Activity

The ATP-sensitive K+ (KATP) channel controls blood glucose levels by coupling glucose metabolism to insulin secretion in pancreatic β-cells. E23K, a common polymorphism in the pore-forming KATP channel subunit (KCNJ11) gene, has been linked to increased risk of type 2 diabetes. Understanding the risk-allele-specific pathogenesis has the potential to improve personalized diabetes treatment, but the underlying mechanism has remained elusive. Using a genetically engineered mouse model, we now show that the K23 variant impairs glucose-induced insulin secretion and increases diabetes risk when combined with a high-fat diet (HFD) and obesity. KATP-channels in β-cells with two K23 risk alleles (KK) showed decreased ATP inhibition, and the threshold for glucose-stimulated insulin secretion from KK islets was increased. Consequently, the insulin response to glucose and glycemic control was impaired in KK mice fed a standard diet. On an HFD, the effects of the KK genotype were exacerbated, accelerating diet-induced diabetes progression and causing β-cell failure. We conclude that the K23 variant increases diabetes risk by impairing insulin secretion at threshold glucose levels, thus accelerating loss of β-cell function in the early stages of diabetes progression.Infantile spasms are a potentially catastrophic form of epilepsy syndrome that are usually associated with substantial developmental delay and commonly occur in children younger than 1 yr. Recent reports on four cases revealed that variants harbored in a novel gene CDK19 were causative for the syndrome. We report a fifth affected individual, a 10-mo-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms. We identified a novel de novo missense variant c.92C > A (p.Thr31Asn) in CDK19 that was classified as a likely pathogenic disease-causing variant. The characterized clinical phenotypes of the proband were similar to the previously reported four patients, but he had few variable features including earlier seizure onset age and earlier occurring developmental abnormality. Protein structure modeling analysis revealed that CDK19 variants may disable its kinase activity, which would further impede the transcriptional regulation, thus leading to detrimental pathologies. Our report expanded CDK19 genotype spectrum and further demonstrated that a CDK19 missense variant was causative of neurodevelopmental disorder clinically marked by infantile spasms.

Risky behaviors are the main threats to adolescents’ health. Consequently, guidelines recommend adolescents be screened annually for high-risk behaviors. Our objectives were to (1) determine rates of physician-documented risk behavior screening of hospitalized adolescents, (2) determine rates of positive screening results, and (3) evaluate associations between risk behavior screening and provision of risk behavior-related health care interventions.

We conducted a cross-sectional study of patients aged 12 to 24 years admitted to the pediatric hospital medicine service at an urban tertiary children’s hospital from January to December 2018. Exclusion criteria were transfer to a different service, nonverbal status, or altered mental status. We reviewed 20 charts per month. Outcomes included (1) documentation of risk behavior screening (mood, sexual activity, substance use, abuse and/or violence, and suicidal ideation), and (2) risk behavior-related health care interventions (eg, testing for sexually transmitteen results, and those who were documented as screened were more likely to receive risk behavior-related interventions.The transfer of a cardiac surgery patient from the operating room (OR) to the intensive care unit (ICU) is both a challenging process and a critical period for outcomes. Information transferred between these two teams-known as the ‘handoff’-has been a focus of efforts to improve patient safety. At our institution, staff have poor perceptions of handoff safety, as measured by low positive response rates to questions found in the Agency for Health Care Research and Quality (AHRQ) Hospital Survey on Patient Safety Culture (HSOPS). In this quality improvement project, we developed a novel handoff protocol after cardiac surgery where we invited the ICU nurse and intensivist into the OR to receive a face-to-face handoff from the circulating nurse, observe the final 30 min of the case, and participate in the end-of-case debrief discussions. Our aim was to increase the positive response rates to handoff safety questions to meet or surpass the reported AHRQ national averages. We used plan, do, study, act cycles over the course of 123 surgical cases to test how our handoff protocol was leading to changes in perceptions of safety. After a 10-month period, we achieved our aim for four out of the five HSOPS questions assessing safety of handoff. Our results suggest that having an ICU team ‘run in parallel’ with the cardiac surgical team positively impacts safety culture.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) cirrhosis is often underestimated in healthcare and administrative databases that define disease burden using International Classification of Diseases (ICD) codes. This retrospective audit was conducted to explore the accuracy and limitations of the ICD, Tenth Revision, Australian Modification (ICD-10-AM) to detect NAFLD, metabolic risk factors (obesity and diabetes) and other aetiologies of chronic liver disease.

ICD-10-AM codes in 308 admitted patient encounters at two major Australian tertiary hospitals were compared with data abstracted from patients’ electronic medical records. K03861 cost Accuracy of individual codes and grouped combinations was determined by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen’s kappa coefficient (κ).

The presence of an ICD-10-AM code accurately predicted the presence of NAFLD/NASH (PPV 91.2%) and obesity (PPV 91.6%)disease.Paratesticular tumours are tumours arising from within the scrotum not of testicular origin. They may originate from the epididymis, spermatic cord, tunica vaginalis and other supporting structures. Preoperative diagnosis can be difficult as benign and malignant cases are often indistinguishable and may be confused with other benign or malignant pathology (testicular tumours or hernias).We describe the presentation and management of a patient managed at our centre (a tertiary referral teaching hospital).A high index of suspicion for malignancy should be considered when managing atypical scrotal lumps to ensure optimal management. This is particularly important when managing sarcomas due to the risk of local recurrence and spread.