What if COVID-19 affects the child: which weapons and how to use them.

Since the reports in Wuhan (China), in December 2019, of the first cluster of cases of pneumonia caused by the new Coronavirus called 2019-nCoV or SARS-CoV-2, there has been a pandemic spread of the infection. By now, we have no specific therapy to counteract this emergency. The latest epidemiological data suggest that children are just as likely as adults to get infected by the virus. Most of them show mild clinical pictures or are completely asymptomatic, but there is an increased risk for severe disease in infancy (<12 months of age) and in children with underlying medical conditions. In this article, research achievements on the treatment of pediatric SARS-CoV-2 infection are examined.

Herbal supplements in pregnancy: unexpected results from a multicentre study.

STUDY QUESTION: How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? SUMMARY ANSWER: The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. DESIGN: A multicenter retrospective cohort study performed over a 15-month period. PARTICIPANTS AND SETTING: Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. MAIN RESULTS AND ROLE OF CHANCE: One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95% confidence interval: 1.08-4.08). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. GENERALIZABILITY TO OTHER POPULATIONS: The population under investigation did not significantly differ from the general population attending the same hospitals. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. TRIAL REGISTRATION NUMBER: None.

Changes in urinary PGE2 after ibuprofen treatment in preterm infants with patent ductus arteriosus.

PURPOSE: To investigate changes in urinary PGE(2) after ibuprofen treatment in preterm infants with patent ductus arteriosus (PDA). METHODS: Twenty preterm infants with a hemodynamically significant PDA (gestational age, 28.6 +/- 2.3 weeks) and 20 controls (gestational age, 30.4 +/- 1.5 weeks) were prospectively enrolled at 48-72 h of life. After enrollment, the former underwent conventional ibuprofen-lysine treatment. At 48-72 h (T(0)) and 108-144 h of life (T(1)), urine samples were noninvasively collected in both groups to measure urinary PGE(2) concentrations (enzyme immunoassay method), and renal function was investigated. RESULTS: Urinary PGE(2) decreased significantly both in ibuprofen-treated patients (66.95 +/- 16.78 vs. 27.15 +/- 17.92 pg/mL, P < 0.001) and in controls (71.7 +/- 16.2 vs. 53.2 +/- 18.4 pg/mL, P < 0.001) from T(0) to T(1). However, urinary PGE(2) at T(1) was significantly lower (P < 0.001) in the ibuprofen group compared to the control group. Acute renal failure occurred in three ibuprofen-treated patients (15%). CONCLUSIONS: Ibuprofen markedly reduces (59.4%) urinary PGE(2) and may alter renal function in the newborn.

Antibiotics and antifungals in neonatal intensive care units: a review.

The incidence of infections is higher in the neonatal period than at any time of life. The basic treatment of infants with infection has not changed substantially over the last years. Antibiotics (with or without supportive care) are one of the most valuable resources in managing sick newborn babies. Early-onset (ascending or transplacental) or late-onset (hospital acquired) infections present different chronology, epidemiology, physiology and outcome. Some classes of antibiotics are frequently used in the neonatal period: penicillins, cephalosporins, aminoglycosides, glycopeptides, monobactams, carbapenems. Other classes of antibiotics (chloramphenicol, cotrimoxazole, macrolides, clindamycin, rifampicin and metronidazole) are rarely used. Due to emergence of resistant bacterial strains in Neonatal Intensive Care Units (NICU), other classes of antibiotics such as quinolones and linezolid will probably increase their therapeutic role in the future. Although new formulations have been developed for treatment of fungal infections in infants, amphotericin B remains first-line treatment for systemic Candida infection. Prophylactic antibiotic therapy is almost always undesirable. Challenges from pathogens and antibiotic resistance in the NICU may warrant modification of traditional antibiotic regimens. Knowledge of local flora and practical application of different antibiotic characteristics are key to an effective and safe utilization of antibiotics and antifungals in critical newborns admitted to the NICU, and especially in very low birth weight infants.

Linezolid: a new antibiotic for newborns and children?

Staphylococcus aureus remains one of the most common and troublesome microorganisms causing disease in humans, despite the development of effective antibiotics. Linezolid is a member of a new class of synthetic antibiotics called oxazolidinones, introduced into therapy due to the increasing resistance of Gram-positive pathogens to traditional antibiotics. Information about the pharmacokinetics and tolerability profile of linezolid in the pediatric population mostly derive from adult studies and especially in the neonatal field relatively few data are available. Here we summarize linezolid's characteristics and report data available in the literature regarding linezolid use in newborns and children. For this purpose, a Medline search was performed between 1990 and 2006 involving the term "linezolid" combined with the terms "newborn", "infant", "child", "pediatrics". Additional information was obtained from Reactions Weekly.

Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study.

AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.

An analysis of the factors influencing the paediatrician-parents relationship: the importance of the socio-demographic characteristics of the mothers.

BACKGROUND: The paediatrician-parents meeting is not always characterized by mutual understanding and final satisfaction. Anxiety and preconceptions of the parents and clinicians may have consequences for the formulation of the diagnosis, for the pharmacological prescription, for the therapeutic alliance. METHODS: We performed a survey in collaboration with a representative sample of Italian paediatricians and mothers in the Veneto region to investigate the influence of paediatricians' and families' socio-demographic characteristics on some clinical aspects of the visit and on their relationship. The survey consisted of a first 7-item anonymous questionnaire addressed to paediatricians and to mothers. An univariate analysis (Pearson chi(2)-test) was applied. RESULTS: A total of 276/527 family paediatricians and 2567/5270 mothers completed the questionnaire. The 69.7% of responding paediatricians reported that mothers are very anxious during the visit and require a therapy (especially antibiotics). However, only 9.74% of mothers said they required a therapy, mainly the younger mothers with a lower level of education. The mothers reported that they were satisfied with the time devoted and the explanations given by paediatrician. The main information sources for mothers are personal experience or health care providers' advice, with a marginal role for mass-media, mentioned especially by the younger, with a lower level of education and less experienced mothers. CONCLUSIONS: Our experience suggests that maternal anxiety and physicians' interpretation of parental expectations are important factors to take into account during the visit. The paediatricians are not always good predictors of parental expectations. Younger mothers, with a lower level of education and with less experience need more time, more information and support by paediatricians. They are more likely to request therapy, are less satisfied, more easily influenced and likely to follow mass-media advice, rather than a reliable source of information.

Antibiotic therapy in pregnancy and lactation.

When considering whether to administer drugs to women during pregnancy and lactation, we have to take into account that these substances may expose the fetus or neonate to multiple effects. This occurs because there is a unique situation where the maternal compartment is connected with the fetal or neonatal compartment through, respectively, the placental barrier or breast milk. The fetus in utero and the breast-fed neonate are to be considered as organisms exposed and sensitive to the effects of drugs that cross the placenta or enter the breast milk. This review focuses on the most frequently used antibiotics during pregnancy and lactation and presents useful suggestions for daily practice. Drugs that must be avoided are clearly underlined.

Urinary nitrite/nitrate concentrations and total antioxidant capacity in patients with chronic hepatitis C in therapy with interferon and ribavirin.

In this study we tried to elucidate the role of nitric oxide (NO) in chronic hepatitis C in relation to antioxidant status, since the mechanisms by which hepatitis C virus (HCV) causes cell damage and the factors underlying its resistance to therapy are not well understood. Before and after one and six months of therapy with alpha-interferon and ribavirin, we measured nitrite/nitrate urinary levels, total antioxidant capacity and selenium serum concentrations in 14 patients with chronic hepatitis C and in 9 healthy subjects. Before therapy, mean urinary nitrite/nitrate levels of patients were not different from those of healthy subjects, but after a 6-month treatment with alpha-interferon and ribavirin, these NO metabolites were higher in virologically negative patients (responders). Moreover, while no changes in selenium were observed in all patients, total antioxidant capacity was significantly higher in non-responders and well correlated with hyperuricemia (due to cell damage) observed in these subjects. Instead, uric acid decreased as free molecule in serum in responders, while we found the excretion of high NO levels as nitrite/nitrate. Our data allow us to hypothesize a role for NO as predictive of the success of therapy, since nitrite/nitrate increase in the urine of some patients precedes disappearance of the virus observed at the end of therapy.

Role of renal PGE2 in the adaptation from foetal to extrauterine life in term and preterm infants.

Urinary PGE(2) concentrations were assayed using a new EIA method, in 16 preterm and 18 term neonates at birth and 3 days later, since there is evidence that PGE(2) in urine are likely to reflect their renal generation and then could be correlated with kidney maturation or renal problems. PGE(2) concentrations were not different at birth (1.50+/-1.12 vs 1.56+/-1.94 ng/day), while resulted significantly higher in preterms, compared to terms, three days after birth (2.22+/-1.23 vs 1.39+/-0.79 ng/day). This increase in daily PGE(2) excretion observed only in preterm neonates could be due to an increased renal biosynthesis as a mechanism of compensatory response to prevent further decrements in renal plasma flow, since prostanoids play an important role in protecting the immature kidney from high levels of angiotensin II. Otherwise, the passive reabsorption of PGE(2) along the distal nephron could be altered because of kidney immaturity. The measurement of PGE(2) in urine of neonates, particularly prematures, could be useful to provide a better understanding of the homeostatic function of the kidney in the phase of adaptation to extra-uterine life.

Plasma nitrite/nitrate and erythropoietin levels in cross-country skiers during altitude training.

BACKGROUND: The aim of this study was to evaluate the effects of training at altitude on plasma nitrite/nitrate and erythropoietin levels since previously it has been reported an interaction of the NO/cGMP system in erythropoietin production. METHODS: Nine physically trained cross-country male skiers, usually living at 800-1200 m altitude, underwent 6 days of intensive training at a moderate altitude of 3100 m preceeded by 2 days of acclimatisation. Six team-managers, selected as controls, did not undergo any regular physical activity in the last 5 years and during the altitude period. Haematological parameters, erythropoietin and nitrite/nitrate were measured prior to reach the place at altitude, at the end of the period at moderate altitude and 7 days after returning at home. RESULTS: Haematocrit significantly increased in controls after 8 days at altitude. Erythropoietin levels significantly increased after the intensive altitude training only in trained subjects (13.1+/-1.7 vs 6.7+/-1.7 mU x ml-1, p<0.001). Nitrite/nitrate baseline values were significantly higher in trained subjects compared to untrained (49.9+/-17.9 vs 25.4+/-2.8 micromol x l(-1), p<0.01); the altitude period significantly increased nitrite/nitrate levels, in untrained subjects, to the same values observed in trained subjects under control conditions (47.0+/-10.3 micromol x l(-1)). CONCLUSIONS: In our experimental conditions we demonstrated the influence of hypoxia on Epo levels in athletes sustaining a short-term training and the role of a regular physical activity (partly independent from altitude hypoxia) on NO production.

Urinary PGE(2) concentrations measured by a new EIA method in infants with urinary tract infections or renal malformations.

In this work PGE(2)concentrations were measured by a new EIA method in the urine of infants (mean age: 9.35+/-4.24 months) with recurrent urinary tract infections or renal malformations. Compared to healthy subjects, PGE(2)excretion rates resulted significantly higher in both pathological groups, in particular in subjects with obstructive uropathies (29.55+/-8.12 vs 18.37+/-4.64 pg/ml). We did not find any age- or pH-dependent difference in urinary excretion of PGE(2); none of the examined indices of renal function showed any significant relationship to PGE(2). These results suggest that this parameter, measured non-invasively in the urine, could help in the differential diagnosis between obstructive vs non-obstructive dilatation and in monitoring renal function in presence of recurrent UTI episodes.

NSAID-induced nephrotoxicity from the fetus to the child.

In this review we report data available from the literature on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the development of nephrotoxicity in the fetus, neonates and children. Up to the present day, several cases of severe and sometimes irreversible renal insufficiency have been described in neonates exposed to indomethacin prenatally or in the first days of life for treatment of patent ductus arteriosus (PDA). Until now, very few studies have been carried out on alternative treatments for PDA in preterm infants; ibuprofen has been shown to be as effective as indomethacin in closing the ductus in this patient group without affecting renal function. In children, NSAID-induced renal failure is a rare event and is usually reversible after discontinuation of the drug. However, caution should be taken when NSAIDs are administered to individuals with preexisting renal problems or with other potentially nephrotoxic drugs. In these situations, new approaches such as cyclo-oxygenase-2 selective inhibitors or prostanoid receptor selective antagonists could lead to alternative therapies for use in paediatrics.

Cytokine and nitric oxide levels in a rat model of immunologic protection from adjuvant-induced arthritis.

In the present study we investigated the correlation between the progression of adjuvant arthritis induced by Mycobacterium butyricum and the production of nitric oxide and some pro- and anti-inflammatory cytokines in arthritic rats and in rats treated with low intra-peritoneal doses of Mycobacterium 3 and 10 days after arthritis induction. The intra-peritoneal administration of Mycobacterium antigen significantly inhibited disease development. Compared to healthy rats, a rise in serum and peritoneal pro-inflammatory cytokines was observed in all arthritic rats already from the 14 day. The treatment with intra-peritoneal Mycobacterium was associated with a significant reduction in IL-6 serum concentrations and a slight decrease of IFN-gamma production by peritoneal macrophages. Nitrite/nitrate plasma and peritoneal levels were significantly higher in all arthritic rats. Intra-peritoneal administration of Mycobacterium caused a further increase in nitrite/nitrate plasma concentrations, while no differences were evident in nitric oxide production by peritoneal macrophages. From our data it is evident that among the variables here investigated, IL-6 seems to be the more representative marker of the disease and of the treatment effect. A possible role of nitric oxide as a modulator rather than a direct mediator in this model of inflammation is discussed.

CD23 and CD69 expression on human neutrophils of healthy subjects and patients with peripheral arterial occlusive disease.

In this work we studied, on human neutrophils from healthy donors and patients with peripheral arterial occlusive disease, the expression of CD23 and CD69 and the modulatory effects of IFN-gamma, GM-CSF and IL-4. Neutrophils were isolated from 9 patients and 9 healthy subjects and cultured for 24 h in absence or presence of IFN-gamma (1000 U/ml), GM-CSF (10 U/ml) and IL-4 (10 ng/ml). Expression of CD23 and CD69 was analyzed by FACScan cytofluorimeter. Neutrophils of both patients and healthy donors resulted negative for CD23 and CD69 expression immediately after isolation. After 24 h without stimuli, neutrophils from some patients and healthy donors expressed CD23 and CD69. IFN-gamma and GM-CSF had opposite effects on these two antigens, down-regulating CD23 and up-regulating CD69. IFN-gamma, GM-CSF and IL-4 were not able to induce CD23 expression, while CD69 expression was induced in some negative healthy donors and patients by IFN-gamma, GM-CSF and IL-4 respectively. From our data, we identified two subpopulations of neutrophils that, independently from the vascular pathology, showed a different behaviour towards temperature and some cytokines.

Nutritional supplementation with copper in the rat. I. Effects on adjuvant arthritis development and on some in vivo- and ex vivo-markers of blood neutrophils.

OBJECTIVE AND DESIGN: The aims of the work were: 1) to confirm the preliminarily observed anti-arthritic potential of a 200 ppm copper-supplemented diet in the rat: 2) to study the impact of the nutritional treatment and of the experimental pathology on neutrophil activity. ANIMALS AND CELLS: Two hundred female Sprague-Dawley rats were used. Polymorphonuclear leukocytes were isolated from these animals for the ex vivo studies. TREATMENT: Control-rats were maintained on a standard diet containing 5 ppm of copper. Supplemented-rats were kept on a diet containing 200 ppm of the metal. METHODS: Mycobacterium butyricum-induced arthritis was studied. Flame atomic absorption spectroscopy was used to assess copper and zinc levels. The "microplate-assay" technique was used to determine serum lysozyme concentration (lysis of Micrococcus lysodeikticus cell walls), as well as neutrophil O2- generation (superoxide dismutase-inhibitable reduction of ferricytochrome-c), and adhesion (activity of the membrane enzyme acid phosphatase). The results were statistically evaluated by the Student's t test. RESULTS: The nutritional copper-supplementation: 1) significantly inhibited the adjuvant-arthritis development (33% +/- 5, P<0.01); 2) did not modify lysozyme secretion or superoxide production; 3) significantly decreased the percentage of cell adhesion by an average of 41% +/- 19 (P<0.01). CONCLUSIONS: The copper-supplemented diet has an anti-arthritic effect which may be also primed by the effect of copper on the expression of the neutrophil cell-adhesion molecules.

Fluoroquinolones in pediatrics and their nephrotoxicity in adults: minireview.

In recent years there is increasing pressure to use fluoroquinolones in pediatric patients but relatively few data have been published in the literature. Therefore this paper reviews the available information about the pharmacokinetics of fluoroquinolones in children and their use in pediatric urinary tract infections, taking into account their potential as nephrotoxic agents. From the available data it seems reasonable to suggest that there is no risk of quinolone-induced nephrotoxicity and that this class of antibiotics may therefore be considered as potential candidates in urinary tract infections in children. Nevertheless adequate pharmacokinetic investigations and further studies on long-term monitoring for potential toxicity need to be conducted in pediatric populations.

Influence of an acute exercise on neutrophil and platelet adhesion, nitric oxide plasma metabolites in inactive and active subjects.

In this work we studied the influence of an acute exercise either on nitrite/nitrate plasma levels or on neutrophil and platelet adhesion in inactive and active subjects. Twelve healthy subjects (6 inactives and 6 actives) exercised on a racing cycle ergometer performing stepwise increases in intensity until reaching, within 5 min, a heart rate of 150 beats x min(-1) which represents an oxygen consumption of about 75 % of the individual maximum rate of oxygen uptake. From peripheral venous blood samples (drawn from all subjects before, immediately after the end of exercise, and 1 hour later) neutrophils and platelets were isolated to test plate adhesion, and nitrite/nitrate concentrations were measured in the plasma. Immediately after the acute exercise, in active subjects we observed a significant decrease in the percentage of neutrophil adhesion (7.96+/-2.38 vs. 14.10+/-3.14), associated with an increase in nitrite/nitrate plasma levels (81.38+/-10.76 vs. 41.08+/-8.13 micromol x l(-1)), restored by a 40 min pre-incubation with NG-nitro-L-arginine methyl ester (L-NAME). In unstimulated platelets we observed a significant lower percentage of platelet adhesion in active subjects compared to inactives after exercise. With thrombin or adenosine 5'-diphosphate as agonists platelet adhesion did not result significantly different in active subjects compared to inactives. In conclusion, our data show that physical exercise can induce changes in some cell activities, even if transient, and favour the generation of nitric oxide. The lower adhesion of neutrophils and platelets induced by regular exercise could be an important goal in the prevention of vascular and inflammatory diseases.