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Background: Obesity drives metabolic disease development. Preventing weight gain during early adulthood could mitigate later-life chronic disease risk. Increased dietary fibre intake, leading to enhanced colonic microbial fermentation and short-chain fatty acid (SCFA) production, is associated with lower body weight. Despite national food policy recommendations to consume 30 g of dietary fibre daily, only 9% of adults achieve this target. Inulin-propionate ester (IPE) selectively increases the production of the SCFA propionate in the colon. In previous studies, IPE has prevented weight gain in middle-aged adults over 6 months, compared with the inulin control. IPE is a novel food ingredient that can be added to various commonly consumed foods with a potential health benefit. This 12-month study aimed to determine whether using IPE to increase colonic propionate prevents further weight gain in overweight younger adults., Methods: This multi-centre randomised-controlled, double-blind trial was conducted in London and Glasgow, UK. Recruited participants were individuals at risk of weight gain, aged between 20 and 40 years and had an overweight body mass index. Sealed Envelope Software was used to randomise participants to consume 10 g of IPE or inulin (control), once per day for 12 months. The primary outcome was the weight gained from baseline to 12 months, analysed by an 'Intention to Treat' strategy. The safety profile and tolerability of IPE were monitored through adverse events and compliance. This study is registered with the International Standard Randomised Controlled Trials (ISRCT) Database (ISRCT number: 16299902)., Findings: Participants (n = 135 per study arm) were recruited from July 2019 to October 2021. At 12 months, there was no significant difference in baseline-adjusted mean weight gain for IPE compared with control (1.02 kg, 95% CI: -0.37 to 2.41; p = 0.15; n = 226). Neither the IPE (+1.22 kg) nor the control arm (+0.07 kg) unadjusted mean gains in body weight reached the expected 2 kg threshold. In the IPE arm, fat-free mass was greater by 1.07 kg (95% CI: 0.21-1.93), and blood glucose elevated by 0.11 mmol/L (95% CI: 0.01-0.21). Compliance, determined by intake of ≥50% sachets, was reached by 63% of IPE participants. There were no unexpected adverse events or safety concerns., Interpretation: Our study indicates that at 12 months, IPE did not differentially affect weight gain, compared with the inulin control, in adults between 20 and 40 years of age, at risk of obesity., Funding: NIHR EME Programme (15/185/16)., Competing Interests: GF, DM, and TP are named inventors of the patent Compounds and their effects on appetite control and insulin sensitivity WO2014020344A1 and are founding directors of a Spinout company aimed at commercialising IPE production. LH and BAS received compensation for their PPI contributions., (© 2024 Published by Elsevier Ltd.)

Background: National estimates of the prevalence of vision impairment and blindness in people with diabetes are required to inform resource allocation. People with diabetes are more susceptible to conditions such as diabetic retinopathy that can impair vision; however, these are often missed in national studies. This study aims to determine the prevalence and risk factors of vision impairment and blindness in people with diabetes in India., Methods: Data from the SMART-India study, a cross-sectional survey with national coverage of 42 147 Indian adults aged 40 years and older, collected using a complex sampling design, were used to obtain nationally representative estimates for the prevalence of vision impairment and blindness in people with diabetes in India. Vulnerable adults (primarily those who did not have capacity to provide consent); pregnant and breastfeeding women; anyone deemed too ill to be screened; those who did not provide consent; and people with type 1 diabetes, gestational diabetes, or secondary diabetes were excluded from the study. Vision impairment was defined as presenting visual acuity of 0·4 logMAR or higher and blindness as presenting a visual acuity of 1·0 logMAR or higher in the better-seeing eye. Demographic, anthropometric, and laboratory data along with geographic distribution were analysed in all participants with available data. Non-mydriatic retinal images were used to grade diabetic retinopathy, and risk factors were also assessed., Findings: A total of 7910 people with diabetes were included in the analysis, of whom 5689 had known diabetes and 2221 were undiagnosed. 4387 (55·5%) of 7909 participants with available sex data were female and 3522 (44·5%) participants were male. The estimated national prevalence of vision impairment was 21·1% (95% CI 15·7-27·7) and blindness 2·4% (1·7-3·4). A higher prevalence of any vision impairment (29·2% vs 19·6%; p=0·016) and blindness (6·7% vs 1·6%; p<0·0001) was observed in those with ungradable images. In known diabetes, diabetic retinopathy (adjusted odds ratio [aOR] 3·06 [95% CI 1·25-7·51]), vision-threatening diabetic retinopathy (aOR 7·21 [3·52-14·75]), and diabetic macular oedema (aOR 5·41 [2·20-13·33]) were associated with blindness in adjusted analysis. Common sociodemographic risk factors for vision impairment and blindness include older age, lower educational attainment, and unemployment., Interpretation: Based on the estimated 101 million people with diabetes in 2021 and the interpretation of the data from this study, approximately 21 million people with diabetes have vision impairment in India, of whom 2·4 million are blind. Higher prevalence is observed in those from lower socio-economic strata and policy makers should focus on these groups to reduce inequalities in health care., Funding: Global Challenge Research Fund of United Kingdom Research and Innovation through the Medical Research Council., Competing Interests: Declaration of interests No competing interests are declared for the submitted work. SS reports consultancy fees from AbbVie, Amgen, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Phamaceuticals, Janssen Pharmaceuticals, Novo Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics, and Sanofi; travel fees from Bayer and Roche; lecture fees from Bayer and Boehringer Ingelheim; stock options from Eyebiotech; and is a member of the data monitoring committee and advisory committee of Bayer and Novo Nordisk, outside of the submitted work. ATP reports payment for a trial design lecture from Bayer and for membership of a trial data monitoring committee from Roche, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept., Methods: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying antirheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every 3 months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis. This trial was registered with EudraCT (2013-003413-18)., Findings: Between Dec 22, 2014, and Jan 14, 2019, 280 individuals were evaluated for eligibility and, of 213 participants, 110 were randomly assigned to abatacept and 103 to placebo. During the treatment period, seven (6%) of 110 participants in the abatacept group and 30 (29%) of 103 participants in the placebo group met the primary endpoint. At 24 months, 27 (25%) of 110 participants in the abatacept group had progressed to rheumatoid arthritis, compared with 38 (37%) of 103 in the placebo group. The estimated proportion of participants remaining arthritis-free at 12 months was 92·8% (SE 2·6) in the abatacept group and 69·2% (4·7) in the placebo group. Kaplan-Meier arthritis-free survival plots over 24 months favoured abatacept (log-rank test p=0·044). The difference in restricted mean survival time between groups was 53 days (95% CI 28-78; p<0·0001) at 12 months and 99 days (95% CI 38-161; p=0·0016) at 24 months in favour of abatacept. During treatment, abatacept was associated with improvements in pain scores, functional wellbeing, and quality-of-life measurements, as well as low scores of subclinical synovitis by ultrasonography, compared with placebo. However, the effects were not sustained at 24 months. Seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment., Interpretation: Therapeutic intervention during the at-risk phase of rheumatoid arthritis is feasible, with acceptable safety profiles. T-cell co-stimulation modulation with abatacept for 12 months reduces progression to rheumatoid arthritis, with evidence of sustained efficacy beyond the treatment period, and with no new safety signals., Funding: Bristol Myers Squibb., Competing Interests: Declaration of interests APC, PE, IBM, RT, KR, and TH received grant funding from Bristol Myers Squibb. APC, PE, and BAF received consulting fees from Bristol Myers Squibb. APC, PE, and MAD'A received speakers' bureau fees from Bristol Myers Squibb. MJ and SQ were beneficiaries of the APIPPRA study grant awarded by Bristol Myers Squibb. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Diethylene glycol (DEG) is nephrotoxic, potentially resulting in high morbidity and mortality. Its main nephrotoxic by-product is diglycolic acid (DGA). This narrative overview summarizes selected literature with a focus on clinical findings, pathophysiology, diagnosis including morphological features of renal biopsies, and management. The kidney injury in DEG poisoning is secondary to proximal tubular necrosis caused by DGA. Marked vacuolization and edema of epithelial cells obstruct the lumen, reducing urine flow and, consequently, resulting in anuria and uremia. The clinical alterations due to DEG poisoning are dose-dependent. Patients may present with gastrointestinal symptoms and anion gap metabolic acidosis, followed by renal failure, and, later, encephalopathy and neuropathy. Although this three-phase pattern has been described, signs and symptoms may be overlapping. Data about DEG intoxication is scarce. Sometimes the diagnosis is challenging. The management includes supportive care, gastric decontamination, correction of acid-base disorders, and hemodialysis. The understanding of the metabolic processes related to DEG poisoning may contribute to its management, preventing death, serious sequels, or irreversible lesions., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: To estimate the prevalence of undiagnosed diabetes and suboptimally controlled diabetes and the associated risk factors by community screening in India., Methods: In this multi-centre, cross-sectional study, house-to-house screening was conducted in people aged ≥40 years in urban and rural areas across 10 states and one union territory in India between November 2018 and March 2020. Participants underwent anthropometry, clinical and biochemical assessments. Capillary random blood glucose and point-of-care glycated haemoglobin (HbA 1c ) were used to diagnose diabetes. The prevalence of undiagnosed diabetes and suboptimal control (HbA 1c ≥53 mmol/mol [≥7%]) among those with known diabetes was assessed., Results: Among the 42,146 participants screened (22,150 urban, 19,996 rural), 5689 had known diabetes. The age-standardised prevalence of known diabetes was 13.1% (95% CI 12.8-13.4); 17.2% in urban areas and 9.4% in rural areas. The age-standardised prevalence of undiagnosed diabetes was 6.0% (95% CI 5.7-6.2); similar in both urban and rural areas with the highest proportions seen in the East (8.0%) and South (7.8%) regions. When we consider all people with diabetes in the population, 22.8% of individuals in urban areas and 36.7% in rural areas had undiagnosed diabetes. Almost 75% of the individuals with known diabetes had suboptimal glycaemic control., Conclusions: High prevalence of undiagnosed diabetes and suboptimally controlled diabetes emphasises the urgent need to identify and optimally treat people with diabetes to reduce the burden of diabetes., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: National and subnational estimates of the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy (VTDR) are needed to inform the stepwise implementation of systematic retinal screening for people with diabetes in India to decrease the rate of blindness. We aimed to assess these national and subnational estimates and to stratify the prevalence of diabetic retinopathy and VTDR on the basis of people with known versus undiagnosed diabetes, urban versus rural residence, and epidemiological transition level (ETL) and Socio-demographic Index (SDI) categories of states., Methods: We did a multicentre cross-sectional screening study for diabetic retinopathy using a complex cluster sampling design in people aged 40 years or older in ten Indian states and one union territory between Dec 20, 2018, and March 20, 2020. We did non-mydriatic retinal screening and assessed risk factor burden for people with diabetes. We estimated nationally weighted prevalence of diabetic retinopathy and VTDR for individuals with known and undiagnosed diabetes by urban versus rural residence, and by state categorisation by ETL and SDI. We also assessed adjusted risk factors., Findings: From 42 146 participants screened, 7910 (18·8%) were identified to have diabetes. Of these, 6133 (77·5%; 4350 with known diabetes and 1783 with undiagnosed diabetes) had gradable retinal images. 3411 (56%) participants were women and 2722 (44%) were men, and the median age was 56 years (IQR 49-65). The estimated national prevalence was 12·5% (95% CI 11·0-14·2) for diabetic retinopathy and 4·0% (3·4-4·8) for VTDR, with no significant differences between urban and rural residence for diabetic retinopathy. Compared with individuals with undiagnosed diabetes, we observed a higher prevalence of diabetic retinopathy (15·5% [13·4-17·8] vs 8·0% [6·3-10·1]) and VTDR (5·3% [4·5-6·3] vs 2·4% [1·6-3·6]) in individuals with known diabetes. The prevalence was significantly lower in low ETL-SDI states compared with high and middle ETL-SDI states for diabetic retinopathy (by 7·0%, 1·9-12·2, p=0·024) and VTDR (by 4·8%, 3·0-6·6, p<0·0001). Hyperglycaemia was the strongest modifiable risk factor., Interpretation: We estimate that, in absolute numbers, approximately 3 million people aged 40 years or older have VTDR in India, with a higher prevalence in those with known diabetes residing in high and middle ETI-SDI states., Funding: UKRI Global Challenge Research Fund., Competing Interests: Declaration of interests SS reports consultancy and payments for lectures from Bayer, Boehringer Ingelheim, Novartis, Oxurion, Roche, Allergan, and Apellis, outside the submitted work. ATP reports payment for a trial design lecture from Bayer and for membership of a trial data monitoring committee from Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of this study was to evaluate the clinical outcome at 5-year follow-up of a one-step procedure combining anterior cruciate ligament (ACL) reconstruction and partial meniscus replacement using a polyurethane scaffold for the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy. Moreover, the implanted scaffolds have been evaluated by MRI protocol in terms of morphology, volume, and signal intensity., Methods: Twenty patients with symptomatic knee laxity after failed ACL reconstruction and partial medial meniscectomy underwent ACL revision combined with polyurethane-based meniscal scaffold implant. Clinical assessment at 2- and 5-year follow-ups included VAS, Tegner Activity Score, International Knee Documentation Committee (IKDC), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lysholm Score. MRI evaluation of the scaffold was performed according to the Genovese scale with quantification of the scaffold's volume at 1- and 5-year follow-ups., Results: All scores revealed clinical improvement as compared with the preoperative values at the 2- and 5-year follow-ups. However, a slight, but significant reduction of scores was observed between 2 and 5 years. Concerning the MRI assessment, a significant reduction of the scaffold's volume was observed between 1 and 5 years. Genovese Morphology classification at 5 years included two complete resorptions (Type 3) and all the remaining patients had irregular morphology (Type 2). With regard to the Genovese Signal at the 5-year follow-up, three were classified as markedly hyperintense (Type 1), 15 as slightly hyperintense (Type 2), and two as isointense (Type 1)., Conclusion: Simultaneous ACL reconstruction and partial meniscus replacement using a polyurethane scaffold provides favourable clinical outcomes in the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy at 5 years. However, MRI evaluation suggests that integration of the scaffold is not consistent., Level of Evidence: Level IV., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Purpose: People with diabetes and Charcot arthropathy have higher mortality than people with diabetes without this complication. Are the causes of this higher mortality exclusively infectious or of a cardiovascular origin? We aimed to study aspects related to cardiovascular risk and inflammation in a population of people with type 2 diabetes with and without Charcot arthropathy., Methods: A cross-sectional study was performed in people with diabetes and Charcot Eickenholtz III arthropathy, matched for sex and age, with two groups of people with diabetes without Charcot arthropathy with and without peripheral sensory-motor neuropathy, in the absence of active infection. All participants underwent clinical and laboratory evaluation at the time of the interview, and their cardiovascular risk was calculated according to the United Kingdom Prospective Diabetes Study (UKPDS) calculator., Results: We evaluated 69 people with type 2 diabetes (21 with Charcot arthropathy, 24 with diabetic peripheral neuropathy and 24 without this neuropathy), with a mean age between 57 and 61 years and with a diabetes duration of more than 10 years. Patients with Charcot arthropathy had a longer duration of diabetes; more frequency of dyslipidemia; and higher levels of uric acid, microalbuminuria and C-reactive protein than the other two groups. A total of 73.9% of the people evaluated had high or very high cardiovascular risk according to the UKPDS score., Conclusion: The people with type 2 diabetes presenting Charcot arthropathy had greater values of systemic inflammatory parameters, even in the chronic phase of the complication, with a higher risk of mortality unrelated to infections., Competing Interests: Conflicts of interestWe declare that we had no personal, academic or financial conflicts of interest in the preparation of this article., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2022.)