A pilot project informing the design of a web-based dynamic nomogram in order to predict survival one year after hip fracture surgery (Preprint)

BACKGROUND Hip fracture is associated with high mortality. Identification of individual risk informs anesthetic and surgical decision making and can reduce the risk of death. However, interpretation of data, and application of research findings can be difficult, and there is a need to simplify risk indices for clinicians and lay-people alike. Results Twenty-four (7.3%) patients died within 30 days, 65 (19.8%) within 120 days and 94 (28.6%) within 365 days of surgery. Independent predictors of mortality common to all models were admission Age, BMI, and creatinine, lactate and their combination. Age and BMI inversely correlated with mortality. Presentation with a creatinine level of 90 mol.L-1 increased the odds of death OR 2.9 (1.4 - 6.0) 365 days after surgery compared to an admission level of 60 mol. L-1 Presentation with a plasma lactate level of 2 mmol. L-1 increased the odds of death OR 2.2 (1.1 - 4.5) 365 days after surgery compared to a plasma lactate level of 1 mmol. L-1. Patients presenting to hospital with a BMI of 30 kg.m-2 were less likely to die within 365 days OR 0.41 (0.17 - 0.99) after surgery compared to patients with a BMI of 20 kg.m-2. We presented four models in Shiny. Data entry created Kaplan-Meier graphs and outcome measures (95%CI). Conclusion We developed easy to read and interpretable web-based nomograms for prediction of survival after hip fracture surgery. OBJECTIVE Our primary objective was to develop a web-based nomogram for prediction of survival 365 days after fracture hip surgery. METHODS We collected data from 329 patients up to 365 days after hip fracture surgery and built four models using packages in RStudio. A global Cox Proportional Hazards Model was developed from all covariates. Covariates included sex, age, BMI, white cell count, lactate, creatinine, hemoglobin, C-reactive protein, ASA status, socio-economic status, duration of surgery, total time in the operating room, side of surgery and procedure urgency. We also developed a Cox proportional hazards model (CPH). a logistic regression model (LRM), and a generalized linear model (GLM) for binomial response data using iterative data reduction and elimination. We wrote an app in Shiny in order to present the models in a user-friendly way. The app consists of a drop-down box for model selection, horizontal sliders for data entry, model summaries, and prediction and survival plots. A slider selects patient follow-up over 365 days. RESULTS Twenty-four (7.3%) patients died within 30 days, 65 (19.8%) within 120 days and 94 (28.6%) within 365 days of surgery. Independent predictors of mortality common to all models were admission Age, BMI, and creatinine, lactate and their combination. Age and BMI inversely correlated with mortality. Presentation with a creatinine level of 90 mol.L-1 increased the odds of death OR 2.9 (1.4 - 6.0) 365 days after surgery compared to an admission level of 60 mol. L-1 Presentation with a plasma lactate level of 2 mmol. L-1 increased the odds of death OR 2.2 (1.1 - 4.5) 365 days after surgery compared to a plasma lactate level of 1 mmol. L-1. Patients presenting to hospital with a BMI of 30 kg.m-2 were less likely to die within 365 days OR 0.41 (0.17 - 0.99) after surgery compared to patients with a BMI of 20 kg.m-2. We presented four models in Shiny. Data entry created Kaplan-Meier graphs and outcome measures (95%CI). CONCLUSIONS We developed easy to read and interpretable web-based nomograms for prediction of survival after hip fracture surgery. CLINICALTRIAL Nil

PSII-4 Effect of increased ruminal propionate on the expression of hepatic gluconeogenic genes in cattle on a finishing ration

The objective of this experiment was to ascertain if supplementing calcium propionate (CaP) in varying amounts would result in the increased expression of genes related to glucose metabolism in the liver. The study utilized cannulated Holstein steers (n = 6) in a 3 × 6 Latin rectangle with three 15-d periods. The treatments were as follows: Control (no CaP), low propionate (100 g/d CaP), and high propionate (300 g/d CaP). The treatments were administered in halves twice a day through rumen cannulas. The steers were provided with ad libitum finishing ration, using Insentec feeders to record feed intake and unrestricted access to water. Liver biopsies were taken on d15 of each period, a day after a glucose tolerance test, and flash frozen. RNA was extracted from the liver tissue, reverse transcribed for cDNA, and analyzed through quantitative real-time PCR. Five target genes involved in gluconeogenesis were analyzed and included solute carrier family 16 member 1 (SLC16A1), phosphoenolpyruvate carboxykinase 1 (PCK1), phosphoenolpyruvate carboxykinase 2 (PCK2), glucose-6-phosphatase (G6PC), and solute carrier family 2 member 2 (SLC2A2). Data were analyzed using a mixed model with treatment, period, and their interaction included as fixed effects and steer as a random effect. There was no treatment effect on hepatic gene expression (P ≥ 0.57). SLC16A1 showed a negative, correlation with d7 plasma lactate concentration (r = -0.84, P < 0.001) and a negative relationship with fasting plasma lactate concentration (r = -0.55, P = 0.028). SLC2A2 tended to show a positive correlation with fasting plasma glucose (r = 0.44, P = 0.09), fasting plasma lactate concentration (r = 0.43, P = 0.09), and glucose area under the curve (r = 0.46, P = 0.07). These data indicate that increased propionate may not have an impact on hepatic gene expression.

Rapid recovery of normal gill morphology and blood physiology in brown trout (Salmo trutta) after short-term exposure to toxic concentrations of aqueous aluminium under non-steady state chemical conditions

Freshwater acidification is characterised by elevated concentrations of aqueous aluminium. Global emissions of acidifying agents are reduced due to international agreements, and freshwater acidification has shifted from chronic to a more episodic character. The recovery of fish populations in acidified areas is likely to depend on the individual’s ability to recover from short-time aluminium exposures. We exposed brown trout (Salmo trutta) to an Al-rich medium, nominal concentration 600 µg L–1, for 0.5, 2, 6, 8 and 11 hours, before transfer to circumneutral Al-poor water for recovery. As controls, fish were either exposed for 11 hours to an acidified Al-poor medium or to untreated water. Some mortality during the first 24 hours of the recovery period occurred in fish exposed for 11, 8 and 6 hours to aluminium. No mortality during recovery was observed in the remaining groups. Aluminium exposure led to increased haematocrit and plasma lactate concentration, decreased plasma chloride concentration, deposition of aluminium on gill surfaces, and morphological alteration of the gill structures. The responses depended on exposure time. Aluminium deposited on the gill disappeared and plasma lactate levels were at control levels after 1 day in the recovery water, while haematocrit and plasma chloride levels were at control levels after 14 days of recovery. Gills in fish exposed to aluminium for 11 hours were almost fully recovered after 14 days. We conclude that the toxic response in brown trout exposed to an acutely toxic aluminium challenge is reversible. Moreover, the first 24 hours after aluminium exposures is the most critical period for the fish recovery. Further, it takes no more than 14 days for brown trout to fully recover from an acute toxic aluminium exposure, and only 1 day if the aluminium challenge is moderate.

Alternative Cerebral Fuels in the First Five Days in Healthy Term Infants: The Glucose in Well Babies (GLOW) Study

Objectives: To determine plasma lactate and beta-hydroxybutyrate (BHB) concentrations of healthy infants in the first 5 days and their relationships with glucose concentrations. Study design: Prospective masked observational study in Hamilton, New Zealand. Term, appropriately grown singletons had heel-prick blood samples, 4 in the first 24 hours then twice daily. Results: In 67 infants, plasma lactate concentrations were higher in the first 12 hours (median, 20; range, 10-55 mg/dL [median, 2.2 mmol/L; range, 1.1-6.2 mmol/L]), decreasing to 12 mg/dL (range, 7-29 mg/dL [median, 1.4 mmol/L; range, 0.8-3.3 mmol/L]) after 48 hours. Plasma BHB concentrations were low in the first 12 hours (median, 0.9 mg/dL; range, 0.5-5.2 mg/dL [median, 0.1 mmol/L; range, 0.05-0.5 mmol/L]), peaked at 48-72 hours (median, 7.3 mg/dL; range, 1.0-25.0 mg/dL [median, 0.7 mmol/L; range, 0.05-2.4 mmol/L]), and decreased by 96 hours (median, 0.9 mg/dL; range, 0.5-16.7 mg/dL [median, 0.1 mmol/L; range, 0.05-1.6 mmol/L]). Compared with infants with plasma glucose concentrations above the median (median, 67 mg/dL [median, 3.7 mmol/L]), those with lower glucose had lower lactate concentrations in the first 12 hours and higher BHB concentrations between 24 and 96 hours. Lower interstitial glucose concentrations were also associated with higher plasma BHB concentrations, but only if the lower glucose lasted greater than 12 hours. Glucose contributed 72%-84% of the estimated potential adenosine triphosphate throughout the 5 days, with lactate contributing 25% on day 1 and BHB 7% on days 2-3. Conclusions: Lactate on day 1 and BHB on days 2-4 may contribute to cerebral fuels in healthy infants, but are unlikely to provide neuroprotection during early or acute hypoglycemia. Trial registration: The Australian and New Zealand Clinical Trials Registry: ACTRN12615000986572.

Alternative Cerebral Fuels in the First Five Days in Healthy Term Infants: The Glucose in Well Babies (GLOW) Study

Objectives: To determine plasma lactate and beta-hydroxybutyrate (BHB) concentrations of healthy infants in the first 5 days and their relationships with glucose concentrations. Study design: Prospective masked observational study in Hamilton, New Zealand. Term, appropriately grown singletons had heel-prick blood samples, 4 in the first 24 hours then twice daily. Results: In 67 infants, plasma lactate concentrations were higher in the first 12 hours (median, 20; range, 10-55 mg/dL [median, 2.2 mmol/L; range, 1.1-6.2 mmol/L]), decreasing to 12 mg/dL (range, 7-29 mg/dL [median, 1.4 mmol/L; range, 0.8-3.3 mmol/L]) after 48 hours. Plasma BHB concentrations were low in the first 12 hours (median, 0.9 mg/dL; range, 0.5-5.2 mg/dL [median, 0.1 mmol/L; range, 0.05-0.5 mmol/L]), peaked at 48-72 hours (median, 7.3 mg/dL; range, 1.0-25.0 mg/dL [median, 0.7 mmol/L; range, 0.05-2.4 mmol/L]), and decreased by 96 hours (median, 0.9 mg/dL; range, 0.5-16.7 mg/dL [median, 0.1 mmol/L; range, 0.05-1.6 mmol/L]). Compared with infants with plasma glucose concentrations above the median (median, 67 mg/dL [median, 3.7 mmol/L]), those with lower glucose had lower lactate concentrations in the first 12 hours and higher BHB concentrations between 24 and 96 hours. Lower interstitial glucose concentrations were also associated with higher plasma BHB concentrations, but only if the lower glucose lasted greater than 12 hours. Glucose contributed 72%-84% of the estimated potential adenosine triphosphate throughout the 5 days, with lactate contributing 25% on day 1 and BHB 7% on days 2-3. Conclusions: Lactate on day 1 and BHB on days 2-4 may contribute to cerebral fuels in healthy infants, but are unlikely to provide neuroprotection during early or acute hypoglycemia. Trial registration: The Australian and New Zealand Clinical Trials Registry: ACTRN12615000986572.

Clinical evaluation of a novel subcutaneous lactate monitor

Lactate levels are commonly used as an indirect measure to assess metabolic stress in clinical conditions like sepsis. Dynamic lactate measurements are recommended to assess and guide treatment in patients with shock and other critical care conditions. A minimally invasive, continuous lactate monitor has potential to improve clinical decisions and patient care. The purpose of the study was to evaluate continuous lactate measurements of a novel enzymatic Continuous Lactate Monitor (CLM) developed in our laboratory. Lactate levels were monitored during incremental cycling exercise challenges as a tool for hyperlactatemia. Six healthy individuals 18–45 y/o (4 males, 2 females) participated in the study. CLM devices were inserted subcutaneously in the postero-lateral trunk below the renal angle, one hour before the exercise challenge. Each exercise challenge consisted of a 3 to 12-min warm up period, followed by up to 7, 4-min incremental workload bouts separated by rest intervals. Continuous lactate measurements obtained from CLM were compared with commercial lactate analyzer (Abbott iSTAT) measurements of venous blood (plasma) drawn from the antecubital vein. Blood was drawn at up to 25 time points spanning the duration of before exercise, during exercise, and up to 120 min post exercise. Area under the curve (AUC), and delay time were calculated to compare the CLM readings with plasma lactate concentration. Average plasma lactate concentration increased from 1.02 to 16.21 mM. Ratio of AUC derived from CLM to plasma lactate was 1.025 (0.990–1.058). Average dynamic delay time of CLM to venous plasma lactate was 5.22 min (2.87–10.35). Insertion sites examined 48 h after CLM removal did not show signs of side effects and none required medical attention upon examination. The newly developed CLM has shown to be a promising tool to continuously measure lactate concentration in a minimally invasive fashion. Results indicate the CLM can provide needed trends in lactate over time. Such a device may be used in the future to improve treatment in clinical conditions such as sepsis.