Etiology In Children Research Articles

Genetic testing in pulmonary hypertension in adults and children

Abstract Pathogenic genetic variants have been found in patients with different forms of pulmonary arterial hypertension (PAH). Our aim was to define the genetic background of patients with idiopathic PAH (IPAH), heritable PAH (HPAH), pulmonary veno-occlusive disease (PVOD) and PAH associated with congenital heart disease (PAH-CHD); both in adult and pediatric age. REHAP and REHIPED are Spanish, voluntary, multicenter registries that include patients with PAH. REHAP started in 2007 and includes patients over 18 years of age. REHIPED started in 2009 and collects patients between 2 months and 18 years of age. Patients with IPAH, HPAH, PVOD and PAH-CHD who have undergone a genetic testing were included. 413 adults and 122 children were analyzed. From 2011, Sanger sequencing and multiplex ligation-dependent probe amplification were used to detect genetic variants in the BMPR2, TBX4, and KCNK3 genes. Since 2014, a next generation sequencing (NGS) panel of 21 genes was applied. In 2017 this panel was expanded to cover 35 genes, and in 2019, it was expanded to 37 genes. Since 2020, whole-exome sequencing has been applied for the previously followed-up patients without known pathogenic/likely pathogenic (P/LP) genetic variants, and for each incident case. There was a statistically significant difference (p 0.031) in the etiologies among adults and children. The etiologies in adults were 242 (59%) IPAH, 25 (6%) HPAH, 83 (20%) PAH-CHD, 63 (15%) PVOD. The etiologies in children were 66 (54%) IPAH, 8 (7%) HPAH, 38 (31%) PAH-CHD, and 10 (8%) PVOD. The genetic testing had a variant in 121 (29%) adults (56% pathogenic, 9% likely pathogenic, 32% VUS) and 63 (52%) children (65% pathogenic, 16% LP, 19% VUS) (adults vs children p < 0.001). BMPR2 was the most frequent variant in both populations, followed by EIF2AK4. Patients with HAPH and PVOD are more likely to have a genetic variant, while PAH-CHD are the less likely to have one; both in adults and children (p<0.001). The etiology was reclassified after the genetic testing in 13% adults and 19% children (p 0.08); including 6 adults and 4 children initially classified as IPAH and then diagnosed of PVOD when a P/LP variant was found in EIF2AK4. Also, 5 children were initially diagnosed as IPAH and then reclassified as multisystemic disorders (4 NFU1 and 1 MECP2) In conclusion, a significant number of patients with PAH have a variant in genetic testing, especially if they are diagnosed in pediatric age. BMPR2 is the most frequent variant in our cohort, followed by EIF2AK4. Knowing the genetic background of our patients enables a better classification and understanding of the disease. This is especially important in patients initially diagnosed of PAHI who are then classified as PVOD. Also, knowing the genetic background may help develop new treatments in the future.

Etiology, clinical profile, and outcomes of crescentic glomerulonephritis in children: a systematic review.

Crescentic glomerulonephritis, if not managed promptly, is associated with unsatisfactory outcomes. There are limited studies reporting the outcomes of crescentic glomerulonephritis in children. This systematic review is aimed at synthesizing the data on etiology, clinical profile, and outcomes of crescentic glomerulonephritis in children. We performed a literature search using PubMed, Embase, and Web of Science from inception to January 2024 without language or geographic restrictions. Cohort and cross-sectional studies with at least 10 participants reporting etiology, clinical features, and outcomes on crescentic glomerulonephritis in children were considered eligible. Children aged less than 18years with crescentic glomerulonephritis. We used a tool by Hoy et al. for assessing the quality of studies. We calculated pooled estimates using random effect meta-analyses. Primary outcome was the pooled proportion of patients progressing to kidney failure. From 1706 records, we included 36 studies (1548 participants) from 16 countries. Etiology was immune-complex glomerulonephritis in 76% (95% CI 67 to 85), pauci-immune in 19% (13 to 25), and anti-GBM disease in 5% (3 to 7) of patients. Gross hematuria, oliguria, edema, and hypertension were observed in 63% (41 to 82), 57% (34 to 79), 79% (65 to 90), and 64% (49 to 77), respectively. In-hospital mortality, reported in 11 studies, was 7% (4 to 11). Progression to kidney failure and chronic kidney disease was reported in 27% (21 to 33) and 50% (29 to 71) ofpatients, respectively. Risk factors for kidney failure included oliguria, dialysis requirement at onset, estimated GFR, proportion of fibrous crescents, and pauci-immune glomerulonephritis as the underlying etiology. High heterogeneity in pooled estimates of the outcomes. Immune-complex glomerulonephritis is the most common etiology in children, with edema, hypertension, gross hematuria, and oliguria being the chief presenting manifestations. Almost one in every four patients with crescentic glomerulonephritis progressed to kidney failure. PROSPERO registration number CRD42024500515.

Клинико-генетическая характеристика детей с подозрением на наследственные заболевания печени. Алгоритм дифференциальной диагностики

Hepatitides of unspecified etiology in children may be caused by genetic disorders. Its early detection can improve the patient management with understanding the pathogenesis, more accurately predicting the course, preventive examinations and prescribing specialized pathogenetic therapy in selected cases. However, currently there are no guidelines for the optimal diagnosis of such cases. The purpose of this research was to develop an algorithm for the differential diagnosis of hepatitides of unspecified etiology in children based on the identified clinical and genetic features of hereditary liver diseases. Materials and methods used: a single-center cohort retrospective study of 179 children with hepatitides of unspecified etiology aged 0 to 18 y/o was conducted. All patients had undergone genetic examination, based on the results of which the two groups were formed as follows: with and without genetic liver disease. Statistical analysis of the patients’ clinical, laboratory and instrumental examinations was aimed at identifying key markers for common hereditary liver diseases in different age groups as well as statistically significant differences in rare genetic reasons for hepatitis. Results: 27 different genetic liver diseases were identified in 101 (56.4%) with hepatitis of unspecified etiology. The most frequently detected diseases were Wilson's disease (41 or 40.6%), alpha-1 antitrypsin deficiency (A1AD or AATD) (9 or 8.9%) and Alagille syndrome (ALGS) (8 or 7.9%). Other hereditary pathologies occurred in isolated cases though its total incidence was nearly half of all cases (43 or 42.6%). In order to identify such cases, it is advisable to perform exome sequencing. In order to determine the indications for genetic examination, Authors have developed the mathematical model for assessing the risk of hereditary liver disease (ROC-AUC 0.787 with 95% CI: 0.696-0.877, sensitivity 69.8% with 95% CI: 57.7%-81.3%, specificity 79.2% with 95% CI: 72.3%-84.8%). Conclusion: Authors offer the suggested algorithm for differential diagnosis of hepatitides of unspecified etiology in children that includes, on the first place, the exclusion of the most common genetic liver diseases followed by exome sequencing in high-risk cases that in its turn is calculated using the developed mathematical model.

The role of Electroencephalography in children with Acute Altered Mental Status of unknown etiology: a prospective study.

Acute alterated mental status (AAMS) is often a challenge for clinicians, since the underlying etiologies cannot always easily be inferred based on the patient's clinical presentation, medical history or early examinations. The aim of this study is to evaluate the role of the electroencephalogram (EEG) as a diagnostic tool in AAMS of unknown etiology in children. We conducted a prospective study involving EEG assessments on children presenting with AAMS between May 2017 and October 2019. Inclusion criteria were age 1 month to 18 years and acute (<1 week) and persistent (>5 minutes) Altered mental status (AMS). Patients with a known etiology of AAMS were excluded. A literature review was also performed. Twenty patients (median age: 7.7 years, range: 0.5-15.4) were enrolled. EEG contributed to the diagnosis in 14/20 cases, and was classified as diagnostic in 9/20 and informative in 5/20. Specifically, EEG was able to identify nonconvulsive status epilepticus (NCSE) in 5 children and psychogenic events in 4. EEG proved to be a poorly informative diagnostic tool at AAMS onset in 6 children, however in 5 of them, it proved useful during follow-up. Limited data exist regarding the role of EEG in children with AAMS of unknown etiology. In our population EEG proved to be valuable tool, and was especially useful in the prompt identification of NCSE and psychogenic events.

Intelligence quotient in children with congenital hypothyroidism on treatment: A cross-sectional study

Introduction: Congenital hypothyroidism (CH) is the most commonly identified endocrine disorder. Early intervention can prevent intellectual deficits. Objective: To determine the intelligence quotient (IQ) and aetiology in children diagnosed with CH undergoing treatment and the associations between the IQ and the age of diagnosis. Method: A cross-sectional study was conducted in a tertiary care hospital in Bangalore, which enrolled 52 children aged 6 months to 15 years diagnosed with CH. Using a pre-designed proforma, we collected demographic data and confirmed CH aetiology. For IQ assessment, children under 3 years underwent the Vineland Social Maturity Scale (VSMS) and developmental screening test (DST), while those over 3 years were evaluated with the VSMS and Binet Kamat test of intelligence (BKT). Results: Among the 52 children with CH, dyshormonogenesis was the predominant aetiology. In the under-3-year age group (n=17), all demonstrated average to above-average intelligence. Among those over 3 years (n=35), 10.9% (95% CI: 6.5% to 17.2%) exhibited low average and borderline intelligence with the VSMS, and 5.7% (95% CI: 2.3% to 12.5%) had extremely low IQ (IQ &lt;70). The BKT scale showed 20% (95% CI: 12.8% to 29.7%) with low average and borderline intelligence, and 2.9% (95% CI: 0.7% to 8.3%) with extremely low IQ (IQ &lt;70). Children diagnosed at a mean age of 4.2 and 4.4 years exhibited intellectual disability on the VSMS and BKT scales, respectively. Conversely, those diagnosed at a mean age of 1.2 and 1.8 years showed average and above-average intelligence on the VSMS (p-value 0.02) and BKT scale (p-value 0.001), respectively. Conclusions: Children diagnosed with CH at mean ages of 4.2 and 4.4 years exhibited intellectual disability on the VSMS and BKT scales, respectively. Conversely, those diagnosed with CH at mean ages of 1.2 and 1.8 years showed average and above-average intelligence on the VSMS (p = 0.02) and BKT scale (p = 0.001), respectively.

Children with bicytopenia and pancytopenia – clinical picture, etiological spectrum, and outcome

Background: Children who develop cytopenias present with several etiological causes, posing diagnosis, and management difficulties for both physicians and pathologists. With these in mind, we assessed the clinical profile and etiology of children who attended a healthcare facility in South India with bicytopenia or pancytopenia. Aims and Objectives: (1) The primary objective of this study was to find out the clinical and etiological spectrum in children with bicytopenia and pancytopenia who were admitted to the Institute of Child Health and Research Center, Government Rajaji Hospital, Madurai. (2) The secondary objective of this study is to follow-up children with bicytopenia and pancytopenia to find out the outcome and prognosis. Materials and Methods: This study was in the Department of Pediatrics at the Government Rajaji Hospital in Madurai, Madurai Medical College’s Institute of Child Health and Research Center, which is where we carried out the study. Two hundred and sixty-four patients with bicytopenia and 36 patients with pancytopenia were included in this study. Once in 2 weeks, all children with bicytopenia and pancytopenia were assessed in our Saturday hematology outpatient clinics. Results: Fever was the most prevalent sign of both pancytopenia and bicytopenia in this investigation. Etiological variables among cases of pancytopenia, cancer, infections, non-infections, and idiopathic causes were recorded in 11%, 58%, 17%, and 14% of cases, respectively. Similarly, bicytopenia, malignancy, infections, non-infections, and idiopathic causes were found in 23%, 70%, 4%, and 3% of cases, respectively. According to the prognosis, 28%, 33%, 6%, and 33% of cases with pancytopenia recovered, passed away, were lost to follow-up, or were undergoing treatment, respectively. Similar to those individuals, 67%, 11%, 4%, and 18% of bicytopenia cases were treated, recovered, or lost to follow-up, respectively. Conclusion: In children, there is a wide etiological range of cytopenias. Infections and dangerous diseases like acute leukemia are among the reasons. The geographical location of the hospital, the frequency of malnutrition, and the regional presence of certain diseases such as malaria and enteric fever determine the causes reported in a hospital environment.

Thrombin Generation Profile Using ST-Genesia after PEG-asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia.

Venous thromboembolism (VTE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. The use of global assays of hemostasis as a thrombin generation test (TGT) is useful to individualize VTE risk in adult patients. This prospective cohort study aimed to evaluate the usefulness of an automated TGT to evaluate VTE risk during ALL treatment in children. TGT (automated analyzer ST Genesia; ThromboScreen) and pro- and anticoagulant plasma proteins were analyzed during ALL treatment in pediatric patients following LAL-SEHOP-PETHEMA-2013 guidelines. Results were compared with a series of pediatric normal controls and evaluated according to pegylated asparaginase PEG-ASP administration and to VTE risk factors. The study included 67 patients: males n = 35, B-ALL (n = 60). None had a VTE during the evaluated period. Compared to healthy controls, the normalized endogenous thrombin potential (N-ETP) ratio in patients was higher and ETP inhibition (ETP-inh) was lower, especially after PEG-ASP administration. Plasmatic protein C and protein S levels decreased after PEG-ASP administration, but antithrombin mean level did not. A bivariant analysis showed that ETP-inh was lower in patients >10 years old (p = 0.05) and in those with non-O blood type (p = 0.005). A linear mixed model also showed a higher TGT prothrombotic profile in patients with inherited thrombophilia. TGT could be a biomarker of a high VTE risk in ALL pediatric patients. Non-O blood group and inherited thrombophilia were associated with a significantly higher thrombotic profile, and an increased profile was also observed after administration of PEG-ASP.

Acute Kidney Injury In Children

Acute kidney injury (AKI) is a clinical condition characterized by sudden deterioration in kidney functions, increase in blood urea nitrogen (BUN) and serum creatinine levels, hyperkalemia, metabolic acidosis and hypertension. When defining AKI, current guidelines that consist of criterias determined by serum creatinine level and urine output are used. There are three main causes of AKI; prerenal, renal and postrenal. Prerenal AKI is most common etiology in children. Clinical symptoms of AKI vary depending on etiology. When evaluating a child with AKI, it should be noted that an increase in creatinine typically occurs 48 hours after renal injury and is the result of events 2-3 days earlier. The prognosis of AKI varies depending on the etiology.

Differentiation of peripheral and non-peripheral etiologies in children with vertigo/dizziness: The video-head impulse test and suppression head impulse paradigm

ObjectivesTo identify the etiology of vertigo/dizziness and determine the effectiveness of the video-head impulse test (vHIT) and the suppression head impulse paradigm (SHIMP) tests in distinguishing between peripheral and non-peripheral etiologies in children who presented to the otolaryngology department with complaints of vertigo/dizziness. MethodsThe vHIT and SHIMP tests were applied to the children. The vestibulo-ocular reflex (VOR) gain and saccade parameters were compared. ResultsIn 27 children presenting with vertigo/dizziness, the most common etiological factor was inner ear malformation (IEM) (n = 6/27, 22.2%), followed by cochlear implant surgery (11.1%) and migraine (11.1%). Vestibular hypofunction was indicated by the vHIT results at a rate of 60% (9/15 children) and SHIMP results at 73.3% (11/15 children) among the children with a peripheral etiology, while these rates were 8.3% (1/12 children) and 25% (3/12 children), respectively, in the non-peripheral etiology group. SHIMP-VOR and vHIT-VOR gain values had a moderate positive correlation (p = 0.01, r = 0.349). While there were overt/covert saccades in the vHIT, anti-compensatory saccade (ACSs) were not observed in the SHIMP test (p = 0.041). The rates of abnormal vHIT-VOR gain (p = 0.001), over/covert saccades (p = 0.019), abnormal vHIT response (p = 0.014), ACSs (p = 0.001), and abnormal SHIMP response (p = 0.035) were significantly higher in the peripheral etiology group. ConclusionsIEM was the most common etiological cause, and the rate of vestibular hypofunction was higher in these children with peripheral vertigo. vHIT and SHIMP are effective and useful vestibular tests for distinguishing peripheral etiology from non-peripheral etiology in the pediatric population with vertigo/dizziness. These tests can be used together or alone, but the first choice should be the SHIMP test, considering its short application time (approximately 4–5 min) and simplicity.

Resuscitation Update - What's New?

Perfect, uninterrupted basic life support (BLS) is the key for successful cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA). Time plays an important role in the treatment of OHCA. This applies both to the time until the start of BLS and the reduction of all pauses during resuscitation, especially chest compressions. In 2022, the rate of bystander-CPR showed an absolute increase of 4% compared to previous years. The bystander-CPR rate is currently above 50%. Compared to OHCA in adults, cardiac arrest in children is rare in Germany. In the period from 2007 to 2021, the incidence was 3.08 per 100000 children. In addition, the etiology in children varies depending on the age group. While hypoxia is often the cause of circulatory arrest in younger children, trauma and drowning accidents are the main causes in school-age children. Different additional diagnostic and therapeutic strategies have been evaluated over the last years. Point-of-care ultrasound during resuscitation should only be performed by experienced users. Interrupting chest compressions and thus prolonging the no-flow phases must be avoided. Double sequential external defibrillation after the third shock can successfully terminate refractory ventricular fibrillation. While further studies are needed, emergency medical systems should train their teams to avoid complications. In refractory OHCA, extracorporeal CPR should be considered. In the case of in-hospital cannulation, immediate transport should be weighed against impaired chest compression quality. Therefore, transportation under CPR is only beneficial if there is an indication for further treatment.

Deaths Associated with Pediatric Hepatitis of Unknown Etiology, United States, October 2021-June 2023.

During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus.

Metabolic etiologies in children with infantile epileptic spasm syndrome: Experience at a tertiary pediatric neurology center

ObjectiveInfantile epileptic spasm syndrome (IESS), including West syndrome (WS) and infantile spasm (IS), causes a challenging prognosis, particularly when associated with metabolic etiologies. MethodsThis study, conducted at a tertiary pediatric neurology center, explored the prevalence and clinical features of inborn errors of metabolism in 112 children with IESS over 10 years. ResultsMost patients presented with seizures, primarily flexor spasms, and the median age at onset was 5 months. Comprehensive clinical evaluation and neuroimaging revealed structural-acquired causes as the most common etiology. Notably, inborn errors of metabolism were identified in 5.4 % of cases, with six distinct diagnoses including nonketotic hyperglycinemia, pyridoxine-dependent epilepsy, primary coenzyme Q10 deficiency 7, congenital disorder of glycosylation type IIM, 6-pyruvoyl tetrahydrobiopterin synthase deficiency, and argininosuccinate lyase deficiency. The prevalence of inborn errors of metabolism in this cohort was consistent with global variations reported in the literature. Genetic testing, including karyotype analysis and whole exome sequencing, was performed in a subset of cases with no clear diagnosis, revealing abnormalities in approximately 50 % of cases. Adrenocorticotropic hormone emerged as the most frequently prescribed antiseizure medication. ConclusionThis study provides insight into the diagnostic challenges associated with IESS and highlights the importance of metabolic investigations, especially in cases without a clear etiology. The findings emphasize the need for further genetic and metabolic studies to enhance prognostic accuracy and guide potential treatment options for children with IESS, particularly in populations with high rates of consanguinity.

Severe Acute Hepatitis of Unknown Etiology in Pediatric Patients: Multidisciplinary Clinical Approach

Introduction: In mid-2022, the World Health Organization (WHO) declared a moderate-risk outbreak due to an increase in severe acute hepatitis cases of unknown etiology in children. Several reports suggested a viral infection link, with the outbreak spanning over 35 countries. By June 2022, Mexico reported 69 probable cases across 5 entities to the WHO. Case Presentation: A 4-year-old boy presented with vomiting, jaundice, choluria, and hepatomegaly. A multidisciplinary approach was employed, using an algorithm developed exclusively for clinical, epidemiological, and biochemical follow-up. Despite the negative identification of any associated microorganism and the absence of antibodies, liver function tests remained elevated. A fine needle liver biopsy was performed for diagnostic support, followed by histopathological study and sequencing and analysis of the complete high-depth transcriptome. Transcriptome analysis identified dysbiosis-related intestinal microbiota, including increased enterogenic and opportunistic pathogenic bacteria of the genus Clostridium, as well as HERV-K113, implicated in autoimmune disease development. Conclusions: The study's findings suggest possible immune-mediated mechanisms involving dysbiosis of the gut microbiota and the potential role of HERV-K113. Management and control of acute liver disease depend on specific causes, with the main challenge being early determination and implementation of optimal management strategies. The exact pathological mechanisms underlying pediatric acute hepatitis of unknown etiology remain elusive, warranting further studies to confirm or refute these hypotheses and elucidate the underlying pathological mechanisms

Etiology and Characteristics of Patients Presenting with Eyelid Lacerations at a Level 1 Trauma Center.

To investigate the etiology and demographic associations of patients presenting with eyelid lacerations to a US level 1 trauma center emergency department (ED). A retrospective chart review of all patients with eyelid lacerations presenting to the ED at a single level 1 trauma center was performed. Eyelid lacerations were categorized as simple eyelid lacerations, eyelid lacerations with eyelid margin involvement, and eyelid lacerations with nasolacrimal system involvement. Data on demographics and clinical characteristics were analyzed. A total of 303 eyelid laceration cases were identified, 56% were simple eyelid lacerations, followed by 24% with nasolacrimal involvement and 20% involving the eyelid margin. Sixty percent of animal bites/scratches resulted in a nasolacrimal system involving laceration, most commonly affecting children. Falls were the most common etiology in children and patients over the age of 60. Black patients, patients presenting with concomitant ophthalmic injuries, and those with Medicaid insurance were more likely to have an assault etiology (p < 0.05 for all). Falls were the most common etiology for eyelid lacerations in children and the elderly, while assault was the most common in adults. Identifying the most common etiology by demographic factors can help raise awareness regarding targeted prevention strategies for high-risk populations.

Challenges in diagnosing pediatric pericarditis and the etiology in remote areas during the COVID-19 pandemic: a socio-clinical dilemma

Inflammation of the visceral and parietal surfaces of the pericardium is defined as pericarditis. It can evolve to excessive production of pericardial effusion if the speed of fluid accumulation is faster than the absorption. Acute pericarditis is rare in children but it can lead to circulatory collapse and death. It accounts for &lt;0.2% of the emergency visits of children without prior heart diseases in tertiary pediatric emergency settings. The etiology of acute pericarditis varies depending on geography, and the most common etiology in children are bacterial infection, viral pericarditis, inflammatory or connective tissue diseases, malignancies, metabolic diseases, and post-cardiac surgery. Idiopathic pericarditis is presumed to have viral or post-viral etiology. It accounts for 37-68% of admissions in children with pericardial effusions or acute pericarditis.

Estimated C-reactive protein (CRP) velocity for rapidly distinguishing bacterial from other etiologies in children presenting to emergency department with remarkably elevated CRP levels.

The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults. This study aims to investigate the association between eCRPv and bacterial etiologies among pediatric patients with very elevated CRP levels. We conducted a retrospective analysis of patients under 18years of age who had been admitted to our Pediatric Emergency Department from 2018 to 2020 with a fever and CRP levels ≥ 150mg/L. Bacterial and non-bacterial etiologies were determined from hospital discharge diagnoses, which were monitored independently by three physicians from the research team. The records of 495 suitable patients (51.2% males, median age 3.2years) were retrieved of whom 444 (89.7%) were eventually diagnosed with bacterial infections. The mean CRP levels were significantly higher for bacterial etiologies compared with other causes (209.2 ± 59.8mg/L vs. 185.6 ± 35.8mg/L, respectively, p < .001), while the mean eCRPv values did not differ significantly (p = .15). In a time course analysis, we found that specifically in patients presenting ≥ 72h after symptom onset, only a eCRPv1 level > 1.08mg/L/h was an independent predictor of bacterial infection (aOR = 5.5 [95% CI 1.7-17.8], p = .004). Conclusion: Pediatric patients with very high CRP levels and fever mostly have bacterial infections. eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72h from symptom onset, warranting further prospective investigations into CRP kinetics in pediatric patients. What is Known: • The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. • Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults, but data on CRP kinetics in pediatric patients is sparse. What is New: • eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72h from symptom onset in pediatric patients with remarkably elevated CRP levels.

Molecular diagnosis is an important indicator for response to growth hormone therapy in children with short stature

BackgroundSignificant differences have been observed in the efficacy of recombinant human growth hormone (rhGH) treatment for short children. The present study aimed to identify the genetic etiology of short stature and to assess the role of molecular diagnosis in predicting responses to rhGH treatment. MethodsA total of 407 short children were included in the present study, 226 of whom received rhGH treatment. Whole-exome sequencing (WES) was conducted on short children to identify the underlying genetic etiology. Correlations between molecular diagnosis and the efficacy of rhGH treatment were examined. ResultsPathogenic or likely pathogenic mutations were identified in 86 of the 407 patients (21.1%), including 36 (41.9%) novel variants. Among the multiple pathways affecting short stature, genes involved in fundamental cellular processes (38.7%) play a larger role, especially the RAS-MAPK pathway. In general, patients without pathogenic mutations responded better to rhGH than those with mutations. Furthermore, patients with hormone signaling pathway mutations had a better response to rhGH, while those with paracrine factor mutations had a worse response to rhGH. ConclusionsThis study highlights the utility of WES in identifying genetic etiology in children with short stature. Identifying likely causal mutations is an important factor in predicting rhGH response.

Wavefront characteristics in amblyopia of different etiologies in children

Forty-five patients (90 eyes) were examined. All patients were divided into five groups: 1 - with dysbinocular amblyopia; 2 - with refractive amblyopia; 3 - with anisometropic amblyopia; 4 - with relative amblyopia due to congenital myopia; 5 (control) - fellow eyes without amblyopia. Aberrometry was performed using the OPD-Scan III device (Nidek, Japan). Fixation parameters were studied on the MP-3 microperimeter (Nidek, Japan). Correlation analysis was performed using Pearson's linear correlation coefficient (r). In amblyopia associated with congenital myopia, a significant increase in corneal and internal aberrations RMS, Total HOA, astigmatism (V) (0.65±0.26; 1.01±0.31; 4.22±1.17; -2.17±0.72; 0.86±0.3, respectively; control group - 0.44±0.19; 0.58±0.27; 1.0±0.75; -0.94±0.89; 0.47±0.65) and internal spherical aberration (0.06±0.02; control group - 0.04±0.03) was found. In dysbinocular amblyopia, a significant increase in internal aberrations Trefoil (V) and Coma (H) (0.75±0.52 and 0.17±0.35, respectively; control group - 0.05±0.28 and -0.07±0.21) was found, which correlated with a decrease in fixation density in the 2° ring (r= -0.40, r= -0.41). The increased level of higher-order aberrations in amblyopia associated with congenital myopia is due to the anatomical and optical features of the eyes. The increase in internal aberrations Trefoil (V) and Coma (H) in dysbinocular amblyopia is associated with a mismatch of the optical elements of the eye due to impaired fixation, i.e., it is not the cause, but the consequence of amblyopia.

Assessment and comparison of model estimated and directly observed weather data for prediction of diarrhoea aetiology.

Recent advances in clinical prediction for diarrhoeal aetiology in low- and middle-income countries have revealed that the addition of weather data to clinical data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare the use of model estimated satellite- and ground-based observational data with weather station directly observed data for the prediction of aetiology of diarrhoea. We used clinical and etiological data from a large multi-centre study of children with moderate to severe diarrhoea cases to compare their predictive performances. We show that the two sources of weather conditions perform similarly in most locations. We conclude that while model estimated data is a viable, scalable tool for public health interventions and disease prediction, given its ease of access, directly observed weather station data is likely adequate for the prediction of diarrhoeal aetiology in children in low- and middle-income countries.

Acute hepatitis of unknown etiology in children: Comparison between the U.K., U.S., and Japan, and ingenious clinical practice attempts

Acute hepatitis of unknown etiology in children: Comparison between the U.K., U.S., and Japan, and ingenious clinical practice attempts