Perioperative management of a parturient with VACTERL association for a caesarean section.

A parturient with VACTERL association (vertebral defects, anal atresia, cardiac defects, trachea-oesophageal fistula, renal abnormalities and limb abnormalities) was listed for an elective caesarean section. She had a short neck with reduced cervical extension and flexion. Magnetic resonance imaging of her whole spine was performed which showed failure of cervical spine segmentation and cervical stenosis. Neuraxial blockade could have resulted in unpredictable spread of local anaesthetic due to the low volume of the spinal canal, and could have caused myelopathic changes within the spinal cord due to cerebrospinal fluid pressure changes. A general anaesthetic using a rapid sequence induction was also predicted to be challenging due to her fixed, unstable neck and severe cervical spine stenosis. After a multidisciplinary discussion Including neurosurgeons, we planned for awake tracheal intubation followed by general anaesthesia. However, before the date of her planned delivery, she required an urgent caesarean section due to severe preeclampsia. This was performed under general anaesthesia following uncomplicated awake tracheal intubation.

Comparison of calcaneal quantitative ultrasound and bone densitometry parameters as fracture risk predictors in type 2 diabetes mellitus.

AIM: To investigate the utility of calcaneal quantitative ultrasound compared with bone densitometry (DXA) in predicting incident low-trauma fracture in type 2 diabetes. METHODS: This retrospective cohort study included a subset of participants in the Dubbo Osteoporosis Epidemiology Study who had concurrent calcaneal quantitative ultrasound and DXA measurement, comprising 809 people without type 2 diabetes and 96 with type 2 diabetes. Fracture data had been collected prospectively. Cox proportional hazard models and receiver operating curves (ROC) were used to compare calcaneal quantitative ultrasound and DXA parameters as predictors for any low-trauma fracture. RESULTS: The median age of participants was 71 years (IQR 68-76, 50% men) for those without type 2 diabetes and 70 years (IQR 68-76, 55% men) for those with type 2 diabetes. There was no difference in low-trauma fracture incidence between groups when stratified by sex. In those without type 2 diabetes, the hazard ratio for fracture per 1 sd decrease in broadband ultrasound attenuation and femoral neck bone mineral density (BMD) was 1.47 [95% confidence interval (CI) 1.26-1.71] and 1.39 (95% CI 1.17-1.64), respectively. The corresponding figures in type 2 diabetes were 1.81 (95% CI 1.03-3.19) for broadband ultrasound attenuation and 2.55 (95% CI 1.28-5.08) for femoral neck BMD. CONCLUSION: Broadband ultrasound attenuation is comparable with femoral neck BMD as a predictor for low trauma incident fracture in type 2 diabetes. Calcaneal quantitative ultrasound offers several advantages over DXA and should be considered in further studies of bone health screening or in clinical practice where DXA is unavailable.

Complex interplay among adiposity, insulin resistance and bone health.

Obesity and osteoporosis are common public health problems. Paradoxically, while obesity is associated with higher bone density, type 2 diabetic obese individuals have an increased fracture risk. Although obesity and insulin resistance co-exist, some obese individuals remain insulin-sensitive. We suggest that the apparent paradox relating obesity, bone density and fracture risk in type 2 diabetes may be at least partly influenced by differences in bone strength and quality between insulin-resistant and insulin-sensitive obese individuals. In this review, we focus on the complex interplay between, adiposity, insulin resistance and osteoporotic fracture risk and suggest that this is an important area of study that has implications for individually tailored and targeted treatment to prevent osteoporotic fracture in obese type 2 diabetic individuals.

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series.

BACKGROUND: Ipilimumab (Yervoy; Bristol-Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4, an immune checkpoint molecule, to augment anti-tumour T-cell responses. It is associated with significant immune-related side-effects including hypophysitis. AIM: We reviewed the clinical and biochemical characteristics of 10 patients with ipilimumab-induced hypophysitis (IH), and developed guidelines for the early detection and management of IH based on our experiences at three major teaching hospitals in Sydney. METHODS: All patients were evaluated at the Crown Princess Mary Cancer Centre and Department of Endocrinology, Westmead Hospital, Department of Endocrinology, Royal Prince Alfred Hospital, the Melanoma Institute Australia and Macarthur Cancer Therapy Centre, Campbelltown Hospital from 2010 to 2014. Relevant data were extracted by review of medical records. Main outcome measures included clinical features, hormone profile and radiological findings associated with IH, and presence of pituitary recovery. RESULTS: Ten patients were identified with IH. In four patients who underwent monitoring of plasma cortisol, there was a fall in levels in the weeks prior to presentation. The pituitary-adrenal and pituitary-thyroid axes were affected in the majority of patients, with the need for physiological hormone replacement. Imaging abnormalities were identified in five of 10 patients, and resolved without high-dose glucocorticoid therapy. To date, all patients remain on levothyroxine and hydrocortisone replacement, where appropriate. CONCLUSIONS: There is significant morbidity associated with development of IH. We suggest guidelines to assist with early recognition and therapeutic intervention.

Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects.

AIMS/HYPOTHESIS: Muscle insulin resistance, one of the earliest defects associated with type 2 diabetes, involves changes in the phosphoinositide 3-kinase/Akt network. The relative contribution of obesity vs insulin resistance to perturbations in this pathway is poorly understood. METHODS: We used phosphospecific antibodies against targets in the Akt signalling network to study insulin action in muscle from lean, overweight/obese and type 2 diabetic individuals before and during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Insulin-stimulated Akt phosphorylation at Thr309 and Ser474 was highly correlated with whole-body insulin sensitivity. In contrast, impaired phosphorylation of Akt substrate of 160 kDa (AS160; also known as TBC1D4) was associated with adiposity, but not insulin sensitivity. Neither insulin sensitivity nor obesity was associated with defective insulin-dependent phosphorylation of forkhead box O (FOXO) transcription factor. In view of the resultant basal hyperinsulinaemia, we predicted that this selective response within the Akt pathway might lead to hyperactivation of those processes that were spared. Indeed, the expression of genes targeted by FOXO was downregulated in insulin-resistant individuals. CONCLUSIONS/INTERPRETATION: These results highlight non-linearity in Akt signalling and suggest that: (1) the pathway from Akt to glucose transport is complex; and (2) pathways, particularly FOXO, that are not insulin-resistant, are likely to be hyperactivated in response to hyperinsulinaemia. This facet of Akt signalling may contribute to multiple features of the metabolic syndrome.

Insulin-sensitive obesity in humans - a 'favorable fat' phenotype?

In most humans, obesity and insulin resistance coexist. However, a unique group of obese individuals, who exhibit better insulin sensitivity than expected for their adiposity, has been the focus of recent research interest. We critically examine cross-sectional and lifestyle intervention studies in obese humans classified as 'insulin-sensitive' versus 'insulin-resistant' and review the few longitudinal studies comparing rates of cardiovascular disease, type 2 diabetes and all-cause mortality in these groups of individuals. We suggest that reduced deposition of fat, particularly of bioactive lipid intermediates, in muscle and liver is potentially protective. We propose that dynamic interventional studies in insulin-sensitive obese humans may increase understanding of the metabolic factors that play a role in obesity-associated insulin resistance in humans.

Hyperglycaemia in hospital inpatients: still a sticky situation.

BACKGROUND: Diabetes diagnosis is delayed 4-7 years and 50% are undiagnosed. Forty percent of hospitalized patients with any blood glucose level (BGL) > or = 10 mmol/L have diabetes 3 months post-discharge, yet less than 5% are detected in hospital. We review identification of, and responses to, hyperglycaemia in inpatients at a teaching hospital. METHODS: The world's largest retrospective review of medical records for inpatients with venous BGL > or = 11.1 mmol/L without known diabetes over 12 months (2005-2006). The primary outcome was recognition of hyperglycaemia; secondary outcomes were treatment and documentation of follow up. Logistic regression was performed with variables including BGL, admitting team, length of stay and endocrine team review. RESULTS: Of 10 973 people screened, 162 were eligible. The median age was 58 years and BGL 13.3 mmol/L, with increased mortality and length of stay. Hyperglycaemia was noted as definitely in 26%, maybe in 24% and definitely not in 50%. Forty percent of patients were treated in hospital and 19% on discharge. Follow up was documented for 24%. A higher BGL and review by the endocrine team were strongly associated with clinical recognition on uni- and multivariate analyses. However, where an endocrine review was sought for non-hyperglycaemia reasons, similar rates of non-recognition occurred. CONCLUSION: Despite evidence for improved inpatient outcomes when treated, and high short-term progression to frank diabetes, inpatient hyperglycaemia remains frequently missed. In-hospital recognition is cheap, and vital for the implementation of activities to improve outcomes and prevent progression and complications. Changes to systems for checking pathology results, medical officer education and inpatient screening guidelines are indicated.

New insulin analogues and perioperative care of patients with type 1 diabetes.

While insulin remains the mainstay of managing type 1 diabetes, much has changed over the last 15 years. These changes should help in managing patients with type 1 diabetes during the perioperative period. More flexible insulin therapy has three components: (1) basal, (2) prandial and (3) corrective. Many patients, particularly younger patients, are using genetically modified recombinant human insulin analogues. Two of these analogues, aspart and lispro insulin, are rapid-acting with faster onset and offset than subcutaneous regular insulin, allowing both prandial and corrective boluses. Other insulin analogues, particularly glargine and possibly detemir have a flat profile of up to 24 hours, providing improved basal insulin delivery. Basal insulin can also be provided by a continuous subcutaneous infusion of rapid-acting insulin via a computerised pump that also provides boluses on demand. There is little evidence to help choose the best management of patients with type 1 diabetes during surgery. Some authors still recommend glucose-potassium-insulin infusions for all patients with type 1 diabetes. We challenge this approach, given the flexibility of the newer insulin analogues and delivery systems. We suggest that for many procedures, patients' usual regimens can be maintained in the perioperative period, providing less disruption and, possibly, greater safety. Both hyperglycaemia and hypoglycaemia reflect poor management: we suggest a target glucose range of 5 to 10 mmol/l. The importance of frequently measuring blood glucose and appropriate responses cannot be overemphasised.

Deep vein thrombosis assessment clinic: Evaluation of a new working practice.

Suspected deep vein thrombosis (DVT) is a common reason for medical referral to hospital. We evaluated our new approach to assessment of DVT using combined automated strain gauge plethysmography and pretest probability score in comparison with venous ultrasonography in 100 consecutive patients with suspected DVT referred to the nurse-led clinic. The combined plethysmography and pretest probability score produced a negative predictive value of 99%, positive predictive value 53%, sensitivity 94% and specificity 83% for detection of a DVT. We conclude that our new working practice for DVT assessment is both safe and cost effective and can lead to a reduction in venous ultrasonography of approximately 70%.