Which laboratory technique is used for the blood sodium analysis in clinical research? A systematic review.

Circulating sodium is analyzed by flame spectrometry and indirect or direct potentiometry. The differences between estimates returned by the three techniques are often relevant. It is unknown whether peer-reviewed international publications focusing on this parameter provide information about the technique. Objectives of the study were to ascertain if information about the employed technique is provided. A search in the National Library of Medicine for articles whose title contains "hyponatr[a]emia" was performed. We restricted the search to clinical reports including 10 or more humans published in the 2013-2015 and 2017-2019 periods. Authors of papers not reporting the technique were contacted to obtain this information. The study design and journal quartile ranking of each article were also evaluated. For the final analysis, we included 361 articles (2013-2015, n=169; 2017-2019, n=192). Information about the laboratory technique was given in 61(17%) articles. Thanks to our inquiry, we collected this information for 116(32%) further reports. Indirect potentiometry was the most frequently used technique, followed by direct potentiometry. Spectrometry was used in a small minority of studies. Study design, journal ranking and study period did not modulate the mentioned frequency. Most articles focusing on hyponatremia do not provide information on the laboratory technique. This parameter is nowadays analyzed by indirect or, less frequently, direct potentiometry. The figures are similar for high and low impact factor journals and for the 2013-2015 and the 2017-2019 periods. Many authors, reviewers and editors likely assume that the results of this parameter are not influenced by the technique

Interferences in the measurement of circulating phosphate: a literature review.

Background Inorganic phosphate in blood is currently determined by the reaction with molybdate. This report aims at reviewing conditions underlying spuriously altered levels of circulating inorganic phosphate. Content A systematic search of the Excerpta Medica, the National Library Database and the Web of Science database was conducted without language restriction from the earliest publication date available through January 31, 2020. Summary For the analysis, 80 reports published in English (n = 77), French (n = 1), German (n = 1) and Spanish (n = 1) were retained. Well-documented pseudohyperphosphatemia was observed in individuals exposed to liposomal amphotericin, in patients affected by a gammopathy, in patients with hyperlipidemia and in patients with hyperbilirubinemia. An unexplained elevated inorganic phosphate level sometimes provided a clue to the diagnosis of a gammopathy. Well-documented cases of pseudohypophosphatemia were observed in patients on large amounts of intravenous mannitol. Finally, pseudohypophosphatemia was occasionally observed on treatment with liposomal amphotericin and in patients with a gammopathy. Outlook In order to avoid unnecessary testing and treatment, the phenomenon of spuriously altered inorganic phosphate should be recognized. An unexplained hyperphosphatemia may provide a clue to the diagnosis of a gammopathy or a severe hyperlipidemia

Trimethoprim-associated electrolyte and acid-base abnormalities.

The antimicrobial trimethoprim is structurally related to potassium-sparing diuretics and may consequently lead to derangements in electrolyte and acid-base balance. Since no report so far analyzed the literature documenting individual cases with electrolyte and acid-base derangements induced by trimethoprim, a systematic review was carried out. We retained 53 reports documenting 68 cases (42 males and 26 females 23 to 96 years of age) of electrolyte or acid-base derangements occurring on trimethoprim for about 5 days. One hundred five electrolyte imbalances were detected in the 68 patients: hyperkalemia (>5.0 mmol/L) in 62 (91%), hyponatremia (<135 mmol/L) in 29 (43%) and metabolic acidosis (pH<7.38 and bicarbonate <19 mmol/L) in 14 (21%) cases. Following possible predisposing factors for electrolyte and acid-base abnormalities were found in 54 (79%) patients: high-dose trimethoprim, comedication with drugs that have been associated with electrolyte and acid-base derangements, preexisting kidney disease, age ≥80 years and diabetes mellitus. High-dose trimethoprim, comedicated with drugs that have been associated with electrolyte and acid-base derangements, poor kidney function, age ≥80 years and diabetes mellitus predispose to trimethoprim-associated electrolyte and acid-base abnormalities. Clinicians must recognize patients at risk, possibly avoid drug combinations that may worsen the problem and monitor the laboratory values

Pyuria and microbiology in acute bacterial focal nephritis: a systematic review.

Presentation and imaging findings of acute focal bacterial nephritis, a localized renal infection not containing drainable pus, have been extensively addressed. The aim of this review was to assess the prevalence of cases without pyuria or bacteriuria and the spectrum of microorganisms underlying this condition. We conducted a systematic review of the literature in the National Library of Medicine and Excerpta Medica databases. For the final analysis, we retained 54 reports published between 1981 and 2018 describing 251 patients affected by focal bacterial nephritis, who have been specifically investigated with respect to urinalysis and standard bacterial cultures. They were 177 (102 females and 75 males) subjects ≤20 and 74 (57 females and 17 males) >20 years of age. Pyuria and bacteriuria were absent in 33 cases, while pyuria was not associated with bacteriuria in 5 further cases. The vast majority of culture-positive cases were caused by Enterobacteriaceae (slightly less than 80%) and Pseudomonas species (approximately 10%). Enterococcus species and Staphylococcus aureus were isolated in slightly more than 10% of the cases. A large subset of patients affected by focal bacterial nephritis present without pyuria and significant bacteriuria. The initial management consists of broad-spectrum antimicrobials with high tissue penetration, active against Enterobacteriaceae, Pseudomonas species, Enterococcus species and Staphylococcus aureus

Trimethoprim-associated hyperkalaemia: a systematic review and meta-analysis.

Trimethoprim is structurally similar to potassium-sparing diuretics and may induce hyperkalaemia. The prevalence and the factors that predispose to trimethoprim-associated hyperkalaemia have never been extensively addressed. A literature search with no date or language limits was carried out using the National Library of Medicine, Embase and Web of Science in March and repeated during August 2021. The principles underlying the Economic and Social Research Council guidance on the conduct of synthesis and the PRISMA guidelines were employed. For the analysis, we retained reports including ≥10 subjects on treatment with trimethoprim, which addressed the possible occurrence of hyperkalaemia. Eighteen reports were retained for the final analysis. The pooled prevalence of potassium value >5.0 mmol/L, >5.5 mmol/L and >6.0 mmol/L or symptomatic, was, respectively, 22%, 10% and 0.2%. The analysis disclosed that the risk of trimethoprim-associated hyperkalaemia is dose-related and enhanced by drugs with known hyperkalaemic potential including potassium-sparing diuretics, renin-angiotensin-aldosterone system inhibitors, β-blockers and non-steroidal anti-inflammatory agents. Poor kidney function also increased the tendency towards hyperkalaemia. The time to onset of hyperkalaemia was generally 1 week or less after starting trimethoprim. The present analysis documents the hyperkalaemic potential of trimethoprim, a widely prescribed drug that was introduced more than 50 years ago. Clinicians must recognize patients at risk of trimethoprim-associated hyperkalaemia

Selective ß2-Adrenoceptor Agonists and Relevant Hyperlactatemia: Systematic Review and Meta-Analysis.

Selective ß <sub>2</sub> -agonists have been imputed as potential cause of l-hyperlactatemia since the 1970s. To document the prevalence of hyperlactatemia associated with selective ß <sub>2</sub> -agonists and to investigate the predisposing factors, we searched for published articles until April 2019 pertaining to the interplay of administration of selective ß <sub>2</sub> -agonists and circulating l-lactic acid in the Excerpta Medica, Web of Science, and the U.S. National Library of Medicine databases. Out of the 1834 initially retrieved records, 56 articles were included: 42 papers reporting individual cases, 2 observational studies, and 12 clinical trials. Forty-seven individual patients receiving a selective ß <sub>2</sub> -agonist were found to have l-lactatemia ≥5.0 mmol/L, which decreased by ≥3.0 mmol/L or to ≤2.5 mmol/L after discontinuing (N = 24), reducing (N = 17) or without modifying the dosage of the selective ß <sub>2</sub> -agonist (N = 6). Clinical trials found that l-lactic acid significantly increased in healthy volunteers administered a ß <sub>2</sub> -agonist. l-lactatemia ≥5.0 mmol/L was observed in 103 (24%) out of 426 patients with asthma or preterm labor managed with a selective ß <sub>2</sub> -agonist and was more common in patients with asthma (30%) than in premature labor (5.9%). A significant relationship was also noted between l-lactate level and intravenous albuterol dose or its circulating level. In conclusion, relevant l-hyperlactatemia is common on high dose treatment with a selective ß <sub>2</sub> -agonist

Ibuprofen-Associated Hypokalemia and Metabolic Acidosis: Systematic Literature Review.

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has been occasionally associated with hypokalemia and metabolic acidosis. The objective of this report is to analyze the literature on this issue and to address the underlying pathophysiology. Excerpta Medica, the National Library of Medicine, and Web of Science were searched from inception to July 16, 2021. Papers reporting individually documented humans on ibuprofen with hypokalemia, acidosis, or both were retained. Data were extracted using a checklist. For the final analysis, we evaluated 41 reports describing 50 cases (26 males and 24 females; 36 adults and 14 children) with often profound hypokalemia, acidosis, or both after ingestion of ibuprofen. Twenty-six cases were acute and 24 long term. Hypokalemia and acidosis occurred not only after ingestion of very high doses but also after ingestion of moderately high or even normal doses of ibuprofen. Laboratory values consistent with an excessive urinary potassium excretion or an altered urinary acidification were often disclosed in most cases. Discontinuation of ibuprofen resulted in a resolution of hypokalemia and acidosis within days in 47 cases. The course was lethal in 3 cases. This review highlights potentially fatal side effects of ibuprofen and can help doctors who are confronted with such a situation. These data highlight the potential of ibuprofen to occasionally induce hypokalemia and acidosis of renal origin. Discontinuation of ibuprofen results in a resolution within days

Magnesium Metabolism in Chronic Alcohol-Use Disorder: Meta-Analysis and Systematic Review.

Chronic alcohol-use disorder has been imputed as a possible cause of dietary magnesium depletion. The purpose of this study was to assess the prevalence of hypomagnesemia in chronic alcohol-use disorder, and to provide information on intracellular magnesium and on its renal handling. We carried out a structured literature search up to November 2020, which returned 2719 potentially relevant records. After excluding non-significant records, 25 were retained for the final analysis. The meta-analysis disclosed that both total and ionized circulating magnesium are markedly reduced in chronic alcohol-use disorder. The funnel plot and the Egger's test did not disclose significant publication bias. The I <sup>2</sup> -test demonstrated significant statistical heterogeneity between studies. We also found that the skeletal muscle magnesium content is reduced and the kidney's normal response to hypomagnesemia is blunted. In conclusion, magnesium depletion is common in chronic alcohol-use disorder. Furthermore, the kidney plays a crucial role in the development of magnesium depletion

Acute Pancreatitis Associated with Atypical Bacterial Pneumonia: Systematic Literature Review.

Extra-pulmonary features sometimes occur in association with atypical bacterial pneumonia and include neurologic manifestations, diarrhea, rashes, altered liver enzymes, or kidney injury, among other conditions. Acute pancreatitis has been associated with atypical pneumonias since 1973. We performed a systematic review of the literature in the Excerpta Medica, National Library of Medicine, and Web of Science databases. We retained 27 reports published between 1973 and 2022 describing subjects with an otherwise unexplained pancreatitis temporally associated with an atypical pneumonia. The reports included 33 subjects (19 males, and 14 females; 8 children and 25 adults) with acute pancreatitis temporally associated with atypical pneumonia caused by Mycoplasma pneumoniae (n = 18), Legionella species (n = 14), or Coxiella burnetii (n = 1). Approximately 90% of patients (n = 29) concurrently presented with respiratory and pancreatic diseases. No cases associated with Chlamydophila pneumoniae, Chlamydophila psittaci, or Francisella species were found. Acute pancreatitis has been associated with various infectious agents. The present review documents the association with atypical pneumonia induced by Mycoplasma pneumoniae, Legionella species, and Coxiella burnetii

Coronavirus disease 2019, vaccination against coronavirus and immunoglobulin A-mediated diseases: systematic literature review.

Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with autoimmune phenomena. However, the interplay between COVID-19 or vaccination against SARS-CoV-2 and Berger glomerulonephritis or Henoch-Schönlein vasculitis, two diseases mediated by immunoglobulin A, has never been comprehensively investigated. Therefore, we carried out a systematic review of the literature on this topic. Following databases were used: Google Scholar, Excerpta Medica and the United States National Library of Medicine. Eighty-seven patients with immunoglobulin A-mediated diseases associated with SARS-CoV-2 infection or vaccination against coronavirus were sorted out (53% males, 47% females; 34 17-51 years of age, median and interquartile range): 47 cases of Berger glomerulonephritis and 40 of Henoch-Schönlein vasculitis. Approximately 50% (N = 24) of Berger glomerulonephritis and 10% (N = 4) of Henoch-Schönlein vasculitis patients presented with a pre-existing history of immunoglobulin A-mediated disease. Almost all cases of Berger glomerulonephritis were vaccine-associated (N = 44; 94%), while most cases of Henoch-Schönlein vasculitis were infection-associated (N = 23; 57%). Among vaccine-associated immunoglobulin A diseases, about 90% were associated to mRNA-based vaccines. Our analysis supports the hypothesis that COVID-19 and vaccination against SARS-CoV-2 may trigger or exacerbate an immunoglobulin A-mediated diseases