The association of depressive symptoms, personality traits, and sociodemographic factors with health-related quality of life and quality of life in patients with advanced-stage lung cancer: An observational multi-center cohort study

Background: Identification of patient-related factors associated with Health-Related Quality of Life (HRQoL) and Quality of Life (QoL) at the start of treatment may identify patients who are prone to a decrease in HRQoL and/or QoL resulting from chemotherapy. Identification of these factors may offer opportunities to enhance patient care during treatment by adapting communication strategies and directing medical and psychological interventions. The aim was to examine the association of sociodemographic factors, personality traits, and depressive symptoms with HRQoL and QoL in patients with advanced-stage lung cancer at the start of chemotherapy. Methods: Patients (n = 151) completed the State-Trait Anxiety Inventory (trait anxiety subscale), the Neuroticism-Extraversion-Openness-Five Factor Inventory (NEO-FFI), the Center for Epidemiologic Studies Depression (CES-D), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Simple linear regression analyses were performed to select HRQoL and QoL associated factors (a P ≤ 0.10 was used to prevent non-identification of important factors) followed by multiple linear regression analyses (P ≤ 0.05). Results: In the multiple regression analyses, CES-D score (β = - 0.63 to - 0.53; P-values < 0.001) was most often associated with the WHOQOL-BREF domains and general facet, whereas CES-D score (β = - 0.67 to - 0.40; P-values < 0.001) and Eastern Cooperative Oncology Group (ECOG) performance status (β = - 0.30 to - 0.30; P-values < 0.001) were most often associated with the scales of the EORTC QLQ-C30. Personality traits were not related with HRQoL or QoL except for trait anxiety (Role functioning: β = 0.30; P = 0.02, Environment: β = - 0.39; P = 0.007) and conscientiousness (Physical health: β = 0.20; P-value < 0.04). Conclusions: Higher scores on depressive symptoms and ECOG performance status were related to lower HRQoL and QoL in patients with advanced-stage non-small cell lung cancer. Supportive care interventions aimed at improvement of depressive symptoms and performance score may facilitate an increase of HRQoL and/or QoL during treatment

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Fib3-3 as a Biomarker for Osteoarthritis in a Rat Model with Metabolic Dysregulation.

Objective Fibulin-3 is a glycoprotein highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent studies have indicated that fibulin-3 has potential value as a biomarker in osteoarthritis. The aim of the present study is to examine the role of 3 fibulin-3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation product in a rat osteoarthritis model with systemic metabolic alterations combined with local cartilage damage. Design Forty, 12-week-old male, Wistar rats were randomly divided over 2 groups: a standard or a high-fat diet inducing metabolic dysregulation. After 12 weeks, articular cartilage damage was induced on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet group. At endpoint, blood was collected and serum was isolated. Enzyme-linked immunosorbent assay on all selected fibulin-3 fragments was performed from serum samples in addition to immunohistochemical analysis for Fib3-3. Results Serum concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was induced in addition to a high-fat diet. Fib3-3 was also associated with an increased histological total joint degeneration ( r = 0.435) and cartilage degeneration ( r = 0.435). Immunostainings demonstrated increased Fib3-3 in the superficial cartilage of animals with high-fat diet and/or cartilage damage. Conclusions In the rat groove model combined with high-fat diet-induced metabolic dysregulation an increased Fib3-3 concentration was observed systemically, which is associated with local joint degeneration. This suggests that systemic Fib3-3 concentrations can indicate the status of joint degeneration and function as a biomarker in osteoarthritis

Formation of Diphosphates. A NMR Study on the Mechanism and Stereochemistry of Diphosphate Formation from Chiral Dioxaphosphorinanes

During the use of chiral 2-oxo-1,3,2-dioxaphosphorinanes as derivatizing reagents in the enantiomeric excess determination of amines, alcohols, and unprotected amino acids, minor traces of side reaction products were observed by 1H and 31P NMR spectroscopy. Analysis of the reaction mixture showed that the side products are in fact diphosphates and several intermediates leading to their formation. From an analytical, mechanistic, and stereochemical point of view, the study of unexpected new reaction intermediates leading to diphosphates is of particular interest. Due to the easy structural modification of the starting materials in both enantiomerically pure and racemic forms as well as easy access to oxygen-labeled materials for complete structural elucidation of both intermediates and diphosphates, we accomplished a complete structural analysis. Also a mechanistic proposal for their formation proved possible using 1D and 2D 1H and 31P NMR techniques as well as the X-ray data of both starting material and two of the products.

Imaging of Folate Receptor Expressing Macrophages in the Rat Groove Model of Osteoarthritis : Using a New DOTA-Folate Conjugate

Objective: To evaluate the presence and localization of folate receptor expressing macrophages in the rat groove model of osteoarthritis and determine the suitability of a new folate conjugate with albumin-binding entity (cm09) for in vivo SPECT (single-photon emission computed tomography) analysis. Design: In male Wistar rats, local cartilage damage was induced in addition to a standard (n = 10) or high-fat diet (n = 6). After 12 weeks, 111In labeled folate conjugates were administered, and SPECT/CT (computed tomography) imaging was performed after 24 hours. Subsequently, osteoarthritis severity and folate receptor expression were assessed using (immuno)-histological sections. Results: In vivo SPECT/CT imaging of the new folate conjugate (cm09) was as useful as a folate conjugate without albumin-binding entity in the groove model of osteoarthritis with less renal accumulation. Induction of cartilage damage on a standard diet resulted in no effect on the amount of folate receptor expressing macrophages compared with the contralateral sham operated joints. In contrast, inducing cartilage damage in the high-fat diet group resulted in 28.4% increase of folate receptor expression as compared with the nondamaged control joints. Folate receptor expressing cells were predominantly present in the synovial lining and in subchondral bone as confirmed by immunohistochemistry. Conclusions: Folate receptor expression, and thus macrophage activation, can clearly be demonstrated in vivo, in small animal models of osteoarthritis using the new 111In-folate conjugate with specific binding to the folate receptor. Increased macrophage activity only plays a role in the groove model of osteoarthritis when applied in a high-fat diet induced dysmetabolic condition, which is in line with the higher inflammatory state of that specific model

Imaging of Folate Receptor Expressing Macrophages in the Rat Groove Model of Osteoarthritis : Using a New DOTA-Folate Conjugate

Objective: To evaluate the presence and localization of folate receptor expressing macrophages in the rat groove model of osteoarthritis and determine the suitability of a new folate conjugate with albumin-binding entity (cm09) for in vivo SPECT (single-photon emission computed tomography) analysis. Design: In male Wistar rats, local cartilage damage was induced in addition to a standard (n = 10) or high-fat diet (n = 6). After 12 weeks, 111In labeled folate conjugates were administered, and SPECT/CT (computed tomography) imaging was performed after 24 hours. Subsequently, osteoarthritis severity and folate receptor expression were assessed using (immuno)-histological sections. Results: In vivo SPECT/CT imaging of the new folate conjugate (cm09) was as useful as a folate conjugate without albumin-binding entity in the groove model of osteoarthritis with less renal accumulation. Induction of cartilage damage on a standard diet resulted in no effect on the amount of folate receptor expressing macrophages compared with the contralateral sham operated joints. In contrast, inducing cartilage damage in the high-fat diet group resulted in 28.4% increase of folate receptor expression as compared with the nondamaged control joints. Folate receptor expressing cells were predominantly present in the synovial lining and in subchondral bone as confirmed by immunohistochemistry. Conclusions: Folate receptor expression, and thus macrophage activation, can clearly be demonstrated in vivo, in small animal models of osteoarthritis using the new 111In-folate conjugate with specific binding to the folate receptor. Increased macrophage activity only plays a role in the groove model of osteoarthritis when applied in a high-fat diet induced dysmetabolic condition, which is in line with the higher inflammatory state of that specific model

Fib3-3 as a biomarker for osteoarthritis in a rat model with metabolic dysregulation

Objective: Fibulin-3 is a glycoprotein highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent studies have indicated that fibulin-3 has potential value as a biomarker in osteoarthritis. The aim of the present study is to examine the role of 3 fibulin-3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation product in a rat osteoarthritis model with systemic metabolic alterations combined with local cartilage damage. Design: Forty, 12-week-old male, Wistar rats were randomly divided over 2 groups: a standard or a high-fat diet inducing metabolic dysregulation. After 12 weeks, articular cartilage damage was induced on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet group. At endpoint, blood was collected and serum was isolated. Enzyme-linked immunosorbent assay on all selected fibulin-3 fragments was performed from serum samples in addition to immunohistochemical analysis for Fib3-3. Results: Serum concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was induced in addition to a high-fat diet. Fib3-3 was also associated with an increased histological total joint degeneration (r = 0.435) and cartilage degeneration (r = 0.435). Immunostainings demonstrated increased Fib3-3 in the superficial cartilage of animals with high-fat diet and/or cartilage damage. Conclusions: In the rat groove model combined with high-fat diet–induced metabolic dysregulation an increased Fib3-3 concentration was observed systemically, which is associated with local joint degeneration. This suggests that systemic Fib3-3 concentrations can indicate the status of joint degeneration and function as a biomarker in osteoarthritis.Biomaterials & Tissue Biomechanic