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 through18 years diagnosed with imaging-confirmed thoracic and lumbar IS from 2000 to 2022 at a tertiary pediatric hospital. Patients with longer intravenous (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) 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 [IQR 34-64] mm/h). Elevated ESR was found in higher proportions (95%) compared with elevated CRP (76%, median 1.8 mg/dL; P< 0.001). Since implementing the shorter clinically directed IV treatment duration for patients with thoracic and lumbar IS, hospitalization duration was reduced from a median of 12 to 8 days (P =0.008) and IV treatment duration by a median of 14 to 8 days (P<0.001). Only 1(1.6%) patient in the clinically directed treatment group required re-hospitalization due to failure of therapy. Conversely, 9/124 children in the cohort suffered from IV treatment related complications; all had been treated IV for prolonged periods. CONCLUSION: Early transition to oral treatment in pediatric spondylodiscitis appears to be appropriate clinically, and shortens hospital stay and intravenous treatment duration without major negative clinical impact.

Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE-related immune thrombocytopenia.

BACKGROUND: Pediatric immune thrombocytopenia (ITP) may precede systemic autoimmune disorders. In adolescent patients with ITP, routine screening for systemic lupus erythematosus (SLE) may be performed by testing for antinuclear antibody (ANA) titer. Hydroxychloroquine (HCQ) is a safe and effective immunomodulatory drug in patients with SLE but rarely used in ITP. We analyzed the platelet count response and safety of HCQ in treating pediatric patients with SLE-related ITP. METHODS: A retrospective study including pediatric patients with ITP and definite or incomplete SLE, who were treated with HCQ during 2010-2021. SLE was defined by ANA titer ≥ 1:160 as measured by immunofluorescence and ≥10 points according to the 2019 EULAR/ACR 2019 classification criteria, while patients with incomplete SLE achieved a score < 10. Complete response (CR) of the platelet count was defined as platelet count > 100 × 109/L; partial response (PR) as platelet count 30-100 × 109/L and exceeding ≥ twice baseline counts. RESULTS: Of the 17 patients included (median age 15.5 years; IQR 3.6), 15 (88.2%) were female, 13 had definite SLE, and four had incomplete SLE. HCQ was initiated at a median of 17 months after ITP diagnosis with a median platelet count of 38 × 109/L (IQR 28). At 8 weeks, 8 (47.1%) patients responded, including 6 (35.3%) achieving CR. After one year, the overall response was 82.4%, with the remaining patients having stable platelet counts requiring no additional ITP therapy. The response was maintained at a median follow-up of 42 months. No adverse effects to HCQ were noted. CONCLUSION: Pediatric patients with SLE-related ITP may benefit from treatment with HCQ.

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.

Risk factors for haemodynamic compromise in multisystem inflammatory syndrome in children: a multicentre retrospective study.

OBJECTIVES: To identify predictors of a severe clinical course of multisystem inflammatory syndrome in children (MIS-C), as defined by the need for inotropic support. METHODS: This retrospective study included patients diagnosed with MIS-C (according to the CDC definition) in nine Israeli and one US medical centre between July 2020 and March 2021. Univariate and multivariate regression models assessed odds ratio (OR) of demographic, clinical, laboratory and imaging variables during admission and hospitalization for severe disease. RESULTS: Of 100 patients, 61 (61%) were male; mean age 9.65 (4.48) years. Sixty-five patients were hypotensive, 44 required inotropic support. Eleven patients with MIS-C fulfilled Kawasaki disease diagnostic criteria; 87 had gastrointestinal symptoms on admission. Echocardiographic evaluation showed 10 patients with acute coronary ectasia or aneurysm, and 37 with left ventricular dysfunction. In a univariate model, left ventricular dysfunction was associated with severe disease [OR 4.178 (95% CI 1.760, 9.917)], while conjunctivitis [OR 0.403 (95% CI 0.173, 0.938)] and mucosal changes [OR 0.333 (95% CI 0.119, 0.931)] at admission were protective. Laboratory markers for a severe disease course were low values of haemoglobin, platelets, albumin and potassium; and high leukocytes, neutrophils, troponin and brain natriuretic peptide. In multivariate analysis, central nervous system involvement and fever >39.5°C were associated with severe disease. Mucosal involvement showed 6.2-fold lower risk for severe disease. Low haemoglobin and platelet count, and elevated C-reactive protein and troponin levels were identified as risk factors for severe disease. CONCLUSION: Key clinical and laboratory parameters of MIS-C were identified as risk factors for severe disease, predominantly during the disease course and not at the time of admission; and may prompt close monitoring, and earlier, more aggressive treatment decisions. Patients presenting with a Kawasaki-like phenotype were less likely to require inotropic support.

Benign transient hyperphosphatasemia in infants and children: a retrospective database study.

Benign transient hyperphosphatasemia is a condition characterized by greatly increased serum alkaline phosphatase (ALP) without laboratory or clinical evidence of underlying bone or liver disease. It is usually identified incidentally during routine blood testing. We describe the demographic and clinical characteristics of benign transient hyperphosphatasemia in a cohort of healthy infants and children. We performed a retrospective review of electronic medical records on all children aged 1 day to 18 years with a diagnosis of benign transient hyperphosphatasemia, who were registered at 3 central districts in Israel from January 1, 2000, to December 31, 2020. The demographic and clinical characteristics were retrieved from the medical files. The study group comprised 382 infants and children aged from 2 months to 14 years who had serum ALP > 1000 U/L (mean 2557 U/L, range 1002-14,589 U/L). The majority of participants (87%) were aged up to 24 months (median age 14 months, IQR 10-18 months). Fifty-four percent of the study participants were male. In many patients, there was a history of recent fever, gastroenteritis or diarrhea, acute otitis media, and viral infection. A seasonal peak was observed in autumn-early winter, but this may be a detection bias. CONCLUSION: Benign transient hyperphosphatasemia seems to be a disorder described among otherwise healthy infants and children, which resolves spontaneously. Other known causes of markedly elevated serum ALP should be excluded, especially bone and liver disease. Higher awareness and recognition of this benign condition are important in order to avoid unnecessary tests and parental anxiety. WHAT IS KNOWN: • Benign transient hyperphosphatasemia is a benign condition characterized by greatly increased serum alkaline phosphatase without laboratory or clinical evidence of underlying bone or liver disease, which usually resolves spontaneously, with no intervention. WHAT IS NEW: • In the case of an incidental finding of high serum alkaline phosphatase in an otherwise healthy infant or child with no other clinical or laboratory suspicion of bone or liver disease, we recommend repeating the alkaline phosphatase level within a few months in order to confirm the resolution of this condition. • When benign transient hyperphosphatasemia is suspected, a "wait and see" approach is optimal in order to avoid unnecessary investigations and parental anxiety.

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.

Thunderclap Headache in Children and Adolescents.

PURPOSE OF REVIEW: This work aimed to review the epidemiology, clinical criteria, and primary and secondary diagnoses of pediatric thunderclap headache and to compare to adult thunderclap headache. RECENT FINDINGS: Thunderclap headache among children aged 6-18 years are rare; this headache presented in 0.08% of the patients admitted to a pediatric emergency department in a tertiary pediatric center. In that recent single-center study, thunderclap was a headache of grade 10 on the pain scale and conferred a benign course. Contrary to adults, in children, most thunderclap headaches are due to either a primary thunderclap headache or another type of primary headache. A number of case reports have attributed pediatric thunderclap to reversible vasoconstriction syndrome and bleeding due to intracranial aneurysm. However, 3-year data from a pediatric emergency department of one center did not find these reasons to be causes of secondary thunderclap headache. This may be due to the rarity of these diagnoses in children compared to adults. Four of the 19 patients with thunderclap headache reported in that single study had secondary thunderclap; the causes were infection in three and malignant hypertension in one. All the patients had a benign course. Although urgent imaging and lumbar puncture are required in the workup of pediatric thunderclap, severe causes are very rare. More research is needed to investigate pediatric thunderclap headache.

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.

Severe abrupt (thunderclap) non-traumatic headache at the pediatric emergency department - a retrospective study.

BACKGROUND: Adult abrupt severe non-traumatic headache (thunderclap) is often related to serious underlying etiologies such as subarachnoid hemorrhage. However, data are sparse regarding thunderclap headache in the pediatric population. OBJECTIVE: The aim of the study was to evaluate the prevalence, characteristics and causes of thunderclap headache in the pediatric and adolescent population, aged 6-18 years, presenting to a pediatric emergency department. METHODS: The electronic database of a tertiary care pediatric emergency department was searched for children presenting with acute headache during 2016-2018. Headache severity was defined by pain scales, either a visual analogue scale or by the Faces Pain Scale-Revised. RESULTS: Thunderclap headache was diagnosed in 19/2290 (0.8%) of the included patients, all of them with a pain score of 10/10. All the patients had a benign course. Primary headache was diagnosed in 15/19 (78.9%), six patients had migraine and eight were diagnosed with primary thunderclap headache. Four of the 19 patients were diagnosed with secondary headache: three with infectious causes and one with malignant hypertension. CONCLUSIONS: Thunderclap headache is rare among children and adolescents presenting to the emergency department. This headache is generally of a primary origin. Extensive evaluation is still needed to rule out severe diagnosis problems.

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.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome - Is It Related to Ethnicity? An Israeli Multicenter Cohort Study.

OBJECTIVES: To evaluate the ethnic distribution of Israeli patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA). STUDY DESIGN: The medical records of patients with PFAPA attending 2 pediatric tertiary medical centers in Israel from March 2014 to March 2019 were retrospectively reviewed. Patients with concomitant familial Mediterranean fever were excluded. Ethnicity was categorized as Mediterranean, non-Mediterranean, and multiethnic. Findings were compared with patients with asthma under treatment at the same medical centers during the same period. RESULTS: The cohort included 303 patients with PFAPA and 475 with asthma. Among the patients with PFAPA, 178 (58.7%) were of Mediterranean descent (Sephardic Jews or Israeli Arabs), 96 (33.0%) were multiethnic, and 17 (5.8%) were of non-Mediterranean descent (all Ashkenazi Jews). Patients with PFAPA had a significantly higher likelihood of being of Mediterranean descent than the patients with asthma (58.7% vs 35.8%; P < .0001). The Mediterranean PFAPA subgroup had a significantly earlier disease onset than the non-Mediterranean subgroup (2.75 ± 1.7 vs 3.78 ± 1.9 years, P < .04) and were younger at disease diagnosis (4.77 ± 2.3 vs 6.27 ± 2.9 years, P < .04). CONCLUSIONS: PFAPA was significantly more common in patients of Mediterranean than non-Mediterranean descent. Further studies are needed to determine the genetic background of these findings.

Safety and efficacy of intravenous Colchicine in children with Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF), the most common monogenic inflammatory disease, is mainly treated by oral Colchicine. However, 5% of patients are considered non-responders and, therefore, candidates for biologic therapy. Intravenous (IV) Colchicine treatment has been shown to be effective and safe in adult patients. The objective of this study was to evaluate the safety of IV Colchicine for pediatric FMF patients in our hospital, refractory to oral Colchicine, by reviewing their medical records. Inclusion criteria were all patients with FMF who commenced treatment with IV Colchicine before the age of 18 years, and received at least 6 months of IV therapy. The patients completed questionnaires to assess the efficacy of the treatment. Between 2004 and 2017, 7 pediatric FMF patients receiving maximal oral Colchicine doses and deemed non-responders were treated with weekly IV Colchicine, including 38 cumulative patient years of follow-up data (a full blood count, renal and liver function tests). All patients were homozygous for the M694V genotype. Long-term follow-up showed normal laboratory results with no Colchicine-related hospital admissions or toxicity. Global health assessment and the number of disease-free days have significantly improved (P < 0.05). Prolonged IV Colchicine use is described in pediatric FMF patients for the first time, with an excellent safety profile in our population, and decrease in intensity and frequency of attacks. In the biological era, IV Colchicine, although not leading to complete remission, may be considered a second-line option in countries where anti-interleukin 1 blockers are not available, or as a third-line option in case of failure to respond to biologics.

Cephalic cutaneous allodynia in children and adolescents with migraine of short duration: A retrospective cohort study.

BACKGROUND: Allodynia is prevalent in adults with migraine and has been associated with long disease duration and severe course. Studies of the pediatric population are sparse. The aim of this study was to evaluate the rate of cephalic cutaneous allodynia in children and adolescents within the first 6 months of migraine onset and to identify associated clinical and migraine-related parameters. METHODS: The electronic database of a tertiary pediatric headache clinic from 2014 to 2017 was retrospectively searched for all children and adolescents diagnosed with migraine headache within 6 months or less of symptom onset. Cephalic cutaneous allodynia was identified by validated questionnaire. Demographics, symptoms, and headache-related parameters were compared between patients with and without allodynia. RESULTS: The cohort included 119 patients, 69 girls (58.0%) and 50 (42.0%) boys, of mean age 11.6 ± 3.6 years. Mean time since onset of migraine disease was 3.6 ± 1.8 months. Cephalic cutaneous allodynia was reported by 31.1% of patients. It was significantly associated with female gender ( p = 0.03), older age at admission ( p = 0.037), older age at onset ( p = 0.042) migraine with aura ( p = 0.002), and higher rate of awakening pain ( p = 0.017). CONCLUSIONS: Cephalic cutaneous allodynia may occur in children and adolescents already in the first 6 months of migraine onset. Contrary to adult studies, we found no association of allodynia with migraine frequency or long disease duration. Allodynia was significantly associated with migraine with aura, female gender, and awakening pain. A genetic tendency may contribute to the appearance of allodynia in the pediatric age group.

Calcineurin inhibitor-free strategies for prophylaxis and treatment of GVHD in children with posterior reversible encephalopathy syndrome after stem cell transplantation.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a distinct clinico-radiologic entity that can occur following allogeneic hematopoietic stem cell transplantation, often in the context of treatment with calcineurin inhibitors (CNIs). PROCEDURE: We describe the results of CNI-free management of 14 children with PRES and review the clinical and radiologic manifestations of their presentation. RESULTS: Discontinuation of CNIs usually resulted in remission of PRES, but patients with established graft versus host disease (GVHD) at the time when treatment was changed often experienced progressive GVHD despite administration of immune suppressive and modulating treatments. All but three patients experienced full neurologic recovery. Nine children died as a result of either GVHD, disease relapse, or severe infection. CONCLUSIONS: Discontinuation of CNIs results in neurologic improvement in most cases, but superior alternative immune modulatory treatment is needed to prevent progression of established GVHD.

Differential Serum Phosphate Levels in Pediatric Febrile Syndromes and Their Clinical Significance.

BACKGROUND: The potential of hypophosphatemia (HP) to differentiate between febrile syndromes and its clinical significance in children without sepsis were not previously described. METHODS: Data were retrospectively collected of febrile children aged 3 months to 18 years, hospitalized at general pediatric wards during 2010-2019. Phosphate levels were compared between bacterial infection (BI), viral infection (VI), and Kawasaki disease (KD). Regression analyses were used to evaluate the relationship between HP and outcome. RESULTS: Of 3963 febrile children, 559 had BI, 3271 had VI, and 133 had KD. In BI compared to VI and KD, HP was more prevalent (49.2%, 19.7%, and 31.6%, respectively; P<0.001) and more severe [median (interquartile range) phosphate standard deviation score: -1.85 (2.08), -0.56 (2.08), and -1.20 (2.28), respectively; P<0.001]. In the BI group, Pi-SDS level was lower among patients with than without bacteremia (-2.33 ± 1.8 vs. -0.79 ± 1.68; P<0.001). Phosphate levels displayed discriminatory potential between bacterial and viral etiologies, with an area under the curve of 0.719 (95% CI, 0.697-0.742). Minimal phosphate standard deviation score values had a negative weak correlation with the maximal C-reactive protein levels and white blood cell count. Univariate and multivariate analyses showed an association of HP with a more severe disease course, manifested by longer hospital stay [+2.10 (95% CI, 0.75-3.46) days; P=0.003] and a higher rate of intensive care unit admission [odds ratio, 2.63 (95% CI, 1.94-3.56); P<0.001). CONCLUSIONS: Hypophosphatemia rates were highest in bacterial etiology, intermediate in KD, and lowest in viral etiology and were associated with poorer outcomes. Phosphate level may serve as a marker for ruling out a bacterial etiology.

Pathogens Causing Pediatric Community Acquired Urinary Tract Infections and Their Increasing Antimicrobial Resistance: A Nationwide Study.

Urinary tract infections (UTIs) in childhood are common and are associated with considerable acute morbidity and long-term complications. The need for updated data to optimize empiric antibiotic therapy is crucial. We aimed to investigate the pathogens causing pediatric community acquired UTIs, their correlation with demographic characteristics, and trends in their antimicrobial resistance. This nationwide cross-sectional study included all 53,203 children (<18 years) diagnosed with UTI in community outpatient clinics in the following selected years: 2007, 2011, 2015, 2019 and 2021. Escherichia coli (E. coli) (82.1%) was the most common uropathogen, followed by Enterobacter, Klebsiella, Proteus, Pseudomonas, and Enterococcus species. The bacterial distribution displayed statistically significant (p < 0.0001) gender- and sector-specific patterns with a higher relative prevalence of non-E. coli UTI in Jewish and males. The rate of extended-spectrum beta-lactamase-positive E. coli increased substantially and significantly (p < 0.001) from only 6.1% in 2007 to 25.4% in 2021. Most non-E. coli uropathogens exhibited resistance to commonly used empiric antibiotics for UTIs in children. These findings are significant in guiding optimal empiric antibiotic treatment for pediatric community acquired UTIs. The resistance of uropathogens to antimicrobials is region- and time-dependent. Therefore, the periodic and local assessment of antibiotic resistance trends is essential to update guidelines and provide the most appropriate antibacterial therapy for children with UTIs.

Discovery of a Novel Missense Variant in NLRP3 Causing Atypical Cryopyrin-Associated Periodic Syndromes With Hearing Loss as the Primary Presentation, Responsive to Anti-Interleukin-1 Therapy.

OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS), also known as NLRP3-associated autoinflammatory diseases, are a spectrum of rare autoinflammatory diseases caused by gain-of-function variants in the NLRP3 gene, resulting in inflammasome hyperactivation and dysregulated release of interleukin-1ß (IL-1ß). Many patients with CAPS develop progressive sensorineural hearing loss (SNHL) because of cochlear autoinflammation, which may be the sole manifestation in rare cases. This study was undertaken to establish the suspected diagnosis of CAPS in a family presenting with autosomal-dominant progressive/acute SNHL and a novel missense variant in the NLRP3 gene of unknown significance (NM_001079821.3:c.1784G>A p.Ser595Asn). METHODS: We conducted an ex vivo functional assessment of the NLRP3 inflammasome in heterozygous individuals (n = 10) and healthy family members (n = 5). RESULTS: The assay revealed hyperactivation of the inflammasome among heterozygous individuals, supporting the hypothesis that this missense variant is a pathogenic gain-of-function variant. Administration of IL-1 receptor antagonist resulted in a substantial clinical improvement among pediatric patients, who exhibited near resolution of hearing impairment within 1 to 3 months of treatment. CONCLUSION: Our findings highlight the crucial role of early diagnosis and treatment with an anti-IL-1 agent in reversing cochlear damage. Furthermore, our results suggest that high- and ultrahigh-frequency ranges need to be included in the auditory assessment to enable early detection of subclinical SNHL. Finally, incorporating functional inflammasome assessment as part of the clinical evaluation could establish the diagnosis in inconclusive cases.