Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma

Background: The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes. Objective: To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease. Design: In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC–MS/MS. Results: Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = − 0.34, P < 0.01). Conclusions: Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health. Clinical trial registrations: Australian and New Zealand Clinical Trial Registry (ANZCTRN12616001703493).

Background: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab. Methods: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6–12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1. Results: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1+ CTCs (14/25, 64%) had significantly longer progression-free survival (PFS) compared with patients with PD-L1− CTCs (26.6 months vs. 5.5 months; p = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1+ versus PD-L1− CTCs groups (p = .012), respectively. A multivariate linear regression analysis confirmed that PD-L1+ CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052–1.012; p = .026). Conclusion: Our results reveal the potential of CTCs as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with melanoma. PD-L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS.

The consortium of trillions of microorganisms that live inside the human gut are integral to health. Little has been done to collate and characterize the microbiome of children. A systematic review was undertaken to address this gap (PROSPERO ID: CRD42018109599). MEDLINE and EMBASE were searched using the keywords: “healthy preadolescent children” and “gut microbiome” to 31 August 2018. Of the 815 journal articles, 42 met the inclusion criteria. The primary outcome was the relative abundance of bacteria at the phylum, family, and genus taxonomic ranks. α-diversity, short chain fatty acid concentrations, diet, 16S rRNA sequencing region, and geographical location were documented. The preadolescent gut microbiome is dominated at the phylum level by Firmicutes (weighted overall average relative abundance = 51.1%) and Bacteroidetes (36.0%); genus level by Bacteroides (16.0%), Prevotella (8.69%), Faecalibacterium (7.51%), and Bifidobacterium (5.47%). Geographic location and 16S rRNA sequencing region were independently associated with microbial proportions. There was limited consensus between studies that reported α-diversity and short chain fatty acids. Broadly speaking, participants from non-Western locations, who were less likely to follow a Westernized dietary pattern, had higher α-diversity and SCFA concentrations. Confirmatory studies will increase the understanding of the composition and functional capacity of the preadolescent gut microbiome.

(1) Background: The Paleolithic diet is popular in Australia, however, limited literature surrounds the dietary pattern. Our primary aim was to compare the Paleolithic diet with the Australian Guide to Healthy Eating (AGHE) in terms of anthropometric, metabolic and cardiovascular risk factors, with a secondary aim to examine the macro and micronutrient composition of both dietary patterns; (2) Methods: 39 healthy women (mean ± SD age 47 ± 13 years, BMI 27 ± 4 kg/m²) were randomised to either the Paleolithic (n = 22) or AGHE diet (n = 17) for four weeks. Three-day weighed food records, body composition and biochemistry data were collected pre and post intervention; (3) Results: Significantly greater weight loss occurred in the Paleolithic group (−1.99 kg, 95% CI −2.9, −1.0), p < 0.001). There were no differences in cardiovascular and metabolic markers between groups. The Paleolithic group had lower intakes of carbohydrate (−14.63% of energy (E), 95% CI −19.5, −9.7), sodium (−1055 mg/day, 95% CI −1593, −518), calcium (−292 mg/day 95% CI −486.0, −99.0) and iodine (−47.9 μg/day, 95% CI −79.2, −16.5) and higher intakes of fat (9.39% of E, 95% CI 3.7, 15.1) and β-carotene (6777 μg/day 95% CI 2144, 11410) (all p < 0.01); (4) Conclusions: The Paleolithic diet induced greater changes in body composition over the short-term intervention, however, larger studies are recommended to assess the impact of the Paleolithic vs. AGHE diets on metabolic and cardiovascular risk factors in healthy populations.

Issue addressed: Currently, two food sufficiency questions are utilised as a proxy measure of national food security status in Australia. These questions do not capture all dimensions of food security and have been attributed to underreporting of the problem. The purpose of this study was to investigate food security using the short form of the US Household Food Security Survey Module (HFSSM) within an Australian context; and explore the relationship between food security status and multiple socio‐demographic variables.Methods: Two online surveys were completed by 2334 Australian participants from November 2014 to February 2015. Surveys contained the short form of the HFSSM and twelve socio‐demographic questions. Cross‐tabulations chi‐square tests and a multinomial logistic regression model were employed to analyse the survey data.Results: Food security status of the respondents was classified accordingly: High or Marginal (64%, n = 1495), Low (20%, n = 460) or Very Low (16%, n = 379). Significant independent predictors of food security were age (P < 0.001), marital status (P = 0.005), household income (P < 0.001) and education (P < 0.001).Conclusion: Findings suggest food insecurity is an important issue across Australia and that certain groups, regardless of income, are particularly vulnerable.So what?: Government policy and health promotion interventions that specifically target “at risk” groups may assist to more effectively address the problem. Additionally, the use of a multi‐item measure is worth considering as a national indicator of food security in Australia.