Phase II study of vinorelbine with protracted fluorouracil infusion as a second- or third-line approach for advanced breast cancer patients previously treated with anthracyclines.

PURPOSE: To evaluate the feasibility and activity of vinorelbine in association with protracted infusional fluorouracil in patients with advanced breast cancer who were previously treated with anthracycline-containing regimens. PATIENTS AND METHODS: Eighty-three consecutive patients were entered onto the study. Forty-three patients experienced treatment failure or relapse after anthracycline-based, first-line chemotherapy for advanced disease and 29 experienced treatment failure or relapse after first- and second-line approaches; 11 patients experienced progressive disease within 6 months of completion of adjuvant anthracycline therapy. Sites of involvement were as follows: liver involvement, 42 patients (50.6%); lung 24 (28.9%); bone, 49 (59.0%); and skin/lymph nodes, 21 (25.3%). Treatment consisted of vinorelbine 30 mg/m(2) administered on days 1 and 15 every 28 days and fluorouracil 200 mg/m(2)/d given continuously over a 24-hour period. RESULTS: Toxicity was recorded for 441 cycles. The scheme was well tolerated: grade 1/2 nausea/vomiting occurred in 13 patients (15.6%), grade 1/2 diarrhea in nine (10.8%), and grade 2/3 stomatitis in six (7.2%). Three patients (3.6%) experienced grade 3/4 leukopenia and four (4.8%) experienced grade 2/3 anemia. Grade 2/3 neurologic toxicity was observed in three cases (3.6%), and grade 2/3 hand-foot syndrome was observed in three (3.6%). The median relative dose-intensity was 92% and 100% for vinorelbine and fluorouracil, respectively. Six patients (7.2%) attained a complete clinical response and 45 (54.2%) attained a partial response, for an overall response rate of 61.4% (95% confidence interval, 50.9% to 71.9%). Twenty-one patients (25.3%) obtained disease stabilization, and 11 (13.3%) experienced disease progression. Median time to progression in responding patients was 15 months; median overall survival of the entire population was 22 months. CONCLUSION: Vinorelbine associated with protracted infusional fluorouracil is an active and manageable scheme in advanced breast cancer patients previously treated with anthracyclines. The response obtained is durable.     

Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses

Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject’s contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges’s g = 2.09, P < .001) and a reduced clustering coefficient (Hedges’s g = 1.07, P < .001) with increased length (Hedges’s g = −2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.     

Treating depression and improving adherence in HIV care with task‐shared cognitive behavioural therapy in Khayelitsha,South Africa: a randomized controlled trial

IntroductionMajor depressive disorder, highly prevalent among people with HIV (PWH) globally, including South Africa, is associated with suboptimal adherence to antiretroviral therapy. Globally, there are insufficient numbers of mental health providers and tested depression treatments. This study''s aim was to test task‐shared cognitive‐behavioural therapy for adherence and depression (CBT‐AD) in HIV, delivered by clinic nurses in South Africa.MethodsThis was a two‐arm randomized controlled effectiveness trial (recruitment: 14 July 2016 to 4 June 2019, last follow 9 June 2020). One‐hundred‐sixty‐one participants with clinical depression and virally uncontrolled HIV were recruited from primary care clinics providing HIV care, in Khayelitsha, South Africa. Arm 1 was task‐shared, nurse‐delivered CBT‐AD; and arm 2 was enhanced treatment as usual (ETAU). Primary outcomes (baseline to 4 months) were blinded Hamilton Depression Rating Scale (HAM‐D) scores, and weekly adherence via real‐time monitoring (Wisepill). Secondary outcomes were adherence and depression over 4‐, 8‐ and 12‐month follow‐ups, proportion of participants with undetectable viremia and continuous CD4 cell counts at 12 months. Additional analyses involved viral load and CD4 over time.ResultsAt 4 months, the HAMD scores in the CBT‐AD condition improved by an estimated 4.88 points more (CI: –7.86, –1.87, p = 0.0016), and for weekly adherence, 1.61 percentage points more per week (CI: 0.64, 2.58, p = 0.001) than ETAU. Over follow‐ups, CBT‐AD had an estimated 5.63 lower HAMD scores (CI: –7.90, –3.36, p < 0.001) and 23.56 percentage points higher adherence (CI: 10.51, 34.21, p < 0.001) than ETAU. At 12 months, adjusted models indicated that the odds of having an undetectable viremia was 2.51 greater at 12 months (CI: 1.01, 6.66, p = 0.047), and 3.54 greater over all of the follow‐ups (aOR = 3.54, CI: 1.59, 20.50; p = 0.038) for those assigned CBT‐AD. CD4 was not significantly different between groups at 12 months or over time.ConclusionsTask‐shared, nurse‐delivered, CBT‐AD is effective in improving clinical depression, ART adherence and viral load for virally unsuppressed PWH. The strategy of reducing depression to allow patients with self‐care components of medical illness to benefit from adherence interventions is one to extend. Implementation science trials and analyses of cost‐effectiveness are needed to translate findings into clinical practice.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02696824","term_id":"NCT02696824"}}NCT02696824 https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02696824","term_id":"NCT02696824"}}NCT02696824     

Total and bioaccessible heavy metals in cabbage from major producing cities in Southwest China: health risk assessment and cytotoxicity

Green leafy vegetables are economical and nutritious, but they may be contaminated with heavy metals. In this study, we assessed the total and bioaccessible concentrations of As, Cd, Pb and Cr in a popular vegetable cabbage (Brassica oleracea) from four major producing cities in Yunnan, Southwest China. With the mean concentrations of As, Cd, Pb and Cr being 0.24, 0.20, 0.32 and 1.28 mg kg⁻¹, the As, Cd and Pb concentrations were within the limits of 0.2–0.5 mg kg⁻¹ based on Chinese National Standards and the WHO/FAO, but Cr concentration was 2.6-times greater than the limit of 0.5 mg kg⁻¹. Based on an in vitro bioaccessibility assay of the Solubility Bioaccessibility Research Consortium (SBRC), As bioaccessibility was the lowest at 11% while those of Cd, Pb and Cr were much greater at 68–87%. The estimated daily intake (EDI) of metals through cabbage ingestion was similar for children and adults. Among the four metals, only Cr''s EDI at 2.29–1.87 exceeded 1 based on total and bioaccessible concentrations. The high Cr concentration at 1.28 mg kg⁻¹ coupled with its high bioaccessibility at 67.5% makes Cr of concern in cabbage. However, human gastrointestinal cells exposed to the gastric digesta with high bioaccessible heavy metals and risky EDI, showed no obvious cytotoxicity, indicating that existing models based on total or bioaccessible heavy metals may overestimate their human health risk. Taken together, to accurately assess the human health risk of heavy metals in cabbage, both total/bioaccessible concentrations and the gastrointestinal cell responses should be considered.

We analyzed the total and bioaccessible concentrations of heavy metals in a popular vegetable cabbage (Brassica oleracea) from producing cities in Yunnan, Southwest China and assessed their health risk based on both bioaccessibility and cytotoxicity.     

Krill-Oil-Dependent Increases in HS-Omega-3 Index,Plasma Choline and Antioxidant Capacity in Well-Conditioned Power Training Athletes

There is evidence that both omega-3 polyunsaturated fatty acids (n-3 PUFAs) and choline can influence sports performance, but information establishing their combined effects when given in the form of krill oil during power training protocols is missing. The purpose of this study was therefore to characterize n-3 PUFA and choline profiles after a one-hour period of high-intensity physical workout after 12 weeks of supplementation. Thirty-five healthy power training athletes received either 2.5 g/day of Neptune krill oil^TM (550 mg EPA/DHA and 150 mg choline) or olive oil (placebo) in a randomized double-blind design. After 12 weeks, only the krill oil group showed a significant HS-Omega-3 Index increase from 4.82 to 6.77% and a reduction in the ARA/EPA ratio (from 50.72 to 13.61%) (p < 0.001). The krill oil group showed significantly higher recovery of choline concentrations relative to the placebo group from the end of the first to the beginning of the second exercise test (p = 0.04) and an 8% decrease in total antioxidant capacity post-exercise versus 21% in the placebo group (p = 0.35). In conclusion, krill oil can be used as a nutritional strategy for increasing the HS-Omega-3 Index, recover choline concentrations and address oxidative stress after intense power trainings.