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Background Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury. Methods We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered. Results For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-[beta]-glucosaminidase, was often noted. Conclusions Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. Graphical abstract, Author(s): Giulia Anguissola [sup.1] , Dennis Leu [sup.2] , Giacomo D. Simonetti [sup.1] [sup.2] , Barbara Goeggel Simonetti [sup.1] [sup.2] [sup.3] , Sebastiano A. G. Lava [sup.4] [sup.5] , Gregorio [...]

Background Kidney diseases are a recognized cause of posterior reversible leukoencephalopathy syndrome, usually abbreviated as PRES. The purpose of this review was to systematically address the association between acute postinfectious glomerulonephritis and PRES. Methods We performed a systematic review of the literature on acute postinfectious glomerulonephritis associated with PRES. The principles recommended by the Economic and Social Research Council guidance on the conduct of narrative synthesis and on the Preferred Reporting Items for Systematic Reviews and Meta-analyses were used. Databases searched included Excerpta Medica, US National Library of Medicine, and Web of Science. Results For the final analysis, we evaluated 47 reports describing 52 cases (32 males and 20 females). Fifty patients were [less than or equal to] 18 years of age. Blood pressure was classified as follows: normal-elevated (n = 3), stage 1 hypertension (n = 3), stage 2 hypertension (n = 5), and severe hypertension (n = 41). Acute kidney injury was classified as stage 1 in 32, stage 2 in 16, and stage 3 in four cases. Neuroimaging studies disclosed a classic posterior PRES pattern in 28 cases, a diffuse PRES pattern in 23 cases, and a brainstem-cerebellum PRES pattern in the remaining case. Antihypertensive drugs were prescribed in all cases and antiepileptic drugs in cases presenting with seizures. A resolution of clinical findings and neuroimaging lesions was documented in all cases with information about follow-up. Conclusions The main factor associated with PRES in acute postinfectious glomerulonephritis is severe hypertension. Prompt clinical suspicion, rapid evaluation, and management of hypertension are crucial. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Corinne Orlando [sup.1] , Gregorio P. Milani [sup.2] [sup.3] , Giacomo D. Simonetti [sup.4] [sup.5] , Barbara Goeggel Simonetti [sup.4] [sup.5] [sup.6] , Sebastiano A. G. Lava [sup.7] , [...]

Background: Inborn errors of glutathione metabolism may cause high anion gap metabolic acidosis due to pyroglutamic acid accumulation. Since 1988, cases of this acidosis have been reported in individuals without these defects. Methods: Given the poorly characterized predisposing factors, presentation, management, and prognosis of acquired pyroglutamic acidosis, we conducted a systematic review using the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar databases. Results: A total of 131 cases were found. Most patients were females (79%), adults (92%) aged 51 years or older (66%) with pre-existing conditions (74%) such as undernutrition, alcohol-use disorder, or kidney disease, and had an ongoing infection (69%). The clinical features included diminished consciousness (60%), Kussmaul breathing (56%), and nausea or vomiting (27%). At least 92% of patients were on paracetamol therapy for >10 days at an appropriate dose, 32% on a β-lactamase-resistant penicillin, and 2.3% on vigabatrin. Besides severe anion gap acidosis, patients also presented with hypokalemia (24%) and kidney function deterioration (41%). Management involved discontinuing the offending drug (100%), bicarbonate (63%), acetylcysteine (42%), and acute kidney replacement therapy (18%). The fatality rate was 18%, which was higher without acetylcysteine (24%) compared to with it (11%). Conclusions: Acquired pyroglutamic acidosis is a rare, potentially fatal metabolic derangement, which usually occurs after paracetamol use, frequently combined with a β-lactamase-resistant penicillin or vigabatrin. This condition predominantly affects adults, especially women with factors like undernutrition, alcohol-use disorder, or kidney disease, often during infection. Increased awareness of this rare condition is necessary. [ABSTRACT FROM AUTHOR]

Background. In high-income countries, shopping for non-prescription multivitamin–multimineral supplements has tremendously increased. Objective and Methods. The purpose of this labeling analysis is to inform on the daily elemental iron (with or without vitamin C) supply provided by multivitamin–multimineral supplements sold online by Amazon in Western and Southern Europe (amazon.es®, amazon.de®, amazon.it®, and amazon.fr®). Results. We identified 298 iron-containing multivitamin–multimineral preparations sold by Amazon marketplaces: 153 preparations sourced from amazon.de®, 68 from amazon.fr®, 54 from amazon.it®, and 23 from amazon.es®. The daily iron dose provided by these preparations was 14 [5–14] mg (median and interquartile range), with no differences among the marketplaces. Approximately 90% (n = 265) of the preparations contained ferrous iron. Moreover, 85% (n = 253) of the preparations were fortified with vitamin C in a dose of 80 [40–100] mg daily. Conclusions. The median supply of iron (about 14 mg) and vitamin C (80 mg) in iron-containing multivitamin–multimineral preparations offered on Amazon platforms in Western and Southern Europe falls below that currently recommended for iron deficiency in review articles, namely 100 mg of iron and 500 mg of vitamin C per day. The iron supply of iron-containing multivitamin–multimineral preparations falls also below the dose of 30–60 mg advocated to prevent iron deficiency in menstruating women. [ABSTRACT FROM AUTHOR]

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta‐analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta‐analysis was performed using random‐effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower‐middle, 12 in upper‐middle, and only two in high‐income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta‐analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta‐analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high‐income countries. [ABSTRACT FROM AUTHOR]