Silvia Consolo

Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia

In order to evaluate the use of an algorithm based on a procalcitonin (PCT) cut-off value as a means of guiding antibiotic therapy, 319 hospitalised children with uncomplicated community-acquired pneumonia (CAP) were randomised 1:1 to be treated on the basis of the algorithm or in accordance with standard guidelines. The children in the PCT group did not receive antibiotics if their PCT level upon admission was <0.25 ng/mL, and those receiving antibiotics from the time of admission were treated until their PCT level was ≥ 0.25 ng/mL. The final analysis was based on 155 patients in the PCT group and 155 in the control group. In comparison with the controls, the PCT group received significantly fewer antibiotic prescriptions (85.8% vs 100%; p < 0.05), were exposed to antibiotics for a shorter time (5.37 vs 10.96 days; p < 0.05), and experienced fewer antibiotic-related adverse events (3.9% vs 25.2%; p < 0.05), regardless of CAP severity. There was no significant between-group difference in recurrence of respiratory symptoms and new antibiotic prescription in the month following enrollment. The results of this first prospective study using a PCT cut-off value to guide antibiotic therapy for pediatric CAP showed that this approach can significantly reduce antibiotic use and antibiotic-related adverse events in children with uncomplicated disease. However, because the study included mainly children with mild to moderate CAP and the risk of the use of the algorithm-based approach was not validated in a relevant number of severe cases, further studies are needed before it can be used in routine clinical practice.

Possible molecular mechanisms linking air pollution and asthma in children

BackgroundAir pollution has many effects on the health of both adults and children, but children’s vulnerability is unique. The aim of this review is to discuss the possible molecular mechanisms linking air pollution and asthma in children, also taking into account their genetic and epigenetic characteristics.ResultsAir pollutants appear able to induce airway inflammation and increase asthma morbidity in children. A better definition of mechanisms related to pollution-induced airway inflammation in asthmatic children is needed in order to find new clinical and therapeutic strategies for preventing the exacerbation of asthma. Moreover, reducing pollution-induced oxidative stress and consequent lung injury could decrease children’s susceptibility to air pollution. This would be extremely useful not only for the asthmatic children who seem to have a genetic susceptibility to oxidative stress, but also for the healthy population. In addition, epigenetics seems to have a role in the lung damage induced by air pollution. Finally, a number of epidemiological studies have demonstrated that exposure to common air pollutants plays a role in the susceptibility to, and severity of respiratory infections.ConclusionsAir pollution has many negative effects on pediatric health and it is recognised as a serious health hazard. There seems to be an association of air pollution with an increased risk of asthma exacerbations and acute respiratory infections. However, further studies are needed in order to clarify the specific mechanism of action of different air pollutants, identify genetic polymorphisms that modify airway responses to pollution, and investigate the effectiveness of new preventive and/or therapeutic approaches for subjects with low antioxidant enzyme levels. Moreover, as that epigenetic changes are inheritable during cell division and may be transmitted to subsequent generations, it is very important to clarify the role of epigenetics in the relationship between air pollution and lung disease in asthmatic and healthy children.

Adenovirus 36 infection and obesity

The most important factors leading to fat accumulation in children are genetic inheritance, endocrine alterations, and behavioural/environmental causes. In addition, experimental animal studies have shown that infections due to various pathogens can lead to overweight and obesity conditions, and studies of humans have found that the incidence of seroconversion against some of these may be significantly more frequent in obese adults and children than in normal subjects. However, the results of these studies are not conclusive and, in some cases, have raised more questions than answers. We reviewed the literature concerning the role of adenovirus 36 (AD-36), the most widely studied infectious agent in animals and humans, because of its potential association with childhood obesity. The available evidence suggests that more studies are needed to evaluate whether or not the association between the presence of AD-36 antibodies and obesity is simply unrelated, and to verify whether there are subjects that have greater tendency to become obese because more easily susceptible to AD-36 infection or with a predisposition to suffer from persistent viral infection more easily leading to the development of obesity. If it is demonstrated that AD-36 does play a role in obesity, it will be important to investigate possible vaccines against the infection itself or antiviral drugs capable of inhibiting disease progression.

Reduction in catheter-related infections after switching from povidone-iodine to chlorhexidine for the exit-site care of tunneled central venous catheters in children on hemodialysis.

Only a few studies have investigated the optimal exit site management of tunneled central venous catheters (CVCs) in pediatric patients on chronic hemodialysis (HD). The aim of this study was to assess the efficacy of chlorhexidine solutions and a 5% povidone‐iodine solution on the incidence of CVC‐related infections in children on HD. The incidence of exit‐site infection (ESI), tunnel infection (TI), and bloodstream infection (BSI) was assessed in two groups of tunneled CVCs. The iodopovidone group consisted of 14 CVCs used between 1 January 2011 and 30 June 2012 in 10 children, whose median age at the time of CVC placement was 11.8 years (range 1.2–19.2): 5% povidone‐iodine was used for CVC exit‐site care. From 1 August 2012 to 31 January 2014, 0.5% chlorhexidine gluconate/70% isopropyl alcohol was used for the exit site, and 2% chlorhexidine gluconate/70% isopropyl alcohol spray for the hub in 13 CVCs was used in 10 patients (chlorhexidine group), whose median age at the time of CVC placement was 10 years (range 1.2–19.2). Ten episodes of ESI were diagnosed in the iodopovidone group (incidence 3.4/1000 CVC days), and only one in the chlorhexidine group (incidence 0.36/1000 CVC days, P = 0.008). One TI was observed in the iodopovidone group (0.34/1000 CVC days), and none in the chlorhexidine group. The incidence of BSIs decreased from 1.7/1000 CVC days (5 cases) to 0.36/1000 CVC days (1 case, P = 0.06) after switching to chlorhexidine. Two CVCs were lost due to CVC‐related infections in the iodopovidone group, whereas no CVC was lost due to infections in the chlorhexidine group. In comparison with 5% povidone‐iodine, the use of chlorhexidine gluconate was associated with a reduction in the incidence of ESI, TI, and BSI in children on HD.

Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with williams or cornelia de lange syndrome

In some subjects with severe neurological diseases, a reduced immune response to seasonal influenza vaccine has been demonstrated. Patients with Williams or Cornelia de Lange syndrome frequently have abnormalities in neurodevelopment. This study has evaluated the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in these subjects. Eighteen patients with Williams syndrome (ten males; mean age ± standard deviation [SD] 12.74 ± 4.49 years), 11 with Cornelia de Lange syndrome (six males; mean age 12.90 ± 4.85 years) and 30 age- and gender-matched healthy controls (16 males; mean age 12.49 ± 4.55 years), never vaccinated against influenza, received a dose of the vaccine between 1 and 30 November 2009. Four weeks later, the seroconversion rates in the three groups were between 72% and 80% and the seroprotection rates were 100%, with a similar increase in antibody levels. Two months later, most of the subjects remained seroconverted with no statistically significant difference between the groups, and about 94% of the patients with Williams syndrome, all of those with Cornelia de Lange syndrome and all of the healthy controls were still seroprotected. Safety and tolerability were very good, with no difference between the groups. None of the patients developed documented influenza during the study period. These results show that the immunogenicity, safety, and tolerability of a single dose of the monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia de Lange syndrome and moderate to severe mental disabilities is very good, and similar to that of healthy subjects.

Blood pressure management in children on dialysis

Hypertension is a leading cause of cardiovascular complications in children on dialysis. Volume overload and activation of the renin–angiotensin–aldosterone system play a major role in the pathophysiology of hypertension. The first step in managing blood pressure (BP) is the careful assessment of ambulatory BP monitoring. Volume control is essential and should start with the accurate identification of dry weight, based on a comprehensive assessment, including bioimpedance analysis and intradialytic blood volume monitoring (BVM). Reduction of interdialytic weight gain (IDWG) is critical, as higher IDWG is associated with a worse left ventricular mass index and poorer BP control: it can be obtained by means of salt restriction, reduced fluid intake, and optimized sodium removal in dialysis. Optimization of peritoneal dialysis and intensified hemodialysis or hemodiafiltration have been shown to improve both fluid and sodium management, leading to better BP levels. Studies comparing different antihypertensive agents in children are lacking. The pharmacokinetic properties of each drug should be considered. At present, BP control remains suboptimal in many patients and efforts are needed to improve the long-term outcomes of children on dialysis.

Comment to “Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome” by Keenswijk et al. Eur J Pediatr 2017; 176(3): 355–360

Dear Sir, We have read with great interest the paper by Keenswijk et al. [5] on the possible usefulness of blood urea nitrogen (BUN)-to-creatinine ratio (BCR) for predicting the outcome of Escherichia coli-related hemolytic uremic syndrome (eHUS) recently published on the European Journal of Pediatrics. An early predictor of outcome in this severe, life-threatening disease would be of paramount importance for guiding the clinician both in the early management of patients and for a correct parental and patient’s information. Unfortunately, the BCR did not prove to be useful when retrospectively applied to eHUS cases treated at our Center. Since 2000, we have managed a total of 184 eHUS (104 females), with a median age of 3.1 years (inter-quartile range (IQR) 1.5–6.3), a serum creatinine at presentation of 1.7 mg/ dL (IQR 0.9–3.23), and a BUN of 56.3 mg/dL (IQR 38.6– 86.9). Our series was categorized, as to disease outcome, using the same outcomes as described by Keenswijk et al. [5]: death, neurological involvement, need for intensive care support (either for hemodynamic instability or for ventilation), and chronic kidney disease or any long-term sequels. The

Plasma-exchange in pediatric patients: a single-center experience.

BACKGROUND Plasma-exchange (PEX) has been well described in pediatrics, but most of the current indications are derived from adult experience. Aim of the study was to review the PEX treatments in our Unit over a six-year period. METHODS Three hundred and seventy-seven PEX sessions were performed in 38 patients (median age 12.1 years, range 0.6-20.5). Double-needle and single-needle PEX combined with hemodialysis and PEX combined with ultrafiltration were performed in 9, 1 and 3 patients respectively. The most common indications to PEX were atypical hemolytic uremic syndrome (aHUS, 9 patients), focal segmental glomerulosclerosis (FSGS, 9 cases), antibody mediated rejection (AMR) in renal transplant (rTx) recipients (8 patients) and hyperimmunization in patients waiting for rTx (4 cases). RESULTS We treated five patients with aHUS on native kidneys with PEX only, with complete remission in 4/6 recurrences; PEX was also successfully used to prevent HUS relapse in three patients undergoing rTx. Only one partial remission was obtained in four patients with FSGS on native kidneys, by means of treatment protocols based on PEX and immunosuppressants; conversely, a partial remission was observed in 6/6 patients with recurrence of FSGS on rTx. Immunosuppressive protocols combined with PEX proved useful in sensitized cadaveric rTx recipients (2/4 successfully transplanted), but failed in 6 patients with chronic AMR. As regards complications, two severe adverse reactions occurred: an anaphylactic shock after the use of albumin and an abdominal hemorrhage. CONCLUSIONS PEX is a relatively safe procedure in children. Pediatric patients with aHUS, recurrent FSGS and sensitized rTx recipients seem to benefit from treatment strategies including PEX.

Total body water measurement in childhood

Sir: Assessment of body fluid volumes is essential in the day-today care for children, especially those admitted to the Intensive Care Unit or on dialysis [1]. Bioimpedance spectroscopy has been claimed to be a noninvasive technology able to reliably measure total body water. In the article BValidating the use of bioimpedance spectroscopy for assessment of fluid status in children,^ Dasgupta et al. [2] evaluated the reliability in children of the FreseniusMedical Care Body Composition Monitor (BCM), a bioimpedance spectroscopy tool for the assessment of fluid status. They found that in healthy children, bioimpedance spectroscopy overestimates total body water by 0.6 L, when compared to the deuterium dilution technique. The authors present both the agreement between the two measurement techniques using a regression analysis (Fig. 1 from reference [2]) and the Bland-Altman plot (Supplementary Fig. S1 from reference [2]). The latter points out that the 95% limits of agreement between the two techniques ranged between − 2.0 to + 3.2 L. As a consequence, in a child with a total body water content of 20 L, BCM measurements of total body water may vary between 18.0 and 23.2 L. The authors found similar results also for overhydration measurements by BCM and urea kinetic modeling in children on hemodialysis. These data hardly support the statement by the authors that bioimpedance spectroscopy can be applied in children. The lack of sufficient accuracy for application in children is similar to that found in a recent study of BCM in children on chronic dialysis [3]. We can only conclude that the BCM is not currently applicable in children for body fluid assessment and that new efforts should be addressed to improve the precision of bioimpedance spectroscopy measurements in childhood.

A simple prognostic index for Shigatoxin-related hemolytic uremic syndrome at onset: data from the ItalKid-HUS network

Shigatoxin Escherichia coli-related hemolytic uremic syndrome (eHUS) is a severe thrombotic microangiopathy (TMA) burdened by life-threatening complications and long-term sequelae. Since hemoconcentration is associated with worse outcome, we tried to develop a reliable and easy-to-calculate index for predicting complications and sequelae based on hemoglobin (Hb) at presentation. The first laboratory examinations with signs of TMA in eHUS patients were analyzed in relation to the outcomes with the receiver operating characteristic curves and their areas under the curve (AUC) for Hb and creatinine (sCr). A total of 197 eHUS patients were identified of whom 24% did not have anemia at presentation. Hb level was the best predictor of a poor outcome (AUC 0.67) but the combination of Hb with sCr, in the formula [(Hb in g/dL + (sCr in mg/dL × 2)], showed an even better AUC of 0.75. The described scoring system was also strongly associated and predictive of all complications and health care needs (8% of patients with scoring > 13 died or entered a permanent vegetative state compared with 0% of those with ≤ 13).Conclusion: The presented score is a simple and early predictor of both short- and long-term outcomes and identifies patients who should undergo rapid volume expansion to counteract hemoconcentration, the spreading of microvascular thrombosis, and the consequent increased organ damage.What is Known:• In eHUS, hemoconcentration is associated with worse short- and long-term outcome.• A prognostic index to identify patients at higher risk for complications at presentation is not available.What is New:• We developed a simple and early prognostic index for eHUS outcome with the combination of Hb and sCr at onset, in the following formula [(Hb in g/dL + (sCr in mg/dL × 2)].• The proposed HUS Severity Score can promptly identify patients with good outcome and those with high risk of worse short- and long-term outcome.