Prevalence of SARS-CoV-2 positivity in infants with bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the leading acute respiratory tract infection in infants during the winter season. Since the beginning of the SARS-CoV-2 pandemic, a reduction in the number of bronchiolitis diagnoses has been registered. OBJECTIVE: The present study aimed to describe the incidence and clinical features of bronchiolitis during the 2020-2021 winter season in a large cohort of children in Europe and Israel, and to clarify the role of SARS-CoV-2. SETTING, PATIENTS, INTERVENTIONS: We conducted a multicentre observational cross-sectional study in 23 paediatric emergency departments in Europe and Israel. Clinical and demographic data about all the cases of infants diagnosed with bronchiolitis from 1 October 2020 to 30 April 2021 were collected. For each enrolled patient, diagnostic tests, treatments and outcomes were reported. MAIN OUTCOME MEASURES: The main outcome was the prevalence of SARS-CoV-2-positive bronchiolitis. RESULTS: Three hundred and fourteen infants received a diagnosis of bronchiolitis during the study period. Among 535 infants who tested positive for SARS-CoV-2, 16 (3%) had bronchiolitis. Median age, male sex predominance, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative groups. Rhinovirus was the most common involved pathogen, while respiratory syncytial virus (RSV) was detected in one case. SARS-CoV-2 bronchiolitis had a mild clinical course, with one patient receiving oxygen supplementation and none requiring paediatric or neonatal intensive care unit admission. CONCLUSIONS: During the SARS-CoV-2 pandemic, a marked decrease in the number of bronchiolitis diagnoses and the disappearance of the RSV winter epidemic were observed. SARS-CoV-2-related bronchiolitis was rare and mostly displayed a mild clinical course.

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.

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

OBJECTIVE: 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. DATA SOURCES: Excerpta Medica, the National Library of Medicine, and Web of Science were searched from inception to July 16, 2021. STUDY SELECTION AND DATA EXTRACTION: Papers reporting individually documented humans on ibuprofen with hypokalemia, acidosis, or both were retained. Data were extracted using a checklist. DATA SYNTHESIS: 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. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review highlights potentially fatal side effects of ibuprofen and can help doctors who are confronted with such a situation. CONCLUSIONS: 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.

Pseudo-hypoaldosteronism secondary to infantile urinary tract infections: role of ultrasound.

BACKGROUND: The biochemical hallmarks of transient pseudo-hypoaldosteronism associated with a pyelonephritis include hyponatremia, hyperkalemia, and acidosis. We tested if the kidney-urinary tract ultrasound helps in predicting the diagnosis of overt pseudo-hypoaldosteronism in infants with a pyelonephritis. CASES PRESENTATION: Between 2013 and 2020, we managed 71 previously healthy infants 4 weeks to 24 months of age with a pyelonephritis (42 males and 29 females) and made the biochemical diagnosis of pseudo-hypoaldosteronism in 17 (24%). Infants with and without pseudo-hypoaldosteronism did not significantly differ with respect to the prevalence of kidney-urinary tract ultrasound abnormalities, graded by means of the UTD classification system of urinary tract abnormalities. CONCLUSIONS: Kidney-urinary tract ultrasound is almost routinely obtained in children with a febrile urinary tract infection. Our experience does not support the hypothesis that ultrasound might be relevant for the diagnosis of overt transient pseudo-hypoaldosteronism in babies affected by a urinary tract infection. Our data confirm the assumption that negative studies may be important for advancing clinical practice.

Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients.

Neurodevelopmental spectrum disorders like autism (ASD) are diagnosed, on average, beyond age 4 y, after multiple critical periods of brain development close and behavioral intervention becomes less effective. This raises the urgent need for quantitative, noninvasive, and translational biomarkers for their early detection and tracking. We found that both idiopathic (BTBR) and genetic (CDKL5- and MeCP2-deficient) mouse models of ASD display an early, impaired cholinergic neuromodulation as reflected in altered spontaneous pupil fluctuations. Abnormalities were already present before the onset of symptoms and were rescued by the selective expression of MeCP2 in cholinergic circuits. Hence, we trained a neural network (ConvNetACh) to recognize, with 97% accuracy, patterns of these arousal fluctuations in mice with enhanced cholinergic sensitivity (LYNX1-deficient). ConvNetACh then successfully detected impairments in all ASD mouse models tested except in MeCP2-rescued mice. By retraining only the last layers of ConvNetACh with heart rate variation data (a similar proxy of arousal) directly from Rett syndrome patients, we generated ConvNetPatients, a neural network capable of distinguishing them from typically developing subjects. Even with small cohorts of rare patients, our approach exhibited significant accuracy before (80% in the first and second year of life) and into regression (88% in stage III patients). Thus, transfer learning across species and modalities establishes spontaneous arousal fluctuations combined with deep learning as a robust noninvasive, quantitative, and sensitive translational biomarker for the rapid and early detection of neurodevelopmental disorders before major symptom onset.

Failure to reproduce period-dependent song cycles in Drosophila is due to poor automated pulse-detection and low-intensity courtship.

Stern has criticized a body of work from several groups that have independently studied the so-called "Kyriacou and Hall" courtship song rhythms of male Drosophila melanogaster, claiming that these ultradian ∼60-s cycles in the interpulse interval (IPI) are statistical artifacts that are not modulated by mutations at the period (per) locus [Stern DL (2014) BMC Biol 12:38]. We have scrutinized Stern's raw data and observe that his automated song pulse-detection method identifies only ∼50% of the IPIs found by manual (visual and acoustic) monitoring. This critical error is further compounded by Stern's use of recordings with very little song, the large majority of which do not meet the minimal song intensity criteria which Kyriacou and Hall used in their studies. Consequently most of Stern's recordings only contribute noise to the analyses. Of the data presented by Stern, only perL and a small fraction of wild-type males sing vigorously, so we limited our reanalyses to these genotypes. We manually reexamined Stern's raw song recordings and analyzed IPI rhythms using several independent time-series analyses. We observe that perL songs show significantly longer song periods than wild-type songs, with values for both genotypes close to those found in previous studies. These per-dependent differences disappear when the song data are randomized. We conclude that Stern's negative findings are artifacts of his inadequate pulse-detection methodology coupled to his use of low-intensity courtship song records.

NF-κB oscillations translate into functionally related patterns of gene expression.

Several transcription factors (TFs) oscillate, periodically relocating between the cytoplasm and the nucleus. NF-κB, which plays key roles in inflammation and cancer, displays oscillations whose biological advantage remains unclear. Recent work indicated that NF-κB displays sustained oscillations that can be entrained, that is, reach a persistent synchronized state through small periodic perturbations. We show here that for our GFP-p65 knock-in cells NF-κB behaves as a damped oscillator able to synchronize to a variety of periodic external perturbations with no memory. We imposed synchronous dynamics to prove that transcription of NF-κB-controlled genes also oscillates, but mature transcript levels follow three distinct patterns. Two sets of transcripts accumulate fast or slowly, respectively. Another set, comprising chemokine and chemokine receptor mRNAs, oscillates and resets at each new stimulus, with no memory of the past. We propose that TF oscillatory dynamics is a means of segmenting time to provide renewing opportunity windows for decision.