Evolving Approach to Antibiotic Treatment of Pediatric Spondylodiscitis.

OBJECTIVE: To describe for intervertebral spondylodiscitis (IS) its clinical characteristics, treatment approaches with intravenous (IV) antibiotics, and clinical implications of changes in treatment approach. STUDY DESIGN: This retrospective study included all children aged 0-18 years diagnosed with imaging-confirmed thoracic and lumbar IS from 2000 to 2022 at a tertiary pediatric hospital. Patients with longer IV treatment regimen were compared with those with a shorter clinically directed IV to oral regimen. RESULTS: In all, 124 cases were included with median age 14.9 months (IQR, 12.7-19.4 months) at diagnosis. Irritability and pain while changing diapers were common symptoms (52.4% and 49.2%, respectively). Elevated erythrocyte sedimentation rate (ESR) was the most common laboratory finding (95%; median, 50 mm/h [IQR 34-64 mm/h]). Elevated erythrocyte sedimentation rate was found in higher proportions (95%) compared with elevated C-reactive protein (76%; median, 1.8 mg/dL; P < .001). Since implementing the shorter clinically directed IV treatment duration for patients with thoracic and lumbar IS, hospitalization duration was decreased from a median of 12 to 8 days (P = .008) and IV treatment duration by a median of 14 to 8 days (P < .001). Only 1 patient (1.6%) in the clinically directed treatment group required rehospitalization owing to failure of therapy. Conversely, 9 of 124 children in the cohort suffered from IV treatment-related complications; all had been treated IV for prolonged periods. CONCLUSIONS: Early transition to oral treatment in pediatric spondylodiscitis seems to be appropriate clinically and shortens hospital stay and IV treatment duration without major negative clinical impact.

Pediatric chest radiograph interpretation in a real-life setting.

Chest radiography is a frequently used imaging modality in children. However, only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. Most studies were not performed in real-world clinical settings. Our aims were to examine the agreement between emergency department pediatricians and board-certified radiologists in a pediatric real-life setting and to identify clinical risk factors for the discrepancies. Included were children aged 3 months to 18 years who underwent chest radiography in the emergency department not during the regular hours of radiologist interpretation. Every case was reviewed by an expert panel. Inter-observer agreement between emergency department pediatricians and board-certified radiologists was assessed by Cohen's kappa; risk factors for disagreement were analyzed. Among 1373 cases, the level of agreement between emergency department pediatricians and board-certified radiologists was "moderate" (k = 0.505). For radiographs performed after midnight, agreement was only "fair" (k = 0.391). The expert panel identified clinically relevant disagreements in 260 (18.9%) of the radiographs. Over-treatment of antibiotics was identified in 121 (8.9%) of the cases and under-treatment in 79 (5.8%). In a multivariable logistic regression, the following parameters were found to be significantly associated with disagreements: neurological background (p = 0.046), fever (p = 0.001), dyspnea (p = 0.014), and radiographs performed after midnight (p = 0.007). CONCLUSIONS: Moderate agreement was found between emergency department pediatricians and board-certified radiologists in interpreting chest radiographs. Neurological background, fever, dyspnea, and radiographs performed after midnight were identified as risk factors for disagreement. Implementing these findings could facilitate the use of radiologist expertise, save time and resources, and potentially improve patient care. WHAT IS KNOWN: • Only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. • Most studies were not performed in real-world clinical settings. Clinical risk factors for disagreements have not been reported. WHAT IS NEW: • In this study, which included 1373 cases at the emergency department, the level of agreement between interpreters was only "moderate." • The major clinical parameters associated with interpretation discrepancies were neurological background, fever, dyspnea, and interpretations conducted during the night shift.

Clinical implications of extremely elevated C-reactive protein among febrile immunocompetent children.

AIM: To identify the various diagnoses associated with extremely elevated C-reactive protein (CRP) (>30 mg/dL) among immunocompetent children and to evaluate its clinical implications during emergency department (ED) workup and hospital management. METHODS: Children (3 months-18 years) with fever in ED were included, retrospectively. The cohort was divided into two groups-'extremely elevated CRP' (>30 mg/dL) and 'highly elevated CRP' (15-30 mg/dL). RESULTS: Included were 1173 patients with CRP 15-30 mg/dL and 221 with CRP > 30 mg/dL. Bacterial infection was more prevalent among the extremely elevated CRP group (94.1% vs. 78.5%, respectively, p = 0.002). Specifically, bacterial pneumonia (52%), cellulitis (7.2%) and sepsis (4.1%) were more prevalent among this group. More of these patients were reported as 'Ill appearing' [78 (35.3%) vs. 166 (17.4%), p < 0.001]. They were more often treated with fluids [33 (14.9%) vs. 50 (5.3%), p < 0.001] and a higher portion of them required admission to an intensive care unit [11 (5.0%) vs. 16 (1.7%), p = 0.007]. CONCLUSION: Febrile children with extremely elevated CRP showed greater illness severity (haemodynamic instability, PICU admissions), thus careful clinical attention is desirable in these cases. More than half of them had bacterial pneumonia, which reinforces the importance of relevant investigation when diagnosis is unclear.

Infant Botulism, Israel, 2007-2021.

Infant botulism (IB) is an intestinal toxemia that manifests as descending paralysis, constipation, and, in some cases, respiratory failure. Laboratory-confirmed IB cases are rare, and recent data in Israel are lacking. We conducted a national multicenter retrospective study of laboratory-confirmed IB cases reported in Israel during 2007-2021. A total of 8 cases were reported during the study period. During 2019-2021, incidence may have increased because of a cluster of 5 cases. Infant median age for diagnosis was 6.5 months, older than previously reported (3 months). Most cases occurred during March-July. Honey consumption was reported in 1 case, and possible environmental risk factors (living nearby rural or construction areas, dust exposure, and having a father who works as a farmer) were reported in 6 cases. Although IB is rare, its incidence in Israel may have increased over recent years, and its epidemiology and risk factors differ from cases reported previously in Israel.

The Effect of the COVID-19 Pandemic on Pediatric Respiratory Hospitalizations.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, less isolation of common winter viruses was reported in the southern hemisphere. OBJECTIVES: To evaluate annual trends in respiratory disease-related admissions in a large Israeli hospital during and before the pandemic. METHODS: A retrospective analysis of medical records from November 2020 to January 2021 (winter season) was conducted and compared to the same period in two previous years. Data included number of admissions, epidemiological and clinical presentation, and isolation of respiratory pathogens. RESULTS: There were 1488 respiratory hospitalizations (58% males): 632 in 2018-2019, 701 in 2019-2020, and 155 in 2020-2021. Daily admissions decreased significantly from a median value of 6 (interquartile range [IQR] 4-9) and 7 per day (IQR 6-10) for 2018-2019 and 2019-2020, respectively, to only 1 per day (IQR 1-3) in 2020-2021 (P-value < 0.001). The incidence of all respiratory viruses decreased significantly during the COVID-19 pandemic, with no hospitalizations due to influenza and only one with respiratory syncytial virus. There was also a significant decline in respiratory viral and bacterial co-infections during the pandemic (P-value < 0.001). CONCLUSIONS: There was a significant decline in pediatric respiratory admission rates during the COVID-19 pandemic. Possible etiologies include epidemiological factors such as mask wearing and social distancing, in addition to biological factors such as viral interference. A herd protection effect of adults and older children wearing masks may also have had an impact.

The effect of COVID-19 pandemic on hospitalizations and disease characteristics of adolescents with anorexia nervosa.

Social distancing and quarantines have major negative psychological implications. Our aim was to study the rate of pediatric hospitalizations due to anorexia nervosa (AN) during the first year of coronavirus disease 2019 (COVID-19) pandemic as compared to previous years, with regard to clinical and laboratory parameters. This is a retrospective study in a tertiary pediatric hospital in Israel. Data regarding inpatient hospitalizations due to AN were retrieved, then epidemiological, clinical, and laboratory parameters compared. During the entire study period, 275 hospitalizations were due to AN: 94 patients were admitted during the 12 months of the pandemic as compared to a yearly mean of 45.25 during 2015-2019, resulting in a 2.4-fold increase (p < 0.001). The mean admission age and female predominance were similar in the two study groups. The weight of the patients at admission was higher during the COVID-19 period (44.5 kg vs. 41.2 kg, p = 0.004), and fewer patients had clinical signs typical of AN upon physical examination (p = 0.022). There was a 35% reduction in median hospitalization duration (9 days [IQR 8.21] in 2020-2021 and 14 [IQR 6, 16.75] days in 2015-2019, p = 0.01). No other differences were found. CONCLUSIONS: During the first year of the COVID-19 pandemic, there was a significant increase in the number of adolescents hospitalized with AN. Nevertheless, disease characteristics were not more severe as compared to the preceding 5 years. WHAT IS KNOWN: • Social distancing and quarantines were announced during the COVID-19 pandemic in numerous countries. These measures have potential negative psychological effects on adolescents. WHAT IS NEW: • During the COVID-19 pandemic period, there was an increase in the number of hospitalizations of adolescents with AN, although disease characteristics were not more severe as compared to the preceding 5 years.

Clinical Features and Comparison of Kingella and Non-Kingella Endocarditis in Children, Israel.

Kingella spp. have emerged as an important cause of invasive pediatric diseases. Data on Kingella infective endocarditis (KIE) in children are scarce. We compared the clinical features of pediatric KIE cases with those of Streptococcus species IE (StIE) and Staphylococcus aureus IE (SaIE). A total of 60 patients were included in the study. Throughout the study period, a rise in incidence of KIE was noted. KIE patients were significantly younger than those with StIE and SaIE, were predominately boys, and had higher temperature at admission, history of oral aphthae before IE diagnosis, and higher lymphocyte count (p<0.05). Pediatric KIE exhibits unique features compared with StIE and SaIE. Therefore, in young healthy children <36 months of age, especially boys, with or without a congenital heart defect, with a recent history of oral aphthae, and experiencing signs and symptoms compatible with endocarditis, Kingella should be suspected as the causative pathogen.

Trend in women representation among authors of high rank rheumatology journals articles, 2002-2019.

OBJECTIVE: The representation of women among authors of peer reviewed scientific papers is gradually increasing. The aims of this study were to examine the trend of the proportion of women among authors in the field of rheumatology during the last two decades. METHODS: Articles published in journals ranked in the top quartile of the field of rheumatology in the years 2002-2019 were analysed. The authorship positions of all authors, country of the article's source and manuscript type were retrieved by specifically designed software. RESULTS: Overall, 153 856 author names were included in the final analysis. Of them, 55 608 (36.1%) were women. There was a significant rise in the percentage of women authors over time (r = 0.979, P <0.001) from 30.9% in 2002 to 41.2% in 2018, with a slight decline to 39.8% in 2019. There were significantly fewer women in the senior author positions compared with the first author positions (24.3% in senior position vs 40.9% as first author, P <0.001). CONCLUSION: The proportion of women among authors of rheumatology articles has increased over the years, both in general and as a first or senior author; however, their proportion is still <50% and there is still a gap between the proportion of women among first authors and the proportion of women among senior authors.

Performance of 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in a paediatric population-a multicentre study.

OBJECTIVES: The European League Against Rheumatism and American College of Rheumatology 2019 (EULAR/ACR-19) criteria for the diagnosis of SLE were recently published, with the stated goal of maintaining the level of sensitivity and raising the level of specificity for classification of SLE in adults. The aim of this study is to examine their application to juvenile SLE (jSLE) patients. METHODS: In this multicentre study the charts of jSLE patients from three tertiary medical centres were reviewed and compared with patients with non-jSLE diagnosis. Paediatric rheumatologists, blinded to the original diagnosis, reviewed and diagnosed all cases. Paediatric patients' clinical and laboratory data were retrospectively extracted and then examined with regard to how they met the new and old criteria. RESULTS: Included were 225 patients (112 jSLE, 113 non-SLE). When applied to juvenile SLE classification, the sensitivity of the new EULAR/ACR-19 criteria was 0.96 (95% CI: 0.9, 0.99) and the specificity was 0.89 (95% CI: 0.82, 0.94). These were comparable to the SLICC criteria. The sensitivity of the EULAR/ACR-19 criteria improves over time and was 0.83 12 months following disease onset, reaching 0.96 after longer than 24 months. CONCLUSION: Among a cohort of jSLE patients, sensitivity of the new EULAR/ACR-19 criteria was found to be high and specificity may have improved slightly compared with the SLICC-12 criteria. We support the use of the new classification criteria for paediatric patients in future jSLE studies, but it should be noted that its specificity is lower than for adults.

Factors predicting efficacy of ethanol lock therapy as catheter salvage strategy for pediatric catheter-related infections.

AIM: Catheter-related infections are difficult to cure, and failure rates are high. We aimed to evaluate the efficacy and safety of ethanol lock therapy (ELT) as catheter salvage strategy in children with central-line-associated bloodstream infection (CLABSI), and to identify factors associated with treatment failure. METHODS: Data were collected of all the children who received ELT for treatment of CLABSI during 2013-2018 due to failure of standard therapy or multiple catheter-related infections. Univariate and multivariate analyses of risk-factors for ELT failure were performed. Catheter salvage rates were compared to those achieved using systemic antimicrobials alone in an historical control group. RESULTS: A total of 123 ELT episodes among 95 patients were analyzed. The majority of patients had underlying hemato-oncological disorders. Approximately half the episodes occurred in patients with implantable ports. Early and late treatment failure rates of ELT were 16% (20/123) and 7% (9/123), respectively. Overall, successful catheter salvage was achieved in 78% (96/123) of episodes, compared to 54% using systemic antimicrobials alone (P < .001), including mycobacterium, candida, and most staphylococcus aureus infections. Adverse events were reported in 9% (11/123) of episodes and were mostly mechanical. Multivariate analysis identified four risk factors for ELT failure: Gram-positive bacteria, elevated C-reactive protein, signs of tunnel infection, and low absolute neutrophil counts. CONCLUSIONS: Our findings support the use of ELT for catheter salvage in children with CLABSI who failed standard therapy or had multiple catheter-related infections. The identified variables associated with ELT failure may help identify patients who can most benefit from ELT.

Pediatrician, watch out for corona-phobia.

The current outbreak of COVID-19 raging globally is taking a heavy toll on the adult population, with a rapidly growing number of newly infected and critically ill patients. However, to date, mortality rate among children is low as they mostly suffer from a mild disease. Yet, other more routinely encountered childhood diseases do not stand still and continue to be the main share of pediatricians' everyday challenges. Here we describe a case series of routinely seen pediatric diseases with delayed diagnosis due to different aspects of what we call "Corona-phobia". These cases were easily collected within a 1-week period which implies that this is a more widespread phenomenon.In conclusion, this raises the possibility that measures taken to mitigate this pandemic may be more damaging to children overall than the virus itself. We believe that pediatricians as well as policy makers should take this important aspect into consideration. What is Known: • COVID-19 manifests as a mild disease in most children; however, children are an important reservoir and may become spreaders of the disease. • Social distancing and isolation are important tools in mitigating COVID-19 transmission. What is New: • This case series describes 7 cases with delayed diagnosis of every-day pediatric diseases that were not caused by COVID-19 but were highly influenced by different aspects of "Corona-phobia". • Our objective is to highlight the possibility that measures taken to mitigate this pandemic may lead to a substantial delay in the diagnosis of other non-COVID-19 related diseases.

The COVID-19 pandemic dramatically reduced admissions of children with and without chronic conditions to general paediatric wards.

AIM: We examined the impact of the COVID-19 pandemic on how many children were admitted to Israel's largest tertiary paediatric hospital and why they were admitted. METHODS: Israel declared COVID-19 a national emergency on 19 March 2020. This study examined daily hospital admissions to our three general paediatric wards during the COVID-19 lockdown period from 20 March to 18 April 2020. These 258 admissions were compared with the 4217 admissions from the period immediately before this, 1 February to 19 March 2020, plus 1 February to 18 April in 2018 and 2019. We also compared why patients were admitted during the study period, and any pre-existing conditions, with 638 children hospitalised during the same period in 2019. RESULTS: The mean number of daily hospitalisations during the COVID-19 lockdown period was 8.6, which was 59% lower than the 20.9 recorded during the other three periods before COVID-19. There was a significant decrease in the number of patients admitted with infectious (74%) and non-infectious (44%) aetiologies from 2019 to 2020, and these occurred among patients with (58%), and without (55%), pre-existing medical conditions. CONCLUSION: The Israeli COVID-19 lockdown had a dramatic effect on admissions to the paediatric wards of a tertiary hospital.

Acute mastoiditis in infants younger than 6 months: is an alternative treatment protocol needed?

OBJECTIVES: Several studies have reported that younger children suffer from increased incidence and more severe episodes of acute mastoiditis (AM) than older children, whereas other researchers have found the opposite. The aim of our study was to describe the occurrence, clinical, and microbiological aspects of AM in children 6 months or younger, and compare them with the results in an older reference age band. METHODS: The medical files of children hospitalized with a diagnosis of AM during 2001-2016 were retrospectively reviewed. Diagnosis of AM was based on the presence of clinical signs of acute otitis media (AOM) accompanied by two or more of the following: auricle protrusion, retro-auricular erythema, swelling, and local tenderness. Children were divided into two age bands, 6 months or younger, and older than 6 months. RESULTS: Fifty patients in the young age band and 335 in the older reference age band were included. Bilateral AOM was identified in 14 (28%) children under 6 months, and 50 (14.9%) in the reference age band (p < 0.001). Fever, mean WBC, and CRP values were similar in both age bands; 4 (8%) children under 6 months had pre-auricular/zygomatic area swelling, as compared to 1(0.02%) in the reference age band (p < 0.001). Complication rates (subperiosteal abscess, sinus vein thrombosis, and epidural abscess) were similar in both age bands. All children were treated with myringotomy and IV antibiotics. Cortical mastoidectomy with the insertion of ventilation tube was performed in 10 (20%) children in the younger age band and 58(17.3%) in the reference age band. Streptococcus pneumoniae was the most common (38%) isolated bacteria in the younger age band, and Group A streptococcous (GAS) (20.6%) in the reference age band. CONCLUSIONS: AM in children 6 months or younger has similar presentation and characteristics as in older children. Pre-auricular swelling and bilateral AOM are more typical in the younger age band; Streptococcus pneumoniae is the most common pathogen in the younger children. We suggest that the treatment approach should be the same for both groups.

Frequency of Multifocal Disease and Pyogenic Arthritis of the Hip in Infants with Osteoarticular Infection in Three Neonatal Intensive Care Units.

OBJECTIVE: To describe the clinical features of osteoarticular infection in infants cared for in neonatal intensive care units (NICUs) and to assess the presence of multifocal infection. STUDY DESIGN: Retrospective medical record review with structured data abstraction of infants with osteomyelitis or pyogenic arthritis or both in NICUs at 3 children's hospitals over a 29-year period. RESULTS: Of the 45 cases identified, 87% occurred in prematurely born infants, with a median gestational age of 27.4 weeks (IQR, 26, 31 weeks). Median postnatal age at diagnosis of infection was 33 days (IQR, 20, 50 days). Osteomyelitis was present without joint involvement in 53% and with joint involvement in 44% of cases. Methicillin-susceptible Staphylococcus aureus (71%) was the predominant pathogen, despite prevalent methicillin-resistant S aureus in community-associated infections. More than 1 bone was infected in 34% of cases. The femur (in 50% of patients) was the most frequently involved bone and the hip (in 20% of patients) was the most frequently involved joint. Bacteremia persisted for 4 or more days in 54% of patients with a positive blood culture despite active antimicrobial therapy. CONCLUSIONS: Among infants with osteoarticular infection in NICUs, multifocal disease is common and frequently is unsuspected. Search for additional sites of infection including the hip is warranted following the diagnosis of osteoarticular infection at a single site. Involvement of contiguous joints should be suspected in cases of osteomyelitis; conversely the presence of pyogenic arthritis usually indicates extant osteomyelitis in a contiguous bone.

Changing epidemiology and resistance patterns of pathogens causing neonatal bacteremia.

To conduct a survey of the local prevalent bacteria and antibiotic resistance in a referral tertiary neonatal intensive care unit (NICU), in order to assess the efficacy of local antibiotic policies. We reviewed all positive blood and cerebrospinal fluid cultures obtained between January 2007 and December 2017 in the NICU of Schneider Children's Medical Center of Israel. Early and late-onset bacteremia were defined as episodes occurring within or after the first 3 calendar days of life respectively. Empiric treatment included ampicillin and gentamicin or piperacillin-tazobactam and amikacin for early or late-onset bacteremia respectively. The prevalence and antibiotic resistance of the bacteria were described and compared over time. Eight hundred and twenty nine of 15,947 (5.2%) newborns had at least one episode of bacteremia; 81 had multiple episodes. The most common bacteria were Escherichia coli (32.35%) and group B Streptococcus (19.11%) or coagulase negative Staphylococcus (CoNS) (60.5%) and Klebsiella sp. (12.4%) in early or late-onset bacteremia respectively. Overall, all Gram-positive bacteria were susceptible to vancomycin and most non-CoNS to ampicillin. Nosocomial vs. vertical bacteremia had increased resistance to ampicillin and cephalosporins. Resistance of nosocomial bacteria to piperacillin-tazobactam was 22.4%, to amikacin 3.3%, and to meropenem 1.8%. Changes over time: Gram-negative bacteria had a significant increase in resistance to cotrimoxazole and piperacillin. The resistance to gentamicin doubled. Our empiric antibiotic regimen covers the most frequent isolates. Amikacin may replace gentamicin for selected sick patients in early-onset bacteremia. Piperacillin-tazobactam should be combined with amikacin until susceptibility is available.

Vacuum-Assisted Closure for the Treatment of Deep Sternal Wound Infection After Pediatric Cardiac Surgery.

OBJECTIVES: Vacuum-assisted closure is being increasingly used to treat deep sternal wound infection following cardiac surgery, but most of the data refer to adults. This study investigated the safety and efficacy of vacuum-assisted closure in pediatric patients. DESIGN: Retrospective file review. SETTING: Tertiary pediatric medical center. PATIENTS: All children with deep sternal wound infection treated with vacuum-assisted closure in 2003-2016. INTERVENTIONS: Epidemiological, clinical, and microbiological data were collected from the medical records. MEASUREMENTS AND MAIN RESULTS: The cohort included 50 patients (0.9% of cardiac patients operated during the study period) of median age 6.5 months (interquartile range, 2-12.75 mo; range, 1 wk to 14 yr) and median weight 5.1 kg (interquartile range, 4-9.75 kg). The most frequent heart defects were tetralogy of Fallot (22%) and ventricular septal defect (20%); 38% of patients had cyanotic heart disease. Deep sternal wound infections appeared a median of 10 days postoperatively (interquartile range, 7-14 d; range 3-100 d). Vacuum-assisted closure was applied a median of 13 days postoperatively (interquartile range, 10-18.5 d; range, 5-103 d) for a median duration of 10 days (interquartile range, 7-13.25 d; range, 1-21 d). Wound cultures were positive in 48 patients (96%); most isolates were Gram-positive (76%). The main bacterial pathogen was methicillin-susceptible Staphylococcus aureus (61%). Most patients were treated with cloxacillin for a median of 38 days (interquartile range, 28-42 d; range, 9-189 d). There were no statistically significant differences in clinical or treatment characteristics between bacteremic (56%) and nonbacteremic patients. Compared with older patients, infants less than 3 months old (36%) had a significantly longer hospitalization time (41 vs 25 d; p = 0.001) and higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category (3 vs 2; p = 0.003). All cases except one (contact dermatitis) were uneventful. In 10 patients, wounds were closed surgically after vacuum-assisted closure. Two patients required a pectoralis flap, both treated before 2005. One of the two deaths was infection-related. CONCLUSIONS: Vacuum-assisted closure is a feasible treatment option of deep sternal wound infection after pediatric cardiac surgery and was not associated with independent morbidity.

A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study.

Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1-97.9%), specificity 94.3% (95% CI 90.7-98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse.

Novel RRM2B Mutation and Severe Mitochondrial DNA Depletion: Report of 2 Cases and Review of the Literature.

Purpose To describe the clinical presentation and implications of mitochondrial DNA depletion disorder of two siblings with early fatal encephalomyopathy and a novel mutation in the RRM2B gene. The relevant literature is reviewed. Methods We describe two brothers aged 2.5 months and 1 month, respectively, who were hospitalized in a tertiary pediatric medical center for evaluation of focal seizures, hypotonia, poor feeding, failure to thrive, lactic acidosis, and developmental delay. The older brother also had seizures, and the younger had severe bilateral neurosensory deafness. Results Genetic sequencing of the RRM2B gene revealed the same novel mutation in both the siblings. Both children died due to respiratory failure at ages 3 and 2.5 months, respectively. Conclusion The combination of neonatal hypotonia, developmental delay, and lactic acidosis should raise a clinician's suspicion of a mitochondrial depletion disorder and prompt further genetic studies.

Nephrologists need to play a key role in improving annual influenza vaccination rates in children with kidney disease.

AIM: This study investigated the under-researched area of annual influenza vaccination rates in children with chronic kidney disease and identified reasons for nonimmunisation. METHODS: A prospective cross-sectional study was conducted in the nephrology clinic and dialysis unit of a tertiary paediatric medical centre from August to October 2011 and September to October 2012. Parents were asked to complete a questionnaire on their child's immunisation against influenza. RESULTS: Of the 217 children studied, 45.6% were vaccinated against influenza. The major reason for nonimmunisation was because the parents had not received the necessary information from the primary physician or treating nephrologist. The nonvaccinated children were significantly more likely to be less than two years old and female and to have parents who did not believe in the benefits of vaccination (p < 0.05). Of the parents who did not vaccinate their child, 38% claimed they would have done so if the vaccine had been offered in the nephrology clinic. CONCLUSION: Children with kidney disease had a higher annual influenza vaccination rate than the general population, but it was still suboptimal. Nephrologists should be alerted to the need to provide parents with information on influenza vaccinations and they should be available in nephrology clinics.