Glucose transport into the brain is depressed in chronically hyperglycemic (diabetic) rats. To determine whether hypoglycemia has the opposite effect, brain transport of hexoses and other substrates was examined in chronically and acutely hypoglycemic rats. We produced chronic hypoglycemia by implanting insulin-secreting tumors or insulin-releasing osmotic mini-pumps or by repeated injection of protamine zinc insulin (PZI) and acute hypoglycemia by intravascular injection of regular insulin. Blood-brain barrier (BBB) transport was measured using the brain uptake index (BUI) method. In the three models of chronic hypoglycemia, brain glucose extraction was increased compared with controls. The extraction of deoxyglucose and several other hexoses was also increased by chronic hypoglycemia. Acute hypoglycemia had no effect on brain transport. The transport of other substrates was either not affected or depressed, suggesting increased brain hexose transport is specific. Studies of freeze-blown brain in insulinoma-engrafted rats showed that brain glucose levels were depressed while creatine phosphate, ATP, and glucose 6-phosphate were maintained. Tumor removal led to a reversion of brain glucose transport to control rates but only after 5-25 days. These findings support the view that glucose transport across the BBB is modulated by chronic alterations in the ambient glucose concentration. They also may explain why some patients with chronic hypoglycemia tolerate low blood glucose concentrations.

Background: Cholecystectomy is commonly performed in general surgery. Despite guidelines recommending chemical thromboprophylaxis in the perioperative period, the most appropriate time for its initiation is unknown. Here, we investigated whether timing of chemoprophylaxis affected venous thromboembolism (VTE) and bleeding rates postcholecystectomy. Methods: Retrospective review of all elective cholecystectomies performed between 1 January 2018 and 30 June 2019, across seven Victorian hospitals. Clinical VTE was defined as imaging-proven symptomatic disease within 30 days of surgery. Major bleeding was defined as the need for blood transfusion, surgical intervention or >20 g/L fall in haemoglobin from baseline. Results: A total of 1744 cases were reviewed. Chemoprophylaxis was given early (pre-or intra-operatively), post-operatively or not given in 847 (48.6%), 573 (32.9%) and 324 (18.6%) patients, respectively. This varied significantly between surgeons, fellows, trainees and institutions. Clinical VTE occurred in 5 (0.3%) patients and was not associated with chemoprophylaxis timing. Bleeding occurred in 42 (2.4%) patients. Of this, half were major events, requiring surgical control in 5 (11.9%) patients and blood transfusion in 9 (21.4%) patients. Bleeding also extended length of stay (mean (SD), 3.1 (4.0) versus 1.4 (2.2) days, P < 0.001). One bleeding-related mortality was recorded. Importantly, when compared with post-operative (risk ratio 1.46, 95% confidence interval 1.21-1.62) and no (RR 1.23, 95% CI 1.03-1.35) chemoprophylaxis, early usage significantly increased bleeding risk and independently predicted its occurrence. Conclusions: Perioperative chemoprophylaxis is variable among patients undergoing elective cholecystectomy. The rate of clinical VTE post-cholecystectomy is low. Early chemoprophylaxis increases bleeding risk without an appreciable additional protection from VTE.

Background: Despite guidelines recommending perioperative thromboprophylaxis for patients undergoing general surgery, we have observed significant variations in its practice. This may compromise patient safety. Here, we quantify the heterogeneity of perioperative thromboprophylaxis across all major general surgical operations, and place them in relation to their risk of bleeding and venous thromboembolism. Methods: Retrospective review of all elective major general surgeries performed between 1 January 2018 and 30 June 2019 across seven Victorian hospitals was conducted. Results: A total of 5912 patients who underwent 6628 procedures were reviewed. Significant heterogeneity was found in the use of chemoprophylaxis, timing of its initiation, type of anticoagulant administered and application of extended chemoprophylaxis. These variations were observed within the same procedure, and between different surgeries and subspecialties. Contrastingly, there was minimal heterogeneity with the use of mechanical thromboprophylaxis. Oesophago-gastric, liver and colorectal cancer resections had the highest thromboembolic risk. Breast, oesophago-gastric, liver, pancreas and colon cancer resections had the highest bleeding risk. Conclusion: Perioperative chemoprophylaxis across general surgery is highly variable. This study has highlighted key areas of variance. Our findings also enable surgeons to compare their practices, and provide baseline data to inform future efforts towards optimizing thromboprophylaxis for general surgical patients.

Introduction The coronavirus disease (COVID‐19) pandemic has continued to have a devastating impact on health worldwide. There has been a rapid evolution of evidence, establishing an increased risk of morbidity and mortality associated with diabetes and concurrent COVID‐19. The objective of this review is to explore the current evidence for inpatient assessment and management of diabetes during the COVID‐19 pandemic and highlight areas requiring further exploration. Methods A literature search of databases was conducted to November 2020 using variations on keywords SARS‐CoV‐2, COVID‐19, SARS, MERS and diabetes. Information relating to the impact of diabetes on severity of COVID‐19 infection, the impact of COVID‐19 infection on diabetes management and diabetes‐related complications was integrated to create a narrative review. Discussion People with diabetes and COVID‐19 are at an increased risk of morbidity and mortality. It is important that people with both known and previously unrecognised diabetes and COVID‐19 be promptly identified and assessed during acute illness, with close monitoring for clinical deterioration or complications. People with diabetes may require titration or alteration of their glycaemic management due to the potential for worse outcomes with hyperglycaemia and COVID‐19 infection. Comprehensive discharge planning is vital to optimise ongoing glycaemic management. Conclusion Further understanding of the risk of adverse outcomes and optimisation of glycaemic management for people with diabetes during COVID‐19 is required to improve outcomes. Increased glucose and ketone monitoring, substitution of insulin for some oral anti‐hyperglycaemic medications and careful monitoring for complications of diabetes such as diabetic ketoacidosis should be considered.

Introduction Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as an important class of blood glucose–lowering medications, due to cardiovascular, metabolic, and renal benefits. However, there is a small but significant risk of diabetic ketoacidosis (DKA) associated with their use. Methods A literature search was conducted in Ovid MEDLINE and Embase to July 2019 using variants on the key search terms sodium-glucose cotransporter 2, diabetic ketoacidosis, and type 2 diabetes. A broad spectrum of evidence was incorporated to facilitate a comprehensive narrative review. Further sources were identified through hand searching of reference lists. Discussion Although cardiovascular outcome trials demonstrated mixed evidence of SGLT2i associated DKA, increasing evidence from case reports and cohort studies has identified an increased risk. SGLT2i use is associated with a ketotic state caused by an increased glucagon:insulin ratio and stimulated by factors including stress-induced hormonal changes, insufficient insulin, decreased glucose, increased ketone resorption, and hypovolemia. Atypical presentations of DKA with lower-than-expected blood glucose levels are possible with SGLT2i use, so clinical and biochemical monitoring is vital for early identification and management. DKA risk is particularly increased with precipitating factors, therefore optimization of risk factors is vital. Recommendations for perioperative and sick day management of patients taking SGLT2i have been suggested based on available evidence. Conclusion SGLT2i are an excellent class of drug in the physician’s toolkit for managing type 2 diabetes. However, both clinicians and patients must be aware of the potential for DKA and the need for increased monitoring, both clinically and biochemically, when potential precipitating factors are present. In acutely unwell patients, these medications should be withheld to reduce the risk of DKA.

No abstract

Background Abdominal visceral resections incur relatively higher rates of postoperative bleeding and venous thromboembolism (VTE). While guidelines recommend the use of perioperative chemical thromboprophylaxis, the most appropriate time for its initiation is unknown. Here, we investigated whether early (before skin closure) versus postoperative commencement of chemoprophylaxis affected VTE and bleeding rates following abdominal visceral resection. Methods Retrospective review of all elective abdominal visceral resections undertaken between January 1, 2018, and June 30, 2019, across four tertiary-referral hospitals. Major bleeding was defined as the need for blood transfusion, reintervention, or > 20 g/L fall in hemoglobin from baseline. Clinical VTE was defined as imaging-proven symptomatic disease < 30 days post-surgery. Results A total of 945 cases were analyzed. Chemoprophylaxis was given early in 265 (28.0%) patients and postoperatively in 680 (72.0%) patients. Mean chemoprophylaxis exposure doses were similar between the two groups. Clinical VTE developed in 14 (1.5%) patients and was unrelated to chemoprophylaxis timing. Postoperative bleeding occurred in 71 (7.5%) patients, with 57 (80.3%) major bleeds, requiring blood transfusion in 48 (67.6%) cases and reintervention in 31 (43.7%) cases. Bleeding extended length-of-stay (median (IQR), 12 (7–27) versus 7 (5–11) days, p < 0.001). Importantly, compared to postoperative chemoprophylaxis, early administration significantly increased the risk of bleeding (10.6% versus 6.3%, RR 1.45, 95% CI 1.05–1.93, p = 0.038) and independently predicted its occurrence. Conclusions The risk of bleeding following elective abdominal visceral resections is substantial and is higher than the risk of clinical VTE. Compared with early chemoprophylaxis, postoperative initiation reduces bleeding risk without an increased risk of clinical VTE.

No abstract