Outcomes of emergency laparoscopy in the elderly.

INTRODUCTION: This paper assessed the association between operative approach and postoperative in-hospital mortality in elderly patients undergoing emergency abdominal surgery. Patients undergoing emergency laparotomy have high morbidity and mortality rates. One-third of patients requiring emergency surgery are over 75 years old, and their in-hospital mortality rate exceeds 17%. Fewer than 20% of emergency abdominal operations in the UK are attempted laparoscopically, and only 10% are completed laparoscopically. Little is known about how laparoscopic emergency surgery in the elderly might affect outcomes. METHODS: An observational UK study was performed using the prospectively maintained National Emergency Laparotomy Audit (NELA) database. Operative approach, NELA risk-prediction score and in-hospital mortality were recorded. The effect of operative approach on in-hospital mortality was analysed, both on a national basis and in a high-volume laparoscopic centre. RESULTS: A total of 47,667 patients were included in the study, of whom 15,068 were over 75 years of age. Nationally, surgery was completed by the laparoscopic approach in 7.8% of patients aged over 75; both crude mortality (9.2%) and risk-adjusted mortality (7.1%) were significantly reduced (p<0.0001). In our unit, surgery was completed laparoscopically in 48.4% of patients aged over 75; both crude mortality (6.6%) and risk-adjusted mortality (3.3%) were significantly reduced (p<0.0001). CONCLUSION: Laparoscopy in emergency surgery has been shown in this study to significantly reduce in-hospital mortality in elderly patients and should be embraced in every centre dealing with emergency abdominal surgery.

Geographic disparities in performance of pediatric polysomnography to diagnose obstructive sleep apnea in a universal access health care system.

BACKGROUND: Diagnostic polysomnography (PSG) is recommended prior to adenotonsillectomy (AT) for children with obstructive sleep apnea (OSA) and certain high-risk characteristics, but resource limitations often prevent this practice. OBJECTIVE: We performed a population-based assessment of children across Ontario, Canada to describe and quantify disparities in PSG. METHODS AND MATERIALS: This retrospective cohort study was performed using provincial health administrative data held at ICES. We identified children 0-10 years old who underwent PSG and AT between 2009 and 2018, and those with a PSG within 18 months prior to and/or 12 months following AT. We calculated the odds of PSG prior to/following AT after adjustment for demographics, medical comorbidities, geographic and socioeconomic characteristics. Our main predictor was driving time/distance to the nearest pediatric sleep centre ascertained using spatial analysis and geographic information systems. RESULTS: We identified 27,837 children <10 years old who underwent AT for OSA in Ontario. Only 12.8% had a PSG within 18 months prior and 5.7% had a PSG within 12 months following AT. Shorter driving time/distance, older age, male sex and certain comorbidities were associated with increased odds of PSG. CONCLUSION: Only a small proportion of children in our cohort underwent PSG prior to or following AT surgery despite universal access to healthcare. This study suggests a need to increase overall PSG access, particularly for those living distant from existing pediatric sleep centres. Future studies could determine if increased PSG testing in 'underserviced areas' would reduce overall surgery rates and/or improve health outcomes.

Clinical frailty and its effect on the septuagenarian population after emergency laparotomy.

INTRODUCTION: The UK has an ageing population with an increased prevalence of frailty in the over 70s. Emergency laparotomy for acute intra-abdominal pathology is increasingly offered to this population. This can challenge decision making and information given to patients should not only be based on mortality outcomes but on relative expected quality of life and change to frailty syndromes. MATERIALS AND METHODS: This was a single site National Emergency Laparotomy Audit (NELA)-based retrospective cohort audit for consecutive cases in the septuagenarian population assessing mortality, length of stay outcome and subjective postoperative functioning. Follow-up was conducted between one and two years postoperatively to determine this. RESULTS: Some 153 patients were identified throughout the single site NELA database. Median age was 79 years with a ratio of 1.7 men to women. Median rate of all-cause mortality was 35.3% at the median follow-up of 19 months. Median time from admission to death was 120 days. Of those who had died by the time of follow-up, significant preoperative indicators included clinical frailty scale (p < 0.0001), preoperative P-POSSUM (mortality). At follow-up, 35% responded to a quality of life follow-up. This revealed a decline in mid-term physical functioning, lower energy, higher fatigue and reduction in social functioning. There was also an increase in pre- and postoperative clinical frailty scale score. CONCLUSION: In the septuagenarian-plus population it is important to consider not only risk stratification with mortality scoring (P-POSSUM or NELA-adjusted risk), but to take into account frailty. Postoperative rehabilitation and careful recovery is paramount. Where possible, during the counselling and consent for emergency laparotomy, significant postoperative long-term deterioration in physical, emotional and social function should be considered.

Clinical outcomes after increasing bladder outlet resistance without augmentation cystoplasty in neurogenic bladder.

INTRODUCTION: Patients with neurogenic bladder (NGB) and urinary incontinence (UI) due to low bladder outlet resistance may require bladder neck procedures (BNPs) to achieve continence. These patients may also have reduced bladder capacity and or elevated detrusor storage pressures that require augmentation cystoplasty (AC). AC is not without complications that include risks for bladder rupture, urolithiasis, urinary tract infections and metabolic issues. Avoidance of AC would be helpful in patients with neurogenic urinary incontinence that have safe bladder parameters in the setting of low bladder outlet resistance. OBJECTIVE: To determine if pre-operative urodynamics could select children with NGBs and UI for isolated BNPs without AC. Additionally we sought to determine the safety of BNPs without AC and future need of AC with long-term follow-up. STUDY DESIGN: This is an IRB-approved retrospective analysis of all patients undergoing BNPs for management of neurogenic UI over a 17-year period. We separated these BNP patients into two groups: No AC + BNP (Group 1) vs. AC + BNP (Group 2). Our primary analyses focused on postoperative outcomes for patients in Group 1. Outcomes assessed included additional surgical procedures, urodynamic changes, development of CKD, new hydronephrosis (HDN) and vesicoureteral reflux (VUR). Secondary analysis included the timeline for the development of any bladder deterioration that necessitated AC in Group 1. RESULTS: 93 patients underwent BNP at a mean age of 10.8 years. Thirty did not have AC at the time of surgery (Group 1). These children had larger (p < 0.001) and more compliant (p < 0.001) bladders than Group 2 having simultaneous augmentation. At 6 years mean follow-up in Group 1 patients, three developed new reflux and three had new hydronephrosis. Nine (30%) had additional continence procedures. Twelve required (40%) AC at a mean of 23 months after the initial BNP. No patients had AC after 5 years. Detrusor end filling pressure increased 14.8 cm H2O (p = 0.028) and expected bladder capacity decreased 26.1% (p = 0.005) after isolated BNP. DISCUSSION: We found that from our cohort of patients who had normal bladder compliance and normal/near normal expected capacity preoperatively 40% required subsequent AC. We were unable to find pre-operative clinical parameters which predicted failure or conversion to AC. We found that 43.3% of our BNP without AC patients had no subsequent invasive procedures with mean 6-year follow-up. We found that none of our patients developed any degree of CKD. Finally, we found that the majority of patients that converted to AC after their BNP did so within the first 2 years after their initial BNP and no patients required augmentation 5 years post their initial BNP. This data validates that these patients require very strict follow up, particularly in the first 5 years after surgery. CONCLUSIONS: BNP without AC is safe in only a few selected patients with NGB. Despite preoperative selection, there are significant changes in bladder dynamics and 40% required subsequent augmentation. Bladder deterioration occurs early and generally in the first 2 years. Since there are no apparent reliable pre-operative variables predicting the need for subsequent AC, parents should be counseled regarding vigilant post-operative follow-up.

Technique and outcome of day case laparoscopic hiatus hernia surgery for small and large hernias: a five-year retrospective review from a high-volume UK centre.

INTRODUCTION: Laparoscopic anti-reflux surgery is the standard surgical treatment for gastro-oesophageal reflux disease in patients for who long-term pharmacotherapy is intolerable or ineffective. Advances in anaesthesia and minimally invasive surgery have led to day case treatment being adopted by some centres. The objective of this study is to describe our day case pathway and peri- and postoperative outcomes. MATERIALS AND METHODS: This is a single centre, retrospective case series review of a prospectively collected database from October 2014 to August 2019 performed in a tertiary centre for upper gastrointestinal surgery. Data collected included demographics, comorbidities, indications, complications, length of stay and readmission. RESULTS: A total of 362 patients underwent laparoscopic anti-reflux surgery with or without hiatus hernia repair of up to 10cm, with day case rates of 59%. Unplanned admission following day surgery was 5.1% (13/225) and 30-day readmission was 2.2% (8/362); 90.6% of patients remained in hospital for less than 24 hours. There was one intraoperative complication and one patient required revisional surgery within 30 days. The rate of all postoperative complications was 1.38% (5/362) with one postoperative mortality. DISCUSSION: The inclusion of larger hernias is unusual, as most studies limit size to 5cm or less. Our results show the safety and feasibility of the procedure even when applied to hiatus hernias up to 10cm. Success was multifactorial and based on standardisation of procedures and support from dedicated specialist nursing staff. CONCLUSION: Laparoscopic anti-reflux surgery can be performed safely as a day case procedure even in larger hiatus hernias, with a dedicated care pathway and specialist nurse practitioners to support it.

Intrathecal drug delivery in the era of nanomedicine.

Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.

Postoperative management factors affect urinary retention following posterior spinal fusion for adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study investigates postoperative urinary retention (POUR) following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and the effects of postoperative analgesia and mobility on retention. High opioid use and decreased postoperative mobility are proposed risk factors for retention in adults. There is a paucity of literature on POUR in the adolescent population undergoing surgery for AIS. The impact of pain control and mobility on POUR in these patients is unknown. METHODS: A retrospective cohort study was conducted of adolescents (11-18 years) undergoing elective PSF for AIS at a single institution (2012-2018). POUR was defined as the inability to void > 8 h after catheter removal. Possible risk factors for retention including opioid usage and ambulatory status at the time of catheter removal were assessed on univariate and binomial logistic regression analyses. RESULTS: One hundred and thirty-six patients were included, with 21 (15.4%) experiencing POUR. On the day of catheter removal, 24 patients had not attempted ambulation; these patients had 2.5 times higher rate of POUR than those who were walking (30% vs. 12%, p = 0.04). Patients who developed retention ambulated a mean threefold shorter distance than those without POUR (45 vs. 136 feet, p = 0.04). On binomial logistic regression, decreased ambulation distance was associated with retention (p = 0.038). While opioid use was not significant on univariate analysis, higher opioid use on the day of catheter removal predicted retention on logistic regression (p = 0.001). POUR resolved in all patients (median duration 0.5 days, range 0-12 days). CONCLUSIONS: The development of POUR after PSF for AIS affects one in six patients but resolves quickly. Non-ambulatory patients and patients who received large doses of opioids on the day of catheter removal were more likely to develop POUR. LEVEL OF EVIDENCE: III.

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

AIMS: Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA1c , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA1c in those with long duration (> 5 years) Type 1 diabetes. METHODS: We conducted a cross-sectional case-control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C-peptide after a mixed-meal tolerance test. We compared self-reported hypoglycaemia (n = 160), HbA1c , insulin dose and microvascular complications (n = 140) in those with preserved and low C-peptide. RESULTS: Stimulated median (IQR) C-peptide was 114 (43, 273) pmol/l and < 3 (< 3, < 3) pmol/l in those with preserved and low C-peptide respectively. Participants with preserved C-peptide had lower reported monthly rates of hypoglycaemia, with 21% fewer symptomatic episodes, 5.9 vs. 7.5 [incidence rate ratio (IRR) 0.79, P = 0.001], and 65% fewer asymptomatic episodes, 1.0 vs. 2.9 (IRR 0.35, P < 0.001). Those with preserved C-peptide had a lower insulin dose (0.68 vs. 0.81 units/kg, P = 0.01) but similar HbA1c (preserved 69 vs. low 67 mmol/mol, P = 0.06). CONCLUSIONS: Adults with Type 1 diabetes and preserved endogenous insulin production receiving usual care in the UK have lower daily insulin doses and fewer self-reported hypoglycaemic episodes, but no difference in HbA1c . This is consistent with non-intensive treatment in previous studies, and suggests a need to consider therapy intensification to gain full benefit of preserved endogenous insulin.

Impact of laparoscopic approach in emergency major abdominal surgery: single-centre analysis of 748 consecutive cases.

Background Acute abdominal pathology requiring emergency laparotomy is a common surgical presentation. Despite its widespread implementation in other surgical procedures, laparoscopy, rather than laparotomy, is sparingly used in major emergency surgery. This study reports outcomes and impact of rising use of laparoscopy for a single high-volume district general hospital. Methods Data were retrieved from the prospective National Emergency Laparotomy Audit database for a 30-month period. Patient, procedural, and in-hospital outcome data were collated. Temporal trends were assessed and regression analysis conducted for clinical outcomes. Results A total of 748 consecutive cases were recorded. There was an increasing use of laparoscopy over the study period, with 49% of cases attempted laparoscopically in the final six-month interval. Patients treated laparoscopically were at reduced risk of mortality (odds ratio 0.114, 95% confidence interval 0.024 to 0.550) and experienced reduced length of intensive care stay (regression coefficient ­1.571, 95% confidence interval ­2.625 to ­0.517) in multivariate adjusted analysis. Conclusions Laparoscopy is safe and feasible in a large proportion of cases. It is associated with improved outcomes versus laparotomy.

Pacemakers in MRI for the Neuroradiologist.

Cardiac implantable electronic devices are frequently encountered in clinical practice in patients being screened for MR imaging examinations. Traditionally, the presence of these devices has been considered a contraindication to undergoing MR imaging. Growing evidence suggests that most of these patients can safely undergo an MR imaging examination if certain conditions are met. This document will review the relevant cardiac implantable electronic devices encountered in practice today, the background physics/technical factors related to scanning these devices, the multidisciplinary screening protocol used at our institution for scanning patients with implantable cardiac devices, and our experience in safely performing these examinations since 2010.

Adipose tissue is influenced by hypoxia of obstructive sleep apnea syndrome independent of obesity.

AIMS: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular risk and diabetes independent of obesity. We investigated whether adipose tissue dysfunction is exacerbated due to increased tissue hypoxia. METHODS: Adipose tissue (AT) oxygenation was measured with a Clarke-type electrode (pATO2) in 16 men with OSAS before and after 4 months of continuous positive airway pressure therapy (CPAP) and in BMI-matched controls. Oxygenation was simultaneously monitored in arterial blood by pulse oximetry (SaO2); mixed blood in AT microcirculation by reflectance spectroscopy (SATO2) along with blood flow. Markers of hypoxia, adipo- and angiogenesis, inflammation and fibrosis were analysed in AT and serum. RESULTS: OSAS subjects were more insulin resistant. Despite lower arterial SaO2 (95.4±1.3% vs. 97.1±1.6%, P=0.013) in subjects with OSAS, there was no difference in the oxygen content of AT microcirculation (61.6±18.4 vs. 72.2±7.0%, P=0.07) or pATO2 (49.2±7.5 vs. 50.4±14.7mmHg, P=0.83) between groups. Resting AT blood flow was higher in OSAS compared to controls (108.5±22.7 vs. 78.9±24.9au, P<0.005) and strongly associated with inflammation markers IL-6 and MCP-1. AT of OSAS subjects showed increased inflammation (TNFA P=0.049) and fibrosis (COL3A1 P=0.02), a trend of higher HIF1A expression (P=0.06) and reduced adipogenesis (PPARG P=0.006). After CPAP, only expression of the lipid deposition marker LPL increased (30%, P=0.047). CONCLUSIONS: Adipose tissue of awake OSAS subjects appears no more hypoxic than adipose tissue of BMI-matched controls despite daytime hypoxaemia. Increased adipose tissue blood flow may be explained by an increased inflammatory response. We observe features of adipose dysfunction in subjects with OSAS, which attribute to increased cardiometabolic risk associated with this condition.

Computed Tomography and Magnetic Resonance Findings of Fat-Poor Angiomyolipomas.

INTRODUCTION: Approximately 5% of angiomyolipomas (AMLs) are classified as "fat poor" due to lack of visually detectable fat on imaging, making them difficult to distinguish from renal cell carcinoma. Recent investigations have proposed CT and MR imaging features suggestive of fat-poor AML (fp-AML). Herein, we determined the frequency of these features in a cohort of fp-AMLs by retrospective review of preoperative imaging. METHODS: A pathology database query from January 2005 to August 2013 identified 49 renal specimens of AML with available imaging. A retrospective review of all CT and MR images of these 49 cases was conducted. Cases with visually detectable fat on imaging were excluded. RESULTS: A total of 26 fp-AMLs were identified. Thirteen lesions had available unenhanced CT images, of which eight (62%) were hyperdense compared to the adjacent renal parenchyma, while five (38%) were isodense. Twenty lesions had enhanced CT images: 14 (70%) and 6 (30%) with homogeneous and heterogeneous enhancement, respectively. Of the nine lesions with enhanced MR sequences, five (56%) were homogeneously enhancing, and four (44%) were heterogeneously enhancing. Eight of nine (89%) lesions had hypointense signal intensity (SI) on T2-weighted MR sequences, while one (11%) had hyperintense SI. None of the eight lesions displayed a decrease in signal on fat-suppressed sequences. CONCLUSIONS: In this study, we confirmed common imaging features of fp-AML: high attenuation on unenhanced CT sequences, homogeneous enhancement on CT, and hypointensity on T2-weighted MR. When these features are present, a renal mass biopsy may be prudent.

Effects of Exendin-4 on human adipose tissue inflammation and ECM remodelling.

BACKGROUND/OBJECTIVES: Subjects with type-2 diabetes are typically obese with dysfunctional adipose tissue (AT). Glucagon-like peptide-1 (GLP-1) analogues are routinely used to improve glycaemia. Although, they also aid weight loss that improves AT function, their direct effect on AT function is unclear. To explore GLP-1 analogues' influence on human AT's cytokine and extracellular matrix (ECM) regulation, we therefore obtained and treated omental (OMAT) and subcutaneous (SCAT) AT samples with Exendin-4, an agonist of the GLP-1 receptor (GLP-1R). SUBJECTS/METHODS: OMAT and abdominal SCAT samples obtained from women during elective surgery at the Royal Devon & Exeter Hospital (UK) were treated with increasing doses of Exendin-4. Changes in RNA expression of adipokines, inflammatory cytokines, ECM components and their regulators were assessed and protein secretion analysed by ELISA. GLP-1R protein accumulation was compared in paired AT depot samples. RESULTS: Exendin-4 induced an increase in OMAT adiponectin (P=0.02) and decrease in elastin expression (P=0.03) in parallel with reduced elastin secretion (P=0.04). In contrast to OMAT, we did not observe an effect on SCAT. There was no change in the expression of inflammatory markers (CD14, TNFA, MCP-1), collagens, TGFB1 or CTGF. GLP-1R accumulation was higher in SCAT. CONCLUSIONS: Independently of weight loss, which may bias findings of in vivo studies, GLP-1 analogues modify human OMAT physiology favourably by increasing the insulin-sensitising cytokine adiponectin. However, the reduction of elastin and no apparent effect on AT's inflammatory cytokines suggest that GLP-1 analogues may be less beneficial to AT function, especially if there is no associated weight loss.

Adolescents with irritable bowel syndrome report increased eating-associated symptoms, changes in dietary composition, and altered eating behaviors: a pilot comparison study to healthy adolescents.

BACKGROUND: About half of adult irritable bowel syndrome (IBS) patients report symptoms with eating and disordered eating habits. However, little is known about eating in adolescent IBS patients, a common age at which eating disorders develop. The aim of the study was to investigate if adolescents with IBS are more likely than healthy controls (HCs) to experience eating-associated symptoms (EAS), report disordered eating patterns, and show differences in diet composition. METHODS: A total of 99 adolescents between 15 and 21 years-of-age participated (n = 48 IBS; n = 51 HCs). All subjects completed three 24-h dietary recalls and questionnaires on EAS and disordered eating. KEY RESULTS: IBS patients were more likely to report EASs than HC (91.7% vs 28%, p < 0.001). Eating-associated symptoms were controlled by avoiding the offending food (97.7%), not eating any food even when hungry (43.2%), or vomiting after eating (13.6%). Compared to HC, IBS patients reported reduced daily intake of overall calories (1828 vs 2139; p < 0.05), fat (65.4 g vs 81.4 g, p < 0.05), and lactose (8.2 g vs 12.8 g, p < 0.01). No differences were found between IBS and HC in screening for disordered eating patterns or BMI, though IBS patients endorsed using potentially unhealthy eating behaviors in an attempt to control symptoms. CONCLUSIONS & INFERENCES: Eating-associated symptoms are very common in adolescents with IBS and associated with changes in eating behaviors and dietary composition. They do not appear to change BMI and risk for eating disorders. More research is needed to guide adolescents with IBS in making appropriate dietary changes to control EASs.

Diagnostic Utility of Selective Upper Tract Urinary Cytology: A Systematic Review and Meta-analysis of the Literature.

The diagnosis of upper tract urothelial carcinoma (UTUC) can be a challenging diagnostic pursuit. To date, there is no large-scale study assessing the statistical utility (eg, sensitivity and specificity) of selective cytology. Herein, we systematically reviewed and meta-analyzed the published literature to evaluate the efficacy of selective cytology for the detection of UTUC in patients with a suspicious clinical profile Selective cytology confers a high specificity but marginal sensitivity for the detection of UTUC. The sensitivity is greater for high-grade UTUC lesions. The statistical assessment of its utility is limited by the heterogeneity and bias of previous studies.

Psychiatric morbidity in children with KCNJ11 neonatal diabetes.

AIMS: Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the pancreatic KATP channel, cause neonatal diabetes. KCNJ11 is also expressed in the brain, and ~ 20% of those affected have neurological features, which may include features suggestive of psychiatric disorder. No previous studies have systematically characterized the psychiatric morbidity in people with KCNJ11 neonatal diabetes. We aimed to characterize the types of psychiatric disorders present in children with KCNJ11 mutations, and explore their impact on families. METHODS: The parents and teachers of 10 children with neonatal diabetes due to KCNJ11 mutations completed the Strengths and Difficulties Questionnaire and the Development and Wellbeing Assessment. Strengths and Difficulties Questionnaire scores were compared with normative data. Diagnoses from the Development and Wellbeing Assessment were compared with known clinical diagnoses. RESULTS: Strengths and Difficulties Questionnaire scores indicated high levels of psychopathology and impact. Psychiatric disorder(s) were present in all six children with the V59M or R201C mutation, and the presence of more than one psychiatric disorder was common. Only two children had received a formal clinical diagnosis, with a further one awaiting assessment, and the coexistence of more than one psychiatric disorder had been missed. Neurodevelopmental (attention deficit hyperactivity disorder and autism) and anxiety disorders predominated. CONCLUSIONS: Systematic assessment using standardized validated questionnaires reveals a range of psychiatric morbidity in children with KCNJ11 neonatal diabetes. This is under-recognized clinically and has a significant impact on affected children and their families. An integrated collaborative approach to clinical care is needed to manage the complex needs of people with KCNJ11 neonatal diabetes.

Random non-fasting C-peptide: bringing robust assessment of endogenous insulin secretion to the clinic.

BACKGROUND: Measuring endogenous insulin secretion using C-peptide can assist diabetes management, but standard stimulation tests are impractical for clinical use. Random non-fasting C-peptide assessment would allow testing when a patient is seen in clinic. METHODS: We compared C-peptide at 90 min in the mixed meal tolerance test (sCP) with random non-fasting blood C-peptide (rCP) and random non-fasting urine C-peptide creatinine ratio (rUCPCR) in 41 participants with insulin-treated diabetes [median age 72 (interquartile range 68-78); diabetes duration 21 (14-31) years]. We assessed sensitivity and specificity for previously reported optimal mixed meal test thresholds for severe insulin deficiency (sCP < 200 pmol//l) and Type 1 diabetes/inability to withdraw insulin (< 600 pmol//l), and assessed the impact of concurrent glucose. RESULTS: rCP and sCP levels were similar (median 546 and 487 pmol//l, P = 0.92). rCP was highly correlated with sCP, r = 0.91, P < 0.0001, improving to r = 0.96 when excluding samples with concurrent glucose < 8 mmol//l. An rCP cut-off of 200 pmol//l gave 100% sensitivity and 93% specificity for detecting severe insulin deficiency, with area under the receiver operating characteristic curve of 0.99. rCP < 600 pmol//l gave 87% sensitivity and 83% specificity to detect sCP < 600 pmol//l. Specificity improved to 100% when excluding samples with concurrent glucose < 8 mmol//l. rUCPCR (0.52 nmol/mmol) was also well-correlated with sCP, r = 0.82, P < 0.0001. A rUCPCR cut-off of < 0.2 nmol/ mmol gave sensitivity and specificity of 83% and 93% to detect severe insulin deficiency, with area under the receiver operating characteristic curve of 0.98. CONCLUSIONS: Random non-fasting C-peptide measures are strongly correlated with mixed meal C-peptide, and have high sensitivity and specificity for identifying clinically relevant thresholds. These tests allow assessment of C-peptide at the point patients are seen for clinical care.