The Northern General Hospital is a large teaching hospital and Major Trauma Centre in Sheffield, England. Its departments include Accident and Emergency for adults, with children being treated at the Sheffield Children's Hospital on Western Bank. The hospital is managed by the Sheffield Teaching Hospitals NHS Foundation Trust.
BACKGROUND:Implantation of drug eluting stents (DESs) is currently the default approach for percutaneous coronary interventions, but long-term adverse events still exist. An approach with minimal stenting deserves to be assessed in a randomized trial. We studied a novel sirolimus-eluting balloon (SEB) that elutes sirolimus over a 90-day period using a biodegradable polymer microreservoir technology. METHODS:In a multicenter, open-label, randomized trial, we compared an SEB-based strategy with provisional DES with one of systematic DES for de novo lesions in coronary arteries between 2 and 5 mm in diameter. Subjects were randomized 1:1 before percutaneous coronary intervention. The primary end point was target vessel failure, a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization. It was tested for noninferiority at 1 year with the use of an absolute margin equal to 50% of the combined event rate at a significance level of 0.025. The primary analysis population included all randomized subjects with completed or attempted percutaneous revascularization, analyzed according to the intention-to-treat principle. A sensitivity analysis was performed on the per-protocol population. RESULTS:Between August 27, 2021, and July 29, 2024, 3323 participants were randomized and treated in 62 sites. Among 1661 participants in the SEB strategy group, bailout stenting was performed in 343 (20.7%). Target vessel failure occurred over 365 days in 88 (5.3%) and 73 (4.4%) participants in the SEB and the systematic DES strategy groups, respectively (risk difference, 0.91% [95% CI -0.55% to 2.38%]; 1-sided P=0.02 for noninferiority with a 2.44% noninferiority margin). Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group (3.3% versus 2.1%; risk difference, 1.22% [95% CI, 0.11%-2.33%). Safety events, including lesion thrombosis, were low and similar in both groups. Although the results of the per-protocol population (3194 participants, 96%) did not confirm noninferiority (upper boundary of the 95% CI, 2.63; P=0.04), they were similar to the intention-to-treat results in both magnitude and direction. CONCLUSIONS:At 1 year, in the primary intention-to-treat analysis population, a strategy of percutaneous coronary intervention with SEB and provisional DES was noninferior to the systematic use of DES for the primary end point of target vessel failure. The per-protocol population sensitivity analysis did not confirm noninferiority. Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group. At 5 years, target vessel failure will be tested again for noninferiority and for superiority if noninferiority is achieved. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04859985.
With the global rise in diabetes prevalence, the burden of diabetic kidney disease (DKD) is projected to escalate substantially, contributing to increased morbidity, mortality, and healthcare costs. This narrative review aims to synthesize contemporary evidence on guideline-directed medical therapy (GDMT) for DKD, with a specific focus on primary prevention, secondary prevention, and real-world implementation of evidence-based pharmacologic and non-pharmacologic strategies to mitigate renal and cardiovascular risk. A comprehensive literature review (published 2012-2025) was conducted, integrating international clinical guidelines, landmark randomized controlled trials, meta-analyses, and implementation studies addressing the prevention and management of DKD. Recent advances in GDMT have reshaped the therapeutic landscape of DKD. Lifestyle interventions - including dietary optimization, regular physical activity, and smoking cessation - demonstrate meaningful renoprotective and cardiometabolic benefits. Pharmacologic therapies, such as renin-angiotensin system (RAS) blockade, sodium-glucose co-transporter 2 (SGLT2) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (MRAs), and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have shown robust efficacy in reducing albuminuria, slowing estimated glomerular filtration rate (eGFR) decline, and lowering cardiovascular events. Landmark trials report relative risk reductions of approximately 30-40% in kidney disease progression with SGLT2 inhibitors and 18-23% reductions in renal and cardiovascular composite outcomes with finerenone and GLP-1 RAs. Despite strong guideline endorsement, real-world uptake of GDMT remains suboptimal, particularly in low-resource healthcare settings. Early detection through routine eGFR and urine albumin-to-creatinine ratio screening, combined with timely initiation and sustained implementation of GDMT, offers the most effective strategy to alter the natural history of DKD. Integrating lifestyle modification with optimized pharmacotherapy is essential to reducing long-term renal and cardiovascular complications.
BACKGROUND:Complete mesocolic excision (CME) has been proposed as a refinement of oncological surgery for right-sided colon cancer, aiming to improve specimen quality, lymph node yield and oncological outcomes. However, its routine adoption remains controversial due to uncertainty regarding oncological benefit and concerns relating to technical complexity, training and service delivery. This position statement from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) examines the contemporary evidence surrounding CME and its role within modern management of right-sided colon cancer. METHODS:This position statement was produced by the authors who represent a range of views on CME surgery. It synthesises contemporary evidence from large cohort studies, recent randomised control trials and international guidelines to evaluate the role of CME compared with standard high-quality right hemicolectomy. RESULTS:CME is consistently associated with higher lymph node yields and improved specimen metrics, but studies demonstrating a definitive survival advantage remain limited. Randomised evidence does not support routine CME for all patients, although potential benefit exists in selected high-risk groups. Recent evidence suggests that surgical plane quality, rather than the extent of lymphadenectomy, may be the principal determinant of oncological outcomes. CME is technically demanding and may carry increased procedural risks, particularly related to central vascular dissection, although these may be mitigated through structured training and optimised perioperative planning. CONCLUSION:Routine use of CME for all right-sided colon cancers is not supported by current evidence. Standard high-quality right hemicolectomy should remain the default approach for most patients. Selective use of CME may be appropriate in physiologically fit patients with high-risk or anatomically complex disease, delivered within experienced units with appropriate training, audit and quality assurance frameworks. Future progress will depend on standardisation of surgical technique, objective assessment of specimen quality and biologically tailored treatment strategies.
One of the most common interventions in the ED and ICU to restore physiologic homeostasis is fluid administration. It is essential for the intensivists and ED physicians to be aware of the physiological characteristics of different fluids and the potential harm associated with their use. In this article, we explore the physiology and pathophysiology of fluid administration in humans, emphasizing how fluid administration can alter acid-base balance, perfusion, osmotic and oncotic pressures, immunologic and inflammatory responses, and hemodynamics. We also discuss fluid resuscitation strategies across common clinical scenarios, such as septic shock, diabetic ketoacidosis, rhabdomyolysis, acute pancreatitis, and acute brain injury. The most recent guidelines, clinical trials, and observational studies on fluid resuscitation were discussed and critically analyzed. We also discussed fluid management in high-risk populations, such as patients with end-stage renal disease or congestive heart failure, who are particularly susceptible to hypervolemia.
AIMS:After the relocation of paediatric spinal surgery services between specialist centres within the same region, monetary rebates for spinal procedures declined, despite consistent case volumes. A long-term quality improvement initiative was undertaken to enhance coding accuracy and ensure correct remuneration. METHOD:A five-year quality improvement project, consisting of three cycles, was undertaken to assess paediatric spinal procedures and related coding practices. Procedures were reviewed and given "optimal" codes by clinicians from the spinal deformity team, and mock rebates were generated. These were compared to actual codes and rebate values from the new site. Meetings were held with lead coders at the new site, and instruction was provided on how to more accurately code spinal procedures. A spinal coding operation manual with lay descriptions of spinal procedures and coding advice was developed. RESULTS:Rebate accuracy rose from 82.16% to 98.40% over the course of the project (p = 0.007). The mean difference between actual and optimal coding rebate fell from -£4,243.16 to -£264.42. The overall accuracy of clinical coding rose from 37.8% to 70.0% (p = 0.003). CONCLUSIONS:This long-term quality improvement project significantly increased the accuracy of clinical coding for paediatric spinal procedures and, when extrapolated to a mean of 150 cases per year, has generated an annual saving of approximately £596,811.00 for the site. This methodology can be easily replicated in institutions facing similar issues.
