Acute Aseptic Meningitis Temporally Associated with Intravenous Polyclonal Immunoglobulin Therapy: A Systematic Review.

An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18 years of age) of meningitis. Ninety percent of cases presented ≤ 3 days after initiating immunoglobulin therapy and recovered within ≤ 7 days (with a shorter disease duration in children: ≤ 3 days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.

Blood pressure screening in Mata Sector, a rural area of Rwanda.

In rural sub-Saharan Africa, knowledge of non-communicable diseases such as high blood pressure (BP) is rather limited. This report provides information about a BP screening in Mata Sector, a rural region in Southern Province of Rwanda. Community-based, house-to-house screening was performed between February and July 2020 on more than 7000 inhabitants. The screening was conducted by a local team composed by 20 community health care workers, five community health care supervisors, and one nurse with hypertension surveillance training. BP and heart rate were recorded after 5 min of resting, using a validated automated oscillometric OMRON M6 IT-HEM-7322-E monitor with Intelli Wrap Cuff (HEM-FL31-E) technology. The mean of the second and third value was retained. BP was normal (<140/90 mm Hg) in 6340 (88%) and elevated in 863 (12%) participants with 95% of unawareness. Grade 1 (140-159/90-99 mm Hg) hypertensive BP readings were detected in 697 (81%), grade 2 (160-179/100-109 mm Hg) in 134 (16%), and grade 3 (≥180/≥110 mm Hg) in 32 (3.7%) individuals. The prevalence of hypertensive readings was significantly age-dependent. Additionally, a slightly greater proportion of participants with high BP (14% versus 11%) had a body mass index (BMI) ≥ 25.0 kg/m2. Also resting heart rate was higher in individuals with high BP (82 versus 77 beats/min). Although individuals identified with occasionally elevated BP values need further confirmatory measurements to establish the diagnosis of hypertension, these data suggest that high BP represents a noteworthy and preventable reason of concern within sub-Saharan Africa.

Kidney and urogenital abnormalities in Down syndrome: a meta-analysis.

BACKGROUND: Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.  METHODS: A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used. RESULTS: Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78-16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15-7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome. CONCLUSIONS: This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.

Nontyphoidal Salmonella Outbreaks Associated With Chocolate Consumption: A Systematic Review.

BACKGROUND: A large, cross-border outbreak of nontyphoidal salmonellosis connected to chocolate product consumption was recently reported. This occurrence motivated us to conduct a comprehensive review of existing literature concerning outbreaks of nontyphoidal salmonellosis associated with chocolate consumption. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022369023) in 3 databases: U.S. National Library of Medicine, Web of Science and Excerpta Medica. Google Scholar and the bibliography of each identified report were also screened. Eligible were articles published after 1970, describing outbreaks of more than 10 patients with a nontyphoidal salmonellosis associated with chocolate consumption. RESULTS: Twenty-three articles were included, which described 12 outbreaks involving a total of 3266 patients. All outbreaks occurred in high-income countries: 1 was limited to 1 city, 6 involved 1 country and the remaining 5 involved 2 or more countries. Six outbreaks peaked in winter, 3 in autumn, 2 in spring and 1 in summer. Children were mainly affected. No predominant serotype was identified. CONCLUSIONS: Our data documents that chocolate is an optimal medium for the transmission of nontyphoidal salmonellosis. A connected worldwide reporting system including high-income, middle-income and low-income countries is crucial to detect infectious diseases outbreaks in an early phase and avoid their spread.

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.

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.

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.

Hair-thread strangulation syndrome in childhood: a systematic review.

INTRODUCTION: Hair-thread strangulation syndrome describes the constriction of a body part by a tightly wound hair or thread. This research aims to review the literature about this entity. METHODS: A systematic review was performed to characterise hair-thread strangulation syndrome in subjects aged ≤16 years. This pre-registered review (PROSPERO ID: CRD42022363996) followed the PRISMA methodology. RESULTS: Subjects with digital strangulation were significantly younger (median = 4.0 [interquartile range: 2.0-6.1] months; n = 143) than females with genital strangulation (9.0 [6.8-11] years; n = 36), males with genital strangulation (5.1 [1.9-8.0] years; n = 36), and subjects with non-digital and non-genital strangulation (24 [13-48] months; n = 11). Digital strangulation was followed by an amputation in five (3.5%) and a reconstructive surgical intervention in seven (4.9%) cases. Sequelae occurred in four (11%) cases after female genital strangulation: clitoris autoamputation (n = 2) and surgical removal of a necrotic labium minus (n = 2). Severe complications were observed in 14 (39%) cases with male genital strangulation: urethral fistula (n = 7), urethral transection (n = 2), and partial penile autoamputation (n = 5). A partial uvular autoamputation was observed in one case (9.0%) with non-digital and non-genital strangulation. CONCLUSIONS: Early recognition and management are crucial to avoid sequelae or long-term care in hair-thread strangulation syndrome.

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.

Valproic Acid-Associated Acute Pancreatitis: Systematic Literature Review.

Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this pancreatitis. A preregistered literature search (CRD42023438294) was performed on the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar. Patients with alcohol abuse disorder, gallstone disease, hypertriglyceridemia or hypercalcemia, patients with acute valproic acid intoxication, and patients with a pre-existing pancreatitis were excluded. For the final analysis, we retained 73 reports published between 1979 and 2023, which described 125 subjects (83 children and 42 adults predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0-24) months (median and interquartile range) after starting valproic acid. One hundred and five cases (84%) recovered and twenty (16%) died. Sex, age, dosage or circulating level of valproic acid, latency time, prevalence of intellectual disability, and antiepileptic co-medication were similar in cases with and without a lethal outcome. Nineteen subjects were rechallenged with valproic acid after recovery: sixteen (84%) cases developed a further episode of pancreatitis. In conclusion, pancreatitis associated with valproic acid presents at any time during treatment and has a high fatality rate.

Nationwide survey on the management of pediatric pharyngitis in Italian emergency units.

BACKGROUND: Acute pharyngitis is a frequent reason for primary care or emergency unit visits in children. Most available data on pharyngitis management come from primary care studies that demonstrate an underuse of microbiological tests, a tendency to over-prescribe antibiotics and a risk of antimicrobial resistance increase. However, a comprehensive understanding of acute pharyngitis management in emergency units is lacking. This study aimed to investigate the frequency of rapid antigen test use to diagnose acute pharyngitis, as well as other diagnostic approaches, the therapeutic attitude, and follow-up of children with this condition in the emergency units. METHODS: A multicentric national study was conducted in Italian emergency departments between April and June 2022. RESULTS: A total of 107 out of 131 invited units (response rate 82%), participated in the survey. The results showed that half of the units use a scoring system to diagnose pharyngitis, with the McIsaac score being the most commonly used. Most emergency units (56%) were not provided with a rapid antigen diagnostic test by their hospital, but the test was more frequently available in units visiting more than 10,000 children yearly (57% vs 33%, respectively, p = 0.02). Almost half (47%) of the units prescribe antibiotics in children with pharyngitis despite the lack of microbiologically confirmed cases of Group A ß-hemolytic streptococcus. Finally, about 25% of units prescribe amoxicillin-clavulanic acid to treat Group A ß-hemolytic streptococcus pharyngitis. CONCLUSIONS: The study sheds light on the approach to pharyngitis in emergency units, providing valuable information to improve the appropriate management of acute pharyngitis in this setting. The routinary provision of rapid antigen tests in the hospitals could enhance the diagnostic and therapeutic approach to pharyngitis.

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.

Gastroenteritis is Less Severe But is More Often Associated With Systemic Inflammation in SARS-CoV-2-positive Than in SARS-CoV-2-Negative Children.

This study aims to characterize the clinical and metabolic features of acute gastroenteritis in children with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A multicenter case-control study was conducted in 2022 including 200 children. Clinical data and laboratory tests were analyzed. Children with SARS-CoV-2 presented less frequently hyponatremia and metabolic acidosis, but more often systemic inflammation as compared with children without SARS-CoV-2.

COVID-19, Coronavirus Vaccines, and Possible Association with Lipschütz Vulvar Ulcer: A Systematic Review.

Lipschütz genital ulcer is a self-limited, non-sexually acquired disorder characterized by the sudden onset of a few ulcers. A primary Epstein-Barr virus infection is currently considered the most recognized cause. Recent reports document cases temporally related with coronavirus disease 2019 (COVID-19) or immunization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We carried out a review of the literature to investigate the possible association between COVID-19 or the immunization against SARS-CoV-2 and genital ulcer. The pre-registered study (CRD42023376260) was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Excerpta Medica, the National Library of Medicine, and Web of Sciences were searched. Inclusion criteria encompassed instances of acute Lipschütz ulcer episodes that were temporally linked to either COVID-19 or a vaccination against SARS-CoV-2. Eighteen articles were retained. They provided information on 33 patients 15 (14-24) years of age (median and interquartile range), who experienced a total of 39 episodes of Lipschütz ulcer temporally associated with COVID-19 (N = 18) or an immunization against SARS-CoV-2 (N = 21). The possible concomitant existence of an acute Epstein-Barr virus infection was excluded in 30 of the 39 episodes. The clinical presentation and the disease duration were similar in episodes temporally associated with COVID-19 and in those associated with an immunization against SARS-CoV-2. In conclusion, COVID-19 and immunization against SARS-CoV-2 add to Epstein-Barr virus as plausible triggers of Lipschütz genital ulcer.

Splenic rupture or infarction associated with Epstein-Barr virus infectious mononucleosis: a systematic literature review.

BACKGROUND: Epstein-Barr virus (EBV), also known as human herpesvirus 4, is one of the most common pathogenic viruses in humans. EBV mononucleosis always involves the spleen and as such it predisposes to splenic rupture, often without a trauma, and splenic infarction. Nowadays the goal of management is to preserve the spleen, thereby eliminating the risk of post-splenectomy infections. METHODS: To characterise these complications and their management, we performed a systematic review (PROSPERO CRD42022370268) following PRISMA guidelines in three databases: Excerpta Medica, the United States National Library of Medicine, and Web of Science. Articles listed in Google Scholar were also considered. Eligible articles were those describing splenic rupture or infarction in subjects with Epstein-Barr virus mononucleosis. RESULTS: In the literature, we found 171 articles published since 1970, documenting 186 cases with splenic rupture and 29 with infarction. Both conditions predominantly occurred in males, 60% and 70% respectively. Splenic rupture was preceded by a trauma in 17 (9.1%) cases. Approximately 80% (n = 139) of cases occurred within three weeks of the onset of mononucleosis symptoms. A correlation was found between the World Society of Emergency Surgery splenic rupture score, which was retrospectively calculated, and surgical management: splenectomy in 84% (n = 44) of cases with a severe score and in 58% (n = 70) of cases with a moderate or minor score (p = 0.001). The mortality rate of splenic rupture was 4.8% (n = 9). In splenic infarction, an underlying haematological condition was observed in 21% (n = 6) of cases. The treatment of splenic infarction was always conservative without any fatal outcomes. CONCLUSIONS: Similarly to traumatic splenic rupture, splenic preservation is increasingly common in the management of mononucleosis-associated cases as well. This complication is still occasionally fatal. Splenic infarction often occurs in subjects with a pre-existing haematological condition.