Survival of patients with mantle cell lymphoma in the rituximab era: Retrospective binational analysis between 2000 and 2020.

Mantle cell lymphoma (MCL) is a rare peripheral B-cell lymphoma characterised by eventual relapse and progression towards a more aggressive disease biology. With the introduction of rituximab- and cytarabine-based immunochemotherapy regimens, the prognosis of the disease has changed dramatically over the last two decades. To assess the real-world survival of patients with MCL, we used a population-based cohort of 564 patients with MCL who were diagnosed and treated between 2000 and 2020. Patient data were collected from seven Finnish treatment centres and one Spanish treatment centre. For the entire patient population, we report a 2-year overall survival (OS) rate of 77%, a 5-year OS of 58%, and a 10-year OS of 32%. The estimated median OS was 80 months after diagnosis. MCL is associated with increased mortality across the entire patient population. Additionally, we assessed the survival of patients after MCL relapse with the aim of establishing a cut-off point of prognostic significance. Based on our statistical analysis of survival after the first relapse, disease progression within 24 months of the initial diagnosis should be considered as a strong indicator of poor prognosis.

Mortality among patients with low-grade follicular lymphoma: A binational retrospective analysis.

BACKGROUND: The life expectancy of patients with follicular lymphoma (FL) has improved considerably since the introduction of rituximab. This study examined the proportion of deaths from progressive lymphoma and the impact of FL on survival compared with that in the general population. METHODS: Altogether, 749 patients with grades 1 and 2 FL in 9 institutions between 1997 and 2016 were enrolled. Competing risk models were used to estimate the cumulative incidences of deaths from progressive lymphoma and from other reasons. Excess mortality was analyzed with respect to the corresponding background populations standardized for age and sex using the excess mortality model based on the penalized spline approach. RESULTS: The median follow-up duration was 69 months (range, 0-226 months). The estimated 10-year overall, disease-specific, and net survival rates were 72.4%, 86.6%, and 86.4%, respectively. The cumulative incidence of deaths from progressive lymphoma was slightly smaller than that of other causes in the study population (estimated 10-year cumulative incidences: 12.3% [95% CI, 9.6%-15.3%] and 15.4% [95% CI, 12.2%-18.8%], respectively). Excess mortality was observed for up to 10 years after diagnosis, and it slightly increased with time. CONCLUSIONS: Deaths from progressive lymphoma are nearly as common as deaths from other causes in FL patients during the rituximab era. Despite the improvements in survival, there was evidence of excess mortality resulting from FL for at least 10 years after diagnosis.

In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury-Lessons Learned.

We developed a pipeline for the discovery of transcriptomics-derived disease-modifying therapies and used it to validate treatments in vitro and in vivo that could be repurposed for TBI treatment. Desmethylclomipramine, ionomycin, sirolimus and trimipramine, identified by in silico LINCS analysis as candidate treatments modulating the TBI-induced transcriptomics networks, were tested in neuron-BV2 microglial co-cultures, using tumour necrosis factor α as a monitoring biomarker for neuroinflammation, nitrite for nitric oxide-mediated neurotoxicity and microtubule associated protein 2-based immunostaining for neuronal survival. Based on (a) therapeutic time window in silico, (b) blood-brain barrier penetration and water solubility, (c) anti-inflammatory and neuroprotective effects in vitro (p < 0.05) and (d) target engagement of Nrf2 target genes (p < 0.05), desmethylclomipramine was validated in a lateral fluid-percussion model of TBI in rats. Despite the favourable in silico and in vitro outcomes, in vivo assessment of clomipramine, which metabolizes to desmethylclomipramine, failed to demonstrate favourable effects on motor and memory tests. In fact, clomipramine treatment worsened the composite neuroscore (p < 0.05). Weight loss (p < 0.05) and prolonged upregulation of plasma cytokines (p < 0.05) may have contributed to the worsened somatomotor outcome. Our pipeline provides a rational stepwise procedure for evaluating favourable and unfavourable effects of systems-biology discovered compounds that modulate post-TBI transcriptomics.

Sensory-based food education in early childhood education and care, willingness to choose and eat fruit and vegetables, and the moderating role of maternal education and food neophobia.

OBJECTIVE: To investigate the association between sensory-based food education implemented in early childhood education and care (ECEC) centres and children's willingness to choose and eat vegetables, berries and fruit, and whether the mother's education level and children's food neophobia moderate the linkage. DESIGN: The cross-sectional study involved six ECEC centres that provide sensory-based food education and three reference centres. A snack buffet containing eleven different vegetables, berries and fruit was used to assess children's willingness to choose and eat the food items. The children's parents completed the Food Neophobia Scale questionnaire to assess their children's food neophobia. SETTING: ECEC centres that provide sensory-based food education and reference ECEC centres in Finland. SUBJECTS: Children aged 3-5 years in ECEC (n 130) and their parents. RESULTS: Sensory-based food education was associated with children's willingness to choose and eat vegetables, berries and fruit. This association was stronger among the children of mothers with a low education level. A high average level of neophobia in the child group reduced the children's willingness to choose vegetables, berries and fruit. No similar tendency was observed in the group that had received sensory-based food education. Children's individual food neophobia had a negative association with their willingness to choose and eat the vegetables, berries and fruit. CONCLUSIONS: Child-oriented sensory-based food education seems to provide a promising method for promoting children's adoption of vegetables, berries and fruit in their diets. In future sensory food education research, more focus should be placed on the effects of the education at the group level.

Occupational well-being of the work community in social and health care education during the COVID-19 pandemic-A cross-sectional study.

AIM: To evaluate factors related to the occupational well-being of social and health care educators' work communities during the COVID-19 pandemic. DESIGN: A cross-sectional study was conducted among social and health care educators in Finland 2020. METHODS: Data (n = 552) were collected through a questionnaire containing continuous, Likert scale and categorical variables. Descriptive, exploratory factor analysis and multiple regression modelling were used for analysing the data. RESULTS: Educators regarded their work as meaningful and experienced collegiality. Age and work experience were related to experiences on work community subscales and community occupational well-being. Personal occupational well-being and activities promoting occupational well-being on the community level were most related to experiences of the work community and its well-being. The activities that promote occupational well-being on the work community level should be emphasized.

Estimating the Lifetime Treatment Burden of Patients With Follicular Lymphoma: A Retrospective Study Using Real-World Multicenter Data.

PURPOSE: Although follicular lymphoma is characterized by long natural history and frequent relapses, data on the number of patients receiving subsequent therapy lines are scarce. To perform reliable health economical calculations for various treatment options, data regarding the lifetime number of therapy courses are needed. The purpose of this study was to use real-world data to create a model that could estimate the treatment burden over a 20-year period. MATERIALS AND METHODS: We performed a 20-year simulation on the basis of retrospectively obtained multicenter data of 743 patients with follicular lymphoma. The simulation was carried out in two steps: First, a competing risk model on the basis of Weibull distribution was used to simulate the state transitions from diagnosis onward and from first-line therapy onward. Then, the data were completed by imputing on the basis of the existing data. Completion of data was repeated for 1,000 times to estimate reliability. RESULTS: In 20 years, 97% (2.5-97.5 percentile range: 96%-98%), 66% (61%-70%), 34% (30%-41%), and 15% (9%-18%) of the patients received first-line, second-line, third-line, and fourth-line therapies, respectively. The median number of therapy lines received by each patient was two. CONCLUSION: Despite long remissions, approximately two thirds of the patients receive at least two lines and one-third at least three lines of therapy during their lifetime.

Children's Fruit and Vegetable Preferences Are Associated with Their Mothers' and Fathers' Preferences.

Children's preference for fruit and vegetables must emerge during childhood. At children's homes, mothers and fathers influence children's developing food preferences with their own preferences and actions. The purpose of the study was to reveal the association parents have with their children's fruit and vegetable preferences. The study was conducted in a sample of Finnish mothers and fathers of 3-5-year-old children. The participants were recruited, and questionnaires distributed through early childhood education and care centers in 2014 and 2015. The results showed considerable variance in the children's preferences, and were more similar with their father's, than their mother's preference. There was an association between mother's and children's preference for "strong-tasting vegetables and berries" (p = 0.005), "sweet-tasting fruit" (p < 0.001) and "common vegetables" (p = 0.037). Fathers preferences associated with children's preferences for "strong-tasting vegetables and berries" (p = 0.003). Food neophobia decreased children's "strong-tasting vegetables and berries" (p < 0.001) and "sweet-tasting fruit" (p < 0.001) preferences. The father's more relaxed attitude towards eating decreased children's preferences for "strong-tasting vegetables and berries" (p = 0.031) and "sweet-tasting fruit" (p = 0.003). These findings indicate a need for more targeted strategies for increasing children's preferences for fruit and vegetables and highlight the importance of taking both parents equally into account.

Nutrition-focused group intervention with a strength-based counseling approach for people with clinical depression: a study protocol for the Food for Mind randomized controlled trial.

BACKGROUND: Depression is a highly prevalent mental disorder with major public health effects globally. It impairs the quality of life and reduces the ability to work and function, leading to increasing costs of sick leaves and disability pensions. Current treatment strategies focus on biological and psychological pathways while understating the role of lifestyle factors. Epidemiological studies have shown convincing evidence of an inverse relationship between diet quality and depression. However, only limited data are available on the therapeutic effects of diet quality improvement on depression. Using a randomized controlled trial design, our primary aim is to investigate the effectiveness and cost-effectiveness of a behavioral nutrition group intervention compared to a social support intervention in the treatment of depression. METHODS: Participants (N=144, aged 20-65 years) with a diagnosis of moderate or severe depression recruited in collaboration with outpatient care units will be randomized into two arms: Food for Mind (FM) nutrition intervention (n=72) or Bring Good Mood (BGM) social support control group (n=72). Both arms will be provided with 6 group sessions over an 8-week period. FM involves improving diet quality by applying strength-based behavioral nutrition counseling and activities facilitated by a registered dietitian. The control arm comprises a befriending protocol. During the interventions, all participants will continue their treatment for depression as usual. Longitudinal data are collected at baseline, at 8 weeks, and at 6- and 12-month follow-ups. Depressive symptoms, diet quality, eating behavior, ability to work and function, and quality of life are assessed by self-reported questionnaires. A treatment expectancy questionnaire will be administered at baseline and an acceptability questionnaire at 8 weeks. The Center for Epidemiologic Studies Depression Scale is used as the primary endpoint at 1 year. The results will be analyzed with linear mixed-effects models. Economic evaluation includes both cost-effectiveness and cost-utility analysis. Two incremental cost-effectiveness ratios will be calculated to evaluate the incremental cost per QALY and the incremental cost per improvement in CES-D. DISCUSSION: If the intervention proves to be cost-effective and acceptable, it be can be implemented in healthcare to support the treatment of depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT03904771 . Retrospectively registered on 5 April 2019.

Bile-duct proliferation as an unexpected side-effect after AAV2-LDLR gene transfer to rabbit liver.

Familial hypercholesterolemia (FH) is an inherited disease of lipoprotein metabolism caused by a defect in the LDL receptor (LDLR) leading to severe hypercholesterolemia, and associated with an increased risk of coronary heart disease and myocardial infarction. We have developed a gene therapy protocol for FH using AAV2, AAV9 and lentiviral vectors and tested safety and efficacy in LDL receptor deficient Watanabe Heritable Hyperlipidemic rabbits. We show that LV-LDLR produced a significant long-lasting decrease in total serum cholesterol whereas AAV9-LDLR resulted only in a transient decrease and AAV2-LDLR failed to reduce serum cholesterol levels. A significant pathological side effect, bile-duct proliferation, was seen in the liver of AAV2-LDLR rabbits associated with an increased expression of Cyr61 matricellular protein. Special attention should be given to liver changes in gene therapy applications when genes affecting cholesterol and lipoprotein metabolism are used for therapy.