Search

Junglee NA, Di Felice U, Dolci A, Fortes MB, Jibani MM, Lemmey AB, Walsh NP, Macdonald JH. Exercising in a hot environment with muscle damage: effects on acute kidney injury biomarkers and kidney function. Am J Physiol Renal Physiol 305: F813-F820, 2013. First published July 3, 2013; doi:10.1152/ajprenal.00091.2013.--Unaccustomed strenuous physical exertion in hot environments can result in heat stroke and acute kidney injury (AKI). Both exercise-induced muscle damage and AKI are associated with the release of interleukin- 6, but whether muscle damage causes AKI in the heat is unknown. We hypothesized that muscle-damaging exercise, before exercise in the heat, would increase kidney stress. Ten healthy euhydrated men underwent a randomized, crossover trial involving both a 60-min downhill muscle-damaging run (exercise-induced muscle damage; EIMD), and an exercise intensity-matched non-muscle-damaging flat run (CON), in random order separated by 2 wk. Both treatments were followed by heat stress elicited by a 40-min run at 33°C. Urine and blood were sampled at baseline, after treatment, and after subjects ran in the heat. By design, EIMD induced higher plasma creatine kinase and interleukin-6 than CON. EIMD elevated kidney injury biomarkers (e.g., urinary neutrophil gelatinase-associated lipocalin (NGAL) after a run in the heat: EIMD-CON, mean difference [95% CI]: 12 [5, 19] ng/ml) and reduced kidney function (e.g., plasma creatinine after a run in the heat: EIMD-CON, mean difference [95% CI]: 0.2 [0.1, 0.3] mg/dl), where CI is the confidence interval. Plasma interleukin-6 was positively correlated with plasma NGAL (r 0.9, P 0.001). Moreover, following EIMD, 5 of 10 participants met AKIN criteria for AKI. Thus for the first time we demonstrate that muscle-damaging exercise before running in the heat results in a greater inflammatory state and kidney stress compared with non-muscle-damaging exercise. Muscle damage should therefore be considered a risk factor for AKI when performing exercise in hot environments. [ABSTRACT FROM AUTHOR]

Abstract: Background: Glycated hemoglobin (HbA1c) has a key role for diagnosing diabetes and monitoring glycemic state. As recently reviewed, available data on HbA1c biological variation show marked heterogeneity. Here we experimentally revaluated these data using a well designed protocol. Methods: We took five EDTA whole blood specimens from 18 apparently healthy subjects on the same day, every two weeks for two months. Samples were stored at −80°C until analysis and assayed in duplicate in a single run by Roche Tina-quant® Gen.2 immunoassay. Data were analyzed by the ANOVA. To assess the assay traceability to the IFCC reference method, we preliminarily carried out a correlation experiment. Results: The bias (mean±SD) of the Roche immunoassay was 0.3%±0.7%, confirming the traceability of the employed assay. No difference was found in HbA1c values between men and women. Within- and between-subject CV were 2.5% and 7.1%, respectively. Derived desirable analytical goals for imprecision, bias, and total error resulted 1.3%, 1.9%, and 3.9%, respectively. HbA1c had marked individuality, limiting the use of population-based reference limits for test interpretation. The estimated critical difference was ~10%. Conclusions: For the first time we defined biological variation and derived indices for the clinical application of HbA1c measurements using an accurately designed protocol and an assay standardized according to the IFCC. [Copyright &y& Elsevier]

Presents various studies on endocrinology and lipid metabolism. Influence of anti-thyroid antibodies on thyroid reference ranges; Antimutagenic effects of food antioxidants; Impact of micronutrients on antioxidant status and metabolic activity in type 2 diabetics.

This letter to the editor addresses the issue of incomplete information provided by manufacturers regarding the metrological traceability of in vitro diagnostic calibrators, using plasma ethanol as an example. The authors argue that this lack of transparency can hinder accurate measurement in laboratories. They provide examples of manufacturers who do not disclose the traceability of their calibrators. The authors stress the importance of accurate information and measurement uncertainty estimation for identifying analytical limitations and improving standardization. The document includes references to scientific articles and resources related to analytical performance specifications and calibration of breath alcohol analyzers, which may be helpful for library patrons researching forensic science or alcohol analysis. [Extracted from the article]

Background: The water content of ingested beverages enters the body water pool at a rate dictated by the rates of gastric emptying and intestinal absorption. Water is subsequently lost from the body by various routes, primarily urine in the absence of sweating. The post-ingestion diuretic response following prior hypohydration is influenced by several characteristics of the drink, including primarily volume, energy density, electrolyte content, and the presence of diuretic agents. Objective: This study investigated the effects of 13 different commonly-consumed drinks on urine output and fluid balance when ingested in a euhydrated state, with a view to establishing a Hydration Index (HI; i.e. volume of urine produced after drinking expressed relative to a standard treatment [still water]). Design: Each subject (n = 72, euhydrated and fasted males) ingested 1 L of still water or one of three other commercially- available beverages over a period of 30 minutes. Urine output was then collected for the subsequent 4 h. HI was corrected for water content of drinks and was calculated as the amount of water retained at 2 h after ingestion, relative to that observed following ingestion of still water. Results: Total urine masses (mean (SD)) over 4 h were smaller than the still water control (1337(330) g) after oral rehydration solution (ORS, 1038(333) g, P=0.004), full-fat milk (1052(267) g, P=0.006) and skimmed milk (1049(334) g, P=0.005). Cumulative urine output at 4h after ingestion of cola, diet cola, tea, cold tea, coffee, lager, orange juice, sparkling water and a sports drink were not different from the response to water ingestion. The mean HI at 2 h was 1.53(0.74) for ORS, 1.32(0.51) for full-fat milk, and 1.44(0.54) for skimmed milk. Conclusions: An HI may be a useful measure to identify the short-term hydration potential of different beverages when ingested in a euhydrated state. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral drug combinations affect dolutegravir trough concentrations. Here, the authors focused on dolutegravir plus booster darunavir antiretroviral regimens to investigate the effect of the booster and/or timing of drug administration on dolutegravir and darunavir plasma trough concentrations., Methods: This retrospective observational study included consecutive people with HIV (PWH) receiving dolutegravir plus booster darunavir antiretroviral regimens for at least 3 months, with at least one assessment of dolutegravir and darunavir plasma trough concentrations., Results: A total of 200 drug therapeutic drug monitoring results from 116 PWH were included. Dolutegravir and darunavir trough concentrations ranged, respectively, from 70 to 3648 mcg/L and from 102 to 11,876 mcg/L. The antiretroviral drug combination associated with the highest dolutegravir trough concentration was dolutegravir plus darunavir/cobicistat, both once daily (1410 ± 788 mcg/L), whereas dolutegravir once daily plus darunavir/ritonavir twice daily had the lowest trough concentrations (686 ± 481 mcg/L). Doubling the dose of dolutegravir did not significantly increase drug trough concentrations compared with that of once-daily regimens. Instead, the highest darunavir trough concentrations were with ritonavir (2850 ± 1456 mcg/L, P < 0.05 versus cobicistat-based regimens). Doubling the drug dose resulted in a significant increase in the darunavir trough concentration (4445 ± 2926 mcg/L, P < 0.05)., Conclusions: Dolutegravir trough concentrations were significantly reduced in PWH receiving darunavir/ritonavir twice daily. This evidence should be carefully considered in clinical conditions requiring higher dolutegravir exposure, such as in the presence of drug-drug interactions with drugs known to reduce dolutegravir bioavailability or in highly experienced PWH., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project aimed to validate the HbA 1c enzymatic method on the Abbott Alinity c platform and to implement the HbA 1c testing process on the total laboratory automation (TLA) system of our institution., Methods: Three different measuring systems were employed: Architect c4000 stand-alone (s-a), Alinity c s-a, and Alinity c TLA. Eight frozen whole blood samples, IFCC value-assigned, were used for checking trueness. A comparison study testing transferability of HbA 1c results from Architect to Alinity was also performed. The alignment of Alinity TLA vs. s-a was verified and the measurement uncertainty (MU) estimated according to ISO 20914:2019. Turnaround time (TAT) and full time equivalent (FTE) were used as efficiency indicators., Results: For HbA 1c concentrations covering cut-offs adopted in clinical setting, the bias for both Architect and Alinity s-a was negligible. When compared with Architect, Alinity showed a mean positive bias of 0.54 mmol/mol, corresponding to a mean difference of 0.87%. A perfect alignment of Alinity TLA to the Alinity s-a was shown, and a MU of 1.58% was obtained, widely fulfilling the desirable 3.0% goal. After the full automation of HbA 1c testing, 90% of results were released with a maximum TAT of 1 h, 0.30 FTE resource was also saved., Conclusions: The traceability of Alinity HbA 1c enzymatic assay to the IFCC reference system was correctly implemented. We successfully completed the integration of the HbA 1c testing on our TLA system, without worsening the optimal analytical performance. The shift of HbA 1c testing from s-a mode to TLA significantly decreased TAT., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

The use of procalcitonin (PCT) as a tool to assist clinicians in using antibiotics in intensive care patients has been postulated. Here we evaluate the efficacy of procalcitonin determination in helping clinicians in the decision to start or discontinue an antibiotic treatment in patients admitted to infectious disease wards. A retrospective observational single centre study was conducted in two infectious disease wards. Descriptive and inferential statistical analysis was carried out and receiver operating characteristic curves and area under the curve (AUC) were used to assess the accuracy of PCT and C-reactive protein (CRP) in separating patients undergoing antibiotic treatment or otherwise. In all, 164 patients were analysed of whom 99 (60.4%) were not on antibiotic treatment at the time of PCT determination, whereas 65 (39.6%) took antibiotics. Regarding the accuracy of PCT and CRP in determining a subsequent antibiotic prescription in patients without an ongoing antibiotic treatment, no statistically significant difference between the two markers was detected [AUC, 0.75; confidence interval (CI) 95%: 0.66-0.84; vs 0.69; CI 95%: 0.59-0.79 for PCT and CRP, respectively; p=0.32]. Conversely, in patients with an ongoing antibiotic treatment a statistically significant difference between PCT and CRP AUC in their ability to determine an antibiotic interruption was observed [0.77 (CI 95%: 0.65-0.89) vs 0.59 (CI 95%: 0.45-0.73) (p=0.03)]. PCT determination appeared to be more helpful than CRP in determining discontinuation of an antibiotic treatment in non-intensive care patients. However, PCT should supplement and not supplant a careful clinical evaluation.

Background: The morphological examination of urinary sediment (MEUS) is traditionally associated with urinalysis (UA), with workload implications and the need for automation of its execution., Methods: Considering MEUS as a test requiring specialized knowhow and skill for its execution, since 2005 in our laboratory it is performed for inpatients only upon specific request. Eleven years after, we have analyzed the long-term impact of this approach on the provided service. We evaluated results in the 2009-2016 period, in which our hospital did not undergo any change both in the number of beds and in the clinical case-mix., Results: From 2009 to 2013 an average of 2264 MEUS and 10,204 UA per year were ordered, respectively, with an average ratio of 22.2%. Since 2014, a change on computerized order entry involving MEUS caused a further decrease of its requests (in average, 923 per year), which was not associated to a decrease in UA (in average, 9810 per year) (in average, MEUS/UA 9.4%). MEUS requests came mainly from Paediatrics (47.8%), Nephrology (20.9%) and Rheumatology (18.3%) wards. By filling a satisfaction survey, clinical wards evaluated the provided service as satisfactory, while highlighting some critical issues, mainly referred to preanalytical phase., Conclusions: The alternative proposal for managing MEUS presented in this paper markedly reduces the number of requests and increases their appropriateness. This is achieved without any negative impact on patient care., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Chemotherapy is a well established therapeutic approach for several malignancies, but its clinical efficacy is often limited by related cardiotoxicity leading to cardiomyopathy evolving towards heart failure that may worsen the patient outcome. To detect cardiac damage, the most frequently adopted diagnostic approach is the estimation of left ventricular ejection fraction by echocardiography, showing, however, low sensitivity in early prediction of cardiomyopathy, when appropriate treatments could still improve the patient's outcome. Cardiospecific biomarkers, like cardiac troponins, show high diagnostic efficacy in the early, subclinical phase of disease, becoming positive approximately 3 months before clinical onset of cardiomyopathy. Furthermore, the increase in their concentrations is well correlated with the disease severity and may predict the occurrence of major cardiac events during follow-up. On the other hand, negative troponin concentrations may identify patients with a very low risk of cardiomyopathy (negative predictive value = 99%). For cardiac natriuretic peptides, definitive evidence about a diagnostic or prognostic role in predicting chemotherapy-induced cardiomyopathy is lacking and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined.

Background: The Joint European Society of Cardiology and the American College of Cardiology Committee has recently reviewed the criteria to diagnose myocardial infarction, focusing on the central role of biochemical criterium and indicating the cardiac troponins as the reference marker. However, at present, little is known upon how "old" and "new" biochemical markers of myocardial damage are utilized in daily clinical practice., Methods: We performed a survey across the whole set of Italian coronary care units (CCUs) to evaluate the actual behavior of the clinicians in detecting myocardial necrosis with the biomarkers. A simple and brief questionnaire was used to pursue such purpose., Results: The feedback from CCUs was positive in 87.6% (303/346). The creatine kinase-MB is the most frequently used biomarker, however the "mass concentration" method was utilized in a minority of centers (38%). More than 60% of the CCUs are still measuring obsolete biomarkers as lactic dehydrogenase or aspartate transaminase. Cardiac troponins are measured only in 70% of the centers, and almost always in conjunction with the "old" biomarkers. Additionally, 14.5% of the Italian CCUs had written guidelines upon how to use the biomarkers to pose diagnosis of myocardial infarction. Biochemical criteria widely differed from center to center, regardless of the biomarker selected as reference standard., Conclusions: The results of our survey show a high degree of difference in the choice as well as in the application criteria of biochemical markers for diagnosing myocardial infarction among the Italian CCUs. A great deal of confusion has been accumulating over the years among Italian cardiologists, and this situation was antecedent to the recently released revised criteria for detecting myocardial necrosis.

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cut-off of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cutoff of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.