Prioritising patients for publicly funded bariatric surgery in Queensland, Australia.

OBJECTIVES: This study reports the development and pilot application of the Bariatric Surgery Assessment and Prioritisation Tool (BAPT) for use in a public health system. The BAPT was designed as a patient prioritisation instrument to assess patients with excessive weight and type 2 diabetes suitable for bariatric surgery. We assessed whether the instrument successfully identified those who gained the greatest benefits including weight loss, diabetes remission, reduction in comorbidities, and health-related quality of life (HR-QoL). METHODS: The BAPT instrument was applied to score 292 patients referred for bariatric surgery in Queensland between 2017 and 2020 based on their, body mass index, diabetes status, surgical risk (e.g. pulmonary embolism) and comorbidities (e.g. non-alcoholic steatohepatitis). These data were collected at referral and at 12-months post-surgery for 130 patients and stratified by BAPT scores. Outcomes included clinical and HR-QoL. RESULTS: Patients' BAPT scores ranged from 12 to 78 (possible range 2-98). Those with higher scores tended to be younger (p < 0.001), have higher BMI (p < 0.001) or require insulin to manage diabetes (p < 0.01). All patients lost similar percentages of body weight (20-25%, p = 0.73) but higher-scoring patients were more likely to discontinue oral diabetes medications (p < 0.001) and the improvement in glycated haemoglobin was four times greater in patients scoring 70-79 points compared to those scoring 20-29 (p < 0.05). Those who scored ≥ 50 on the BAPT were substantially more likely to obtain diabetes remission (57% vs 31%). BAPT scores of 40 and above tended to have greater improvement in HR-QoL. CONCLUSIONS: The BAPT prioritised younger patients with higher BMIs who realised greater improvements in their diabetes after bariatric surgery. Higher-scoring BAPT patients should be prioritised for bariatric surgery as they have a greater likelihood of attaining diabetes remission.

Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2-Bl/HLA-G.

BACKGROUND AND AIMS: Growth hormone (GH) is important for liver regeneration after partial hepatectomy (PHx). We investigated this process in C57BL/6 mice that express different forms of the GH receptor (GHR) with deletions in key signaling domains. APPROACH AND RESULTS: PHx was performed on C57BL/6 mice lacking GHR (Ghr-/- ), disabled for all GH-dependent Janus kinase 2 signaling (Box1-/- ), or lacking only GH-dependent signal transducer and activator of transcription 5 (STAT5) signaling (Ghr391-/- ), and wild-type littermates. C57BL/6 Ghr-/- mice showed striking mortality within 48 hours after PHx, whereas Box1-/- or Ghr391-/- mice survived with normal liver regeneration. Ghr-/- mortality was associated with increased apoptosis and elevated natural killer/natural killer T cell and macrophage cell markers. We identified H2-Bl, a key immunotolerance protein, which is up-regulated by PHx through a GH-mediated, Janus kinase 2-independent, SRC family kinase-dependent pathway. GH treatment was confirmed to up-regulate expression of the human homolog of H2-Bl (human leukocyte antigen G [HLA-G]) in primary human hepatocytes and in the serum of GH-deficient patients. We find that injury-associated innate immune attack by natural killer/natural killer T cell and macrophage cells are instrumental in the failure of liver regeneration, and this can be overcome in Ghr-/- mice by adenoviral delivery of H2-Bl or by infusion of HLA-G protein. Further, H2-Bl knockdown in wild-type C57BL/6 mice showed elevated markers of inflammation after PHx, whereas Ghr-/- backcrossed on a strain with high endogenous H2-Bl expression showed a high rate of survival following PHx. CONCLUSIONS: GH induction of H2-Bl expression is crucial for reducing innate immune-mediated apoptosis and promoting survival after PHx in C57BL/6 mice. Treatment with HLA-G may lead to improved clinical outcomes following liver surgery or transplantation.

The relationship between early post-operative ACTH / cortisol following pituitary surgery and long-term glucocorticoid requirement - Do ultradian rhythms matter?

OBJECTIVE: To determine whether early (4-8h) post-operative ACTH after trans-sphenoidal surgery (TSS) predicts long-term hypothalamic-pituitary-adrenal (HPA) axis function and to investigate early morning day 1 ACTH/cortisol variability using rapid sampling. DESIGN: Prospective observational study. METHODS: Participants undergoing TSS were included; those treated with glucocorticoids pre-operatively received 100 mg intravenous hydrocortisone on anaesthetic induction. ACTH and cortisol were measured post-operatively at + 4h and + 8h after induction and on day 1 every 10 minutes between 0700h and 0900h. PRIMARY OUTCOME: glucocorticoid requirement at 6 months. RESULTS: Nineteen participants (10F, 9M): 6/19 (32%) were treated with replacement glucocorticoids pre-operatively; 4 had ceased by 6 weeks post-operatively. One patient developed new hypopituitarism post-operatively meaning 3/19 (16%) required glucocorticoids at 6 months. Post-operative + 4h ACTH < 14.3 pmol/L (65 ng/L) predicted secondary adrenal insufficiency (SAI) (sensitivity 100%, specificity 75%), whilst no participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months. Day 1 ACTH and cortisol showed a significant circadian fall between 0700h-0900h; ACTH 4.2 pmol/L (IQR 2.9-5.9) to 3.7 pmol/L (IQR 2.9-5.1) P = .006 and cortisol 549 nmol/L (IQR 337-618) to 439 nmol/L (IQR 315-606) P < .001, with clinically insignificant ultradian secretory pulses. CONCLUSIONS: No participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months; however, given only 3/19 participants had the primary outcome of interest, this must be confirmed in a larger cohort. The timing of a day 1 morning cortisol between 0700h and 0900h influences the accuracy of a single cut-off to diagnose SAI after pituitary surgery.

Copeptin is increased by nausea and vomiting during hypertonic saline infusion in healthy individuals.

OBJECTIVE: Measurement of hypertonic saline-stimulated copeptin has recently been described for the differentiation of polyuria-polydipsia syndrome. This study aims to determine the copeptin response to intravenous 3% hypertonic saline, including evaluation of adverse effects, in a local cohort of healthy adults >18 years in Australia. DESIGN: Prospective clinical study. METHODS: Twenty healthy volunteers (10 males and 10 females) were recruited. Participants underwent infusion of 3% hypertonic saline via a previously described standardized protocol, until the plasma sodium was ≥150 mmol/L, with measurement of plasma copeptin. RESULTS: Mean peak sodium was 152 mmol/L ± SD 1.4 with osmolality 315 mmol/kg ± SD 3.9. Median volume of hypertonic saline infused to reach target sodium ≥ 150 mmol/L was 1536 mL (IQR 1362, 1992). Mean rate of plasma sodium rise was 5.9 mmol/L/hour ± SD 1.5. Hypertonic saline-stimulated copeptin had non-parametrical distribution with median of 33.8 pmol/L (IQR 27.6, 63.6). Overall median symptom burden was 6/10 (range 3/10-9/10). Copeptin was significantly higher for those who experienced nausea and/or vomiting (n = 13) (median 39.0 pmol/L; IQR 32.5, 90), compared to those participants who did not experience either (median 20.0 pmol/L; IQR 13.0, 31.0) (P = 0.003). There were no serious adverse events. CONCLUSION: Hypertonic saline-stimulated copeptin measurements were similar in our population compared with previously reported reference intervals in healthy volunteers. There is a wide range of stimulated copeptin measurements in the healthy population. Nausea and vomiting are common adverse effects which enhance the copeptin response.

Elevated insulin-like growth factor-1 in Cushing's disease.

OBJECTIVE: To determine if patients with untreated Cushing's disease have higher serum insulin-like growth factor-1 (IGF-1) compared to matched controls, and if IGF-1 decreases following remission of Cushing's disease. DESIGN: Retrospective case-control study matching Cushing's disease cases to control patients for adenoma size, age, sex, diabetic and gonadal status, body mass index and serum IGF-1 measured within one year. Paired analysis of pre-operative (untreated) and >3 months post-operative (remission) serum IGF-1 for cases. PATIENTS AND MEASUREMENTS: All patients were investigated at the Princess Alexandra Hospital Endocrine Unit between 2005 and 2017. Serum IGF-1 was measured in 25 cases and 49 controls, 23 case-control pairs and 13 cases pre- and post-operatively. RESULTS: Mean serum IGF-1 in cases was significantly higher compared to controls-32 ± 12 nmol/L compared to 25 ± 8 nmol/L, (P = 0.005). The proportion of cases with elevated serum IGF-1 above an age-adjusted reference range was higher compared to 1:1 matched controls (8/23 (35%) vs 1/23 (4%), P = 0.02). In 13 cases in remission post-operatively, serum IGF-1 decreased significantly from 31 (IQR 29-40.5) nmol/L to 23 (IQR 15-28.5) nmol/L, (P < 0.001), despite no difference in the prevalence of pre- vs post-operative pituitary hormone dysfunction (P = 0.47). CONCLUSION: Patients with untreated Cushing's disease may have elevated IGF-1, which decreases following remission. Mildly elevated IGF-1 in Cushing's disease does not imply pathological growth hormone (GH) excess.

Growth hormone (GH) enhances anaerobic capacity: impact on physical function and quality of life in adults with GH deficiency.

CONTEXT: Anaerobic capacity is impaired in adults with GH deficiency (GHD), adversely affecting physical function and quality of life (QoL). OBJECTIVE: To investigate whether GH replacement improves anaerobic capacity, physical function and QoL in adults with GHD. DESIGN: One-month double-blind placebo-controlled crossover study of GH (0·5 mg/day), followed by a 6-month open phase. PATIENTS: A total of 18 adults with GHD. MEASUREMENTS: Anaerobic power (watts) was assessed by the 30-s Wingate test, and aerobic capacity by the VO2 max (l/min) test. Physical functional was assessed by the stair climb test, chair stand test, 7-day pedometry and QoL by the AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy X-ray absorptiometry. RESULTS: GH replacement normalized IGF-1 levels during both study phases. During the 1-month placebo-controlled study, improvement in stair climb and chair stand performance was observed during GH and placebo treatment; however, there were no significant GH effects observed in any outcome measure compared to placebo. Six months of GH treatment significantly increased anaerobic power (P < 0·05), chair stand repetitions (P < 0·0001), daily step count (P < 0·05) and QoL scores (P < 0·001) compared to baseline measurements. GH treatment did not significantly improve VO2 max. Improvement in anaerobic power independently predicted an improvement in energy and vitality domain of QoL (P = 0·03). CONCLUSIONS: GH replacement improves anaerobic capacity, physical function and QoL in a time-dependent manner in adults with GHD. Improvement in the anaerobic but not aerobic energy system is likely to underlie the improvement in QoL in patients with GHD during GH replacement.

Improving equitable access to publicly funded bariatric surgery in Queensland, Australia.

BackgroundPeople living in regional Queensland, Australia, have less access to health care than their metropolitan neighbours; a gap that is wider if they are also of Aboriginal and Torres Strait Islander ethnicity. The Bariatric Surgery Initiative (BSI) aims to provide metabolic bariatric surgery as a public service accessible to all Queenslanders for patients with morbid obesity according to need, regardless of location or ethnicity.MethodsWe investigated the BSI's progress in closing the metro-regional gap by comparing the distribution of referrals for surgery with the geographic and ethnic spread of obesity across Queensland in 2017-2019.ResultsRegional Queensland is home to 59.8% of Queensland's individuals with obesity, whereas 40.2% live in metropolitan Brisbane. In contrast, 47.8% of referrals were from regional areas, with 52.2% received from Brisbane. We found that more patients from metropolitan than regional areas underwent metabolic bariatric surgery, probably due to a paucity of referrals from regional locations. Aboriginal and Torres Strait Islander peoples were able to access the service and all patients realised significant health benefits after surgery.ConclusionsThe BSI improved access to this service, and inequities in metro-regional access may depend on patient choice and healthcare provider awareness of the BSI.Trial registrationThis initiative was a quality improvement study focused on providing access to care rather than a clinical trial; as such it was not registered as a clinical trial.

Developing a Decision Aid for Clinical Obesity Services in the Real World: the DACOS Nationwide Pilot Study.

PURPOSE: The purpose of this study is to develop a decision aid tool using "real-world" data within the Australian health system to predict weight loss after bariatric surgery and non-surgical care. MATERIALS AND METHODS: We analyzed patient record data (aged 16+years) from initial review between 2015 and 2020 with 6-month (n=219) and 9-/12-month (n=153) follow-ups at eight clinical obesity services. Primary outcome was percentage total weight loss (%TWL) at 6 months and 9/12 months. Predictors were selected by statistical evidence (p<0.20), effect size (±2%), and clinical judgment. Multiple linear regression and bariatric surgery were used to create simple predictive models. Accuracy was measured using percentage of predictions within 5% of the observed value, and sensitivity and specificity for predicting target weight loss of 5% (non-surgical care) and 15% (bariatric surgery). RESULTS: Observed %TWL with bariatric surgery vs. non-surgical care was 19% vs. 5% at 6 months and 22% vs. 5% at 9/12 months. Predictors at 6 months with intercept (non-surgical care) of 6% include bariatric surgery (+11%), BMI>60 (-3%), depression (-2%), anxiety (-2%), and eating disorder (-2%). Accuracy, sensitivity, and specificity were 58%, 69%, and 56%. Predictors at 9/12 months with intercept of 5% include bariatric surgery (+15%), type 2 diabetes (+5%), eating disorder (+4%), fatty liver (+2%), atrial fibrillation (-4%), osteoarthritis (-3%), sleep/mental disorders (-2-3%), and ≥10 alcohol drinks/week (-2%). Accuracy, sensitivity, and specificity were 55%, 86%, and 53%. CONCLUSION: Clinicians may use DACOS to discuss potential weight loss predictors with patients after surgery or non-surgical care.

Health outcomes of patients with type 2 diabetes following bariatric surgery: Results from a publicly funded initiative.

OBJECTIVE: Bariatric surgery is an effective treatment for type 2 diabetes and morbid obesity. This paper analyses the clinical and patient-reported outcomes of patients treated through the Bariatric Surgery Initiative, a health system collaboration providing bariatric surgery as a state-wide public service in Queensland, Australia. RESEARCH DESIGN AND METHODS: A longitudinal prospective cohort study was undertaken. Eligible patients had type 2 diabetes and morbid obesity (BMI ≥ 35 kg/m2). Following referral by specialist outpatient clinics, 212 patients underwent Roux-en-Y gastric bypass or sleeve gastrectomy. Outcomes were tracked for a follow-up of 12-months and included body weight, BMI, HbA1c, comorbidities, health-related quality of life, eating behaviour, and patient satisfaction. RESULTS: Following surgery, patients' average body weight decreased by 23.6%. Average HbA1c improved by 24.4% and 48.8% of patients were able to discontinue diabetes-related treatment. The incidence of hypertension, non-alcoholic steatohepatitis, and renal impairment decreased by 37.1%, 66.4%, and 62.3%, respectively. Patients' emotional eating scores, uncontrolled eating and cognitive restraint improved by 32.5%, 20.7%, and 6.9%, respectively. Quality of life increased by 18.8% and patients' overall satisfaction with the treatment remained above 97.5% throughout the recovery period. CONCLUSIONS: This study confirmed previous work demonstrating the efficacy of publicly funded bariatric surgery in treating obesity, type 2 diabetes and related comorbidities, and improving patients' quality of life and eating behaviour. Despite the short follow-up period, the results bode well for future weight maintenance in this cohort.

Progressive resistance training in young people with Prader-Willi syndrome: protocol for a randomised trial (PRESTO).

INTRODUCTION: Preliminary evidence suggests that progressive resistance training may be beneficial for people with Prader-Willi Syndrome (PWS), a rare genetic condition that results in muscle weakness and low muscle tone.To establish whether community-based progressive resistance training is effective in improving the muscle strength of people with PWS; to determine cost-effectiveness; and, to complete a process evaluation assessing intervention fidelity, exploring mechanisms of impact, understanding participant experiences and identifying contextual factors affecting implementation. METHODS AND ANALYSIS: A multisite, randomised controlled trial will be completed. Sixty participants with PWS will be randomised to receive either progressive resistance training (experimental) or non-progressive exercise (placebo control). Participants will be aged 13 to 60 years, be able to follow simple instructions in English and have no contraindications to performing progressive resistance training. The experimental group will complete progressive resistance training two times weekly for 24 weeks supervised by an exercise professional at a community gym. The control group will receive all aspects of the intervention except progressive overload. Outcomes will be assessed at week 25 (primary endpoint) and week 52 by a blinded assessor. The primary outcome is muscle strength assessed using one repetition maximum for upper limb and lower limb. Secondary outcomes are muscle mass, functional strength, physical activity, community participation, health-related quality of life and behaviour. Health economic analysis will evaluate cost-effectiveness. Process evaluation will assess safety and intervention fidelity, investigate mechanism of impact, explore participant experiences and identify contextual factors affecting implementation. Data collection commenced in February 2020 and will conclude in September 2023. ETHICS AND DISSEMINATION: Ethical approval was obtained from The Royal Children's Hospital Human Research Ethics Committee (HREC/50874/RCHM-2019) under the National Mutual Acceptance initiative. Research governance approvals were obtained from five clinical sites. Results will be disseminated through published manuscripts, conference presentations, public seminars and practical resources for stakeholder groups. TRIAL REGISTRATION NUMBER: ACTRN12620000416998; Australian and New Zealand Clinical Trial Registry.

Impairment of anaerobic capacity in adults with growth hormone deficiency.

CONTEXT: The anaerobic energy system underpins the initiation of all physical activities, including those of daily living. GH supplementation improves sprinting in recreational athletes, a performance measure dependent on the anaerobic energy system. The physiological and functional link between GH and the anaerobic energy system is unknown. OBJECTIVE: The objective was to investigate whether anaerobic capacity is impaired in adults with GH deficiency (GHD) and to assess its functional significance. DESIGN: This was a cross-sectional study. PARTICIPANTS: The participants were 13 adults with GHD and 13 age-, gender- and body mass index-matched normal subjects. MAIN OUTCOME MEASURES: Anaerobic power (watts) was assessed by the 30-second Wingate test, and aerobic capacity was assessed by the VO2max (L/min) test. The functional assessment comprised the stair-climb test, chair-stand test, and 7-day pedometry. Quality of life (QoL) was assessed by the QoL-AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy x-ray absorptiometry. RESULTS: Mean anaerobic power (5.8 ± 0.4 vs 7.1 ± 0.3 W · kg LBM(-1); P < .05) and VO2max were significantly lower in adults with GHD. The duration of the stair-climb test was longer (19.4 ± 0.7 vs 16.5 ± 0.7 s; P < .01) in adults with GHD and correlated negatively (R(2) = 0.7; P < .0001) with mean anaerobic power. The mean number of chair-stand repetitions and daily step counts were lower, and the QoL-AGHDA score was higher in adults with GHD (P < .05). In a multiple regression analysis, age, gender, LBM, and GH status were significant predictors of mean anaerobic power. Mean anaerobic power significantly predicted stair-climb performance (P < .01) and QoL (P < .05). CONCLUSIONS: Anaerobic capacity is subnormal, and it independently predicts stair-climbing capacity and QoL in adults with GHD. We conclude that GH regulates anaerobic capacity, which determines QoL and selective aspects of physical function.

Action of GH on skeletal muscle function: molecular and metabolic mechanisms.

Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports and muscle function in the elderly. This paper critically reviews information on the effects of GH on muscle function covering structure, protein metabolism, the role of IGF1 mediation, bioenergetics and performance drawn from molecular, cellular and physiological studies on animals and humans. GH increases muscle strength by enhancing muscle mass without affecting contractile force or fibre composition type. GH stimulates whole-body protein accretion with protein synthesis occurring in muscular and extra-muscular sites. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. GH exerts complex multi-system effects on skeletal muscle function in part mediated by the IGF system.

Pituitary metastases from papillary carcinoma of thyroid: a case report and literature review.

UNLABELLED: Metastases to the pituitary gland are an uncommon complication of thyroid cancer. They resemble pituitary neoplasms posing a diagnostic challenge. We present a case of an aggressive non-radioiodine avid papillary thyroid cancer with recurrent pituitary metastases and a review of the literature. A 70-year-old woman with a history of papillary thyroid cancer and bony metastases presented with symptoms of hypoadrenalism and peripheral vision loss. Magnetic resonance imaging showed a large pituitary mass impinging on the optic chiasm. She underwent transsphenoidal resection followed by (131)I ablation. Post-therapy scintigraphy showed no iodine uptake in the sellar region or bony metastases. Histology of the pituitary mass confirmed metastatic papillary thyroid cancer. Fifteen months later, she had a recurrence of pituitary metastases affecting her vision. This was resected and followed with external beam radiotherapy. Over 2 years, the pituitary metastases increased in size and required two further operations. Radioactive iodine was not considered due to poor response in the past. Progressively, she developed a left-sided III and IV cranial nerve palsy and permanent bitemporal hemianopia. There was a rapid decline in the patient's health with further imaging revealing new lung and bony metastases, and she eventually died 8 months later. To our knowledge, this is the first case of pituitary metastases from a radioiodine-resistant papillary thyroid cancer. Radioiodine-resistant metastatic thyroid cancer may exhibit rapid aggressive growth and remain poorly responsive to the currently available treatment. LEARNING POINTS: Differentiated thyroid cancer (DTC) has an excellent prognosis with <5% of the cases presenting with distant metastases, usually to lung and bone.Metastasis to the pituitary is a rare complication of DTC.The diagnosis of pituitary insufficiency secondary to pituitary metastases from DTC may be delayed due to the non-specific systemic symptoms of underlying malignancy and TSH suppression therapy for thyroid cancer.The imaging characteristics of metastases to the pituitary may be similar to non-functioning pituitary adenoma.Radioiodine refractory metastatic thyroid cancer has significantly lower survival rates compared with radioactive iodine-avid metastases due to limited therapeutic options.