The lived experience of food insecurity among adults with obesity: a quantitative and qualitative systematic review.

BACKGROUND: Food insecurity and obesity are increasing both globally and in the UK. In this review we systematically assess the lived experiences of people with obesity who are food insecure and often turn to food banks. METHODS: We systematically searched electronic databases from January 2007 until October 2022. Data from eligible studies were extracted and the studies assessed for quality. Thematic analysis and narrative synthesis approach was used to analyse the extracted data. RESULTS: Six themes were identified among 25 included studies, including: the financial cost of food; psychological aspects related to food insecurity; geographical access and the food environment; food practices in the home; experience of food assistance; and parental-child relationships. The cost of healthy food and psychological factors were identified as key driving factors of the relationship between food insecurity and obesity. Psychological factors such as depression, low self-esteem and stress played an important part in the lived experience of people with obesity and food insecurity. CONCLUSION: The food environment provides context in which food decisions are made, therefore, systems change is necessary to ensure families can afford the food that enables a healthy diet. For clinicians, identification, and attention to the impact of food insecurity on people with obesity are important.

The effectiveness of group-based gardening interventions for improving wellbeing and reducing symptoms of mental ill-health in adults: a systematic review and meta-analysis.

BACKGROUND: There is increasing interest in the association between nature, health and wellbeing. Gardening is a popular way in which interaction with nature occurs and numerous gardening projects aim to facilitate wellbeing among participants. More research is needed to determine their effectiveness. AIM: To systematically evaluate the effectiveness of group-based gardening interventions for increasing wellbeing and reducing symptoms of mental ill-health in adults. METHODS: A systematic review of Randomised Controlled Trials was conducted following the protocol submitted to PROSPERO (CRD42020162187). Studies reporting quantitative validated health and wellbeing outcomes of the community residing, adult populations (18+) were eligible for inclusion. RESULTS: 24 studies met inclusion criteria: 20 completed and four ongoing trials. Meta-analyses suggest these interventions may increase wellbeing and may reduce symptoms of depression, however, there was uncertainty in the pooled effects due to heterogeneity and unclear risk of bias for many studies. There were mixed results for other outcomes. RESEARCH LIMITATIONS/IMPLICATIONS: Heterogeneity and small sample sizes limited the results. Poor reporting precluded meta-analysis for some studies. Initial findings for wellbeing and depression are promising and should be corroborated in further studies. The research area is active, and the results of the ongoing trials identified will add to the evidence base.

Bcl-xL Is a Key Mediator of Apoptosis Following KRASG12C Inhibition in KRASG12C-mutant Colorectal Cancer.

Novel covalent inhibitors of KRASG12C have shown limited response rates in patients with KRASG12C-mutant (MT) colorectal cancer. Thus, novel KRASG12C inhibitor combination strategies that can achieve deep and durable responses are needed. Small-molecule KRASG12C inhibitors AZ'1569 and AZ'8037 were used. To identify novel candidate combination strategies for AZ'1569, we performed RNA sequencing, siRNA, and high-throughput drug screening. Top hits were validated in a panel of KRASG12CMT colorectal cancer cells and in vivo. AZ'1569-resistant colorectal cancer cells were generated and characterized. We found that response to AZ'1569 was heterogeneous across the KRASG12CMT models. AZ'1569 was ineffective at inducing apoptosis when used as a single agent or combined with chemotherapy or agents targeting the EGFR/KRAS/AKT axis. Using a systems biology approach, we identified the antiapoptotic BH3-family member BCL2L1/Bcl-xL as a top hit mediating resistance to AZ'1569. Further analyses identified acute increases in the proapoptotic protein BIM following AZ'1569 treatment. ABT-263 (navitoclax), a pharmacologic Bcl-2 family inhibitor that blocks the ability of Bcl-xL to bind and inhibit BIM, led to dramatic and universal apoptosis when combined with AZ'1569. Furthermore, this combination also resulted in dramatically attenuated tumor growth in KRASG12CMT xenografts. Finally, AZ'1569-resistant cells showed amplification of KRASG12C, EphA2/c-MET activation, increased proinflammatory chemokine profile and cross-resistance to several targeted agents. Importantly, KRAS amplification and AZ'1569 resistance were reversible upon drug withdrawal, arguing strongly for the use of drug holidays in the case of KRAS amplification. Taken together, combinatorial targeting of Bcl-xL and KRASG12C is highly effective, suggesting a novel therapeutic strategy for patients with KRASG12CMT colorectal cancer.

Efficacy of a Gluten-Free Diet in Subjects With Irritable Bowel Syndrome-Diarrhea Unaware of Their HLA-DQ2/8 Genotype.

BACKGROUND & AIMS: A gluten-containing diet alters bowel barrier function in patients with irritable bowel syndrome with diarrhea (IBS-D), particularly those who are positive for HLA allele DQ2/8. We studied the effects of a gluten-free diet (GFD) in patients with IBS-D who have not previously considered the effects of gluten in their diet and were unaware of their HLA-DQ2/8 genotype. METHODS: We performed a prospective study of 41 patients with IBS-D (20 HLA-DQ2/8-positive and 21 HLA-DQ2/8-negative) at the Royal Hallamshire Hospital in Sheffield, United Kingdom, from September 2012 through July 2015. All subjects were placed on a 6-week GFD following evaluation by a dietician. Subjects completed validated questionnaires at baseline and Week 6 of the GFD. The primary endpoint was mean change in IBS Symptom Severity Score; a 50-point reduction was considered to indicate a clinical response. Secondary endpoints were changes in hospital anxiety and depression score, fatigue impact score, and Short Form-36 results. Clinical responders who chose to continue a GFD after the study period were evaluated on average 18 months later to assess diet durability, symptom scores, and anthropometric and biochemical status. RESULTS: A 6-week GFD reduced IBS Symptom Severity Score by ≥50 points in 29 patients overall (71%). The mean total IBS Symptom Severity Score decreased from 286 before the diet to 131 points after 6 weeks on the diet (P < .001); the reduction was similar in each HLA-DQ group. However, HLA-DQ2/8-negative subjects had a greater reduction in abdominal distention (P = .04). Both groups had marked mean improvements in hospital anxiety and depression scores, fatigue impact score, and Short Form-36 results, although HLA-DQ2/8-positive subjects had a greater reduction in depression score and increase in vitality score than HLA-DQ2/8-negative subjects (P = .02 and P = .03, respectively). Twenty-one of the 29 subjects with a clinical response (72%) planned to continue the GFD long term; 18 months after the study they were still on a GFD, with maintained symptom reductions, and demonstrated similar anthropometric and biochemical features compared with baseline. CONCLUSIONS: A dietitian-led GFD provided sustained benefit to patients with IBS-D. The symptoms that improved differed in magnitude according to HLA-DQ status. Clinical trials.gov no: NCT02528929.

An observational study investigating the effect of platelet function on outcome after colorectal surgery.

INTRODUCTION: Previous studies have assumed patients have uniform responses to aspirin, yet significant numbers are occult hypo- or hyper-responders. A new validated test of platelet function measures platelet P-selectin expression, which rises with increased platelet activity. This study investigated the measured perioperative changes in platelet function in response to aspirin, and subsequently whether quantitative variations in platelet activity affected perioperative complication severity and frequency. METHODS: 107 patients undergoing major colorectal surgery were recruited and assigned to either control (no antiplatelet therapy) or aspirin groups. P-selectin was measured following platelet stimulation at recruitment prior to cessation of medication, and at surgery before intervention. Perioperative complications, hemoglobin changes and blood transfusions were also recorded. RESULTS: Platelet function was higher in control (n = 87) than aspirin group (n = 20) at recruitment (median 1303u [IQR 1102-1499] vs 77u [IQR 63.5-113.5],P < 0.01) and surgery (median 1224u [IQR 944-1496] vs 281.5u [IQR 106.8-943], P < 0.01). There was a positive correlation between length of aspirin cessation and platelet function at surgery (R(S) = 0.66, P < 0.01). Complication rates and hemorrhagic complication rates (P < 0.05) were higher with aspirin than control, although complication severity was not increased. Platelet function of the entire cohort at surgery was not associated with complication rate, severity or transfusion use. DISCUSSION: Although complication rates were higher in aspirin group, impaired platelet function within ranges seen with aspirin continuation did not affect complication severity or rate or blood transfusion use. Consequently, aspirin continuation may not affect clinical outcome in patients undergoing major colorectal surgery and requires further investigation with a large randomized trial.