Procena psihomotornog razvoja dece s Vestovim sindromom

Introduction. West Syndrome (WS) is age-related epileptic encephalopathy characterised by a triad of symptoms: specific seizure type, pathognomonic electroencephalographic (EEG) pattern - hypsarrhythmia and delay and/or regression in psychomotor development (PMD). Aetiologically, it occurs in three forms: symptomatic, cryptogenic and idiopathic. Objective. Estimation of PMD in children with WS according to aetiology. Methods. The observed group consisted of 65 children. Age range was between 6 and 30 months. The patients were divided into three groups according to aetiology. All patients underwent psychological examination with Brunet-Lesine test, as well as PMD evaluation based on achieved developmental milestones for the corresponding age. Results. Statistically significant better values in the Human Developmental Index (HDI) had patients with idiopathic compared to other forms of WS, at testing after 12 months (93.0±8.1 vs. 46.8±6.1 vs. 45.6±3.8), as well as after 24 months (93.9±7.7 vs. 51.9±5.5 vs. 50.9±4.4). The best values of HDI after 24 months had patients with improvement in PMD with the average of 66.2±4.4, which was statistically significant compared to those with unchanged PMD (41.5±5.3) and with further regression in PMD (28.3±4.4). Significant correlation was obtained between PMD after 12 and 24 months (r=0.477), as well as a considerable improvement in HDI from the 12th to 24th month (49.4±4.0 vs. 53.7±3.9). Conclusion. The patients with idiopathic WS accomplished the best PMD. Improvement in PMD after 12 and 24 months of treatment was associated with improved HDI. Improvement in PMD was observed in all patients after 2 years of follow-up.Uvod. Vestov (West) sindrom (VS) je uzrasno zavisna epileptična encefalopatija koju odlikuje trojstvo simptoma: specifičan obrazac napada, tipičan elektroencefalografski (EEG) obrazac - hipsaritmija i zastoj, odnosno regresija u psihomotornom razvoju (PMR). Etiološki, javlja se u tri oblika: simptomatskom, kriptogenom i idiopatskom. Cilj rada. Cilj istraživanja bila je procena PMR dece sa VS u odnosu na etiologiju. Metode rada. Ispitivanu grupu činilo je 65 dece sa VS uzrasta 6-30 meseci. Bolesnici su svrstani u tri grupe prema etiologiji oboljenja. Svi su podvrgnuti psihološkom testiranju Brine-Lesinovim (Brunet- Ljsine) testom i proceni PMR na osnovu ostvarivanja miljokaza razvoja. Rezultati. Statistički značajno bolju vrednost indeksa razvoja (IR) ostvarili su bolesnici s idiopatskim oblikom VS, kako pri testiranju posle 12 meseci (93,0±8,1 prema 46,8±6,1 prema 45,6±3,8), tako i nakon 24 meseca kliničkog praćenja (93,9±7,7 prema 51,9±5,5 prema 50,9±4,4). Najbolje vrednosti IR posle 24 meseca postigli su bolesnici s napretkom u PMR, kod kojih je srednja vrednost ovog parametra bila 66,2±4,4, što je bilo statistički značajno u odnosu na bolesnike s nepromenjenim PMR (41,5±5,3) i regresijom u PMR (28,3±4,4). Dobijena je značajna korelacija između PMR posle godinu dana i dve godine (r=0,477), a uočeno je i značajno poboljšanje vrednosti IR između 12. i 24. meseca (49,2±4,0 prema 53,7±3,9). Zaključak. Deca s idiopatskim oblikom VS ostvaruju najbolji PMR. Napredak u PMR posle 12 meseci i 24 meseca lečenja bio je udružen sa boljim IR. Kod svih bolesnika uočen je napredak u PMR posle dve godine lečenja

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Mitotic crossover promotes leukemogenesis in children born with TEL-AML1 via the generation of loss of heterozygosity at 12p

TEL-AML1 (ETV6-RUNX1) fusion gene which is formed prenatally in 1% of the newborns, is a common genetic abnormality in childhood Bcell precursor acute lymphoblastic leukemia. But only one child out of a hundred children born with this fusion gene develops leukemia (bottleneck phenomenon) later in its life, if contracts the second mutation. In other words, out of a hundred children born with TEL-AML1 only one child is at risk for leukemia development, which means that TEL-AML1 fusion gene is not sufficient for overt leukemia. There is a stringent requirement for a second genetic abnormality for leukemia development and this is the real or the ultimate cause of the leukemia bottleneck phenomenon. In most cases of TEL-AML1+ leukemia, the translocation t(12;21) is complemented with the loss of the normal TEL gene, not involved in the translocation, on the contralateral 12p. The loss of the normal TEL gene, i.e. loss of heterozygosity at 12p, occurs postnatally during the mitotic proliferation of TEL-AML1+ cell in the mitotic crossing over process. Mitotic crossing over is a very rare event with a frequency rate of 10–6 in a 10 kb region. The exploration and identification of the environmental exposure(s) that cause(s) proliferation of the TELAML1+ cell in which approximately 106 mitoses are generated to cause 12p loss of heterozygosity, i.e. TEL gene deletion, may contribute to the introduction of preventive measures for leukemia

Intraoperative anaphylactic shock in a child with no history of type I hypersensitivity

Natural rubber latex is the second most implicated agent in intraoperative anaphylactic reactions. This report describes a case of intraoperative anaphylaxis occurring in a non-atopic fourteen-year-old girl undergoing multiple surgical procedures, but without spina bifida, in which latex surgical gloves were the main culprit for the anaphylactic reactions. Clinical manifestations of an anaphylactic reaction were also experienced during the examination of the possible cause of intraoperative anaphylaxis by skin prick testing with a latex allergen extract. Skin tests with anesthetics were negative. Specific IgE to latex was positive at 92.9 kUA/L (class 5). The molecular basis for the reported intraoperative anaphylaxis was ascribed to three low-molecular mass latex allergens (10-15 kD) detected in the brand of latex surgical gloves used during the operation. Given the potential of a dramatic outcome, latex allergy, testing as a regular preoperative measure may contribute to the reduction of anaphylactic reactions during surgical interventions

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin