ABSTRACT
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.
Subject(s)
Biomarkers , Cisplatin , Hypertension , Renal Insufficiency, Chronic , Humans , Cisplatin/adverse effects , Biomarkers/blood , Child , Renal Insufficiency, Chronic/diagnosis , Kidney Tubules/pathology , Kidney Tubules/metabolism , Kidney Tubules/drug effects , Female , Male , Child, Preschool , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Adolescent , Hepatitis A Virus Cellular Receptor 1/metabolismABSTRACT
BACKGROUND AND OBJECTIVE: Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2, leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature. DESIGN: Retrospective cohort study. METHODS: Clinical, laboratory, and molecular data from patients' records were collected. RESULTS: Five patients presented at early childhood with normal estimated glomerular filtration rate (eGFR), while 2 patients presented during late childhood with CKD. Molecular analysis revealed 2 novel homozygous mutations in HSD11B2. All patients presented with severe hypertension and hypokalemia. While all patients developed nephrocalcinosis, only 1 showed hypercalciuria. All individuals were managed with potassium supplements, mineralocorticoid receptor antagonists, and various antihypertensive medications. One patient survived cardiac arrest secondary to severe hyperkalemia. At last follow-up, those 5 patients who presented early exhibited normal eGFR and near-normal blood pressure, but 2 have hypertension complications. The 2 patients who presented with CKD progressed to end-stage kidney disease (ESKD) necessitating dialysis and kidney transplantation. CONCLUSIONS: In this 11-year follow-up report of 2 Israeli families with AME, patients who presented early maintained long-term normal kidney function, while those who presented late progressed to ESKD. Nevertheless, despite early diagnosis and management, AME is commonly associated with serious complications of the disease or its treatment.
Subject(s)
Mineralocorticoid Excess Syndrome, Apparent , Humans , Israel/epidemiology , Male , Female , Mineralocorticoid Excess Syndrome, Apparent/genetics , Mineralocorticoid Excess Syndrome, Apparent/diagnosis , Retrospective Studies , Child , Child, Preschool , 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics , Adolescent , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Mutation , Hypertension/epidemiology , Hypokalemia , AdultABSTRACT
BACKGROUND: Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity. OBJECTIVE: To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel. METHODS: We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for ELANE or G6PC3, and patients with wild-type ELANE/G6PC3 were referred for next-generation sequencing. RESULTS: Sixty-five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in ELANE (15 patients). Nine patients had biallelic variants in G6PC3, all of consanguineous Muslim Arab origin. Other genes involved were SRP54, JAGN1, TAZ, and SLC37A4. Seven patients had cyclic neutropenia, all with pathogenic variants in ELANE, and seven had Shwachman-Diamond syndrome caused by biallelic SBDS variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte-colony stimulating factor or due to myeloid transformation. CONCLUSIONS: The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of G6PC3 variants and an absence of HAX1 mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow-up.
Subject(s)
Congenital Bone Marrow Failure Syndromes , Mutation , Neutropenia , Humans , Neutropenia/genetics , Neutropenia/congenital , Neutropenia/epidemiology , Neutropenia/diagnosis , Male , Israel/epidemiology , Female , Child , Congenital Bone Marrow Failure Syndromes/genetics , Congenital Bone Marrow Failure Syndromes/diagnosis , Child, Preschool , Adolescent , Genetic Predisposition to Disease , Adult , Hematopoietic Stem Cell Transplantation , Infant , Consanguinity , Glucose-6-Phosphatase/genetics , Alleles , Registries , High-Throughput Nucleotide Sequencing , Young Adult , Phenotype , Genetic Association StudiesABSTRACT
BACKGROUND: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes. METHODS: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. RESULTS: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]). CONCLUSIONS: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.
Subject(s)
Acute Kidney Injury , Hypertension , Renal Insufficiency, Chronic , Humans , Child , Child, Preschool , Cisplatin/adverse effects , Prospective Studies , Retrospective Studies , Canada , Kidney , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Acute Kidney Injury/diagnosis , Renal Insufficiency, Chronic/complications , Hypertension/drug therapy , Risk Factors , ElectrolytesABSTRACT
Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. Objective: To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Design: Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Setting: Five Ontario pediatric oncology centers. Patients: The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Measurements: Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Methods: Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Limitations: Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Conclusions: Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.
ABSTRACT
CONTEXT: Bartter syndrome (BS) is a group of rare autosomal-recessive tubulopathies characterized by hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption. Type 2 BS results from a defect in the renal outer medullary potassium channel encoded by the KCNJ1 gene. Type 2 BS presents with polyhydramnios, intrauterine growth retardation, prematurity, failure to thrive, polyuria, hypercalciuria, and life-threatening episodes of dehydration. Hypocalcemia is a very rare presenting symptom of BS, with only a few published cases reporting it as the initial manifestation of type 2 BS. OBJECTIVE: To describe a child who presented with hypocalcemic seizure at the age of 2.3 years that was first related to vitamin D deficiency and high-phosphate soft drink consumption. METHODS: Whole exome sequencing (WES) was used to evaluate the biochemical abnormalities of the proband. RESULTS: We identified a previously described homozygous missense mutation c.212C>T, p.T71M in the KCNJ1 gene associated with type 2 BS. Six additional family members with the same mutation and diagnosed clinically with BS are also reported, 2 presenting with hypocalcemia associated with vitamin D deficiency. CONCLUSION: This report expands the clinical spectrum associated with KCNJ1 mutations and emphasizes the role of WES in unsolved cases of hypocalcemia when genetic disease is suspected. It also highlights the hazardous effects of phosphate-containing soft drinks on calcium metabolism.
Subject(s)
Alkalosis , Bartter Syndrome , Hypocalcemia , Vitamin D Deficiency , Alkalosis/complications , Bartter Syndrome/complications , Bartter Syndrome/diagnosis , Bartter Syndrome/genetics , Child , Child, Preschool , Female , Humans , Hypercalciuria/diagnosis , Hypercalciuria/genetics , Hypocalcemia/etiology , Hypocalcemia/genetics , Male , Phosphates , Pregnancy , Vitamin D Deficiency/complicationsABSTRACT
Urinary tract infection (UTI) is common in preterm infants and may have long-term sequela, such as recurrent infections and renal scarring in older children. We assessed long-term outcomes of preterm infants with UTI, born during 1996-2008 in Schneider Children's Medical Center's neonatal intensive care unit (NICU), and incidence of UTI recurrence. Of 89 preterm infants, seven were excluded due to prenatal diagnosis of congenital anomalies of the kidney and urinary tract (CAKUT), 41 interviewed by phone, 18 presented for follow-up evaluation in the nephrology clinic, and 23 lost to follow-up. No patient who completed follow-up reported additional UTI episodes or issues related to kidney and urinary tract. Clinically evaluated participants were 17.1 ± 3.6 years, born prematurely at 29.4 ± 4 weeks. All had a normal estimated glomerular filtration rate of >90 ml/min/1.73m2; four (22%) had systolic blood pressure >90th percentile; none had proteinuria (mean protein/creatinine ratio 0.09 ± 0.04 mg/mg) or albuminuria (mean albumin/creatinine ratio 10.2 ± 6.3 mcg/mg). Renal ultrasonography done in the first years of life in 12 (66%) patients demonstrated normal kidney size and structure.Conclusion: In this pilot study, a single episode of UTI in premature infants without CAKUT did not constitute a risk factor for recurrence of infections or kidney injury in their first two decades of life. Thus, normal ultrasound in NICU excluding CAKUT may be sufficient for premature patients with UTI, with no need of further imaging or long-term nephrology follow-up. What is Known: ⢠Urinary tract infection (UTI) is one of the most common bacterial infections in neonates and premature infants. Risk factors for UTI recurrence in children are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder and bowel dysfunction. ⢠The recurrence rate and long-term renal sequela of UTI in preterm infants have not been studied. Guidelines regarding management and long-term follow-up for infants less than 2 months old are lacking. What is New: ⢠A single episode of UTI in premature infants without CAKUT probably does not constitute a risk factor for UTI recurrence, and it is unlikely to cause renal injury in the first two decades of life. ⢠For premature infants with UTI without sonographic diagnosis of CAKUT in NICU, prophylactic antibiotic treatment, further imaging, or long-term nephrology follow-up may be unnecessary.
Subject(s)
Infant, Premature, Diseases , Urinary Tract Infections , Urinary Tract , Child , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/epidemiology , Pilot Projects , Pregnancy , Urinary Tract/diagnostic imaging , Urinary Tract Infections/diagnosis , Urinary Tract Infections/epidemiologyABSTRACT
Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM-1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM-1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0-13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, -0.33). Urine platinum was not associated with postinfusion AKIor KIM-1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.
Subject(s)
Acute Kidney Injury/diagnosis , Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Neoplasms/drug therapy , Platinum/urine , Antineoplastic Agents/urine , Biomarkers , Child , Child, Preschool , Cisplatin/urine , Dose-Response Relationship, Drug , Electrolytes/urine , Female , Hepatitis A Virus Cellular Receptor 1/metabolism , Humans , Kidney Function Tests , Lipocalin-2/urine , MaleABSTRACT
PURPOSE OF REVIEW: The current review will describe the current evidence and mechanisms of acute kidney injury (AKI) as a risk factor for long-term kidney complications, summarize the rationale for AKI follow-up and present an approach to monitoring children with AKI. Despite emerging evidence linking AKI with risk for long-term kidney and cardiovascular outcomes, many children who develop AKI are not followed for kidney disease development after hospital discharge. Better understanding of long-term complications after AKI and practical algorithms for follow-up will hopefully increase the rate and quality of post-AKI monitoring. RECENT FINDINGS: Recent evidence shows that pediatric AKI is associated with long-term renal outcomes such as chronic kidney disease (CKD) and hypertension, both known to increase cardiovascular risk. The mechanism of AKI progression to CKD involves maladaptive regeneration of tubular epithelial and endothelial cells, inflammation, fibrosis and glomerulosclerosis. Many AKI survivors are not followed, and no guidelines for pediatric AKI follow-up have been published. SUMMARY: Children who had AKI are at increased risk of long-term renal complications but many of them are not monitored for these complications. Recognizing long-term outcomes post-AKI and integration of follow-up programs may have a long-lasting positive impact on patient health.
Subject(s)
Acute Kidney Injury/complications , Renal Insufficiency, Chronic/physiopathology , Acute Kidney Injury/physiopathology , Child , Glomerular Filtration Rate/physiology , Humans , Hypertension/etiology , Hypertension/physiopathology , Outcome Assessment, Health Care , Renal Insufficiency, Chronic/etiology , Risk Factors , Severity of Illness IndexABSTRACT
Infections is a common complication of nephrotic syndrome (NS). Our objective was to evaluate the frequency and risk factors for serious bacterial infections (SBI) in febrile children with NS. We reviewed 239 admissions of 107 children with NS who were admitted with fever to a tertiary hospital in Israel, during 1995 to 2016. SBI was diagnosed in 35 admissions (14.6%), most commonly with pneumonia (n = 12), bacteremia/sepsis (n = 8), and urinary tract infection (n = 6). Patients with SBI were more likely to be female (60.0% vs 36.3%, P = .008) and have nephrotic-range proteinuria (71.4% vs 43.6%, P = .010) and edema (62.9% vs 27.0%, P < .001) on admission. No differences were found between the SBI and non-SBI groups in the clinical and histopathological type of NS, immunosuppressive treatment, rate of pneumococcal vaccination, and prophylactic antibiotics. In summary, 1 of 7 children had SBI, most commonly pneumonia, bacteremia/sepsis, and urinary tract infection. Active nephrosis was associated with an increased risk for SBI.
Subject(s)
Bacterial Infections/epidemiology , Nephrotic Syndrome/epidemiology , Child , Child, Preschool , Comorbidity , Female , Hospitalization/statistics & numerical data , Humans , Israel/epidemiology , Male , Retrospective Studies , Risk Factors , Severity of Illness Index , Sex Factors , Tertiary Care CentersABSTRACT
Adenovirus is a common pediatric pathogen responsible for a wide variety of infections. Despite this, secondary bacteremia following an adenovirus infection has not been previously systematically described. Herein, we describe seven cases of secondary bacteremia following an adenovirus infection in hospitalized children during an 8-year period. Pediatricians should be informed of this serious complication.
Subject(s)
Adenoviridae Infections/complications , Bacteremia/complications , Female , Fever , Hospitalization , Humans , Infant , Male , Retrospective StudiesABSTRACT
Our aim was to identify miRNAs that can predict risk of relapse in pediatric patients with acute lymphoblastic leukemia (ALL). Following high-throughput miRNA expression analysis (48 samples), five miRs were selected for further confirmation performed by real time quantitative PCR on a cohort of precursor B-cell ALL patients (n = 138). The results were correlated with clinical parameters and outcome. Low expression of miR-151-5p, and miR-451, and high expression of miR-1290 or a combination of all three predicted inferior relapse free survival (P = 0.007, 0.042, 0.025, and <0.0001, respectively). Cox regression analysis identified aberrant expression of the three miRs as an independent prognostic marker with a 10.5-fold increased risk of relapse (P = 0.041) in PCR-MRD non-high risk patients. Furthermore, following exclusion of patients harboring IKZF1 deletion, the aberrant expression of all three miRs could identify patients with a 24.5-fold increased risk to relapse (P < 0.0001). The prognostic relevance of the three miRNAs was evaluated in a non-BFM treated precursor B-cell ALL cohort (n = 33). A significant correlation between an aberrant expression of at least one of the three miRs and poor outcome was maintained (P < 0.0001). Our results identify an expression profile of miR-151-5p, miR-451, and miR-1290 as a novel biomarker for outcome in pediatric precursor B-cell ALL patients, regardless of treatment protocol. The use of these markers may lead to improved risk stratification at diagnosis and allow early therapeutic interventions in an attempt to improve survival of high risk patients.
Subject(s)
MicroRNAs/biosynthesis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Child , Child, Preschool , Cohort Studies , Female , Gene Expression Profiling , Humans , Infant , Male , MicroRNAs/genetics , Oligonucleotide Array Sequence Analysis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/physiopathology , Prognosis , RecurrenceABSTRACT
BACKGROUND: The relative frequency of mutated genes among patients with severe congenital neutropenia (SCN) may differ between various ethnic groups. To date, few population-based genetic studies have been reported. This study describes the genetic analysis of 32 Israeli patients with SCN. PROCEDURES: Clinical data were retrieved from the prospective Israeli Inherited Bone Marrow Failure Registry. Recruitment included living and deceased patients who were diagnosed between 1982 and 2012, for whom molecular diagnosis was performed. ELANE, HAX1 and G6PC3 genes were sequenced in all patients, and GFI-1 and WAS genes were sequenced if other genes were wildtype. RESULTS: Eleven patients (34%) had heterozygous mutations in ELANE (10 kindreds), eight (25%) had homozygous mutations in G6PC3 (5 kindreds) and 13 (41%) had no detected mutations. No patients had mutations in HAX1 or WAS. Four of the eight patients with G6PC3 mutations had congenital anomalies. The probability of survival for all patients was 50% at age of 18. Deaths were mainly due to sepsis (5 patients, 4/5 not responding to G-CSF, none with G6PC3 mutation). Two patients developed acute myelogenous leukemia (AML) and one myelodysplastic syndrome (MDS), none with G6PC3 mutation. CONCLUSIONS: We found a unique pattern of SCN mutations in Israel with homozygous G6PC3 mutations in eight (25%) patients, the highest frequency described so far. HAX1 mutations, reported mainly in Sweden and Iran, were absent. Patients with G6PC3 mutations had congenital anomalies, appeared to have a better response to G-CSF, and so far have not developed AML or MDS.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Genetic Testing , Glucose-6-Phosphatase/genetics , Mutation/genetics , Neutropenia/congenital , Adolescent , Child , Child, Preschool , Combined Modality Therapy , Congenital Bone Marrow Failure Syndromes , DNA-Binding Proteins/genetics , Female , Follow-Up Studies , Genotype , Granulocyte Colony-Stimulating Factor/therapeutic use , Homozygote , Humans , Infant , Infant, Newborn , Israel/epidemiology , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Male , Myelodysplastic Syndromes/epidemiology , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/therapy , Neutropenia/genetics , Neutropenia/mortality , Neutropenia/pathology , Prognosis , Prospective Studies , Stem Cell Transplantation , Survival Rate , Transcription Factors/genetics , Wiskott-Aldrich Syndrome Protein/geneticsABSTRACT
OBJECTIVE: To evaluate the predictive value of clinical features at diagnosis of immune thrombocytopenia (ITP) for resolution of disease. STUDY DESIGN: Hospital records of 472 consecutive children (<18 years old) with ITP cared for at 2 participating centers were reviewed retrospectively and data related to the initial presentation were recorded. Logistic regression analysis was used for calculating prediction of resolution at 3, 6, and 12 months from diagnosis. RESULTS: The most significant predictors for resolution of ITP at 3, 6, and 12 months were age at onset <10 years and abrupt onset (history of <2 weeks of bleeding). We designed a prediction rule for ITP chronicity based on these criteria. The rate of developing chronic ITP for low, intermediate, and high risk children at diagnosis of ITP was 11%, 39%, and 63%, respectively. Recovery rate at 3 months for low, intermediate, and high risk children was 72%, 43% and 30%, respectively. CONCLUSIONS: We present a simple rule to predict recovery from ITP at 3, 6, and 12 months from diagnosis. For prediction of resolution at 3 months, our rule was in agreement with the more complex, previously described Nordic score. Prediction of resolution of ITP may enable practitioners to better inform children and parents at the time of diagnosis, resulting in reduced anxiety and improved quality of life.
Subject(s)
Hemorrhage/diagnosis , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/therapy , Adolescent , Age of Onset , Child , Child, Preschool , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Logistic Models , Male , Multivariate Analysis , Platelet Count , Quality of Life , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Autoimmune hepatitis (AIH) is a chronic and progressive disease. The etiology and epidemiologic characterizations of AIH are not fully understood. It has a prolonged course and can affect all age groups. Symptoms and signs may appear years before diagnosis, and may be manifested for extended periods only as minor liver enzymes abnormalities. Clinical manifestations vary from lethargy and jaundice, to extremely severe deterioration in quality of life, hepatic failure and liver transplantation or death. In most cases there is a good response to therapy, making it important to diagnose the disease early in its course. The objectives of this review are to increase the awareness to AIH, to the diagnostic methods and to the treatment modalities and to discuss updates regarding AIH.