High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Maori to phaeochromocytoma/paraganglioma.

BACKGROUND: Phaeochromocytomas (PCC) and paragangliomas (PGL; together PPGL) are rare tumours of the adrenal medulla or extra-adrenal paraganglia. They may secrete catecholamines with significant cardiovascular effects. Management of PPGL is predominantly surgical, despite the anaesthetic risks related to potential haemodynamic instability. Meticulous pre-treatment and intra-operative management are required to improve cardiovascular outcomes. AIMS: There are limited local data regarding the incidence of PPGL and the clinical characteristics of individuals diagnosed with these tumours in New Zealand. We undertook a retrospective study investigating the local practice and patient characteristics with an additional focus on intra-operative haemodynamic stability and post-operative outcomes. METHODS: Electronic patient records were searched for individuals with a diagnosis of PPGL. Clinical records and electronic databases were interrogated for pre-operative, intra-operative and post-operative data points. Particular attention was paid to rates and types of germline mutations, intra-operative haemodynamic stability and post-operative renal and cardiovascular outcomes. RESULTS: We identified 49 individuals with PPGL, of whom 34 were from the local area. This gave a local incidence of PPGL of around five cases per million people per year. Maori were significantly over-represented in our cohort, with this being in part due to high rates of the SDHB R46Q mutation. Over 95% of our cohort met pre-specified pre-operative blood pressure parameters. Intra-operative monitoring revealed a tendency to hypotension, but this did not translate into adverse post-operative outcomes, which were infrequent. CONCLUSIONS: Maori were over-represented due to high rates of germline SDHB R46Q mutations. There were few post-operative adverse outcomes in this contemporary cohort.

Mortality after discharge from hospital following an episode of diabetic ketoacidosis.

AIMS: The rate of inpatient mortality associated with diabetic ketoacidosis (DKA) has steadily decreased in recent decades. However, there remains a significantly increased outpatient death rate following an episode of survived DKA. We undertook this study to investigate the observed increase in mortality following an episode of DKA. METHODS: We completed a retrospective cohort study to investigate rates and causes of death in people admitted to our hospital with DKA between 2013 and 2018. DKA was confirmed by pre-defined biochemical parameters and cause of death data was extracted from multiple sources. Follow-up was for two years after discharge for all participants with one-year mortality being the main time point for analysis. RESULTS: We identified 818 admissions to hospital with DKA, affecting 284 people. Twenty people died as inpatients and a further 40 people died during the two-year follow-up. Of these 60 participants, cause of death was able to be determined for 41 (68%), with most deaths occurring due to infection or macrovascular disease. Risk factors for death within a year of hospital discharge included older age, vascular complications of diabetes, intellectual impairment and residential care living. Those who survived an episode of DKA had a one-year age-corrected mortality rate 13 times higher than the general population. This was more marked in the younger cohort with those aged 15-39 years being 49 times more likely to die in the year after surviving a DKA admission compared to their general population counterparts. CONCLUSION: An episode of diabetic ketoacidosis is associated with a significant outpatient mortality risk with most deaths due to infectious or macrovascular causes. This study should prompt investigation of predictive scoring tools to identify those at increased mortality risk after DKA and encourage the development of targeted interventions to reduce mortality.

Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature.

The mitochondrial DNA mutation mt.3243A>G is most commonly associated with maternally inherited diabetes and deafness (MIM 52,000), but it has protean phenotypes including renal disease due to focal segmental glomerulosclerosis. We describe monozygotic twins who both harboured this mutation and developed ESRD. Although otherwise genetically identical, the twins differed in their peripheral blood leucocyte levels of circulating mt.3243A>G heteroplasmy: 20 versus 10%, when assessed at 42 years of age. The twin with the higher heteroplasmy load developed end-stage kidney disease 15 years earlier than her sister. A review of the published literature supports a relationship between heteroplasmy level and the age at the development of the end stage of renal failure in patients with mt.3243A>G-related kidney disease.

The Fentanyl Patch Boil-Up - A Novel Method of Opioid Abuse.

Fentanyl is a potent opioid analgesic used in the treatment of pain. Transdermal fentanyl patches are now widely utilized as an acceptable and efficacious method of medication delivery. Unfortunately, the potential for their abuse is well recognized. Previous case reports have documented deaths after intravenous (IV) misuse of fentanyl which had been extracted from Duragesic (liquid reservoir type) patches. We present a case of IV fentanyl abuse after the extraction from a Mylan (matrix type) patch. This method of abuse has not previously been described in the literature.