Hoigné's syndrome, an uncommon mimicker of anaphylaxis: Systematic literature review.

The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.

A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

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.

Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.

The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of ß-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and ß-hydroxybutyrate.

Epstein-Barr virus as promoter of Lemierre syndrome: systematic literature review.

PURPOSE: To investigate a possible link between acute Epstein-Barr virus infection and Lemierre syndrome, a rare yet life-threatening infection. METHODS: A systematic review was conducted adhering to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnosis criteria for Lemierre syndrome were established, and data extraction encompassed demographic data, clinical, and laboratory information. RESULTS: Out of 985 initially identified papers, 132 articles were selected for the final analysis. They reported on 151 cases of Lemierre syndrome (76 female and 75 male patients with a median of 18 years) alongside interpretable results for Epstein-Barr virus serology. Among these, 38 cases (25%) tested positive for acute Epstein-Barr virus serology. There were no differences in terms of age, sex, or Fusobacterium presence between the serologically positive and negative groups. Conversely, instances of cervical thrombophlebitis and pulmonary complications were significantly higher (P = 0.0001) among those testing negative. The disease course was lethal in one case for each of the two groups. CONCLUSIONS: This analysis provides evidence of an association between acute Epstein-Barr virus infection and Lemierre syndrome. Raising awareness of this link within the medical community is desirable.

Autoimmune markers and vascular immune deposits in Finkelstein-Seidlmayer vasculitis: Systematic literature review.

Finkelstein-Seidlmayer vasculitis, also called acute hemorrhagic edema of young children or infantile immunoglobulin A vasculitis, is habitually a benign skin-limited small vessel leukocytoclastic vasculitis that mainly affects infants 24 months or less of age. Since this disease is commonly triggered by an infection, an immune-mediated origin has been postulated. To better appreciate the possible underlying immune mechanism of this vasculitis, we addressed circulating autoimmune markers and vascular immune deposits in patients contained in the Acute Hemorrhagic Edema BIbliographic Database, which incorporates all original reports on Finkelstein-Seidlmayer vasculitis. A test for at least one circulating autoimmune marker or a vascular immune deposit was performed in 243 cases. Subunits of complement system C4 resulted pathologically reduced in 4.7% and C3 in 1.4%, rheumatoid factor was detected in 6.1%, and antinuclear antibodies in 1.9% of cases. Antineutrophil cytoplasmic antibodies were never demonstrated. Immunofluorescence studies were performed on 125 skin biopsy specimens and resulted positive for complement subunits in 46%, fibrinogen in 45%, immunoglobulin A in 25%, immunoglobulin M in 24%, immunoglobulin G in 13%, and immunoglobulin E in 4.2% of cases. Infants testing positive for vascular immunoglobulin A deposits did not present a higher prevalence of systemic involvement or recurrences, nor a longer disease duration. In conclusion, we detected a very low prevalence of circulating autoimmune marker positivity in Finkelstein-Seidlmayer patients. Available immunofluorescence data support the notion that immune factors play a relevant role in this vasculitis. Furthermore, vascular immunoglobulin A deposits seem not to play a crucial role in this disease.

Protein and growth during the first year of life: a systematic review and meta-analysis.

Dietary protein intake in the first year of life might influence later growth. We conducted a systematic review to investigate the growth effects of interventions based on infant formula composition providing different amounts of protein within the first year of life of healthy term infants; in the absence of other comparable information over the investigated period, a meta-analysis further compared weight or length gain at 120 days from high- (>2.0 g/100 kcal) and low-protein (≤2.0 g/100 kcal) content formula groups. Twelve papers (n = 2275) were included and five of them (n = 677) contributed to the meta-analysis. Most studies compared a high-protein formula, a low-protein formula, and breastfeeding. Evidence from the systematic review was inconclusive due to heterogeneity in design and treatments. In the presence of modest heterogeneity but in the absence of publication bias, the weighted mean difference for weight gain at 120 days was -0.02 g/day (95% CI: -1.41, 1.45); with higher heterogeneity, the weighted MD estimate of length gain at 120 days was 0.004 cm/month (95% CI: -0.26, 0.27). Although limited and underpowered, evidence from the meta-analysis does not support the assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first months of life. Prospero registration number: CRD42017058535. IMPACT: The optimal amount of dietary protein that should be given to healthy full-term infants early in life is still debated. Despite heterogeneity in study design, treatments, and outcomes, this systematic review showed that there is no clear-cut effect on the growth of different amounts of protein intake from formulas or complementary feeding. Evidence from the meta-analysis based on the five articles enrolling infants <1 month of life does not support the previous assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first 4 months of life.

Perception, knowledge and attitude towards childhood fever: A survey among final-year medical students.

AIMS: Undue concerns about the consequences of fever and its inappropriate management have been documented worldwide among physicians. However, no data exist on medical students. We investigated the perception, knowledge and attitude towards childhood fever among final-year medical students. METHODS: Between June and September 2021, final-year medical students of six Italian universities were invited to complete an online survey on their conceptions and attitude towards pharmacological and non-pharmacological management of childhood fever. History of relevant personal or second-hand experience with childhood fever was also addressed. Both quantitative and qualitative approaches were used. RESULTS: Of 1095 (69%) final-year medical students, 756 completed the survey. Many students believe that high fever might cause brain damage, would recommend physical methods and alternate two drugs for fever. Most students do not think that fever has mainly beneficial effects. In Northern Italy, students are less likely to believe that fever might lead to brain damage (OR 0.55, 95% CI 0.33-0.94), and in Southern Italy students are more likely to advise physical methods (OR 1.77, 95% CI 1.22-2.57) and less likely to believe that fever has mainly beneficial effects (OR 0.55, 95% CI 0.39-0.77). History of a relevant personal episode of fever during childhood was not associated with these outcomes. CONCLUSIONS: Misconceptions about fever are common among final-year medical students in Italy. Cultural factors rather than individually learned traits might underlie these beliefs. Medical students are a promising target for educational interventions to improve childhood fever management.

Bilateral upper eyelid swelling (Hoagland sign) in Epstein-Barr infectious mononucleosis: prospective experience.

BACKGROUND: The typical presentation of Epstein-Barr virus infectious mononucleosis includes fever, pharyngitis, measles-like rash, jaundice, and enlarged lymph nodes, liver, or spleen. A painless bilateral swelling of the upper eyelid, sometimes with drooping of the lateral aspect, may also occur. This sign, referred to as Hoagland sign, is not or only marginally mentioned in reviews and textbooks. METHODS: Between 2019 and 2021, two of us evaluated all subjects with a positive acute Epstein-Barr virus serology for the typical signs of mononucleosis and for the possible existence of the Hoagland sign. RESULTS: During the mentioned period, the diagnosis of mononucleosis was made in 26 (14 females and 12 males) subjects aged from 9.0 to 33 years. The initial presentation included fever in 24, enlarged cervical lymph nodes in 23, pharyngitis in 21, a palpable liver in 7, a palpable spleen in 7, jaundice in 2, and a measles-like rash in 2 cases. The Hoagland sign was noted in 14 cases. Patients with and without Hoagland sign did not significantly differ with respect to age and sex. CONCLUSIONS: The Hoagland sign is an easily identifiable clinical sign that is common and likely helpful early in the course of Epstein-Barr virus infectious mononucleosis. There is a need to expand awareness of this sign among physicians.

Kidney tubular injury induced by valproic acid: systematic literature review.

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-ß-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. A higher resolution version of the Graphical abstract is available as Supplementary information.

New insights into fever phobia: a pilot qualitative study with caregivers and their healthcare providers.

Despite the availability of clinical guidelines on the correct symptomatic management of fever in children, several studies have reported inaccurate knowledge about this symptom and inappropriate management behaviours among caregivers. There is evidence that caregivers' management of fever is largely influenced by unrealistic and unwarranted concerns about the potential harm that elevated body temperature can cause, a phenomenon commonly referred to as fever phobia. Research on fever phobia has predominantly focused on the role of fever misconceptions in triggering anxiety and impeding a proper fever management, in terms of both concept and operationalization, with little attention to the influence of the relationship between caregivers and the healthcare team. The aim of this pilot study was to explore and describe fever-related knowledge, experience and behaviour among a sample of caregivers, paediatricians and their medical assistants in the Canton of Ticino, Switzerland. We used a qualitative study design with semi-structured, one-to-one interviews with paediatricians employed in private healthcare facilities, their medical assistants and caregivers with at least one child between the ages of 0 and 3 years. We conducted individual interviews either in person or by phone, according to participants' preferences, between October 2020 and February 2021. We performed an inductive-deductive analysis of the transcripts to identify the most meaningful themes from participants' reports. The analysis of the transcripts yielded three main themes. The first theme refers to participants' awareness of the emotional component in managing the child's fever and the challenges this component presents. The second theme refers to the risk of overtreating when the child's right to be sick is not recognized and respected. The third theme refers to the importance of the relational component, showing how a solid therapeutic alliance with the healthcare team helps caregivers develop self-confidence in managing the child's fever. This study contributes to advance our understanding of fever phobia and to a better conceptualization and operationalization of this phenomenon. CONCLUSION: Our results point out to the importance of going beyond a knowledge gap paradigm and recognizing both the emotional and the relational component of fever phobia, the former being entrenched in latter, that is, the unique relationship caregivers establish with their child's paediatrician and the medical assistant. WHAT IS KNOWN: • Research on fever phobia has predominantly focused on the role of fever misconceptions in triggering anxiety and impeding a proper fever management, in terms of both concept and operationalization, with little attention to the relational component of this phenomenon. WHAT IS NEW: • Our results point out to the importance of recognizing the emotional component of fever phobia, beyond its declarative and procedural knowledge dimensions. They also suggest that overtreating is not necessarily and not only the result of a phobia but also of a particular conception of health and the relational component of this phenomenon, which is entrenched in the unique relationship caregivers establish with their child's paediatrician and the medical assistant.

Propofol-Associated Urine Discoloration: Systematic Literature Review.

INTRODUCTION: Propofol occasionally induces a green or pink-cloudy urine discoloration. A lesser-known effect is green discoloration of hair, milk, liver, or stool. We aimed to gain insight into the features of these disturbances. METHODS: The terms ("propofol" OR "fospropofol") AND ("green" OR "pink" OR "cloudy" OR "pink-cloudy") were searched in Excerpta Medica, MEDLINE/PubMed®, and Web of Sciences databases, with no language limit, from inception up to February 2023 (CRD4202236804). Articles reporting individually documented cases were retained, and data were extracted using a checklist. RESULTS: Seventy-seven original reports documented 95 cases (including 13 subjects ≤18 years of age). Completeness of reporting was satisfactory in 33, good in 35, and excellent in 27 cases. Propofol-associated green urine discoloration was observed in 54 patients. In most instances (n = 21, 39%), propofol was given for ≥24 h. Sometimes, however, the urine discoloration developed after propofol for ≤3 h (n = 12, 22%). Propofol-associated urine discoloration was usually observed during the administration of this agent, but it was at times (n = 11) first recognized ≥3 h after propofol discontinuation. The duration of green urine discoloration was usually ≤24 h after stopping propofol. Propofol-associated green urine discoloration was never associated with worsening kidney function. A pink-cloudy urine discoloration was observed in 32 subjects with an acidic urine pH and increased uric acid excretion given propofol for ≤24 h. A stage I acute kidney injury was observed in 2 cases (6.3%) of propofol-associated pink-cloudy urine discoloration. Nine cases of non-urinary green discoloration were observed: hair (n = 4), breast milk (n = 1), liver (n = 1), stool (n = 1). CONCLUSION: Propofol is sometimes associated with a green (benign) or pink-cloudy (occasionally associated with mild acute kidney injury) urine discoloration. Rarely, non-urinary green discoloration has been reported.

Childhood fever and medical students: A multicentre, educational intervention.

AIM: Misconceptions and non-evidence-based practices toward childhood fever are reported worldwide. Medical students might be ideal candidates to introduce long-lasting changes in clinical practice. However, no study has gauged the effectiveness of an educational intervention to improve fever management in this population. We conducted an educational, interventional study on childhood fever among final-year medical students. METHODS: We conducted a prospective, multicentre interventional study employing a pre/post-test design. Participants from three Italian Universities filled in a questionnaire just before the intervention (T0), immediately after (T1) and 6 months later (T2) in 2022. The intervention was a two-hour lecture focused on the pathophysiology of fever, recommendations for its treatment and risks associated with improper management. RESULTS: 188 final-year medical students (median age of 26 years, 67% females) were enrolled. Relevant improvements in the criterion for treating fever and conceptions about the beneficial effects of fever were observed at T1 and T2. Similar data were found for the reduction of physical methods advice to decrease body temperature and concerns for brain damage from fever. CONCLUSION: This study shows for the first time that an educational intervention is effective in changing students' conceptions and attitudes toward fever both in the short and medium term.

Alpha-Linolenic Acid and Cardiovascular Events: A Narrative Review.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1.7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant omega-6/omega-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in both adult and pediatric populations. Furthermore, ALA has shown protective effects against hypertension, contributing to balancing blood pressure through customary diet. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardioprotective effects.

Approach to fever in children among final-year nursing students: a multicenter survey.

BACKGROUND: Unfounded concerns regarding fever are increasingly observed among nurses worldwide. However, no study has so far explored the preferred approach towards pediatric fever among nursing students. Therefore, we aimed to investigate the attitude towards pediatric fever among final-year nursing students. METHODS: Between February and June 2022, final-year nursing students of 5 Italian university hospitals were asked to answer an online survey on their approach to fever in children. Both quantitative and qualitative methods were utilized. Multiple regression models were employed to explore the existence of moderators on fever conceptions. RESULTS: The survey was filled in by 121 nursing students (response rate 50%). Although most students (98%) do not consider discomfort to treat fever in children, only a minority would administer a second dose of the same antipyretic in nonresponsive cases (5.8%) or would alternate antipyretic drugs (13%). Most students would use physical methods to decrease fever (84%) and do not think that fever has mainly beneficial effects in children (72%). The own know-how adequacy on fever was inversely associated (OR 0.33, 95% CI 0.13-0.81) with the beliefs that high fever might lead to brain damage. No further predictive variable was significantly associated with the concern that fever might be associated with brain damage, the advice of physical methods use, and the assumption that fever has mostly positive effects. DISCUSSION: This study shows for the first time that misconceptions and inappropriate attitudes towards fever in children are common among final-year nursing students. Nursing students could potentially be ideal candidates for improving fever management within clinical practice and amongst caregivers.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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, ß-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. CONCLUSIONS: 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.

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.

Outdoor temperature and circulating sodium in children with acute gastroenteritis.

BACKGROUND: Dysnatremias are frequent in acute gastroenteritis. High outdoor temperatures have been associated with hyponatremia in both adults and the elderly, but no data are available among children with gastroenteritis. METHODS: Children <10 years of age admitted to the emergency department of the Policlinico Hospital, Milan (Italy) between 2009 and 2019 with acute moderate-severe gastroenteritis were enrolled. The association between hyponatremia (sodium < 135 mmol/L) and daily mean levels of temperature or apparent temperature from day of admission up to 14 days before was analyzed by multivariable logistic regression models. RESULTS: In 202 included children (46% females), we observed an increased risk of hyponatremia per unit increase in outdoor temperature of the sixth, eighth and ninth day before admission [Odds Ratio = 1.24 (95% Confidence Interval: 1.04-1.47), 1.14 (1.01-1.28), and 1.14 (1.01-1.28), respectively]. Analyses considering average temperature levels of the ten days preceding admission returned similar findings as well as those on apparent temperature. CONCLUSIONS: Our data suggest the existence of an association between outdoor temperature and circulating sodium levels in children with acute gastroenteritis. The role of meteorological conditions on electrolyte imbalance should be further explored in the context of climate change. IMPACT: The role of meteorological variables in the development of dysnatremias has been demonstrated in children and adolescents with cystic fibrosis. This study shows for the first time that higher outdoor temperatures are associated with a higher risk of hyponatremia in children with gastroenteritis. In the context of climate change, the role of external climate conditions on the risk of electrolyte imbalance in children should be more and more considered and explored in future studies.

Tubulointerstitial nephritis and uveitis syndrome: a systematic review.

BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is defined as the occurrence of tubulointerstitial nephritis (TIN) and uveitis in the absence of other systemic diseases. The most comprehensive review on this condition was published in 2001. METHODS: We conducted a systematic review of the literature for cases of TINU syndrome. MEDLINE and Embase databases were screened. Full-length articles or letters reporting cases with both TIN and uveitis were selected. We investigated differences between males and females and paediatric and adult cases. Multivariate analysis was performed to identify potential risk factors for chronic kidney disease (CKD) development. RESULTS: A total of 233 articles reporting 592 TINU cases were retained for the analysis. The median age of the included subjects was 17 years (interquartile range 13-46) with a female predominance (65%). Uveitis most frequently (52%) followed renal disease and was mostly anterior (65%) and bilateral (88%). Children tended to have more ocular relapses, while they were slightly less likely than adults to suffer from acute kidney injury and to develop CKD. Adult age as well as posterior or panuveitis were associated with an increased risk of developing CKD. CONCLUSIONS: TINU affects both children and adults, with some differences between these two categories. Adult age and the presence of a posterior uveitis or panuveitis appear to be associated with the development of CKD.

PM2 .5, PM10 and bronchiolitis severity: A cohort study.

BACKGROUND: A few studies suggest that particulate matter (PM) exposure might play a role in bronchiolitis. However, available data are mostly focused on the risk of hospitalization and come from retrospective studies that provided conflicting results. This prospective study investigated the association between PM (PM2.5 and PM10 ) exposure and the severity of bronchiolitis. METHODS: This prospective cohort study was conducted between November 2019 and February 2020 at the pediatric emergency department of the Fondazione IRCCS Ca' Ospedale Maggiore Policlinico, Milan, Italy. Infants <1 year of age with bronchiolitis were eligible. The bronchiolitis severity score was assessed in each infant and a nasal swab was collected to detect respiratory viruses. The daily PM10 and PM2.5 exposure in the 29 preceding days were considered. Adjusted regression models were employed to evaluate the association between the severity score and PM10 and PM2.5 exposure. RESULTS: A positive association between the PM2.5 levels and the severity score was found at day-2 (ß 0.0214, 95% CI 0.0011-0.0417, p = .0386), day-5 (ß 0.0313, 95% CI 0.0054-0.0572, p = .0179), day-14 (ß 0.0284, 95% CI 0.0078-0.0490, p = .0069), day-15 (ß 0.0496, 95% CI 0.0242-0.0750, p = .0001) and day-16 (ß 0.0327, 95% CI 0.0080-0.0574, p = .0093).Similar figures were observed considering the PM10 exposure and limiting the analyses to infants with respiratory syncytial virus. CONCLUSION: This study shows for the first time a direct association between PM2.5 and PM10 levels and the severity of bronchiolitis.

Vaptans for oedematous and hyponatraemic disorders in childhood: A systematic literature review.

AIMS: The aim of this study was to systematically review the use of vaptans (nonpeptide vasopressin receptor antagonists) in children. METHODS: Through a database search (Web of Science, the National Library of Medicine, Excerpta Medica), we identified case series and case reports and extracted clinical and laboratory data. RESULTS: Twenty-six articles, published since 2008, reported on 226 patients. Among 115 children with hyponatraemic (n = 63) and oedematous disorders (n = 52), a 48 hour course of tolvaptan with an initial dose of 0.38 ± 0.27 mg/kg was administered in 106 cases, while intravenous conivaptan was reported in nine cases. An increase (P < .02) in urine output was shown in both oedematous (from 3.2 ± 2.0 to 5.3 ± 6.7 mL/kg/day) and hyponatraemic (from 3.0 ± 1.5 to 4.4 ± 2.3 mL/kg/day) patients. In these latter, sodium increased from 125 ± 6 to 133 ± 6 mmol/L (P < .0001). The increase in sodium level correlated with its basal value, but not with the administered vaptan dose. Among 111 children undergoing cardiac surgery, after tolvaptan 0.21 ± 0.01 mg/kg/day, mostly combined with conventional diuretics, an increase in diuresis by 41 ± 4% was seen within 24 hours (P < .0001). Similarly, a single add-on dose of tolvaptan 0.45 mg/kg allowed a reduced additional intravenous furosemide administration (0.26 ± 0.23 vs 0.62 ± 0.48 mg/kg, P < .005). Side effects were rarely reported, and included excessive thirst and xerostomia in seven, skin rash in one and elevated aminotransferases in one patient(s). CONCLUSION: Vaptans appear to be safe for oedematous and hyponatraemic disorders also in children. Although they increase diuresis and natraemia, no superiority to traditional diuretics and sodium supplements has been demonstrated. Reported side effects are rare and non-serious.