Phase I Study of Dalteparin in Combination With Sunitinib in Patients With Metastatic Clear Cell Renal Carcinoma

Background

Based on the tumor-driven concomitant activation of angiogenesis and coagulation we conducted a phase I combination study of sunitinib with the low molecular weight heparin dalteparin in patients with metastatic clear cell renal cell carcinoma (ccRCC).

Absence of a PDX-1 mutation and normal gastroduodenal immunohistology in a child with pancreatic agenesis

Pancreatic agenesis is a rare condition, of which only a limited number of cases have been described. One recent paper reported a homozygous mutation in the pancreatic duodenal homeobox gene 1 (PDX-1) in a child with pancreatic agenesis. We report a 6-year-old boy with pancreatic agenesis, treated medically, without abnormalities in the PDX-1 gene coding sequence and with normal gastroduodenal endocrine cell distribution. Genes other than PDX-1 also appear to be involved in human pancreatic agenesis.     

Plant versus animal based diets and insulin resistance,prediabetes and type 2 diabetes: the Rotterdam Study

Vegan or vegetarian diets have been suggested to reduce type 2 diabetes (T2D) risk. However, not much is known on whether variation in the degree of having a plant-based versus animal-based diet may be beneficial for prevention of T2D. We aimed to investigate whether level of adherence to a diet high in plant-based foods and low in animal-based foods is associated with insulin resistance, prediabetes, and T2D. Our analysis included 6798 participants (62.7?±?7.8 years) from the Rotterdam Study (RS), a prospective population-based cohort in the Netherlands. Dietary intake data were collected with food-frequency questionnaires at baseline of three sub-cohorts of RS (RS-I-1: 1989–1993, RS-II-1: 2000–2001, RS-III-1: 2006–2008). We constructed a continuous plant-based dietary index (range 0–92) assessing adherence to a plant-based versus animal-based diet. Insulin resistance at baseline and follow-up was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Prediabetes and T2D were collected from general practitioners’ records, pharmacies’ databases, and follow-up examinations in our research center until 2012. We used multivariable linear mixed models to examine association of the index with longitudinal HOMA-IR, and multivariable Cox proportional-hazards regression models to examine associations of the index with risk of prediabetes and T2D. During median 5.7, and 7.3 years of follow-up, we documented 928 prediabetes cases and 642 T2D cases. After adjusting for sociodemographic and lifestyle factors, a higher score on the plant-based dietary index was associated with lower insulin resistance (per 10 units higher score: β?=??0.09; 95% CI: ??0.10; ??0.08), lower prediabetes risk (HR?=?0.89; 95% CI: 0.81; 0.98), and lower T2D risk [HR?=?0.82 (0.73; 0.92)]. After additional adjustment for BMI, associations attenuated and remained statistically significant for longitudinal insulin resistance [β?=??0.05 (??0.06; ??0.04)] and T2D risk [HR?=?0.87 (0.79; 0.99)], but no longer for prediabetes risk [HR?=?0.93 (0.85; 1.03)]. In conclusion, a more plant-based and less animal-based diet may lower risk of insulin resistance, prediabetes and T2D. These findings strengthen recent dietary recommendations to adopt a more plant-based diet.Clinical Trial Registry number and website NTR6831, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831.     

Glutathione-S-transferase pi (GSTP1) codon 105 polymorphism is not associated with oxaliplatin efficacy or toxicity in advanced colorectal cancer patients

PurposeOxaliplatin is detoxified by conjugation to glutathione via the enzyme Glutathione-S-transferase pi (GSTP1). The aim of this study is to investigate the association of GSTP1 Ile105Val genetic polymorphism with oxaliplatin efficacy and toxicity in advanced colorectal cancer (ACC) patients.Experimental designA total of 91 ACC patients received capecitabine and oxaliplatin (CAPOX) as a part of a multicentre phase-III study of the Dutch Colorectal Cancer Group. Tumour response was evaluated according to RECIST, toxicity was graded using CTC, and GSTP1 Ile105Val was determined by pyrosequencing.ResultsOverall survival after CAPOX was similar for patients with the Ile/Ile (11.5 mo), Ile/Val (11.6 mo) and Val/Val (12.6 mo) genotypes (p = 0.602). Likewise, there were no statistically significant differences in progression-free survival (p = 0.252). Overall grades 3–4 toxicity was not related to genotype (p = 0.313). There were no differences in any grade or grades 3–4 neurotoxicity amongst the patients who received ?500 mg/m² of oxaliplatin (p-values of 0.376 and 0.772, respectively).ConclusionsThe results of this study indicate that the GSTP1 genotype is not predictive for progression-free survival or overall survival in ACC patients treated with CAPOX. Moreover, overall neurotoxicity and neurotoxicity in patients receiving ?500 mg/m² of oxaliplatin was not associated with GSTP1 genotype.     

Trajectories and Determinants of Physical Activity during COVID-19 Pandemic: A Population-Based Study of Middle-Aged and Elderly Individuals in The Netherlands

Physical inactivity is a major public health problem, and there are concerns this might have increased during the COVID-19 pandemic. We aimed to identify distinct trajectories of physical activity over a 6-week period after the first restrictive measures and to explore determinants of these trajectories in a population-based cohort of middle-aged and elderly in the Netherlands (n = 5777). We observed that at least 59% of participants did not meet the World Health Organization recommendations for physical activity. Using latent class trajectory analyses over three time points, we identified five distinct trajectories, including four steady trajectories at different levels (very low, low, medium and high) and one increasing trajectory. Using multinomial logistic regression analyses, we observed that, compared to the ‘steadily high’ trajectory, participants in the ‘steadily very low’ trajectory were more often older, lower educated, reporting poorer physical health, more depressive symptoms, consuming a less healthy diet, smoking, and lower alcohol use, and were less often retired. A similar pattern of determinants was seen for those in the increasing trajectory, albeit with smaller effect sizes. Concluding, we observed low levels of physical activity that generally remained during the pandemic. The determinants we described can help identify groups that require additional preventive interventions.     

Diet Quality and Risk of Parkinson’s Disease: The Rotterdam Study

The Mediterranean diet has been associated with the risk of Parkinson’s disease (PD), but limited research has been performed on other dietary patterns. We studied the relationship between overall diet quality and PD risk in the general population. We included 9414 participants from the Rotterdam Study, a prospective population-based study in the Netherlands. Diet was defined using a Dutch diet quality score, a Mediterranean diet score and data-driven dietary patterns constructed with principal component analysis (PCA). During an average follow-up of 14.1 years, PD was diagnosed in 129 participants. We identified a ‘Prudent’, ‘Unhealthy’ and ‘Traditional Dutch’ pattern from the PCA. We found a possible association between the Mediterranean diet (Hazard ratio (HR) per standard deviation (SD) 0.89 (95% confidence interval (CI) 0.74–1.07)), the ‘Prudent’ pattern (HR per SD 0.81 (95% CI 0.61–1.08)) and the risk of PD. However, no associations with PD risk were found for the Dutch diet quality score (HR per SD 0.93 (95% CI 0.77–1.12)), the ‘Unhealthy’ pattern (HR per SD 1.05 (95% CI 0.85–1.29)) or the ‘Traditional Dutch’ pattern (HR per SD 0.90 (95% CI 0.69–1.17)). In conclusion, our results corroborate previous findings of a possible protective effect of the Mediterranean diet. Further research is warranted to study the effect of other dietary patterns on PD risk.     

Correction to: The antioxidant Trolox restores mitochondrial membrane potential and Ca2+-stimulated ATP production in human complex I deficiency

Journal of Molecular Medicine - A Correction to this paper has been published: https://doi.org/10.1007/s00109-021-02057-3