International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Malignant upgrade rate and associated clinicopathologic predictors for concordant intraductal papilloma without atypia: A systematic review and meta-analysis.

Previously reported upgrade rates for benign breast intraductal papilloma (IDP) are widely variable. However, many previous studies have failed to consider radiologic-pathologic discordance of lesions. This review aims to synthesize malignant upgrade data for benign, concordant IDP at surgical excision. Thirteen studies were included in our meta-analysis. The pooled estimate for percentage underestimation of carcinoma was 1.4% (95% CI: 0.8%-2.0%). We conclude that these lesions can be safely managed by active surveillance.

Adding a Gene Expression Profile Test to Aid Differential Diagnosis and Treatment in Aggressive Large B-Cell Lymphoma: An Early Exploratory Economic Evaluation.

BACKGROUND AND OBJECTIVE: Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq® technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.) adding bortezomib to R-CHOP therapy (RB-CHOP). This study aims to estimate the potential impact of a GEP test on costs and health outcomes to inform pricing and evidence generation strategies. METHODS: Three decision models were developed comparing diagnostic strategies with and without GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from a recent clinical trial, literature and expert opinion. We estimated the maximum price of the test using a threshold of Great Britain Pound (GBP) 30,000 per quality-adjusted life-year (QALY). Sensitivity analyses were conducted. RESULTS: The estimated maximum threshold price for a combined test to be cost effective is GBP 15,352. At base-case values, the BL signature delivers QALY gains of 0.054 at an additional cost of GBP 275. This results in a net monetary benefit at a threshold of GBP 30,000 per QALY of GBP 1345. For PMBCL, the QALY gain was 0.0011 at a cost saving of GBP 406 and the net monetary benefit was GBP 437. The hazard ratio for the impact of treating BL less intensively must be at least 1.2 for a positive net monetary benefit. For identifying patients with the DLBCL subtype responsive to bortezomib, QALY gain was 0.2465 at a cost saving of GBP 6175, resulting in a net monetary benefit of GBP 13,570. In a probabilistic sensitivity analysis using 1000 simulations, a testing strategy was superior to a treat all with R-CHOP strategy in 81% of the simulations and with a cost saving in 92% assuming a cost price of zero. CONCLUSIONS: Our estimates show that the combined test has a high probability of being cost effective. There is good quality evidence for the benefit of subtyping DLBCL but the evidence on the number of patients reclassified to or from BL and PMBCL and the impact of a more precise diagnosis and the cost of treatment is weak. The developers can use the price estimate to inform a return on investment calculations. Evidence will be required of how well the TempO-Seq® technology performs compared to the testing GEP technology used for subtyping in the recent clinical trial. For BL and PMBCL elements of the test, evidence would be required of the number of patients reclassified and improved costing information would be useful. The diagnostic and therapeutic environment in haematological malignancies is fast moving, which increases the risk for developers of diagnostic tests.

'ACOPP' chemotherapy for older and less fit patients with Hodgkin lymphoma-A multicentre, retrospective study.

Management of classical Hodgkin lymphoma in older patients is challenging due to poor tolerance of the chemotherapy regimens used in younger patients. We modified the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone), whereby bleomycin and etoposide were removed and cyclophosphamide dose was reduced, for older patients with co-morbidities. Here we present data from the first 41 patients treated with 'ACOPP' across 3 centres, demonstrating that it can be delivered, with a favourable toxicity profile (TRM 2%) and promising efficacy (2-year PFS and OS, 73% (95% CI: 52-94) and 93% (95% CI: 80-100) respectively).

The role of preoperative vitamin D and calcium in preventing post-thyroidectomy hypocalcaemia: a systematic review.

BACKGROUND: The thyroid gland plays an important endocrine function regulating metabolism, growth and development. A variety of benign and malignant conditions necessitate surgical removal of the thyroid gland, either in its entirety, or partially. Thyroidectomy is the most commonly undertaken endocrine surgery. Hypocalcaemia, occurring at a rate of approximately 25%, is the most common complication following total thyroidectomy. Hypocalcaemia can increase healthcare costs requiring further investigations, treatment and delaying discharge. Severe hypocalcaemia can be potentially life threatening. It has been demonstrated that routine post-operative supplementation with Vitamin D and calcium, can reduce post-operative hypocalcaemia, at present it is unclear whether preoperative supplementation has a similar effect. METHODS: This systematic review includes randomised controlled trials on human adult subjects, who received preoperative Vitamin D and/or calcium, and which studied the effect on post-operative hypocalcaemia following total or near total thyroidectomy. There were no restrictions in respect of post-operative supplementation regimen. Studies were limited to those published in English. RESULT: Seven of the eleven trials demonstrated a reduction in either laboratory or clinical hypocalcaemia with preoperative supplementation. This benefit was most likely to be seen when postoperative supplementation was performed on an as needed basis. IV calcium was required to treat resistant or severe hypocalcaemia, in five of the eleven trials, in each of these five trials, rates of IV replacement were lower in the preoperative supplementation group. CONCLUSION: The use of preoperative Vitamin D, with or without calcium, may provide a modest reduction in the incidence of laboratory and clinic hypocalcaemia following total or near total thyroidectomy. There is a trend toward a reduced requirement for IV calcium with preoperative supplementation. Larger robust randomised trials are needed to provide a definitive answer. Preoperative supplementation can be considered in patients undergoing total or near total thyroidectomy.

Automated image curation in diabetic retinopathy screening using deep learning.

Diabetic retinopathy (DR) screening images are heterogeneous and contain undesirable non-retinal, incorrect field and ungradable samples which require curation, a laborious task to perform manually. We developed and validated single and multi-output laterality, retinal presence, retinal field and gradability classification deep learning (DL) models for automated curation. The internal dataset comprised of 7743 images from DR screening (UK) with 1479 external test images (Portugal and Paraguay). Internal vs external multi-output laterality AUROC were right (0.994 vs 0.905), left (0.994 vs 0.911) and unidentifiable (0.996 vs 0.680). Retinal presence AUROC were (1.000 vs 1.000). Retinal field AUROC were macula (0.994 vs 0.955), nasal (0.995 vs 0.962) and other retinal field (0.997 vs 0.944). Gradability AUROC were (0.985 vs 0.918). DL effectively detects laterality, retinal presence, retinal field and gradability of DR screening images with generalisation between centres and populations. DL models could be used for automated image curation within DR screening.

Isolated soft tissue mass of the finger as the first presentation of oligometastatic renal cell carcinoma.

A man in his 70s was referred to plastic surgery with a suspected foreign body in the pulp of his right index finger. An excisional biopsy was performed for a presumed foreign body granuloma. Histology revealed metastatic renal cell carcinoma (mRCC). CT imaging demonstrated a 7.4 cm heterogeneous mass arising from the upper pole of the left kidney consistent with primary renal malignancy, in addition to a 9 mm lung nodule. He underwent an uncomplicated left laparoscopic cytoreductive nephrectomy and made a satisfactory recovery. To our knowledge, this is the first reported case of primary mRCC presenting with digital soft tissue metastasis. Cytoreductive nephrectomy with metastasectomy is the preferred management for mRCC where feasible. For unfavourable mRCC cases, first-line systemic therapy is indicated. Adjuvant systemic therapy in mRCC is currently limited to clinical trials, though promising data emerging on the use of pembrolizumab may herald a future shift in practice.

Effect of energy metabolism and proteolysis on the toughness of intermediate ultimate pH beef.

The objective of this study was to identify the tenderness and energy metabolism attributes in normal ultimate pH (pHu, 5.4-5.8, NpHu), intermediate pHu (5.8-6.2, IpHu) and high pHu (> 6.2, HpHu) Longissimus lumborum from beef. During 21 days of aging, the IpHu group exhibited a higher Warner-Bratzler shear force, lower activity of µ-calpain, and a higher content of heat shock protein 27 and greater protein oxidation. Metabolomics analysis revealed that 24 differential metabolites were detected during the first 24 h postmortem between pH groups, and these were mainly the products of glycolysis, the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. The relatively higher adenosine triphosphate content in the IpHu group could delay tenderization by being used as key substrate for protein phosphorylation. In addition, the relationship between guanosine triphosphate, diphosphate and monophosphate, and beef tenderness was worthy to be verified in the future study.

Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial.

OBJECTIVE: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). DESIGN: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. RESULTS: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. CONCLUSIONS: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG. TRIAL REGISTRATION NUMBER: NCT02879383.

Analysis of driving simulator performance for post-call orthopaedic surgery residents.

PURPOSE: Despite the associations between workhours, fatigue and motor vehicle accidents, driving abilities for residents post-call have been infrequently analysed. Our purpose was to compare orthopaedic surgery resident performance on a driving simulator after a night of call compared with their baseline. STUDY DESIGN: All residents from a single orthopaedic programme were asked to complete baseline and post-call driving simulator assessments and surveys. The primary outcome measure was brake reaction time (BRT) and secondary outcome measures included lane variance, speed variance and accidents on the driving simulator. RESULTS: All 19 orthopaedic residents agreed to participate. Compared with the baseline assessment, residents demonstrated significantly higher levels of sleepiness on the Stanford Sleepiness Scale post-call (1.6 vs 3.4; p<0.0001). Despite higher levels of fatigue post-call, there was no statistically significant differences between baseline and post-call assessments for mean BRT, accidents, lane variation and speed variation. CONCLUSIONS: These data suggest that for orthopaedic residents, driving simulator performance does not appear to be worse after a single night of call compared with baseline. Future collaborative, multicentre investigations on post-call driving safety that incorporate different call types and frequencies are necessary to better define the impact of post-call fatigue on driving performance. Recognising that motor vehicle accidents remain the leading cause of death for people under the age of 30 years, these continued areas of study are necessary to truly establish a culture of resident safety.

Total volatile basic nitrogen and trimethylamine in muscle foods: Potential formation pathways and effects on human health.

The use of total volatile basic nitrogen (TVB-N) as a quality parameter for fish is rapidly growing to include other types of meat. Investigations of meat quality have recently focused on TVB-N as an index of freshness, but little is known on the biochemical pathways involved in its generation. Furthermore, TVB-N and methylated amines have been reported to exert deterimental health effects, but the relationship between these compounds and human health has not been critically reviewed. Here, literature on the formative pathways of TVB-N has been reviewed in depth. The association of methylated amines and human health has been critically evaluated. Interventions to mitigate the effects of TVB-N on human health are discussed. TVB-N levels in meat can be influenced by the diet of an animal, which calls for careful consideration when using TVB-N thresholds for regulatory purposes. Bacterial contamination and temperature abuse contribute to significant levels of post-mortem TVB-N increases. Therefore, controlling spoilage factors through a good level of hygiene during processing and preservation techniques may contribute to a substantial reduction of TVB-N. Trimethylamine (TMA) constitutes a significant part of TVB-N. TMA and trimethylamine oxide (TMA-N-O) have been related to the pathogenesis of noncommunicable diseases, including atherosclerosis, cancers, and diabetes. Proposed methods for mitigation of TMA and TMA-N-O accumulation are discussed, which include a reduction in their daily dietary intake, control of internal production pathways by targeting gut microbiota, and inhibition of flavin monooxygenase 3 enzymes. The levels of TMA and TMA-N-O have significant health effects, and this should, therefore, be considered when evaluating meat quality and acceptability. Agreed international values for TVB-N and TMA in meat products are required. The role of feed, gut microbiota, and translocation of methylated amines to muscles in farmed animals requires further investigation.

Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection.

Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.

Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery.

The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.

The effect of whole carcase medium voltage electrical stimulation, tenderstretching and longissimus infusion with actinidin on alpaca meat quality.

The effect on alpaca meat quality from applying medium voltage electrical stimulation (ES) in combination with tenderstretching (TS; pubic symphysis suspended) to whole carcases was investigated, along with the effect of actinidin infusion on alpaca longissimus (LTL) quality. Carcases (n = 36) were allocated to either no ES + achilles hung; or ES + TS. The left- and right-hand side LTL of each carcase was allocated to one of three infusion treatments; no infusion (control), infusion with water or infusion with enzyme. Processing treatments reduced LTL and semimembranosus shear force without negatively impacting colour or oxidation traits. Infusion with enzyme reduced LTL shear force relative to control and water treatments but resulted in reduced consumer acceptance. The use of TS with ES in commercial alpaca processing is supported. There was no advantage to infusing alpaca LTL with actinidin as results indicate a net negative effect on consumer acceptance of this novel meat.

Is Less Actually More? An Evaluation of Surgical Outcomes Between Endoscopic Suturectomy and Open Cranial Vault Remodeling for Craniosynostosis.

BACKGROUND: Both open cranial vault remodeling (CVR) and endoscopic suturectomy are effective in treating the anatomical deformity of craniosynostosis. While parents are increasingly knowledgeable about these 2 treatment options, information regarding the perioperative outcomes remains qualitative. This makes preoperative counseling regarding surgical choices difficult. The purpose of this study was to evaluate the outcomes in patients with craniosynostosis who underwent traditional CVR versus endoscopic suturectomy. METHODS: Open and endoscopic craniosynostosis surgeries performed at our institution from January 2014 through December 2018 were retrospectively reviewed and perioperative data, including operative time, estimated blood loss, transfusion rate and length of stay, was analyzed. A student t test was used with significance determined at P < 0.05. RESULTS: CVR was performed for 51 children while 33 underwent endoscopic procedures. Endoscopic suturectomy was performed on younger patients (3.8 versus 14.0 months, P < 0.001), had shorter operative time (70 versus 232 minutes, P < 0.001), shorter total anesthesia time (175 versus 352 minutes, P < 0.001), lower estimated blood loss (10 versus 28 ml/kg, P < 0.001), lower percentage transfused (42% versus 98%, P < 0.001), lower transfusion volume (22 versus 48 ml/kg, P < 0.001), and shorter length of stay (1.8 versus 4.1 days, P < 0.001) when compared to open CVR. CONCLUSION: Both open CVR and endoscopic suturectomy are effective in treating deformities due to craniosynostosis. The endoscopic suturectomy had significantly shorter operative and anesthesia time as well as overall and PICU length of stay. CVR was associated with greater intraoperative blood loss and more frequently required higher rates of blood transfusions.

Association Between HEDIS Performance and Primary Care Physician Age, Group Affiliation, Training, and Participation in ACA Exchanges.

BACKGROUND: There are a limited number of studies investigating the relationship between primary care physician (PCP) characteristics and the quality of care they deliver. OBJECTIVE: To examine the association between PCP performance and physician age, solo versus group affiliation, training, and participation in California's Affordable Care Act (ACA) exchange. DESIGN: Observational study of 2013-2014 data from Healthcare Effectiveness Data and Information Set (HEDIS) measures and select physician characteristics. PARTICIPANTS: PCPs in California HMO and PPO practices (n = 5053) with part of their patient panel covered by a large commercial health insurance company. MAIN MEASURES: Hemoglobin A1c testing; medical attention nephropathy; appropriate treatment hypertension (ACE/ARB); breast cancer screening; proportion days covered by statins; monitoring ACE/ARBs; monitoring diuretics. A composite performance measure also was constructed. KEY RESULTS: For the average 35- versus 75-year-old PCP, regression-adjusted mean composite relative performance scores were at the 60th versus 47th percentile (89% vs. 86% composite absolute HEDIS scores; p < .001). For group versus solo PCPs, scores were at the 55th versus 50th percentiles (88% vs. 87% composite absolute HEDIS scores; p < .001). The effect of age on performance was greater for group versus solo PCPs. There was no association between scores and participation in ACA exchanges. CONCLUSIONS: The associations between population-based care performance measures and PCP age, solo versus group affiliation, training, and participation in ACA exchanges, while statistically significant in some cases, were small. Understanding how to help older PCPs excel equally well in group practice compared with younger PCPs may be a fruitful avenue of future research.

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study.

BACKGROUND: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. METHODS: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. RESULTS: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. CONCLUSIONS: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. TRIAL REGISTRATION NUMBER: NCT02413567.