We tested the
susceptibility of ceftazidime-avibactam and ceftolozane-tazobactam and 13 other antibiotics against 91
complex (BCC) strains isolated from cystic fibrosis patients since 2012. The ...highest susceptibility (82%) was found for trimethoprim-sulfamethoxazole. Eighty-one and 63% of all BCC strains were susceptible to ceftazidime-avibactam and ceftolozane-tazobactam, respectively. For temocillin, ceftazidime, piperacillin-tazobactam, and meropenem, at least 50% of the strains were susceptible.
seems to be more resistant than other BCC species.
When using indirect ion-selective electrode (ISE) methods, hypertriglyceridemia leads to pseudohyponatremia due to water displacement artifacts. Multiple strategies exist to minimize this ...interference. Our objective was to create a patient-friendly one-tube-fits-all testing setup without compromising the method robustness.
Four strategies were evaluated in a single patient with hypertriglyceridemia. Additionally, the interchangeability between the Cobas 8000 and ABL Flex was evaluated on samples (n = 2274) with different total protein (TP) concentrations. Finally, a proof-of-concept (n = 40) was performed by re-measuring the routine sample with the ABL90 Flex.
ABL90 flex results and calculated sodium did not suffer from the presence of high triglyceride levels. We did not observe any significant differences between the three groups (P > 0.05) of sample types (arterial vs. venous plasma vs. venous whole blood after mixing up) nor for the analysers (Roche vs. ABL90 Flex). Passing-Bablok and Bland-Altman tests revealed interchangeability.
In future cases of hypertriglyceridemia, 1500 mg/dL will be used as a preliminary threshold for reliable sodium determination. Routine Li-heparin samples can be used for accurate sodium determination without any need for extra arterial or venous blood gas tubes, offering a patient-friendly test setup for similar cases.
Summary
In first‐degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA‐2) and zinc transporter 8 (ZnT8) antibody ...status (IA‐2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA‐2A with or without ZnT8A in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow‐up of 6444 siblings and offspring aged 0–39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA+, GADA+, IA‐2A+ and/or ZnT8A+ relatives (6·1%). After a median follow‐up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0–9, 10–19 and 20–39 years) progression to diabetes was significantly quicker in the presence of IA‐2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age‐independent in IA‐2A+ and/or ZnT8A+ relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10–39 years), screening for IA‐2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for ≥ 2 antibodies among IAA, GADA, IA‐2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA‐2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost‐effective to select participants for intervention trials than conventional screening.
Multi-modality imaging is rapidly becoming an essential tool in oncology. Clinically, the best example of multimodality imaging is seen in the rapid evolution of hybrid positron emission tomography ...(PET)/computed tomography (CT) and single positron emission computed tomography (SPECT)/CT scanners. However, use of multi-modality imaging is prone to artefacts and pitfalls. Important artefacts that may lead to clinical misinterpretation result from the use of CT data to correct for attenuation and the existence of mismatches between the fused images, for example due to respiratory movement. Furthermore, for institutions who proceed from a standalone PET to a hybrid PET-CT, there is an issue of interchangeability between these systems, especially for quantitative studies. Another issue is visualisation: hospital PACS is not sufficiently capable of adequately viewing integrated images. This article reviews and illustrates the most common artefacts and pitfalls that can be encountered in multi-modality nuclear medicine imaging. For correct management of oncological patients it is essential to be able to detect and correctly interpret these artefacts and pitfalls. Therefore, solutions and recommendations to these problems are provided.
Background and Aims
Thiazolidinediones (TZDs) and glucagon‐like peptide‐1 (GLP‐1) receptor agonists are potential pharmacological treatment options for patients at risk of NAFLD. Therefore, we ...examined the association between the risk of NAFLD and the use of TZDs and GLP‐1 receptor agonists compared with the use of sulfonylureas (SUs) and insulins. Additionally, we calculated the incidence of HCC in users of TZDs and GLP‐1 receptor agonists.
Approach and Results
We conducted a population‐based cohort study using primary care data from the Clinical Practice Research Datalink database (2007‐2018). All patients aged ≥18 with a prescription of an oral glucose‐lowering agent or GLP‐1 receptor agonist were included. The first prescription defined the start of follow‐up. The primary outcome was a new diagnosis of NAFLD. Cox proportional hazards regression was used to estimate HRs and 95% CIs of the primary outcome. Incidence rates of HCC were determined per 1,000 person‐years for all exposures. The study identified 207,367 adults with a prescription for a glucose‐lowering agent. The risk of NAFLD was lower in patients prescribed a TZD than in those prescribed an SU (adjusted HR aHR, 0.32; 95% CI, 0.20‐0.51). No difference in risk of NAFLD was observed comparing GLP‐1 receptor agonist use with insulin use (aHR, 1.22; 95% CI, 0.91‐1.63).
Conclusions
Results of our study endorse the use of TZDs for selected patients at risk of NAFLD but do not support previous findings regarding the beneficial effect of GLP‐1 receptor agonists. The low number of events in several subgroups may affect the generalizability of the current findings.
Aim
To investigate the association between the use of incretin agents and the risk of pancreatic cancer.
Methods
A retrospective population‐based cohort study, using data from the Clinical Practice ...Research Datalink, 2007–2012, was conducted. Patients (n = 182 428) with at least one non‐insulin antidiabetic drug (NIAD) prescription and aged ≥18 years during data collection, were matched one‐to‐one to control patients without diabetes. Multivariable Cox proportional hazards models and a new user design were used to estimate the hazard ratio (HR) of pancreatic cancer in incretin users (n = 28 370) compared with control subjects without diabetes and other NIAD‐treated patients. Time‐dependent adjustments were made for age, sex, lifestyle, comorbidities and drug use.
Results
The mean duration of follow‐up was 4.1 years for incretin users. Current NIAD use was associated with a fourfold increased risk of pancreatic cancer HR 4.28, 95% confidence interval (CI) 3.49–5.24. This risk was almost doubled among current incretin users as compared with control subjects. Incretin use was not associated with pancreatic cancer when compared with control subjects with diabetes (HR 1.36, 95% CI 0.94–1.96); however, the ‘new user’ design did show an association between incretin use and pancreatic cancer when compared with control subjects with diabetes. In both cohorts with prevalent and incident users of antidiabetic drugs, the risk of pancreatic cancer almost doubled in those who had recently initiated incretin therapy (up to seven prescriptions), whereas this elevated risk dropped to baseline levels with prolonged use.
Conclusions
We found that incretin use was not associated with pancreatic cancer after adjustment for the severity of the underlying Type 2 Diabetes Mellitus (T2DM). The elevated risk of pancreatic cancer in those recently initiating incretin agents is likely to be caused by protopathic bias or other types of unknown distortion. The presence of considerable confounding by disease severity and the lack of a duration‐of‐use relationship do not support a causal explanation for the association between incretin agents and pancreatic cancer.
The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive ...function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release.
Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive first-degree relatives (n = 49; age 5-39) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range).
TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r2 = 0.96-0.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day %CV for PI:C at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods). In high-risk relatives fasting PI:C was significantly and inversely correlated (rs = -0.596; P<0.001) with first-phase C-peptide release during clamp (also with second phase release, only available for age 12-39 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release.
The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test.
Chloride measurement is crucial for calculating the anion gap. Bicarbonate can interfere with chloride measurements; however, there is no information on the specific types of electrodes affected or ...the changes in bicarbonate non-selectivity over time. We evaluated the interference of bicarbonate on chloride measurements using different electrodes and the stability of this interference over time.
The effect of bicarbonate on chloride measured with electrodes of various manufacturers was assessed. When non-selectivity toward bicarbonate was observed, the stability of this interference during the electrode's lifetime was explored. The impact of the bicarbonate concentration on the calibrator was also evaluated.
Non-selectivity was observed for electrodes using quaternary ammonium salts (Beckman Coulter, Siemens, and Roche), with overestimated or underestimated chloride values observed at high or low bicarbonate concentrations, respectively. The degree of selectivity varied among electrodes. With the Roche electrode, interference became more pronounced over time, whereas the Siemens electrode appeared to gain selectivity during its lifetime. For the Roche system, adjusting the calibrator's bicarbonate concentration from 30 mmol/L to 20-24 mmol/L reduced the number of samples with unacceptable bias (>3%) from 77.3% to 12.6%. Lot-to-lot variations in the calibrator bicarbonate concentration increased the uncertainty of chloride measurements.
The extent of bicarbonate-induced error varied according to the type, manufacturer, and wear of the electrode; the bicarbonate concentration in the calibrators and the tested sample; and the chloride content. Laboratories should be aware of the impact of bicarbonate on routine chloride measurements to establish appropriate QC procedures.
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