose of this research is to evaluate the anti-cancer activity of sodium salt of ethyl (E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-yl)-3-(4-hydroxyphenyl) acrylate against Ehrlich ascites carcinoma (EAC) cells residing in female mice's peritoneal cavity. The docking study exhibited a favourable interaction between the compound and the receptors 1MOY and 3KJF of osteopontin and caspase 3, respectively. The compound's sodium salt showed potential antioxidant and anti-cancer effects against Ehrlich ascites carcinoma (EAC) cells in vivo. Herein, the results elucidated that treatment with the compound's sodium salt exerted significant chemopreventive and chemotherapeutic effects, which reduced both EAC cell volume and count. Our results revealed that treatment with the sodium salt of the compound demonstrated a remarkable in vivo apoptotic effect through elevation of the expression of caspase 3 and reduction of osteopontin levels. Histopathological examination confirmed that the compound's sodium salt improved liver and kidney tissues without any apparent adverse effects.

A Striking Case of Perfusion-Metabolism "Flip-Flop" in a Patient With Left Anterior Descending Artery Total Occlusion.

ABSTRACT: A 57-year-old man diagnosed with left anterior descending artery chronic total occlusion underwent rest gated 99mTc-MIBI scan showing moderately to markedly decreased perfusion with abnormal wall motion in the apex, anterior, anteroseptal, and apical anterolateral walls. 18F-FDG PET showed a "flip-flop" phenomenon with markedly increased FDG uptake in the hypoperfused regions and absent/markedly decreased uptake in the normally perfused, normokinetic myocardium, presumably due to the predominant use of free fatty acids under normoxic conditions. After coronary artery bypass grafting, left ventricular motion normalized except for surgery-related paradoxical septal motion and the left ventricular ejection fraction improved from 52% to 68%.

Restricted feeding could enhance feed conversion ratio and egg quality of laying Japanese quail kept under different stocking densities.

Impacts of different stocking densities and feed restriction on egg production and quality and blood biochemicals of laying Japanese quail (Coturnix coturnix Japonica) were studied. A total number of 360 adult Japanese quails were used in an experiment, including two stocking densities (300 and 200 cm2/bird) and four feed restriction levels (ad libitum, 25, 30 and 35 g/day/bird). As a result of this study, feed restriction (30 g/bird/day) enhanced most of egg production traits and improved hatchability. Albumen and egg shell thickness showed the highest values when birds fed ad libitum and 35 g/bird/day. Blood total protein, albumin, Aspartate Aminotransferase (AST) and cholesterol were higher in quails housed at 200 cm2/bird than those kept at 300 cm2/bird. The highest values of blood total protein, albumin, AST and cholesterol were found in quails fed ad libitum. Activity of superoxide dismutase was the highest estimate when birds stocked at 300 cm2/bird and fed ad libitum or 25 g/day. Conclusively, decreasing space per bird had a negative effect on performance. Feed restriction can achieve a better feed conversion ratio (FCR).

Assessment of Discrimination, Bias, and Inclusion in a United States Hematology and Oncology Fellowship Program.

Importance: Medical trainees frequently experience discrimination. Understanding their experiences is essential to improving learning environments. Objective: To characterize trainee experiences of discrimination and inclusion to inform graduate medical education (GME) policies. Design, Setting, and Participants: This qualitative study used an anonymous telephone interview technique to gather data from hematology and oncology fellows. All current trainees and recent graduates were eligible. Interviews were conducted anonymously with interviewer and participant in separate locations and recorded and transcribed. Data were analyzed in an iterative process into major themes using a general inductive analysis approach. Demographic information was obtained via anonymous survey. Data collection and analysis were conducted from July 2018 to November 2019. Main Outcomes and Measures: Emergent themes illustrating bias and inclusion in a GME program. Results: Among 34 fellows and recent graduates who were approached for this study, 20 consented and 17 were interviewed. Of those interviewed, 10 were men, and the median (range) age was 32 (29-53) years. The racial and ethnic distribution included 6 Asian individuals, 2 Black individuals, 3 Hispanic individuals, 2 multiracial individuals, and 4 White individuals. All fellows reported having experienced and/or witnessed discriminatory behavior. The themes elucidated were (1) foreign fellows perceived as outsiders, (2) US citizens feeling alien at home, (3) gender role-typing, (4) perception of futility of reporting, (5) diversity and inclusion, and (6) coping strategies. The majority of reported biases were from patients. Only 1 trainee reported any incidents. Reasons for not reporting were difficulty characterizing discrimination and doubt action would occur. Participants reported that diversity of cotrainees, involvement in committees, and open discussions promoted inclusivity. Conclusions and Relevance: In this study, reports of discriminatory behavior toward trainees were common. The anonymous hotline methodology cultivated a safe environment for candid discussions. These findings suggest that GME programs should assess their learning climate regarding bias and inclusivity anonymously and develop processes to support trainees.

Internet Addiction and Depression Among Postgraduate Residents: A cross-sectional survey.

OBJECTIVES: This study aimed to estimate the prevalence of social media usage and Internet addiction among Oman Medical Specialty Board (OMSB) residents and to determine associations between Internet addiction, sociodemographic characteristics and symptoms of depression. METHODS: This cross-sectional study took place between January and March 2017. All 499 residents enrolled in OMSB training programmes during the 2016-2017 academic year were targeted. A self-administered questionnaire was distributed to collect information concerning sociodemographic characteristics. In addition, the Patient Health Questionnaire-9 and Internet Addiction Test were used to screen for depression and Internet addiction, respectively. RESULTS: A total of 399 residents participated in the study (response rate: 80%). Overall, 115 residents (28.8%) had varying degrees of depression and 149 (37.3%) were addicted to the Internet; moreover, among those addicted, 54 (36.2%) had depression. While no significant associations were observed between Internet addiction and sociodemographic characteristics, the association between Internet addiction and depression was statistically significant (P = 0.012). CONCLUSION: Internet addiction was clearly detected among many OMSB residents, with a significant association observed between Internet addiction and depression. Although a causal link between these two variables cannot be established as depression is multifactorial in origin, the disadvantages and harmful effects of excessive Internet and social media usage need to be addressed. Further research on the consequences of Internet addiction and its effect on quality of life and academic achievement is recommended.