Aim
Recruitment of renal functional reserve (RFR) with amino acid loading increases renal blood flow and glomerular filtration rate. However, its effects on renal cortical and medullary oxygenation ...have not been determined. Accordingly, we tested the effects of recruitment of RFR on renal cortical and medullary oxygenation in non‐anesthetized sheep.
Methods
Under general anesthesia, we instrumented 10 sheep to enable subsequent continuous measurements of systemic and renal hemodynamics, renal oxygen delivery and consumption, and cortical and medullary tissue oxygen tension (PO2). We then measured the effects of recruitment of RFR with an intravenous infusion of 500 ml of a clinically used amino acid solution (10% Synthamin® 17) in the non‐anesthetized state.
Results
Compared with baseline, Synthamin® 17 infusion significantly increased renal oxygen delivery mean ± SD maximum increase: (from 0.79 ± 0.17 to 1.06 ± 0.16 ml/kg/min, p < 0.001), renal oxygen consumption (from 0.08 ± 0.01 to 0.15 ± 0.02 ml/kg/min, p < 0.001), and glomerular filtration rate (+45.2 ± 2.7%, p < 0.001). Renal cortical tissue PO2 increased by a maximum of 26.4 ± 1.1% (p = 0.001) and medullary tissue PO2 increased by a maximum of 23.9 ± 2.8% (p = 0. 001).
Conclusions
In non‐anesthetized healthy sheep, recruitment of RFR improved renal cortical and medullary oxygenation. These observations might have implications for the use of recruitment of RFR for diagnostic and therapeutic purposes.
BackgroundIn the cetuximab after progression in KRAS wild-type colorectal cancer patients (CAPRI) trial patients with metastatic colorectal cancer (mCRC) received 5-fluorouracil, folinic acid and ...irinotecan (FOLFIRI) and cetuximab in first line followed by 5-Fluorouracil, folinic acid, oxaliplatin (FOLFOX) with or without cetuximab until progression. Limited data are available on the efficacy and safety of anti-epidermal growth factor receptor (anti-EGFR) agents on elderly patients with mCRC. In the current study we evaluated the efficacy and safety of FOLFIRI plus cetuximab in age-defined subgroups.MethodsA post-hoc analysis was performed in CAPRI trial patients; outcomes (progression-free survival (PFS), overall response rate (ORR), safety) were analysed by age-groups and stratified according to molecular characterisation. 3 age cut-offs were used to define the elderly population (≥65; ≥70 and ≥75 years).Results340 patients with mCRC were treated in first line with FOLFIRI plus cetuximab. Among those, 154 patients were >65 years, 86 >70 years and 35 >75 years. Next-generation sequencing (NGS) was performed in 182 patients. Among them, 87 patients were >65 years, 46 >70 and 17 >75. 104 of 182 patients were wild type (WT) for KRAS, NRAS, BRAF, PIK3CA genes. In the quadruple WT group, 51 patients were ≥65 years; 29 were ≥70; 9 were ≥75. Median PFS was similar within the age-subgroups in the intention-to-treat population, NGS cohort and quadruple WT patients, respectively. Likewise, ORR was not significantly different among age-subgroups in the 3 populations. Safety profile was acceptable and similarly reported among all age-groups, with the exception of grade ≥3 diarrhoea (55% vs 25%, p=0.04) and neutropaenia (75% vs 37%, p=0.03) in patients ≥75 years and grade ≥3 fatigue (31% vs 20%, p=0.01) in patients <75 years.ConclusionsTolerability of cetuximab plus FOLFIRI was acceptable in elderly patients. Similar ORR and PFS were observed according to age-groups. No differences in adverse events were reported among the defined subgroups with the exception of higher incidence of grade ≥3 diarrhoea and neutropaenia in patients ≥75 years and grade ≥3 fatigue in patients <75 years.Trial Registration number2009-014041-81.
•The majority of patients received fixed dose (10 units) IV insulin for hyperkalemia.•Hypoglycemia was not different between fixed and reduced dosing groups.•Patient weight and pre-insulin glucose ...may contribute to hypoglycemia risk.•IV insulin dosing for hyperkalemia should be individualized.
While intravenous (IV) insulin is often administered at a fixed dose of 10 units for acute hyperkalemia, optimal dosing for minimizing hypoglycemia while effectively reversing hyperkalemia has not been established. The purpose of this analysis was to evaluate the effect of insulin dosing strategies on hypoglycemia in patients with hyperkalemia.
Adult patients presenting to an academic medical center who received IV insulin for hyperkalemia between 2016 and 2020 were retrospectively identified. Patients treated with 10 units of insulin (fixed) were compared to those who received < 10 units (reduced). The primary outcome was the incidence of hypoglycemia (blood glucose < 70 mg/dL) within 12 hours of insulin administration. Secondary outcomes included the incidence of severe hypoglycemia (blood glucose < 40 mg/dL) and change in potassium. Multivariable analyses were used to assess for risk factors for hypoglycemia and severe hypoglycemia.
Of the 2576 patients included, 305 (11.8%) received reduced dosing and 2271 (88.2%) received fixed dosing. Hypoglycemia occurred in 16.7% of the reduced group and 15.9% of the fixed group (P = 0.70). Severe hypoglycemia occurred in 2.3% of the reduced group and 2.5% of the fixed group (P = 0.86). Median potassium reduction from baseline to first check post-insulin was less with reduced dosing (−0.6 mEq/L vs −0.8 mEq/L, P < 0.001). On multivariable regression analysis, greater weight-based insulin dose and ED location were significant predictors for hypoglycemia and severe hypoglycemia. Location in the intensive care unit was associated with a decreased risk of hypoglycemia. Higher pre-insulin glucose was protective for hypoglycemia and severe hypoglycemia.
The incidence of hypoglycemia was similar among both groups. Greater weight-based insulin dose was a significant risk factor for hypoglycemia, while higher baseline glucose levels were associated with a decreased risk, indicating that patient-specific insulin dosing for hyperkalemia may be warranted.
Debris disks are extrasolar analogs to our own Kuiper Belt and they are detected around at least 17% of nearby Sun-like stars. The morphology and dynamics of a disk encode information about its ...history, as well as that of any exoplanets within the system. We used the Atacama Large Millimeter/submillimeter Array (ALMA) to obtain 1.3 mm observations of the debris disk around the nearby F5V star HD 170773. We image the face-on ring and determine its fundamental parameters by forward-modeling the interferometric visibilities through a Markov Chain Monte Carlo approach. Using a symmetric Gaussian surface density profile, we find a 71 4 au wide belt with a radius of au, a relatively large radius compared with most other millimeter-resolved belts around late A/early F type stars. This makes HD 170773 part of a group of four disks around A and F stars with radii larger than expected from the recently reported planetesimal belt radius-stellar luminosity relation. Two of these systems are known to host directly imaged giant planets, which may point to a connection between large belts and the presence of long-period giant planets. We also set upper limits on the presence of CO and CN gas in the system, which imply that the exocomets that constitute this belt have CO and HCN ice mass fractions of <77% and <3%, respectively. This is consistent with solar system comets and other exocometary belts.
Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of ...such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.
Understanding the nature of bulges in disc galaxies can provide important insights into the formation and evolution of galaxies. For instance, the presence of a classical bulge suggests a relatively ...violent history, in contrast, the presence of simply an inner disc (also referred to as a "pseudobulge") indicates the occurrence of secular evolution processes in the main disc. However, we still lack criteria to effectively categorise bulges, limiting our ability to study their impact on the evolution of the host galaxies. Here we present a recipe to separate inner discs from classical bulges by combining four different parameters from photometric and kinematic analyses: The bulge Sérsic index \(n_\mathrm{b}\), the concentration index \(C_{20,50}\), the Kormendy (1977) relation and the inner slope of the radial velocity dispersion profile \(\nabla\sigma\). With that recipe we provide a detailed bulge classification for a sample of 45 galaxies from the integral-field spectroscopic survey CALIFA. To aid in categorising bulges within these galaxies, we perform 2D image decomposition to determine bulge Sérsic index, bulge-to-total light ratio, surface brightness and effective radius of the bulge and use growth curve analysis to derive a new concentration index, \(C_{20,50}\). We further extract the stellar kinematics from CALIFA data cubes and analyse the radial velocity dispersion profile. The results of the different approaches are in good agreement and allow a safe classification for approximately \(95\%\) of the galaxies. In particular, we show that our new "inner" concentration index performs considerably better than the traditionally used \(C_{50,90}\) when yielding the nature of bulges. We also found that a combined use of this index and the Kormendy (1977) relation gives a very robust indication of the physical nature of the bulge.
The misuse of pharmaceutical opioids is a major public health issue. In Australia, codeine was re-scheduled on 1 February 2018 to restrict access; it is now only available on prescription. The aim of ...this study was to measure the change in dental opioid prescriptions, one year before and after the codeine re-scheduling in Australia and to assess dental prescribing rates of opioids for 2018 by population and by clinician. Data was extracted for dental opioids for the year immediately prior and after the codeine up-schedule (1 February 2017-31 January 2019) from the publicly-available national prescription database (Pharmaceutical Benefits Scheme). Descriptive statistics, T-tests and odds ratios were used to identify significant prescribing differences. Codeine, codeine/paracetamol, oxycodone and tramadol use increased significantly the year after the codeine restriction than the previous year (13.8-101.1%). Australian dentists prescribed 8.6 prescriptions/1,000 population in 2018, with codeine/paracetamol accounting for most prescriptions (96%). The significant increase in opioid prescribing highlights that Australian dentists may be contributing to the misuse of pharmaceutical opioids. Educational efforts should be targeted at the appropriate use of opioids and patient selection. Dentists should be added to the prescription monitoring system SafeScript so they can make informed decisions for patients who are potentially misusing opioids.
Introduction
Hepatic hematoma is a rare but possible complication of ERCP. We describe the case of a 75-year old man with a large, 8 × 12 cm, sub-capsular and intra-parenchymal hematoma post ERCP, ...affecting the right liver segments and treated conservatively.
Areas covered
A review of literature has been performed, highlighting two possible mechanisms: hematoma may occur as the result of accidental laceration of a small intrahepatic vessel by the guidewire, whereas the other hypothesis posits that the hepatic damage is secondary to traction on the biliary system exerted by the balloon. We speculate that in case of anomalies of the biliary tree, the incidence of this complication is higher than expected.
Expert commentary
In case of hepatic hematoma post ERCP, a conservative approach should always be considered before proceeding to interventional radiologic procedures or to surgical therapy.
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