Observational study of the relative efficacy of insulin-glucose treatment for hyperkalaemia in patients with liver cirrhosis.

OBJECTIVES: To determine if liver cirrhosis is associated with reduced efficacy of insulin-glucose treatment in moderate to severe hyperkalaemia. DESIGN: Retrospective, cohort study. SETTING: Two secondary and one tertiary care hospital at a large metropolitan healthcare network in Melbourne, Australia. PARTICIPANTS: This study included 463 adults with a mean age of 68.7±15.8 years, comprising 79 patients with cirrhosis and 384 without cirrhosis as controls, who received standard insulin-glucose treatment for a serum potassium ≥6.0 mmol/L from October 2016 to March 2020. Patients were excluded if they received an insulin infusion, or if there was inadequate follow-up data for at least 6 hours after IDT due to death, lost to follow-up or inadequate biochemistry monitoring. The mean Model for End-stage Liver Disease score in patients with cirrhosis was 22.2±7.5, and the distribution of the Child-Pugh score for cirrhosis was: class A (24%), class B (46%), class C (30%). OUTCOME MEASURES: The primary outcome was the degree of potassium lowering and the secondary outcome was the proportion of patients who achieved normokalaemia, within 6 hours of treatment. RESULTS: The mean pretreatment potassium for the cohort was 6.57±0.52 mmol/L. After insulin-glucose treatment, mean potassium lowering was 0.84±0.58 mmol/L in patients with cirrhosis compared with 1.33±0.75 mmol/L for controls (p<0.001). The proportion of patients achieving normokalaemia was 33% for patients with cirrhosis, compared with 53% for controls (p=0.001). By multivariable regression, on average, liver cirrhosis was associated with a reduced potassium lowering effect of 0.42 mmol/L (95% CI 0.22 to 0.63 mmol/L, p<0.001) from insulin-glucose treatment, after adjusting for age, serum creatinine, cancer, pretreatment potassium level, ß-blocker use and cotreatments (sodium polystyrene sulfonate, salbutamol, sodium bicarbonate). CONCLUSIONS: Our observational data suggest reduced efficacy of insulin-glucose treatment for hyperkalaemia in patients with cirrhosis.

The Effect of Patient Factors and Cotreatments on the Magnitude of Potassium Lowering with Insulin-Glucose Treatment in Patients with Hyperkalemia.

The management of hyperkalemia with insulin-glucose/dextrose treatment (IDT) may be influenced by patient factors and cotreatments. We aimed to determine the magnitude of potassium lowering by IDT while considering patient factors and cotreatments. We observed the change in serum potassium in 410 patients with a mean serum potassium of 6.6 mmol/L (SD, 0.6 mmol/L) treated with IDT at three major metropolitan hospitals. Mean potassium lowering was 1.4 mmol/L (SD, 0.8 mmol/L) and 53% achieved normokalemia. Cotreatment with sodium polystyrene sulfonate, salbutamol, or sodium bicarbonate occurred in 64%, 12%, and 10% of patients, respectively. In multiple linear regression analysis, cotreatment with sodium polystyrene sulfonate or sodium bicarbonate was not associated with any significant reduction in serum potassium beyond that achieved by IDT, within the initial 6 h of treatment. We observed an additional lowering of serum potassium with salbutamol of 0.3 mmol/L (95% CI: 0.1 to 0.6 mmol/L; p = 0.009) but the clinical significance was unclear as the proportion of patients achieving normokalemia was not affected by cotreatment within the initial 6 h after IDT. We also found evidence that the potassium-lowering effect of IDT was dependent on the pre-treatment serum potassium. For every 1 mmol/L increase in pre-treatment serum potassium over 6.0 mmol/L, there was an associated 0.7 mmol/L increase in the potassium-lowering effect of IDT, on average, which was independent of any cotreatment. There was no significant impact of acute kidney injury or chronic kidney disease status on the efficacy of IDT.

Pericoronary adipose tissue computed tomography attenuation distinguishes different stages of coronary artery disease: a cross-sectional study.

AIMS: Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and this can be detected on coronary computed tomography angiography (CCTA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). In this cross-sectional study, we assessed the utility of PCAT CT attenuation as an imaging biomarker of coronary inflammation in distinguishing different stages of coronary artery disease (CAD). METHODS AND RESULTS: Sixty patients with acute myocardial infarction (MI) were prospectively recruited to undergo CCTA within 48 h of admission, prior to invasive angiography. These participants were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, gender, BMI, risk factors, medications, and CT tube voltage. PCAT attenuation around the proximal RCA was quantified per-patient using semi-automated software. Patients with MI had a higher PCAT attenuation (-82.3 ± 5.5 HU) compared with patients with stable CAD (-90.6 ± 5.7 HU, P < 0.001) and controls (-95.8 ± 6.2 HU, P < 0.001). PCAT attenuation was significantly increased in stable CAD patients over controls (P = 0.01). The association of PCAT attenuation with stage of CAD was independent of age, gender, cardiovascular risk factors, epicardial adipose tissue volume, and CCTA-derived quantitative plaque burden. No interaction was observed for clinical presentation (MI vs. stable CAD) and plaque burden on PCAT attenuation. CONCLUSION: PCAT CT attenuation as a quantitative measure of global coronary inflammation independently distinguishes patients with MI vs. stable CAD vs. no CAD. Future studies should assess whether this imaging biomarker can track patient responses to therapies in different stages of CAD.

The Association of Insulin-dextrose Treatment with Hypoglycemia in Patients with Hyperkalemia.

Treatment of hyperkalemia with intravenous insulin-dextrose is associated with a risk of hypoglycemia. We aimed to determine the factors associated with hypoglycemia (glucose < 3.9 mmol/L, or < 70 mg/dL) and the critical time window with the highest incidence. In a retrospective cohort study in a tertiary hospital network, we included 421 adult patients with a serum potassium ≥ 6.0 mmol/L who received insulin-dextrose treatment. The mean age was 70 years with 62% male predominance. The prevalence of diabetes was 60%, and 70% had chronic kidney disease (eGFR < 60 ml/min/1.73 m2). The incidence of hypoglycemia was 21%. In a multivariable logistic regression model, the factors independently associated with hypoglycemia were: body mass index (per 5 kg/m2, OR 0.85, 95% CI: 0.69-0.99, P = 0.04), eGFR < 60 mL/min/1.73 m2 (OR 2.47, 95% CI: 1.32-4.63, P = 0.005), diabetes (OR 0.57, 95% CI 0.33-0.98, P = 0.043), pre-treatment blood glucose (OR 0.84, 95% CI: 0.77-0.91, P < 0.001), and treatment in the emergency department compared to other locations (OR 2.53, 95% CI: 1.49-4.31, P = 0.001). Hypoglycemia occurred most frequently between 60 and 150 min, with a peak at 90 min. Understanding the factors associated with hypoglycemia and the critical window of risk is essential for the development of preventive strategies.

Myocardial Infarction Associates With a Distinct Pericoronary Adipose Tissue Radiomic Phenotype: A Prospective Case-Control Study.

OBJECTIVES: This study sought to determine whether coronary computed tomography angiography (CCTA)-based radiomic analysis of pericoronary adipose tissue (PCAT) could distinguish patients with acute myocardial infarction (MI) from patients with stable or no coronary artery disease (CAD). BACKGROUND: Imaging of PCAT with CCTA enables detection of coronary inflammation. Radiomics involves extracting quantitative features from medical images to create big data and identify novel imaging biomarkers. METHODS: In a prospective case-control study, 60 patients with acute MI underwent CCTA within 48 h of admission, before invasive angiography. These subjects were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, sex, risk factors, medications, and CT tube voltage. PCAT was segmented around the proximal right coronary artery (RCA) in all patients and around culprit and nonculprit lesions in patients with MI. PCAT segmentations were analyzed using Radiomics Image Analysis software. RESULTS: Of 1,103 calculated radiomic parameters, 20.3% differed significantly between MI patients and controls, and 16.5% differed between patients with MI and stable CAD (critical p < 0.0006); whereas none differed between patients with stable CAD and controls. On cluster analysis, the most significant radiomic parameters were texture or geometry based. At 6 months post-MI, there was no significant change in the PCAT radiomic profile around the proximal RCA or nonculprit lesions. Using machine learning (XGBoost), a model integrating clinical features (risk factors, serum lipids, high-sensitivity C-reactive protein), PCAT attenuation, and radiomic parameters provided superior discrimination of acute MI (area under the receiver operator characteristic curve [AUC]: 0.87) compared with a model with clinical features and PCAT attenuation (AUC: 0.77; p = 0.001) or clinical features alone (AUC: 0.76; p < 0.001). CONCLUSIONS: Patients with acute MI have a distinct PCAT radiomic phenotype compared with patients with stable or no CAD. Using machine learning, a radiomics-based model outperforms a PCAT attenuation-based model in accurately identifying patients with MI.

Radiosynthesis and 'click' conjugation of ethynyl-4-[(18)F]fluorobenzene--an improved [(18)F]synthon for indirect radiolabeling.

Reproducible methods for [(18)F]radiolabeling of biological vectors are essential for the development of new [(18)F]radiopharmaceuticals. Molecules such as carbohydrates, peptides and proteins are challenging substrates that often require multi-step indirect radiolabeling methods. With the goal of developing more robust, time saving, and less expensive procedures for indirect [(18)F]radiolabeling of such molecules, our group has synthesized ethynyl-4-[(18)F]fluorobenzene ([(18)F]2, [(18)F]EYFB) in a single step (14 ± 2% non-decay corrected radiochemical yield (ndc RCY)) from a readily synthesized, shelf stable, inexpensive precursor. The alkyne-functionalized synthon [(18)F]2 was then conjugated to two azido-functionalized vector molecules via CuAAC reactions. The first 'proof of principle' conjugation of [(18)F]2 to 1-azido-1-deoxy-ß-D-glucopyranoside (3) gave the desired radiolabeled product [(18)F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [(18)F]2 to matrix-metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [(18)F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [(18)F]4 and [(18)F]6 including [(18)F]F(-) drying, two-step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70 min. The radiochemical purity of synthon [(18)F]2 and the conjugated products, [(18)F]4 and [(18)F]6, were all greater than 98%. The specific activities of [(18)F]2 and [(18)F]6 were low, 5.97 and 0.17 MBq nmol(-1), respectively.

Synthesis and in Vivo Evaluation of [123I]Melanin-Targeted Agents.

This study reports the synthesis, [(123)I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [(131)I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [(123)I]4 (ICF01012). The most favorable compounds ([(123)I]20, [(123)I]23, [(123)I]41, and [(123)I]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [(123)I]20 and [(123)I]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [(123)I]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [(123)I]41 and [(123)I]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [(123)I]53 displays favorable in vivo pharmacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [(131)I] therapeutic evaluation.