Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement.

Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. Design, Setting, and Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Exposure: Primary TKA with ALBC vs plain bone cement. Main Outcomes and Measures: The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Results: Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. Conclusions and Relevance: In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.

SunGold Kiwifruit Supplementation of Individuals with Prediabetes Alters Gut Microbiota and Improves Vitamin C Status, Anthropometric and Clinical Markers.

Kiwifruit are a nutrient dense food and an excellent source of vitamin C. Supplementation of the diet with kiwifruit enhances plasma vitamin C status and epidemiological studies have shown an association between vitamin C status and reduced insulin resistance and improved blood glucose control. In vitro experiments suggest that eating kiwifruit might induce changes to microbiota composition and function; however, human studies to confirm these findings are lacking. The aim of this study was to investigate the effect of consuming two SunGold kiwifruit per day over 12 weeks on vitamin C status, clinical and anthropometric measures and faecal microbiota composition in people with prediabetes. This pilot intervention trial compared baseline measurements with those following the intervention. Participants completed a physical activity questionnaire and a three-day estimated food diary at baseline and on completion of the trial. Venous blood samples were collected at each study visit (baseline, 6, 12 weeks) for determination of glycaemic indices, plasma vitamin C concentrations, hormones, lipid profiles and high-sensitivity C-reactive protein. Participants provided a faecal sample at each study visit. DNA was extracted from the faecal samples and a region of the 16S ribosomal RNA gene was amplified and sequenced to determine faecal microbiota composition. When week 12 measures were compared to baseline, results showed a significant increase in plasma vitamin C (14 µmol/L, p < 0.001). There was a significant reduction in both diastolic (4 mmHg, p = 0.029) and systolic (6 mmHg, p = 0.003) blood pressure and a significant reduction in waist circumference (3.1 cm, p = 0.001) and waist-to-hip ratio (0.01, p = 0.032). Results also showed a decrease in HbA1c (1 mmol/mol, p = 0.005) and an increase in fasting glucose (0.1 mmol/L, p = 0.046), however, these changes were small and were not clinically significant. Analysis of faecal microbiota composition showed an increase in the relative abundance of as yet uncultivated and therefore uncharacterised members of the bacterial family Coriobacteriaceae. Novel bacteriological investigations of Coriobacteriaceae are required to explain their functional relationship to kiwifruit polysaccharides and polyphenols.

Inadequate Vitamin C Status in Prediabetes and Type 2 Diabetes Mellitus: Associations with Glycaemic Control, Obesity, and Smoking.

Vitamin C (ascorbate) is an essential micronutrient in humans, being required for a number of important biological functions via acting as an enzymatic cofactor and reducing agent. There is some evidence to suggest that people with type 2 diabetes mellitus (T2DM) have lower plasma vitamin C concentrations compared to those with normal glucose tolerance (NGT). The aim of this study was to investigate plasma vitamin C concentrations across the glycaemic spectrum and to explore correlations with indices of metabolic health. This is a cross-sectional observational pilot study in adults across the glycaemic spectrum from NGT to T2DM. Demographic and anthropometric data along with information on physical activity were collected and participants were asked to complete a four-day weighed food diary. Venous blood samples were collected and glycaemic indices, plasma vitamin C concentrations, hormone tests, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were analysed. A total of 89 participants completed the study, including individuals with NGT (n = 35), prediabetes (n = 25), and T2DM managed by diet alone or on a regimen of Metformin only (n = 29). Plasma vitamin C concentrations were significantly lower in individuals with T2DM compared to those with NGT (41.2 µmol/L versus 57.4 µmol/L, p < 0.05) and a higher proportion of vitamin C deficiency (i.e. <11.0 µmol/L) was observed in both the prediabetes and T2DM groups. The results showed fasting glucose (p = 0.001), BMI (p = 0.001), smoking history (p = 0.003), and dietary vitamin C intake (p = 0.032) to be significant independent predictors of plasma vitamin C concentrations. In conclusion, these results suggest that adults with a history of smoking, prediabetes or T2DM, and/or obesity, have greater vitamin C requirements. Future research is required to investigate whether eating more vitamin C rich foods and/or taking vitamin C supplements may reduce the risk of progression to, and/or complications associated with, T2DM.

Marginal effects of glucose, insulin and insulin-like growth factor on chemotherapy response in endothelial and colorectal cancer cells.

Resistance to chemotherapy is a major clinical issue for patients with colorectal cancer. Obesity has been associated with a poorer outcome and is a possible mechanism of resistance. The aim of the present study was to investigate the effect of obesity-related factors on the cell response to standard chemotherapy in stromal and colorectal cancer cells. Viability was measured following the treatment of colorectal cancer cell lines (WiDr and SW620) and stromal cells (human microvascular endothelial cells) in vitro with 5-fluorouracil, irinotecan and oxaliplatin under obesity-related conditions [elevated levels of insulin, insulin-like growth factor-1 (IGF-1) and glucose] and compared with non-elevated conditions. Obesity-related conditions alone increased cell viability and in selected cases, accumulation of the transcription factor, hypoxia-inducible factor-1. However, these conditions did not consistently increase resistance to the chemotherapy agents tested. The combination of IGF-1 and extremely low-dose chemotherapy significantly induced cell viability in WiDr colorectal cancer cells. These in vitro results may have clinical importance in an environment of increasing rates of obesity and colorectal cancer, and the frequent under-dosing of obese cancer patients.

Consumption of a plant sterol-based spread derived from rice bran oil is effective at reducing plasma lipid levels in mildly hypercholesterolaemic individuals.

To establish the effectiveness of a new phytosterol-containing spread derived from rice bran oil (RBO), a randomised, double-blind, cross-over human clinical trial was conducted over 12 weeks. A total of eighty mildly hypercholesterolaemic (total blood cholesterol level ≥ 5 and ≤ 7·5 mmol/l with a serum TAG level of ≤ 4·5 mmol/l) individuals were randomised into two groups (n 40). Group 1 consumed spread only daily for 4 weeks. They were randomised to consume 20 g RBO spread (RBOS), 20 g standard spread (SS) or 20 g phytosterol-enriched spread (PS). After a 4-week period, individuals changed to the next randomised treatment until all three treatments had been consumed. Group 2 consumed spread plus oil daily for 4 weeks. They consumed 20 g RBOS plus 30 ml RBO, 20 g SS plus 30 ml sunflower oil or 20 g RBOS. Blood samples were collected for the analysis of lipid parameters, and 3 d diet records were collected. Compared with SS, RBOS significantly reduced total cholesterol by 2·2 % (P = 0·045), total cholesterol:HDL by 4·1 % (P = 0·005) and LDL-cholesterol by 3·5 % (P = 0·016), but was not as effective overall as PS, which reduced total cholesterol by 4·4 % (P = 0·001), total cholesterol:HDL by 3·4 % (P = 0·014) and LDL-cholesterol by 5·6 % (P = 0·001). In group 2, the addition of RBO to the RBOS produced no differences in cholesterol levels. These results confirm that RBOS is effective in lowering serum cholesterol when consumed as part of a normal diet.

Cause-specific mortality in insulin-treated diabetic patients: a 20-year follow-up.

BACKGROUND: Diabetes is one of the most common chronic diseases in Western populations. There have been few large published cohort studies of diabetes with 20 years of follow-up worldwide, and none other than the present one in NZ. AIMS: To establish cause-specific death rates, by age and sex in insulin-treated diabetic individuals living in Canterbury, NZ. METHODS: Insulin-treated diabetic subjects on the Canterbury Diabetes Registry were followed over 20 years and vital status determined. Following notification of deaths, age- and sex-specific mortality rates, and sex-specific mortality ratios (SMRs) were calculated. RESULTS: During follow-up 966 diabetic subjects contributed 13,495 person-years and 525 deaths occurred (261 females and 264 males). At all ages mortality rates were considerably higher than expected mortality. Relative mortalities were increased for cardiovascular (SMR women 3.73, 95% CI: 3.16-4.30; men 3.27, 95% CI: 2.76-3.78), renal (SMR women 5.55, 95% CI: 2.53-8.57; men 7.15, 95% CI: 3.40-10.90), respiratory disease (SMR women 3.31, 95% CI: 1.98-4.63; men 2.32, 95% CI: 1.41-3.23) and malignancy (SMR women 4.99, 95% CI: 2.99-6.99; men 2.19, 95% CI: 1.42-2.96) with cardiovascular disease accounting for the single greatest cause of excess death at all ages. CONCLUSIONS: Mortality rates for diabetic individuals remain high, resulting in shortened life spans relative to the general population. To reduce these death rates attention must be paid to the early detection and treatment of CVD and associated risk factors.

The deleted in colorectal carcinoma (DCC) gene 201 R --> G polymorphism: no evidence for genetic association with autoimmune disease.

The product of the deleted in colorectal carcinoma (DCC) gene has a role in apoptosis and is a positional candidate for IDDM6, the putative chromosome 18q12-q23 autoimmune disease locus. We hypothesised that a nonconservative substitution (DCC 201 R --> G; nucleotide (nt) 601 C --> G), located in an extracellular immunoglobulin-like domain of DCC, is an aetiological determinant of autoimmunity. We tested this hypothesis by genetically testing the nt 601 C --> G polymorphism for association with three autoimmune phenotypes in a large population-based case-control study. There was no evidence for association of DCC nt 601 C --> G with autoimmune disease in cohorts comprising 2253 subjects with rheumatoid arthritis, type I diabetes and Graves' disease, and 2225 control subjects, from New Zealand and the United Kingdom. Furthermore, using the transmission disequilibrium test, there was no significant evidence for biased transmission of the nt 601 C --> G polymorphism to probands within a 382 family type I diabetes affected sibpair cohort from the United Kingdom. Thus, the DCC 201 R --> G polymorphism does not appreciably influence risk of developing the autoimmune diseases tested.