Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma.

OBJECTIVES: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). METHODS: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R2) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method. RESULTS: The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R2 = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation. CONCLUSION: Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.

Anabolic steroid misuse is an important reversible cause of cardiomyopathy: a case report.

Background: Anabolic steroid misuse is very common and has been linked to the development of a severe cardiomyopathy, arrhythmias, and sudden death. Case summary: A 46-year-old miner presented to hospital with subacute dyspnoea and palpitations. Investigations revealed atrial fibrillation and a severe dilated cardiomyopathy with left ventricular ejection fraction of 12%. The patient had a history of longstanding exogenous testosterone administration. Haematological investigations demonstrated a marked polycythaemia, with haematocrit of 0.60 L/L (normal 0.40-0.54 L/L). Hormonal investigations revealed an elevated testosterone level of 46.4 nmol/L (normal 8.0-30.0 nmol/L) and suppressed luteinizing and follicle-stimulating hormones, consistent with excess testosterone use. The patient was referred to the endocrinology specialty team for support with ceasing excess testosterone use, while commencing guideline-directed heart failure therapy. At 6 months of follow-up, the patient's left ventricular ejection fraction had normalized and he was asymptomatic. Biochemical indicators of testosterone excess had also normalized. Discussion: Anabolic steroids are widely misused, particularly among young and middle-aged males. Cardiovascular complications include a potentially reversible severe cardiomyopathy, accelerated coronary disease, dyslipidaemia, arrhythmias, and sudden death. It is important to identify a history of anabolic steroid misuse when investigating cardiomyopathy and be alert for indicators such as polycythaemia. Cessation of anabolic steroid misuse may lead to complete reversal of cardiomyopathy but should be undertaken in close partnership with the patient and endocrinologists.

Case Report: Hypoglycemia Due to a Novel Activating Glucokinase Variant in an Adult - a Molecular Approach.

We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic ß cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in GCK cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. Glucose stimulated insulin secretion revealed increased insulin secretion in response to glucose. Cytoplasmic calcium, which triggers exocytosis of insulin-containing granules, revealed normal basal but increased glucose-stimulated level. Unbiased gene expression analysis using 10X single cell sequencing revealed upregulated INS and CKB genes and downregulated DLK1 and NPY genes in ß-cells. Further studies are required to see if alteration in expression of these genes plays a role in the metabolic and histological phenotype associated with glucokinase pathogenic variant. There were more large islets in the patient's pancreas than in control subjects but there was no difference in the proportion of ß cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion.

Upload and Review of Insulin Pump and Glucose Sensor Data by Adults with Type 1 Diabetes: A Clinic Audit.

Devices have facilitated improvement in glycemia in individuals with type 1 diabetes mellitus (T1DM), but self-management remains key. It is unclear whether people review their device data before clinic appointment. We assessed this by a survey. T1DM adults using glucose sensors and/or insulin pumps attending an Australian public hospital (diabetes clinics >4 months) were prospectively surveyed. The percentage who uploaded and reviewed their data was determined and their interest in education facilitating understanding of their device data was assessed. Of 138 adults (100% participation rate), 79% uploaded and 32% reviewed their device data before their clinic appointments. Individuals using pumps with sensors were most likely to review their data. Median HbA1c levels were lower in those who did versus did not review their device data (50.8 vs. 61.8 mmol/mol, P = 0.0001). Most (89%) were interested in education. Although diabetes technology has improved glycemia in T1DM, the benefits may be maximized through device-specific education programs enhancing self-management.

Utility of semi-quantitative quick cortisol assay with low-dose adrenocorticotropic hormone infusion adrenal vein sampling.

BACKGROUND: Adrenal vein sampling (AVS) is integral to identifying surgically remediable unilateral primary aldosteronism (PA). However, right adrenal vein (AV) cannulation can be challenging, limiting its success. Intra-procedural cortisol assays can improve the reliability of AVS. The aim of this study was to validate the use of semi-quantitative cortisol estimates obtained utilizing a quick cortisol assay (QCA) during AVS procedures at our institution. METHODS: Retrospective review of results of AVS procedures before and after the introduction of the QCA. Twenty-three AVS procedures were performed with the provisional success determined by intra-procedural QCA. Successful AV cannulation was defined by an AV to peripheral vein cortisol ratio ≥ 4.0 (the selectivity index) from laboratory measurements. The control cohort consisted of 23 consecutive procedures prior to introduction of the QCA. RESULTS: QCA correctly predicted all AV cannulation attempts. Successful bilateral AV cannulation increased from 52% to 91% of procedures when performed with the QCA (P = 0.01) and adequate cannulation of the right AV increased from 61% to 91% (P = 0.03). There was no increase in procedural time, number of AV cannulation or sampling attempts. CONCLUSIONS: Point-of-care, semi-quantitative cortisol estimates can be performed accurately during AVS with QCA, facilitating improvements in AVS success rates without increasing procedural time.

Statistical optimization for lipase production from solid waste of vegetable oil industry.

The production of biofuel using thermostable bacterial lipase from hot spring bacteria out of low-cost agricultural residue olive oil cake is reported in the present paper. Using a lipase enzyme from Bacillus licheniformis, a 66.5% yield of methyl esters was obtained. Optimum parameters were determined, with maximum production of lipase at a pH of 8.2, temperature 50.8°C, moisture content of 55.7%, and biosurfactant content of 1.693 mg. The contour plots and 3D surface responses depict the significant interaction of pH and moisture content with biosurfactant during lipase production. Chromatographic analysis of the lipase transesterification product was methyl esters, from kitchen waste oil under optimized conditions, generated methyl palmitate, methyl stearate, methyl oleate, and methyl linoleate.