In all, 15-30% of pediatric immune thrombocytopenia (ITP) patients will remain chronically thrombocytopenic at 1 year post diagnosis. All attempts to classify patients at diagnosis have proven ...unsuccessful. We hypothesized that a different pathophysiology is responsible for non-chronic versus chronic pediatric ITP. We aimed to examine differences in the apoptotic markers' presentation at diagnosis between non-chronic and chronic patients.
Blood samples were collected from 42 pediatric patients with newly diagnosed ITP prior to initiation of treatment. We incubated patients' sera with control platelets and compared the results among three research groups: healthy controls, chronic ITP, and non-chronic ITP patients. We measured apoptotic markers phosphatidylserine (PS) exposure and mitochondrial inner membrane potential (ΔΨm) by flow cytometry and the level of human apoptotic proteins by Human Apoptosis Array.
We found increased platelet PS exposure and decreased ΔΨm in response to all ITP patients' sera compared to control subjects. Human Apoptotic Array revealed an increased expression of five apoptotic proteins: BIM, CD40, IGFBP2, P21, and SMAC, following sera incubation of non-chronic pediatric ITP patients, compared to chronic patients' sera, at diagnosis.
Our data contribute to knowledge on apoptosis markers that may aid in predicting the prognosis of children with ITP.
The key message of our article is that children with chronic ITP have a different apoptotic profile compared to non-chronic ITP. Addition to existing literature: This is the first study comparing apoptotic markers between children with chronic ITP to non-chronic ITP.
Our findings indicate that, in the future, apoptotic markers may help to classify ITP patients into non-chronic versus chronic ones, at diagnosis.
Prolonged cytopenias are a non-specific sign with a wide differential diagnosis. Among inherited disorders, cytopenias predisposing to leukemia require a timely and accurate diagnosis to ensure ...appropriate medical management, including adequate monitoring and stem-cell transplantation prior to the development of leukemia. We aimed to define the types and prevalences of the genetic causes leading to persistent cytopenias in children. The study comprises children with persistent cytopenias, myelodysplastic syndrome, aplastic anemia, or suspected inherited bone marrow failure syndromes, who were referred for genetic evaluation from all pediatric hematology centers in Israel during 2016-2019. For variant detection, we used Sanger sequencing of commonly mutated genes and a custommade targeted next-generation sequencing panel covering 226 genes known to be mutated in inherited cytopenias; the minority subsequently underwent whole exome sequencing. In total, 189 children with persistent cytopenias underwent a genetic evaluation. Pathogenic and likely pathogenic variants were identified in 59 patients (31.2%), including 47 with leukemia predisposing syndromes. Most of the latter (32, 68.1%) had inherited bone marrow failure syndromes, 9 (19.1%) had inherited thrombocytopenia predisposing to leukemia, and 3 each (6.4%) had predisposition to myelodysplastic syndrome or congenital neutropenia. Twelve patients had cytopenias with no known leukemia predisposition, including nine children with inherited thrombocytopenia and three with congenital neutropenia. In summary, almost one-third of 189 children referred with persistent cytopenias had an underlying inherited disorder; 79.7% of whom had a germline predisposition to leukemia. Precise diagnosis of children with cytopenias should direct follow-up and management programs and may positively impact disease outcome.
Syndromes of Thrombotic Microangiopathy Aviner, Shraga; Bibi, Haim; Villa, Fabio ...
New England journal of medicine/The New England journal of medicine,
11/2014, Volume:
371, Issue:
19
Journal Article
Peer reviewed
Open access
To the Editor:
In their review of the thrombotic microangiopathy syndromes, George and Nester (Aug. 14 issue)
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do not mention the option of treating severe neurologic deficits in patients with shiga ...toxin–mediated hemolytic–uremic syndrome (ST-HUS) with IgG depletion through immunoadsorption.
2
In the 2011 outbreak in northern Germany, the delay in the onset of neurologic symptoms (5 to 12 days after the onset of diarrhea; mean and median, 8.0 days) strongly suggested antibody involvement in the pathogenesis of these symptoms. Consequently, all 12 patients had substantial improvement, and 10 of them fully recovered after IgG depletion through immunoadsorption, despite the failure . . .
In 2005, Clalit Health Services (CHS), the largest health maintenance organization in Israel, initiated an intervention program aimed at reducing the prevalence rate of infantile anemia (IA). This ...study evaluated the progress made during the intervention (2005-2014) and its yield 5 years after it ended (2019).
The CHS database was retrospectively reviewed twice yearly from 2005 to 2014 for repetitive samples of children aged 9 to 18 months regarding the previous half-year interval, and a single sample in 2019. Data were collected on gender, ethnicity (Jewish/non-Jewish), socioeconomic class (SEC; low/intermediate/high), hemoglobin testing (yes/no), and hemoglobin level (if tested). Excluded were infants with documented or suspected hemoglobinopathy.
At study initiation, the rate of performance of hemoglobin testing was 54.7%, and the IA prevalence rate was 7.8%. The performance rate was lower in the Jewish than the non-Jewish subpopulation. The low-SEC subpopulation had a similar hemoglobin testing rate to the high-SEC subpopulation but double the IA prevalence rate. Overall, by the end of the intervention (2014), the performance rate increased to 87.5%, and the AI prevalence rate decreased to 3.4%. In 2019, there was little change in the performance rate from the end of the intervention (88%) and the IA prevalence was further reduced to 2.7%. The non-Jewish and low-SEC subpopulations showed the most improvement which was maintained and even bettered 5 years after the intervention ended.
The 10-year IA intervention program introduced by CHS in 2005 led to a reduction in IA prevalence rate to about 3.5% in all sub-populations evaluated. By program end, the results in the weaker subpopulations, which had the highest prevalence of IA at baseline, were not inferior to those in the stronger subpopulations. We recommended to the Israel Ministry of Health to adopt the intervention countrywide, and we challenge other countries to consider similar interventions.
An apparent life-threatening event (ALTE) caused by ingestion of drugs or toxins has been reported rarely among infants. None of these agents was homeopathic medication. We report 11 infants who ...presented with an ALTE after ingestion of Gali-col Baby, a homeopathic agent indicated for "infantile colic."
A retrospective case-control study was conducted. Charts of all infants who were younger than 1 year and were admitted with an ALTE from January 2005 through August 2008 to the pediatric division at the Barzilai Medical Center were reviewed. Age-matched infants who were admitted on the same dates for a reason other than ALTE served as a control group. Information on medications administered before admission was recorded.
During the study period, 36 635 children visited the pediatric emergency department of the Barzilai Medical Center. There were 11 057 admissions to the pediatric division during this period, 115 of which were because of an ALTE. Eleven of these infants received Gali-col Baby before the event as opposed to none in the control group (P < .005). Three infants received a significant overdose, compared with the manufacturer's recommended dosage. After a thorough investigation, no other presumptive causes for ALTE were found among the 11 infants.
Gali-col Baby is associated with an ALTE in some infants. There are no published controlled trials on the efficacy or safety of its use; therefore, better control and supervision of Gali-col Baby and probably other homeopathic medications are needed to prevent possible serious adverse effects.
Inherited bone marrow failure syndromes are rare genetic disorders characterized by bone marrow failure, congenital anomalies, and cancer predisposition. Available single disease registries provide ...reliable information regarding natural history, efficacy and side effects of treatments, and contribute to the discovery of the causative genes. However, these registries could not shed light on the true incidence of the various syndromes. We, therefore, established an Israeli national registry in order to investigate the relative frequency of each of these syndromes and their complications.
Patients were registered by their hematologists in all 16 medical centers in Israel. We included patients with Fanconi anemia, severe congenital neutropenia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, dyskeratosis congenita, Shwachman-Diamond syndrome, and thrombocytopenia with absent radii.
One hundred and twenty-seven patients diagnosed between 1966 and 2007 were registered. Fifty-two percent were found to have Fanconi anemia, 17% severe congenital neutropenia, 14% Diamond-Blackfan anemia, 6% congenital amegakaryocytic thrombocytopenia, 5% dyskeratosis congenita, 2% Shwachman-Diamond syndrome, and 2% thrombocytopenia with absent radii. No specific diagnosis was made in only 2 patients. Of the thirty patients (24%) developing severe bone marrow failure, 80% had Fanconi anemia. Seven of 9 patients with leukemia had Fanconi anemia, as did all 6 with solid tumors. Thirty-four patients died from their disease; 25 (74%) had Fanconi anemia and 6 (17%) had severe congenital neutropenia.
This is the first comprehensive population-based study evaluating the incidence and complications of the different inherited bone marrow failure syndromes. By far the most common disease was Fanconi anemia, followed by severe congenital neutropenia and Diamond-Blackfan anemia. Fanconi anemia carried the worst prognosis, with severe bone marrow failure and cancer susceptibility. Diamond-Blackfan anemia had the best prognosis. The data presented provide a rational basis for prevention programs and longitudinal surveillance of the complications of inherited bone marrow failure syndromes.
Highlights • A prospective nationwide IPD surveillance was conducted in Israeli children <5 years. • Our aim was to report the impact of PCV7/PCV13 sequential introduction on IPD. • A substantial ...2-step reduction of IPD rates was observed. • Serotype-specific rate reduction reflected the sequential PCV7/PCV13 introduction.
Rotavirus gastroenteritis is a prevalent childhood illness rarely complicated by secondary bacterial sepsis. Although there are case reports of septicemia after rotavirus infection, there are no ...recent reviews on this topic.
To add new cases of septicemia after rotavirus to the literature, review the few cases of septicemia after rotavirus that have been reported, calculate the incidence of septicemia in children hospitalized for rotavirus gastroenteritis, and discuss the characteristics of septicemia after rotavirus infection and implications for current pediatric practice.
We identified children whose illness was complicated by septicemia from among all hospitalizations at our facility for rotavirus gastroenteritis from May 1999 through May 2010. We also review the few cases reported in the English literature.
We identified two cases of septicemia from among 632 hospitalizations for rotavirus gastroenteritis in this time period, for an incidence rate of 0.32%, which is comparable to other estimates in the English literature. The typical course for cases of bacterial superinfection involves a second peak of high fever; other clinical signs are variable.
Septicemia after rotavirus gastroenteritis is a rare but dangerous entity. Early identification of a child developing bacterial superinfection after rotavirus, as in any case of sepsis, is of the utmost importance, as is obtaining blood cultures in a child with a rotavirus infection and a second fever spike.
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