Incidence, associated factors, and effect on renal function of amoxicillin crystalluria in patients receiving high doses of intravenous amoxicillin (The CRISTAMOX Study): A cohort study.

Background: Amoxicillin crystalluria (AC), potentially responsible for acute kidney injury (AKI), is reported more and more frequently in patients treated with high doses of intravenous amoxicillin (HDIVA). The main objective of this study was to evaluate AC incidence in these patients. The secondary objectives were to identify factors associated with AC and to evaluate its impact on the risk of AKI. Methods: This multicentre, observational, cohort study was conducted between Mar 18, 2014 and Aug 16, 2019 in Dijon, Nancy, and Reims University Hospitals as well as Châlon-sur-Saône, Charleville-Mézières, and Troyes general hospitals in France. Adult patients (≥18 years) treated with HDIVA and having been tested for AC at least once during treatment were included. Clinical, biological, and therapeutic characteristics of the patients were collected. A univariable mixed logistic regression model assessed the factors associated with AC. A multivariable Cox model with AC as a time-dependent variable assessed the prognostic factors for AKI. ClinicalTrials.gov number: NCT02853292. Findings: Of the 112 included patients, 27 (24.1%, 95% CI [16.2-32.0]) developed at least one episode of AC within a mean of 5.1 days. The factors associated with its occurrence were the concomitant use of angiotensin converting enzyme (ACE) inhibitors (OR=4.6, 95% CI [2.2-9.3], p<0.0001) and the decrease of urinary pH (OR=2.1 for one pH point decrease, 95% CI [1.2-3.7], p=0.009). 20 patients (17.9%) presented with AKI, within a mean time of 10.9 days. The main factor associated with the occurrence of AKI was the occurrence of AC (aHR=7.4, 95% CI [2.5-22.2], p=0.0003). Interpretation: AC occurred in a quarter of patients treated with HDIVA and was highly prognostic of AKI. Funding: None.

LogiKEy workbench: Deontic logics, logic combinations and expressive ethical and legal reasoning (Isabelle/HOL dataset).

The LogiKEy workbench and dataset for ethical and legal reasoning is presented. This workbench simultaneously supports development, experimentation, assessment and deployment of formal logics and ethical and legal theories at different conceptual layers. More concretely, it comprises, in form of a dataset (Isabelle/HOL theory files), formal encodings of multiple deontic logics, logic combinations, deontic paradoxes and normative theories in the higher-order proof assistant system Isabelle/HOL. The data were acquired through application of the LogiKEy methodology, which supports experimentation with different normative theories, in different application scenarios, and which is not tied to specific logics or logic combinations. Our workbench consolidates related research contributions of the authors and it may serve as a starting point for further studies and experiments in flexible and expressive ethical and legal reasoning. It may also support hands-on teaching of non-trivial logic formalisms in lecture courses and tutorials. The LogiKEy methodology and framework is discussed in more detail in the companion research article titled "Designing Normative Theories for Ethical and Legal Reasoning: LogiKEy Framework, Methodology, and Tool Support" [5].

[Evaluation of an automated system of immunofluorescence analysis in daily practice]. / Évaluation des performances d'un système automatisé de lecture d'immunofluorescence en pratique quotidienne.

Since a few years indirect immunofluorescence (IIF) enjoys automated screening. These automated systems give an interpretation for the detection of anti-nuclear (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) and take images in the case of the research of anti-tissue antibodies. We propose an evaluation of the Image Navigator® system for all these kinds of research. 1,435 sera samples are included: 810 for ANA detection, 450 for ANCA detection, 175 for anti-tissue antibodies research. Visual interpretation using microscope is compared to automated interpretation and visual interpretation using the pictures. Sensibility of the automated interpretation to artifacts is assessed too. Accordance between automated interpretation and visual interpretation using microscope is moderate (kappa=0.46) in the case of ANA detection, poor in the case of ANCA detection (kappa=0.30). Accordance between visual interpretation using microscope and visual interpretation using pictures is strong for ANA (kappa=0.79) and for ANCA (kappa=0.63), very strong for anti-tissues antibodies (kappa=0.87). The blur of more than one photography interferes with the interpretation of the system (p<0.01). In any case, a second reading is necessary. The results of our study validate the use of the pictures for the interpretation of AAN but require visual interpretation using microscope for ANCA. The screening of anti-tissue antibodies can be achieved using pictures.

[Chronic kidney failure and biotin: A combination inducing unusual results in thyroid and parathyroid investigations, report of 2 cases]. / Insuffisance rénale chronique et biotine : un duo propice aux bilans thyroïdiens et parathyroïdiens erronés, à propos de 2 cas.

In clinical chemistry, many immunoassays apply biotin and streptavidin in the assay principle. Presence of high levels of biotin in patient samples can produce negative or positive interference depending on the assay format. In this study, we describe 2 clinical cases with chronic kidney failure and with unusual thyroid and parathyroid function test results due to biotin interference. We studied the impact of biotin levels on thyroid stimulating hormone (TSH), free thyroxine (T4L) and parathormone (PTH) results with a pool of sera loaded with several concentrations of biotin. In sandwich assays (TSH and PTH), excess biotin displaces biotinylated antibodies resulting in apparently low concentration of the analyte. With competitive immunoassays (T4L), excess biotin competes with biotinylated analog for the binding sites on streptavidin resulting in low signal and falsely high concentration of the analyte. In conclusion, chronic kidney failure combined to therapeutic biotin is in favour of high levels of biotin which causes seriously misleading results in assays using biotin-streptavidin mechanisms.

[Crystalluria in ethylene glycol intoxication]. / La cristallurie dans l'intoxication à l'éthylène glycol.

When seen, some habits of calcium oxalate monohydrate crystals (whewellite) are so typical of ethylene glycol intoxication that they may be helpful for its diagnosis when circumstances are not clearly established.

[Felbamate crystalluria]. / Cristallurie de felbamate.

This report describes the case of an 11-year-old child, who presents crystalluria occurring after several years of treatment with antiepileptic felbamate (Taloxa®). The crystalline morphologies observed were very heterogeneous, long and thin needle shapped-crystals or even hairy crystals or large needle asymmetric crystals. Crystals showed an intense polarization and a strong tendency to aggregation. An infrared spectrum (KBr pellets) recorded in washed and dried urinary sediment demonstrated that these crystals are felbamate crystals. Crystal does not contain any Ca2+ and is not sensitive to pH changes suggesting that crystallization risk will not be affected by the potential association of felbamate with an inhibitor of carbonic anhydrase. After admission, creatinine level was in normal range but hematuria described by the child's mother could be symptomatic of even greater crystallization episodes and substantiate obstructive risk. A permanent good dilution of urine is the key measure to control risk of crystallization. Regular monitoring of urine specific gravity and urinary red cells by simple urine dipstick test can be proposed.

[Acute renal failure following a treatment with acyclovir]. / Insuffisance rénale aiguë lors d'un traitement par aciclovir.

UNLABELLED: The antiviral molecule acyclovir can be responsible of severe renal dysfunction. Intratubular crystal precipitation of the drug may represent a major pathogenetic mechanism. OBSERVATION: A 30-year old, immunocompetent woman was admitted in the neurology unit for a viral meningo-encephalitic syndrome. Intravenous acyclovir was delivered at the dose of 45 mg/kg per day. Despite a neurological improvement, she developed an acute renal insufficiency with the serum creatinine increasing from 63 to 385 micromol/L within 12 days. The urine study revealed great amounts of birefringent crystals which were typical of acyclovir derived crystals according to the spectrophotometric examination. Withdrawal of acyclovir treatment in combination with oral and parenteral hydration resulted in a complete recovery of the renal function. The conditions favouring acyclovir-induced nephrotoxicity are discussed.

[Delayed measurement of PTH in patients with CKD: storage of the primary tube in the dialysis unit, which temperature? Which kind of tube?]. / Conservation du tube primaire sur le site de dialyse en vue du dosage différé de la PTH : quels tubes ? Quelle température ?

Parathyroid hormone (PTH) is measured in patients with chronic kidney disease (CKD) to evaluate the spread of secondary hyperparathyroidism and to identify renal osteodystrophy subtypes. An important intermethod variability that can significantly influence the clinical decision has been highlighted recently. Similarly, it is acknowledged that the preanalytical conditions are important to optimize the interpretation of a PTH level by comparison with the K/DOQI guidelines. Considering the frequent case of a dialysis patient in whom blood is handled in the evening and addressed to the clinical laboratory the next morning, we have evaluated the stability of the PTH concentration during a 18-hour period. We thus measured PTH with three automated assays in three kinds of tubes (plain tubes with a gel separator, EDTA tubes, EDTA+aprotinin tubes) which were either immediately centrifugated with a prompt freezing of the serum or plasma, or stored for 18hours at room temperature or at 4 degrees C. Our results demonstrate that, whatever the kind of tube, the PTH concentration is not altered by a 18-hour storage at 4 degrees C which is not the case at room temperature. Using a tube with a gel separator necessitates however to centrifugate the tube in the dialysis unit. On the other hand, the use of serum, by contrast with EDTA plasma, allows the measurement of other biological parameters including calcium, does not need that the tube is fully filled and, according to our results, reduces the intermethod variability. In conclusion, this study shows that the measurement of PTH may be delayed by 18hours if the primary tube is kept at 4 degrees C. Assuming that the primary tube is centrifugated but not opened in the dialysis unit, serum may be the sample of choice for the measurement of PTH in patients with CKD.